OTO-201 for the Treatment of Acute Otitis Externa: Results from a Phase 3 Randomized Clinical Study.

OBJECTIVES: OTO-201 is a ciprofloxacin otic suspension previously approved by the US Food and Drug Administration to treat children with bilateral otitis media with effusion requiring tympanostomy tube placement. In this phase 3, double-blind, randomized, prospective, sham-controlled, multicenter study, a single dose of OTO-201 was administered to the external auditory canal in subjects with unilateral or bilateral acute otitis externa. METHODS: Two hundred sixty-two subjects, 3 to 83 years of age, were randomized, and 260 subjects were included in the intent-to-treat analysis population: OTO-201 (0.2 mL, 12 mg, n = 130) or sham (air injection, n = 130). The primary efficacy measure was clinical cure (CC) on day 8, judged by blinded assessor for erythema, edema, otorrhea, and tenderness. Subjects were monitored over 28 days for efficacy and safety. RESULTS: OTO-201 demonstrated a significant increase in CC compared with sham at day 8 (69.2% vs 46.1%, P < .001). Higher CC was also noted on day 4 ( P = .028), day 15 ( P < .001), and day 29 ( P < .001). A similar effect was observed in the pathogen-positive population. Single OTO-201 administration in the office setting was well tolerated by subjects. CONCLUSIONS: In this study in subjects with acute otitis externa, a single administration of 12 mg OTO-201 to the external auditory canal demonstrated a significantly higher proportion of subjects with CC and bacterial eradication compared with sham starting on day 4 and on all other observation days through day 29, with no safety or tolerability concerns identified. OTO-201 is the first agent in a randomized phase 3 study to demonstrate the efficacy and safety of a single-dose, health care professional-administered topical antibiotic for the treatment of acute otitis externa.

Safety and Efficacy of Intratympanic Ciprofloxacin Otic Suspension in Children With Middle Ear Effusion Undergoing Tympanostomy Tube Placement: Two Randomized Clinical Trials.

IMPORTANCE: Otorrhea after tympanostomy tube placement (TTP) in children is common. Although not approved by the US Food and Drug Administration, antibiotic ear drops are routinely used intraoperatively and prescribed for multidose, multiday postoperative administration by caregivers. OBJECTIVE: To investigate the safety and efficacy of a single-dose intratympanic, intraoperative, thermosensitive, otic suspension of ciprofloxacin (OTO-201) in children requiring TTP. DESIGN, SETTING, AND PARTICIPANTS: Two identically designed, prospective, double-blind, sham-controlled, multicenter phase 3 randomized clinical trials included 532 patients aged 6 months to 17 years with middle ear effusions. Patients with confirmed bilateral effusions on the day of TTP were randomized to TTP alone or to TTP with OTO-201 injection. Children underwent a 28-day observation period. Data were collected from November 14, 2013, to June 3, 2014. Final follow-up was completed on June 16, 2014, and intent-to-treat data were analyzed from June 10 to August 27, 2014. MAIN OUTCOMES AND MEASURES: Efficacy was assessed as treatment failure, including the presence of otorrhea, use of otic or systemic antibiotics, loss to follow-up, or missed visits. Safety was assessed for serious adverse events and treatment-emergent adverse events using audiometry, otoscopy, and tympanometry. RESULTS: Among the 532 patients included in the trials, 175 were randomized to TTP only and 357 to OTO-201 treatment (304 boys [57.1%]; 228 girls [42.9%]; mean [SD] age, 2.4 [2.1]). At day 15, the cumulative proportion of treatment failures (primary end point) was 24.6% (44 of 179 patients) in trial 1 and 21.3% (38 of 178 patients) in trial 2 in the OTO-201 groups vs 44.8% (39 of 87 patients) in trial 1 and 45.5% (40 of 88 patients) in trial 2 in the TTP-alone groups. At day 15 otorrhea-only treatment failures in trial 1 included 21 of 179 (11.7%) in the OTO-201 group vs 22 of 87 (25.3%) in the TTP-only group; in trial 2, 17 of 178 (9.6%) in the OTO-201 group vs 29 of 88 (33.0%) in the TTP-only group. The odds of otorrhea-only failure were significantly reduced in the OTO-201 groups compared with the TTP-only groups in both trials (age-adjusted odds ratios, 0.38 [95% CI, 0.19-0.75] and 0.19 [95% CI, 0.09-0.38]; P < .001 for both trials, post hoc analysis). No drug-related serious adverse events were seen, and most adverse events were mild or moderate. No evidence of increased tube occlusion and no negative effect on results of audiometry, tympanometry, or otoscopy were noted with OTO-201 administration. CONCLUSIONS AND RELEVANCE: Two large phase 3 randomized clinical trials demonstrate the safety and efficacy of a single intraoperative administration of OTO-201 for middle ear effusion at the time of TTP. TRIAL REGISTRATION: clinicaltrials.gov Identifiers: NCT01949142 and NCT01949155.

