Trichloroacetic acid Alloderm™ Myringoplasty as a novel option for tympanic membrane reconstruction in children.

PURPOSE: A novel "Modified TCA Alloderm™ Myringoplasty" (TCA myringoplasty) technique for reconstruction of uncomplicated chronic tympanic membrane (TM) perforations is described. MATERIALS AND METHODS: Descriptive surgical technique for TCA myringoplasty on 12 total patients from 1/1/2020 to 12/31/2020. 3 patients were excluded for incomplete records. Statistical analysis employed Wilcoxon signed-rank tests. Both structural (pre/post visual inspection and tympanogram) and functional (pre/post pure tone average, PTA) outcome measures are reported. RESULTS: 12 total ears were analyzed from 9 patients. Average age at surgery was 6 (range 3-22). Perforation size ranged from 10 to 60 %. Rate of structural success was 100 %. Functionally, postoperative PTA were significantly decreased from preoperative (mdn(range) = 18.44(13.13-24.38) vs mdn(range) = 11.25(6.25-22.50), p = .008). Only one TM required >1 procedure to achieve closure. CONCLUSIONS: Chronic TM perforations are typically reconstructed via Type I tympanoplasties with temporalis fascia, reserving myringoplasty for favorable perforations (<25 % in size and posterior). Our novel TCA myringoplasty technique has excellent outcomes independent of size and location. We apply a chemical peel concept to a modified myringoplasty technique, obviating incisions and graft harvest. Advantages of Alloderm™ include: 1) a more rigid graft, facilitating manipulation and precise placement; 2) various size and thickness options, especially useful for dimeric tympanic membranes, tympanolysis of adhesions, and bilateral perforations; 3) no donor morbidity and harvest time; 4) autologous tissue preservation. The sole disadvantage of cost is mitigated by reduced operative time and complication management. This study revealed encouraging proof-of-concept preliminary data warranting prospective and sufficiently powered analysis, supporting the technique as a viable alternative to the gold standard.

Initiation of acid suppression therapy for laryngomalacia.

OBJECTIVE: Evidence supporting the use of acid suppression therapy (AST) for laryngomalacia (LM) is limited. The objective of this study was to determine if outpatient-initiated AST for LM was associated with symptom improvement, weight gain, and/or avoidance of surgery. METHODS: A retrospective cohort was reviewed at a tertiary-care children's hospital. Patients were included if they were diagnosed with LM at ≤6 months of age, seen in an outpatient otolaryngology clinic between 2012 and 2018, and started on AST. Primary outcomes were improvement of airway and dysphagia symptoms, weight gain, and need for surgery. Severity was assessed by symptom severity. RESULTS: Of 2693 patients reviewed, 199 met inclusion criteria. Median age of diagnosis was 4 weeks (range: 0-29 weeks). LM was classified as mild/moderate (71.4%) and severe (28.6%) based on symptom severity. Severity on flexible fiberoptic laryngoscopy (FFL) was not associated with clinical severity. Weight percentile, airway symptoms, and dysphagia symptoms improved within the cohort. In total, 26.1% underwent supraglottoplasty (SGP). In multivariate analysis, only severe LM on FFL was predictive of SGP (OR: 7.28, 95%CI: 1.91-27.67, p = .004). CONCLUSION: Clinical symptom severity did not predict response to AST raising the question of utility of AST in LM. Severity of LM based on FFL, not clinical severity, was associated with decision to pursue SGP. Prospective randomized trials are needed to better understand the role of AST in LM. LEVEL OF EVIDENCE: Level 3.

Pediatric otolaryngology telemedicine amid a pandemic - And beyond.