Randomized Clinical Trial of a Sustained-Exposure Ciprofloxacin for Intratympanic Injection During Tympanostomy Tube Surgery.

OBJECTIVE: This exploratory clinical trial evaluated the safety and clinical activity of a novel, sustained-exposure formulation of ciprofloxacin microparticulates in poloxamer (OTO-201) administered during tympanostomy tube placement in children. METHODS: Double-blind, randomized, prospective, placebo- and sham-controlled, multicenter Phase 1b trial in children (6 months to 12 years) with bilateral middle ear effusion requiring tympanostomy tube placement. Patients were randomized to intraoperative OTO-201 (4 mg or 12 mg), placebo, or sham (2:1:1 ratio). RESULTS: Eighty-three patients (52 male/31 female; mean age, 2.80 years) were followed for safety (otoscopic exams, cultures, audiometry, and tympanometry) and clinical activity, defined as treatment failure (physician-documented otorrhea and/or otic or systemic antibiotic use ≥3 days post surgery). At baseline, 14.3% to 36.8% of children showed positive cultures of middle ear effusion samples in at least 1 ear. Through day 15, treatment failures accounted for 14.3%, 15.8%, 45.5%, and 42.9% of patients (OTO-201 4 mg, OTO-201 12 mg, placebo, and sham, respectively); treatment failure reductions for OTO-201 doses were significant compared to pooled control (P values = .023 and .043, respectively). Observed OTO-201 safety profile was indistinguishable from placebo or sham. CONCLUSIONS: Results of this first clinical trial suggest that OTO-201 was well tolerated and shows preliminary clinical activity in treating tympanostomy tube otorrhea.

Facial cutaneous necrosis associated with suspected levamisole toxicity from tainted cocaine abuse.

OBJECTIVE: This study aimed to illustrate the otorhinolaryngologic manifestations of levamisole toxicity and illuminate the features of this diagnosis. METHODS: We describe a case of a known cocaine abuser with suspected levamisole toxicity who developed cutaneous necrosis of the cheeks, earlobes, nose, upper and lower lip, and the midline hard palate. We also review the existing clinical literature about this emerging phenomenon. RESULTS: Levamisole is a common adulterant in cocaine distributed in the United States and has been reported to cause microvascular thrombosis and vasculitis with resultant skin necrosis in cocaine abusers. The distribution of skin findings characteristically involves the cheeks, earlobes, nose, lips, and hard palate and responds variably to cessation of cocaine use. In its most severe cases, immune suppression and/or surgical debridement may be required. CONCLUSION: Levamisole toxicity can frequently involve the ears, nose, and throat tissues. Otorhinolaryngologists should recognize these manifestations to expeditiously diagnose and manage this condition. Failure to do so promptly can lead to complications that may necessitate reconstructive or amputation surgery.

Can plastic tracheotomy tubes harm baby boys?

Pediatric tracheotomy tubes are often made from polyvinyl chloride (PVC). Di(2-ethylhexyl) phthalate (DEHP) is a common additive to PVC to increase tracheotomy tube flexibility and strength. Unfortunately, DEHP is a reproductive toxicant that alters the male reproductive system in animals, in vitro tests, and limited human data. DEHP leaches from PVC tracheotomy tubes in children. The FDA and multiple international health agencies urge health care professionals to use DEHP-free medical materials for vulnerable patients, especially the male infant. The observed toxicity of DEHP and the readily available alternative materials to PVC tracheotomy tubes present a compelling argument to use pediatric tracheotomy tubes made from non-PVC materials such as polyurethane or silicone. More clinical research is needed.