INTRODUCTION: The coronavirus disease of 2019 (COVID-19) pandemic catalyzed an unprecedented redesign and innovative overhaul of health care delivery thrusting from fringe to mainstream virtual care. With a return to conventional practice, we now must create a research and policy agenda using the changes wrought by COVID-19 to help create a better health care system in its aftermath. The purpose of this study was to assess satisfaction of otolaryngology outpatient visits during the pandemic. METHODS: A prospective survey study was performed on caregivers of all patients ages 0-26 years old seen in the Division of Pediatric Otolaryngology at our large tertiary care children's hospital from February-April 2020. The three study groups were those seen in-person 6 weeks before telemedicine was implemented (IBTM), those seen in telemedicine during the first 6 weeks (TM) it was implemented at our hospital, and those seen in-person during the telemedicine period (IDTM) in the same timeframe. The survey consisted of satisfaction questions related to their visit, if their child was recommended surgery at the time of the visit, and if the caregiver agreed with the recommendation. A medical record review was also performed. RESULTS: A total of 176 caregivers completed the survey with 113(64.2%) completing the survey for an IBTM appointment, 59(33.5%) for a TM appointment, and 4(2.3%) for an IDTM appointment. There were 100(56.8%) male patients and 167(94.9%) were white. Families gave a higher response for the statement "The ability to communicate with the physician" (p = .012) and "The overall outpatient experience" (p = .004) in the IBTM cohort compared to the TM group. There were no significant differences for the other statements regarding the ability to understand recommendations, courtesy, and knowledge of the physician. Regardless of group, 98.6% of caregivers agreed with surgical recommendation when surgery was recommended. However, when surgery was not recommended at the appointment, caregivers were 11x more likely to disagree with the surgical recommendations, OR:11.49,95%CI:1.44-91.38,p = .005. CONCLUSION: We conclude that telemedicine was equally well received by patients as compared to traditional live assessments suggesting that virtual care is a viable post-pandemic paradigm change. Satisfaction was rated as "Good" or "Excellent", however, messaging when surgery is not recommended was less acceptable and must be improved to obtain increased caregivers' agreement in an era of shared decision making.

Cognitive Mechanisms in Pediatric Voice Therapy - An Initial Examination.

INTRODUCTION: Voice disorders are a common communication disorder in children. Behavioral voice therapy is recommended by both Otolaryngologists and Speech-Language Pathologists as a first-line approach for treatment of benign vocal fold lesions that affect children in large numbers. However, the role of cognitive mechanisms critical to voice therapy have not yet been explored. OBJECTIVE: This proof-of-concept study aims to provide preliminary data on the potential relation between cognitive abilities and behavioral results of voice therapy for children with benign phonotraumatic vocal fold lesions. METHODS: Six children (4;05 -9;02 years) diagnosed with vocal fold nodules completed a battery of cognitive tests from the NEuroPSYchological (NEPSY-II) Assessment and a standard course of "Adventures in Voice" therapy. Recordings pre and post intervention were analyzed acoustically using the Cepstral Spectral Index of Dysphonia (CSID) and perceptually using visual analog scales (VAS) for severity and resonance separately. Raw and age-corrected scaled scores from the NEPSY-II were then examined for their possible relation to voice outcomes. RESULTS: Multiple cognitive functions correlated with voice outcomes. Raw score measures for Design Fluency, Inhibition, Fingertip Tapping, and Narrative Memory correlated favorably with all voice outcome measures. Age correlated with all NEPSY-II raw scores and perceptual voice outcome measures. Scaled scores for Auditory Attention, Design Fluency, Fingertip Tapping (Dominant hand), and Narrative Memory correlated with all voice outcome measures. CONCLUSION: Results suggest that there is merit to further investigation of the relation between cognitive skills and their development and voice treatment outcomes in children with benign phonotraumatic lesions. Future studies with larger samples will build on present findings.

Otitis media prone children with cystic fibrosis: A new normal.

OBJECTIVES: To determine if children with cystic fibrosis (CF) who are otitis media prone and treated with tympanostomy tube placement (TTP) follow the natural course of non-CF children regarding the incidence of tympanostomy tube otorrhea (TTO) (21-34%). METHODS: All CF patients seen at a large tertiary pediatric hospital were retrospectively reviewed from 2010 to 2019. A total of 483 patients were identified and seventeen met the inclusion criteria and were included in the analysis. Data collected included demographics, CF diagnosis history including date of diagnosis and genotype, TTP notes, and otorrhea found in otolaryngology clinic and pediatrician clinic notes for up to 18 months post-TTP. RESULTS: CF was diagnosed at a median age of 13 days (0 days to 6 years). In terms of surgical frequency, 14/17 (82.4%) patients had one TTP, 2/17 (11.8%) had two TTPs, and 1/17 (5.9%) had five TTPs. The median (range) age at first TTP was 2 years (3 months to 13 years). After the first TTP, TTO occurred in 5 (29.4%) patients at 3 months, 6 (35.3%) at 6 and 9 months, and 7 (41.2%) at 12 and 18 months at median (range) = 1 (0-5) otolaryngology appointments and median (range) = 0 (0-8) pediatrician appointments. CONCLUSION: To our knowledge this is the first study to report that CF children are more likely to be severely affected with recurrent acute otitis media (RAOM), to require TTP, and to exhibit a natural history of TTO commensurate with the non-CF population.

Cystic fibrosis mutation classes in pediatric otitis media - Fickle or faulty?

PURPOSE: Recent data have challenged the historical paradigm that cystic fibrosis (CF) protects against otitis media (OM). These findings raised questions about the pathogenesis of this ostensible change. In this study our aim is to characterize acute OM (AOM) risk based on CF genotype. METHODS: A retrospective chart review was completed at a tertiary care pediatric hospital. Charts of 159 CF patients seen at our facility from 2010 to 2019 were reviewed. Data collected included demographics, AOM infections, cystic fibrosis transmembrane conductance regulator (CFTR) allele mutations, pulmonary exacerbations (PE), and pancreatic insufficiency (PI) status. Mutation alleles were divided into five classes based on CF guidelines, which were further classified as severe (classes I-III) or mild (classes IV-V). RESULTS: 54% of patients had at least one episode of AOM with a mean of 1.5 episodes of AOM (standard deviation = 2.3). 86% of patients had severe/severe (S/S) alleles and 14% had severe/mild (S/M). S/S patients had significantly more PE (p = .004) and increased rates of PI (p < .001). Of the 131 patients with S/S mutations, 57% had an episode of AOM while only 46% the 22 S/M patients had an AOM episode (p = .357). CONCLUSIONS: To our knowledge this is the first report showing a clinical trend towards increased middle ear disease in patients with severe CFTR mutations. Future prospective studies will be powered to demonstrate whether this trend is statistically significant. Patients with S/S mutations not only have more severe clinical phenotypes but may have additional unexpected complications such as middle ear disease.

Tympanostomy Tubes or Medical Management for Recurrent Acute Otitis Media.

BACKGROUND: Official recommendations differ regarding tympanostomy-tube placement for children with recurrent acute otitis media. METHODS: We randomly assigned children 6 to 35 months of age who had had at least three episodes of acute otitis media within 6 months, or at least four episodes within 12 months with at least one episode within the preceding 6 months, to either undergo tympanostomy-tube placement or receive medical management involving episodic antimicrobial treatment. The primary outcome was the mean number of episodes of acute otitis media per child-year (rate) during a 2-year period. RESULTS: In our main, intention-to-treat analysis, the rate (±SE) of episodes of acute otitis media per child-year during a 2-year period was 1.48±0.08 in the tympanostomy-tube group and 1.56±0.08 in the medical-management group (P = 0.66). Because 10% of the children in the tympanostomy-tube group did not undergo tympanostomy-tube placement and 16% of the children in the medical-management group underwent tympanostomy-tube placement at parental request, we conducted a per-protocol analysis, which gave corresponding episode rates of 1.47±0.08 and 1.72±0.11, respectively. Among secondary outcomes in the main analysis, results were mixed. Favoring tympanostomy-tube placement were the time to a first episode of acute otitis media, various episode-related clinical findings, and the percentage of children meeting specified criteria for treatment failure. Favoring medical management was children's cumulative number of days with otorrhea. Outcomes that did not show substantial differences included the frequency distribution of episodes of acute otitis media, the percentage of episodes considered to be severe, and antimicrobial resistance among respiratory isolates. Trial-related adverse events were limited to those included among the secondary outcomes of the trial. CONCLUSIONS: Among children 6 to 35 months of age with recurrent acute otitis media, the rate of episodes of acute otitis media during a 2-year period was not significantly lower with tympanostomy-tube placement than with medical management. (Funded by the National Institute on Deafness and Other Communication Disorders and others; ClinicalTrials.gov number, NCT02567825.).

Pediatric subperiosteal orbital abscess characterization and prediction of size, location, and management.