Does an oral appliance reduce palatal flutter and tongue base snoring?

OBJECTIVES: Oral appliances are designed to treat snoring and sleep apnea by advancing the mandible and tongue. We test the hypothesis that an oral appliance affects palatal snoring as well as tongue base obstruction. METHODS: Prospective observational cohort study. Sixty patients with a chief complaint of snoring with or without apnea were enrolled. Each patient underwent a home sleep test followed by 3 weeks sleeping with an oral appliance. Each patient then underwent a repeat home sleep test while using the device. RESULTS: There was a statistically significant improvement in the snores per hour (P = 0.0005), the maximum snoring loudness (P = 0.0001), average snoring loudness (P = 0.00001), and the percentage of palatal snoring (P = 0.0007). There was also a significant decrease in oxygen desaturation events (P = 0.003). CONCLUSIONS: This study suggests oral appliances may be effective treatment for both palatal and tongue base snoring.

Acoustical analysis of pediatric snoring: what can we learn?

OBJECTIVE: Evaluate a database of pediatric patients who underwent snoring acoustical analysis for associations between snoring measurements, demographics, and obstructive sleep apnea/hypopnea syndrome (OSAHS) severity. STUDY DESIGN AND SETTING: A database of pediatric patients who underwent home testing with a polysomnogram device (SNAP Test, Glenview, IL) that includes acoustical snoring analysis was reviewed. RESULTS: Four hundred fifty-six patients were included (mean age, 6.87 years). Four hundred twenty-nine (94.1%) patients had measurable snoring. Snoring index (events/hr) (r = 0.2073; P < 0.0001) and maximal loudness (dB) (r = 0.2218; P < 0.0001) were directly proportional to the apnea/hypopnea index. Among patients without OSAHS (apnea index <1), increasing snoring index (r = -0.2102; P < 0.0001) and volume (P < 0.005 ANOVA) were associated with increasing oximetry desaturation events. CONCLUSION: The majority of children evaluated had objective snoring. Increasing snoring index and loudness are associated with increased severity of OSAHS. In the absence of OSAHS, increasing snoring is associated with oxygen desaturations. SIGNIFICANCE: Pediatric snoring is objectively related to OSAHS severity.

Validations of a portable home sleep study with twelve-lead polysomnography: comparisons and insights into a variable gold standard.

OBJECTIVES: Accurate and timely diagnosis for patients with obstructive sleep apnea (OSA) is imperative. Unfortunately, growing interest in this diagnosis has resulted in increased requests and waiting times for polysomnography (PSG), as well as a potential delay in diagnosis and treatment. This study evaluated the accuracy and viability of utilizing SNAP (SNAP Laboratories, LLC, Wheeling, Illinois), a portable home sleep test, as an alternative to traditional PSG in diagnosing OSA. METHODS: This prospective clinical trial included 59 patients evaluated at our institution's sleep laboratory. Concurrent PSG and SNAP testing was performed for 1 night on each patient. Independent, blinded readers at our institution and at an outside-accredited institution read the PSG data, and 2 independent, blinded readers interpreted the SNAP data at SNAP laboratories. The apnea-hypopnea index (AHI) was used to compare the 2 testing modalities. The correlation coefficient, receiver operating characteristic curve analysis, and the Bland-Altman curves, as well as sensitivity, specificity, inter-reader variability, positive predictive value, and negative predictive value, were used to compare SNAP and PSG. RESULTS: There is a definitive, statistically sound correlation between the AHIs determined from both PSG and SNAP. This relationship holds true for all measures of comparison, while displaying a concerning, weaker correlation between the different PSG interpretations. CONCLUSIONS: There is a convincing correlation between the study-determined AHIs of both PSG and SNAP. This finding supports SNAP as a suitable alternative to PSG in identifying OSA, while accentuating the inherent variation present in a PSG-derived AHI. This test expands the diagnostic and therapeutic prowess of the practicing otolaryngologist by offering an alternative OSA testing modality that is associated with not only less expense, decreased waiting time, and increased convenience, but also statistically proven accuracy.