INTRODUCTION: Subperiosteal orbital abscess (SPOA) is a serious suppurative complication of pediatric sinusitis. The objective of this study is to stratify patient selection into those best treated medically versus surgically based on clinical outcomes. METHODS: This is a retrospective review of patients diagnosed with SPOA complicating sinusitis treated at a tertiary care pediatric hospital from 2002 through 2016. SPOA was diagnosed by CT scan. Characteristics evaluated include demographics, abscess size, location, and measurements, length of hospital stay, medical and surgical interventions, presenting symptoms, and complications. RESULTS: A total of 108 total SPOA secondary to sinusitis patients were included. A majority, 72.2%, were male with an average age at presentation of 6.8 years. The mean ± standard deviation abscess cubic volume was 0.98 ± 1.27 cm3 (median(range) = 0.44(0.01-7.34 cmcm3)). With an abscess volume of 0.510 cm3, there was a sensitivity of 71.2% and a specificity of 84.4% for needing surgical drainage. Those with large abscesses at our volume threshold were 13 times more likely to require surgery than those with small abscesses, OR: 13.41, 95%CI: 5.02-35.86, p < .001. Patients that required surgery had an abscess closer to the orbital apex with the majority, 25 (61.0%), being the most proximal to the apex, p = .004. The likelihood of surgery decreased with increased distance from the orbital apex in medial abscesses (OR:.92, 95%CI: 0.86-0.98, p = .009). CONCLUSION: In the pediatric population, SPOA is a serious consequence of sinusitis. This study provides evidence supporting that larger abscess size is a significant risk factor for requiring surgery. The appeal of our study is that it provides evidence and support that employ clinical parameters already assessed as standard practice in evaluating these patients. In summarizing the clinical translational relevance of our study, when determining whether to treat a patient with surgery and antimicrobial/medical therapy vs. non-surgical medical therapy alone, the clinician should focus on size of 0.510 cm3 or larger for abscesses in any location as a relative indication for surgery.

It's a rash: Antibiotic allergies in the modern era of antibiotic stewardship.

OBJECTIVES: To determine whether current guidelines emphasizing antibiotic stewardship in pediatrics have been associated with reduced prevalence of antibiotic allergies in children severely affected by otitis media undergoing bilateral myringotomy with tympanostomy tube insertion (BMT) or by recurrent sinusitis or adenotonsillitis undergoing adenoidectomy with or without tonsillectomy. METHODS: Case series of consecutive patients undergoing BMT or adenoidectomy with/without tonsillectomy for recurrent acute otitis media, recurrent sinusitis, or recurrent tonsillitis during November 2008 or November 2017 at a tertiary care children's hospital. Children with primarily obstructive indications for surgery, with prior tube placement or adenoidectomy, or with surgery by an outside provider were excluded. Demographics, type of surgery, and allergies or allergic symptoms were collected from the electronic medical record. Factors associated with antibiotic allergies were compared using logistic regression, Wilcoxon rank-sum, or Chi-squared test. RESULTS: Seventy-five children who underwent surgery during 2008 and 75 children who underwent surgery in 2017 were included. Overall, median age at surgery was 3.24 years (range 0.56-17.49 years). Seventy-nine (52.7%) patients were female and 95 (63.3%) had private insurance. BMT was the most common surgery (82 children, 54.7%) followed by tonsillectomy with adenoidectomy (46 children, 30.7%), and adenoidectomy without tonsillectomy (39 children, 26.0%). Symptoms of allergic rhinitis were reported by 53 (35.3%) patients, and 11 (7.3%) and 5 (3.3%) had positive environmental and food allergy testing, respectively. Surprisingly, there was not a significant difference between the prevalence of antibiotic allergies in patients undergoing surgery during 2017 (17 patients, 22.7%) compared with 2008 (14 patients, 18.7%) (OR: 1.28, 95% CI: 0.578-2.82, p = 0.546). However, antibiotic allergies were less common in females (OR: 0.413, 95% CI: 0.182-0.937, p = 0.034) and more common in patients with a family history of antibiotic allergies (OR: 36.9, 95% CI: 5.12-∞, p < 0.001). CONCLUSION: Pediatric otolaryngology surgical patients continue to exhibit a similar and high prevalence of antibiotic allergies in 2017 compared with 2008. Future studies are needed to determine whether this is because of overdiagnosis of antibiotic allergies or a failure of antibiotic guideline adherence to reduce antibiotic allergy prevalence.

Heterotopic gastric mucosa of the proximal esophageal (HGMPE) and its potential role in pediatric dysphonia and dysphagia.

OBJECTIVE: Despite a reported incidence of HGMPE of 10%, proof of acid production, and an increased incidence of respiratory symptoms, the pediatric otolaryngology, swallowing and voice care literature is silent on this entity. This case series describes pediatric patients confirmed to have HGMPE with dysphonia and/or dysphagia. METHODS: Retrospective case series of Pediatric Voice, Resonance, and Swallowing Center patients at a tertiary Children's Hospital in 2019. SETTING: Tertiary academic medical center. SUMMARY OF RESULTS: Three patients who underwent triple endoscopy for dysphonia or dysphagia were histologically diagnosed with HGMPE. Esophageal biopsies were otherwise normal. Two of the three patients resolved their primary aerodigestive symptoms following treatment with acid suppression and a protectant (sucralfate). The third patient reported significant improvement in symptoms by phone. The significance of this case series cannot be understated: 1) A need for increased awareness among pediatric otolaryngologists, voice care and swallowing professionals of this entity given its relatively common incidence of 10% offset by a dearth of presentations & scientific publications in our literature clearly exists. 2) Otolaryngologists have abandoned operative upper aerodigestive tract endoscopy in lieu of office-based less comprehensive videolaryngostroboscopy and fiberoptic endoscopic evaluation of swallowing. HGMPE & other esophageal disorders (i.e. eosinophilic esophagitis) support revisiting triple endoscopy in select patients where office endoscopy has failed to diagnose and successfully treat such patients. 3) Both acid suppression therapy and a protectant (sucralfate) may be useful in these patients. 4) Modification of rigid esophagoscopy technique to carefully assess the introitus and superior esophageal segment is paramount 5) Otolaryngologists over-diagnose & over-treat laryngopharyngeal reflux. The pediatric & adult literature is replete with significant safety warnings associated with acid suppression therapy and guidelines admonish their indiscriminate use, raising the liability bar of empiric treatment. Large scale prospective, randomized and controlled studies are needed to confirm the pathophysiologic role of this entity in pediatric aerodigestive disorders. CONCLUSION: HGMPE is a clinical entity that can be easily missed upon swift entry into the esophagus with rigid endoscopy. Careful scrutiny and visualization of the proximal esophagus is critical in order to identify HGMPE, as there is a higher rate of laryngospasm, stricture, and potentially neoplasm in this population.

Evidence-based telehealth clinical pathway for pediatric tympanostomy tube otorrhea.

INTRODUCTION: As healthcare moves away from volume-based to value-based delivery models, evidence based clinical pathways detail essential steps in patient care to reduce the costs and utilization of health care resources. Ideal pathways lead towards standardized, patient-centered care through an algorithm that is evidence-based, interventions with criteria-based progression, and measurable endpoints or quality indicators. Using these standards, a clinical pathway for managing tympanostomy tube otorrhea beginning with phone triage was developed in accordance with AAO-HNSF Guidelines. METHODS: A retrospective case series of all consecutive patients calling the otolaryngology nurse's line at a tertiary pediatric hospital 3/2018-11/2018 regarding otorrhea was performed. Nurses completed a standardized and evidence-based form based on parent responses regarding purulence, tympanostomy tubes/perforation, fever>102°, ear redness, bacterial rhinosinusitis, sore throat, and immunodeficiency, which was sent to the advanced practice providers (APPs) to assess for antibiotic drops. Otorrhea form information and tympanostomy tube history, subsequent phone calls, clinic visits, and antibiotic prescriptions for otorrhea were extracted. RESULTS: Eighty-two patients were included. Median child age at phone call was 2.5 years (range 0.3-20.2 years), and 45.1% were female. All patients had prior tubes and active purulent otorrhea. No parents reported cellulitis or immunodeficiency. One patient had symptoms of bacterial rhinosinusitis and a sore throat but had already been seen by their primary care provider (PCP) for systemic antibiotics. Antibiotic drops were prescribed by an APP in 96.3% of cases [ofloxacin (n = 57), ciprofloxacin (n = 17), or ciprofloxacin with dexamethasone (n = 5)]. The remaining patients already had drops (2.5%) or were referred to their PCP (1.2%). Twenty (24.4%) received another antibiotic prescription and 17.1% had a subsequent clinic or urgent care visit for otorrhea. CONCLUSIONS: This pathway obviated clinic visits in 82.9% of patients with a 75.6% treatment cure.