Does obstructive sleep apnea affect aerobic fitness?

OBJECTIVES: We sought to determine whether patients with obstructive sleep apnea (OSA) had an objective change in aerobic fitness during cycle ergometry compared to a normal population. The most accurate test of aerobic fitness is measurement of maximum oxygen consumption (VO2max) with cycle ergometry. METHODS: We performed a retrospective cohort analysis (247 patients with OSA) of VO2max from annual cycle ergometry tests compared to a large control group (normative data from 1.4 million US Air Force tests) in a tertiary care setting. RESULTS: Overall, individuals with OSA had increased VO2max when compared to the normalized US Air Force data (p < .001). Patients with an apnea-hypopnea index of greater than 20 demonstrated a decreased VO2max as compared to normalized values (p < .001). No differences in VO2max were observed after either medical or surgical therapy for OSA. CONCLUSIONS: Overall, in a US Air Force population, OSA does not predict a decrease in aerobic fitness as measured by cycle ergometry. However, patients with an apnea-hypopnea index of greater than 20 have a statistically significant decrease in aerobic fitness compared to the normal population. This study demonstrates the effects of OSA on aerobic fitness. Further correlation of fitness testing results with OSA severity and treatment is needed.

Pediatric functional endoscopic sinus surgery: frequently asked questions.

Pediatric endoscopic sinus surgery is a controversial procedure that has evolved considerably over the past 2 decades. We present a current review of the literature regarding the treatment of children with refractory sinusitis with a focus on the use of endoscopic sinus surgery. Preoperative evaluation, surgical technique, postoperative care, and unusual applications are discussed.

Acoustical analysis of snoring: can the probability of success be predicted?

PURPOSE: Palatal flutter snoring is the most common form of snoring. However, other types of snoring do exist. Does identifying palatal snoring beforehand translate into improved subjective treatment success with palatal stiffening procedures? METHODS: Fifty-three patients presenting with snoring were evaluated with a commercially available device. The proportion (%) and magnitude of palatal flutter (dB) were quantified. Patients then underwent a palatal stiffening procedure and subjective success/failure was assessed. RESULTS: Overall subjective treatment success was 85% (45 of 53). The percent palatal flutter was the most predictive of success (area under ROC = 0.8556, 95% CI = .7428-.9683). Patients exceeding 68% palatal flutter had a 95% (39 of 41) success rate (P = 0.001, Fisher's exact) and an adjusted odds ratio of treatment success of 25.2 (95% CI = 3.22-196, P = 0.002). CONCLUSION: Palatal stiffening treatments are successful in the majority of patients. However, identifying patients with predominant palatal flutter snoring significantly increases the probability of subjective treatment success. EBM RATING: B-2b.

Submucosal minimally invasive lingual excision: an effective, novel surgery for pediatric tongue base reduction.

OBJECTIVES: The aim of this study was to develop an effective single intraoral, minimally invasive technique to reduce the enlarged tongue base in children with obstructive macroglossia. METHODS: We present the anatomic dissection of fresh cadavers and a representative case series of children who underwent submucosal minimally invasive lingual excision (SMILE) with a plasma-mediated radiofrequency device (coblation) under intraoral ultrasonic and endoscopic guidance. Multiple anatomic dissections determined the relative location of the hypoglossal nerve and lingual neurovascular bundle in relation to removable tongue base musculature. A pediatric case series demonstrates the straightforward SMILE technique. RESULTS: Laboratory anatomic dissection and clinical lingual ultrasonography revealed the surgical safety borders for SMILE. The surgical safety and efficacy of SMILE is demonstrated by preoperative and postoperative clinical examinations and polysomnograms in children with obstructive macroglossia (such as Beckwith-Wiedemann and Down syndromes and tongue vascular malformation). Coblation submucosally removes excessive tongue base tissue through a small anterior tongue incision. SMILE was performed without excessive pain, bleeding, edema, infection, or tongue dysfunction. CONCLUSIONS: SMILE is an effective novel operation that incorporates coblation with ultrasonography and endoscopic guidance for children who need tongue base reduction. Anatomic dissection and clinical cases demonstrate the potential for aggressive yet relatively safe tissue removal by this minimally invasive technique. SMILE also has significant potential for adults with obstructive sleep apnea due to a large tongue base.