Middle ear disease in CF? It's not just about the sinuses anymore!

INTRODUCTION: Historically cystic fibrosis (CF), in contrast to primary ciliary dyskinesia (PCD), has been considered protective of the middle ear from otitis media and rarely were such patients "severely affected" to require tympanostomy tube placement (BMT). Previously the Pittsburgh Otitis Media Research group reported a 10% prevalence of otitis media in the pediatric CF population which is significantly lower than age matched non-CF children. We studied the prevalence of OM in pediatric CF patients to assess if the otologic phenotype has changed in parallel with changes in the diagnosis itself. METHODS: The medical records of 133 CF patients seen either inpatient or outpatient from one of the largest tertiary pediatric CF centers in the world from 2010 to 2019 were reviewed for demographics, acute otitis media (AOM) episodes, risk factors for AOM, placement of myringotomy tubes, genotype, BMI, pancreatic status, respiratory culture results, and pulmonary exacerbations. RESULTS: Just over half (52.6%) the patients were male. A median age for CF diagnosis was 11 days old (range 0 days-16 years). The most common genotype (49.6%) was homozygous for ΔF508 mutation. Fifty-five (41.4%) patients had 1-2 episodes of AOM, and 15 (11.3%) were severely affected (i.e. ≥3 episodes/6 months or ≥4 episodes/year). COME was diagnosed in 4 (3.0%) of the patients. Twelve (9.0%) patients had tympanostomy tubes at least once, including 3 patients with multiple sets of tubes. Having at least one AOM episode was not predicted by genetic mutation groups, BMI, age at diagnosis, or comorbidities, p > .05. CONCLUSIONS: The time-honored adage of CF protecting against otitis media is no longer true and pediatric otolaryngologists must now prioritize the management of middle ear disease as highly as sino-nasal and pulmonary disease. Future study into mechanisms explaining the change is needed.

Button battery versus stacked coin ingestion: A conundrum for radiographic diagnosis.

OBJECTIVES: Given the potential for devastating complications associated with esophageal impaction of a button battery, there is a need to distinguish between a button battery and look-alike stacked coins at the time of presentation. Given there have been no studies analyzing differences in radiographic density between these two entities, the study objective was to determine if a difference exists between esophageal coin and button battery radiographic density on plain radiograph and to describe the operative and treatment course following these two distinct entities of ingestion. METHODS: Retrospective case series following button battery or stacked coin ingestion in a tertiary care pediatric hospital from 2003 to present. Radiographic density of each button battery and stacked coin was calculated by dividing the foreign body radiographic density by the mean density of two background radiographic sections. Radiographic density of coins versus batteries was compared using t-tests. RESULTS: There were 22 patients identified with button battery ingestion and 47 with stacked coins. Median (range) radiographic density of button batteries on anteroposterior view was 1.16 (0.37-2.19) x background compared to 1.13 (0.09-2.65) x background of stacked coins, p = 0.198. There was similarly no statistically significant difference in lateral views, p = 0.622. CONCLUSION: Our study suggests that radiographic density measured on diagnostic x-ray does not prove a reliable adjunctive measure to distinguish an innocuous stacked coin ingestion from the far more ominous button battery and highlights the need for prompt operative evaluation for any suspected button battery ingestion.

Pediatric dysphonia: It's not about the nodules.