Two babies, one heart, and no airway.

The medical literature on conjoined twins is replete with descriptions of the complexity of surgical separations. However, airway management, although quite challenging, is neglected in literature. We present experience with conjoined twins united anteriorly at the thorax and abdomen sharing one six-chambered heart. Laryngoscopy and intubation recommendations, bronchoscopy techniques, and tracheotomy strategies are outlined for the face-to-face twins. Difficult, unique case report at tertiary care medical center. Conjoined thoraco-omphalopagus twins were successfully intubated at birth using the rigid Seldinger-assisted videotelescopic intubation (SAVI) technique. Flexible airway endoscopy allows for timely management of ventilator-dependent conjoined twins. Tracheotomy was later performed with the twins in the upright position with heads slightly rotated. Meticulous attention to detail, monitoring and vigilance are mandatory. Successful management of conjoined twins relies on close communication and cooperation of all members of the multidisciplinary team. Conjoined thoraco-omphalopagus twins united anteriorly require a challenging airway management strategy. A three-dimensional perspective is utilized for intubation and tracheotomy. The SAVI technique is helpful for difficult intubations in the emergent twin airways.

Total nasopharyngeal stenosis: treatment with laser excision, nasopharyngeal obturators, and topical mitomycin-c.

OBJECTIVE: Severe nasopharyngeal stenosis after uvulopalatopharyngoplasty (UPPP) is a dreaded complication. Very little has been written about successful treatment because attempts at correction frequently fail. Severe stenosis of the nasopharynx drastically worsens speech, swallowing, and obstructive sleep apnea (OSA). We present our successful experience with severe stenosis focusing on a simple functional repair using topical mitomycin-c as well as differing daytime and nighttime palatal obturators. METHODS: Three adults with total or near-total nasopharyngeal stenosis secondary to UPPP were referred to our institution after multiple failed attempts at repair. Each presented with significant OSA on polysomnogram (PSG), with excessive daytime somnolence and voice and swallowing complaints. Under general anesthesia, a CO2 laser is used to create an opening in the nasopharynx. Removable and adjustable palatal obturators are fashioned to keep the nasopharynx open with a daytime insert piece with a small obturator hole for diminished velopharyngeal insufficiency and a nighttime piece without an insert to maximize recumbent airflow. Obturators are removed 6 months later with topical application of mitomycin-c as a fibroblast inhibitor. All patients were followed clinically for at least 1 year and received posttreatment PSG. RESULTS: All patients experienced resolution of their stenoses. Swallowing and voice complaints resolved. Either OSA was eliminated or any residual OSA was successfully treated with nasal continuous positive airway pressure. Serial videoendoscopic images throughout the treatment phase demonstrate the effectiveness of this new technique. CONCLUSIONS: Severe nasopharyngeal stenosis is a rare but devastating complication of UPPP. We introduce a simple technique that uses functional palatal obturators and topical mitomycin-c and describe our success with this treatment algorithm.

Potential applications of the da Vinci minimally invasive surgical robotic system in otolaryngology.

Anatomic constraints and instrumentation design characteristics have limited the exploitation of endoscopic surgery in otolaryngology. The move toward less invasive and less morbid procedures has paved the way for the development and application of robotic and computer-assisted systems in surgery. Surgical robotics allows for the use of new instrumentation in our field. We review the operative advantages, limitations, and possible surgical applications of the da Vinci Surgical System in otolaryngology. In the laboratory setting, we explored the setup and use of the da Vinci system in porcine and cadaveric head and neck airway models; the setup was configuredfor optimal airway surgery. Endoscopic cautery, manipulation, and suturing of supraglottic tissues were performed in both the porcine and cadaveric models. We found that the da Vinci system provided the advantages of the lower morbidity associated with endoscopic surgery, more freedom of movement, and three-dimensional open surgical viewing. We also observed that the system has several limitations to use in otolaryngology.