OBJECTIVE: Despite the fact that vocal nodules are the most common cause of chronic dysphonia in children, uncertainty and lack of consensus complicates practically every diagnostic and management decision. Selecting an optimal staging system is fundamental to understanding a disease process, mandatory for uniform reporting, and crucial to predicting natural history and treatment outcomes. The ideal prognostic model for vocal nodules is under intense debate. The purpose of this study was to analyze the predictive power of vocal nodule grade to severity of voice metrics in children. METHODS: Seventy-nine patients diagnosed with vocal cord nodules between 2006 and 2012 were drawn from UPMC Children's Hospital of Pittsburgh Voice, Resonance and Swallowing Center Research Registry. Subject age at time of diagnosis, nodule grade, relevant co-morbidities, scores on The Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V), parent-reported Pediatric Voice Handicap Index (pVHI), the phonotraumatic behaviors profile, habitual speaking pitch fundamental frequencies, pitch range, volume intensity, and s/z ratio were recorded and compiled into a de-identified database for analysis. RESULTS: Based on the Kruskal-Wallis H Test, there was no statistically significant correlation between nodule grade and total pitch range (p = .21), s/z ratio (p = .50), volume intensity (p = .33), overall CAPE-V Scores (p = .15), or pVHI Scores (p = .29). Chi-squared tests also revealed no significant associations between nodule grade and abnormality in habitual speaking pitch (p = .14 for fundamental frequency while sustaining a vowel sound, p = .37 for fundamental frequency while speaking structured tasks i.e. counting, or p = .76 while speaking in conversation). CONCLUSION: The current "gold-standard" for grading vocal nodule size suggests that the nodules themselves are not driving the standard dysphonic metrics that are most commonly collected and monitored in such children. This outcome is consistent with other studies reporting similar findings and was expected based on the inconsistencies in the reported literature to date. By extension, the conventional wisdom of avoiding surgical treatment of vocal nodules in children seems prudent as there is little evidence to suggest that the nodules themselves are "driving" the severity of the dysphonia. Ultimately identifying the true "drivers" of dysphonia in children will suggest alternative therapies that are more specific and directed to the pathophysiology. Most pediatric voice care professionals will welcome such discoveries as those in the front line of patient care are often rendered helpless and frustrated.

Age at diagnosis, but not HPV type, is strongly associated with clinical course in recurrent respiratory papillomatosis.

BACKGROUND: Recurrent Respiratory Papillomatosis (RRP) is a rare disease characterized by the growth of papillomas in the airway and especially the larynx. The clinical course is highly variable among individuals and there is poor understanding of the factors that drive an aggressive vs an indolent course. METHODS: A convenience cohort of 339 affected subjects with papillomas positive for only HPV6 or HPV11 and clinical course data available for 1 year or more, from a large multicenter international study were included. Exploratory data analysis was conducted followed by inferential analyses with frequentist and Bayesian statistics. RESULTS: We examined 339 subjects: 82% were diagnosed prior to the age of 18 years, 65% were infected with HPV6, and 69% had an aggressive clinical course. When comparing age at diagnosis with clinical course, the probability of aggressiveness is high for children under five years of age then drops rapidly. For patients diagnosed after the age of 10 years, an indolent course is more common. After accounting for confounding between HPV11 and young age, HPV type was minimally associated with aggressiveness. Fast and Frugal Trees (FFTs) were utilized to determine which algorithms yield the highest accuracy to classify patients as having an indolent or aggressive clinical course and consistently created a branch for diagnostic age at ~5 years old. There was no reliable strong association between clinical course and socioeconomic or parental factors. CONCLUSION: In the largest cohort of its type, we have identified a critical age at diagnosis which demarcates a more aggressive from less aggressive clinical course.

Sialorrhea & aspiration control - A minimally invasive strategy uncomplicated by anticholinergic drug tolerance or tachyphylaxis.

OBJECTIVE: Sialorrhea complicated by aspiration is a primary source of morbidity and mortality in neurologically impaired children. Anticholinergics are an effective treatment option, but have traditionally been considered only adjuncts due to tachyphylaxis and drug tolerance. Similarly, Botox-A® salivary gland injections are also considered adjunctive due to the need to repeat treatment every 3 months. This retrospective case series assessed these two adjunctive strategies used in combination as definitive minimally invasive primary treatment. METHODS: 112 subjects diagnosed with sialorrhea and treated at UPMC Children's Hospital of Pittsburgh between 2004 and 2011 were identified. Charts were carefully reviewed for pertinent information regarding the treatment of their sialorrhea and related outcomes. RESULTS: Over half of the subject undergoing BTX-A injections were able to reduce their dosage of anticholinergics after receiving injection (58%, n = 28 for glycopyrrolate users and 61%, n = 20 for scopolamine users). Subjects experienced a significant reduction in days spent in the hospital in the year following Botox-A® injection (P-Value = 0.03), and the number of pneumonia episodes in the year following injection (P-Value = 0.04). CONCLUSION: Patients treated effectively with both BTX-A injections into their salivary glands and anticholinergics developed neither tachyphylaxis nor drug tolerance with up to 9.6 years of continuous treatment. During the year following combined therapy, patients' average length hospital stay was reduced by a full week and the number of pneumonia episodes was statistically decreased. The failure rate of combined therapy was below that reported for any other intervention or combination of interventions in the literature. Finally, patients did not require BTX-A re-injection at the reported frequency. We hypothesize that anticholinergic medications competitively block acetylcholine attachment to post-synaptic receptors while BTX-A inhibits acetylcholine release at the pre-synaptic terminal, tachyphylaxis/drug tolerance mechanisms resulting in up-regulation of post-synaptic receptors are disrupted. Although salivary production may increase in the year following BTX-A injection, there is enough remaining activity at a molecular level to inhibit release of acetylcholine allowing salvage with anticholinergic medications at tolerable dosages.

Tube patency: Is there a difference following otic drop administration?

PURPOSE: Many surgeons instill peri-operative otic drops to maintain tube patency. A post-hoc analysis of three randomized, controlled studies involving a one-time administration of ciprofloxacin (OTO-201) given instead of otic drops perioperatively was conducted to evaluate tube patency in patients who did and did not receive otic drops as defined within the study protocol. MATERIALS AND METHODS: Post-hoc, retrospective analysis from three prospective, randomized, double-blind trials, (Phase 1b study [n = 83] and two Phase 3 studies [n = 532]) which enrolled children with confirmed middle ear effusion on the day of tympanostomy tube surgery and then randomized to placebo/sham (tubes alone) or OTO-201 and studied over a 28-day observation period. Patients with observed otorrhea post-tube were provided otic drops in the studies. An analysis was performed on the combined studies to evaluate tube patency, determined by pneumatic otoscopy and tympanometry, at four defined study visits over 28 days after the initial tube placement. RESULTS: The analysis included 591 total patients with similar baseline demographics across groups. Tube patency ranged from 87 to 95% for patients who received otic drops, and from 96 to 99% for patients who did not receive otic drops. CONCLUSION: Based on a retrospective post-hoc analysis from three randomized controlled trials in nearly 600 patients, tympanostomy tube occlusion rates was not increased in patients who did not receive otic drops. From this analysis, occlusion is likely caused primarily by peri-operative otorrhea since patency rates approached 99% in the absence of this complication.

Safety and efficacy of intratympanic ciprofloxacin otic suspension post-tubes in a real-world pediatric population.

PURPOSE: Otorrhea frequently follows tympanostomy tube (TT) placement. We evaluated otorrhea following single 6mg OTO-201 (OTIPRIO®, ciprofloxacin otic suspension 6%) intraoperative injection into each middle ear in a variety of effusion types and concurrent procedures in children undergoing TT placement. SECONDARY OBJECTIVE: Efficacy based on Medicaid status and safety. BASIC PROCEDURES: In this prospective, 8-week, multicenter, open-label study, 501 patients were enrolled: mean age 2.9years, male (56.9%), wet/wet ears (66.9%), wet/dry (16.8%), dry/dry (16.3%), and Medicaid-insured (32.9%). MAIN FINDINGS: In per-protocol population (n=410), otorrhea rate through Day 15 were 8.8% (CI:5.7%-12.8%), 6.6% (CI:2.2%-14.7%), 3.3% (CI:0.4%-11.3%) in wet/wet, wet/dry, and dry/dry ears, respectively. For Medicaid patients through Day 15, Week 4 and Week 8, otorrhea rates were 8.1% (CI:4.1%-14.1%), 17.0% (CI:11.1%-24.5%), and 17.8% (CI:11.7%-25.3%) compared with those non-Medicaid insured: 7.3% (CI:4.5%-11.0%), 14.5% (CI:10.6%-19.3%), and 21.8% (CI:17.1%-27.2%), respectively. Safety was similar to previous Phase 3 trials. PRINCIPAL CONCLUSIONS: OTO-201 demonstrated otorrhea rates consistent with Phase 3 trials in a broader, real-world, ENT practice-based pediatric population. Outcomes were similar in Medicaid- and non-Medicaid insured patients. OTO-201 was well-tolerated.

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.