Hearing Loss in Adults: Differential Diagnosis and Treatment.

More than 30 million U.S. adults have hearing loss. This condition is underrecognized, and hearing aids and other hearing enhancement technologies are underused. Hearing loss is categorized as conductive, sensorineural, or mixed. Age-related sensorineural hearing loss (i.e., presbycusis) is the most common type in adults. Several approaches can be used to screen for hearing loss, but the benefits of screening are uncertain. Patients may present with self-recognized hearing loss, or family members may observe behaviors (e.g., difficulty understanding conversations, increasing television volume) that suggest hearing loss. Patients with suspected hearing loss should undergo in-office hearing tests such as the whispered voice test or audiometry. Patients should then undergo examination for cerumen impaction, exostoses, and other abnormalities of the external canal and tympanic membrane, in addition to a neurologic examination. Sudden sensorineural hearing loss (loss of 30 dB or more within 72 hours) requires prompt otolaryngology referral. Laboratory evaluation is not indicated unless systemic illness is suspected. Computed tomography or magnetic resonance imaging is indicated in patients with asymmetrical hearing loss or sudden sensorineural hearing loss, and when ossicular chain damage is suspected. Treating cerumen impaction with irrigation or curettage is potentially curative. Other aspects of treatment include auditory rehabilitation, education, and eliminating or reducing use of ototoxic medications. Patients with sensorineural hearing loss should be referred to an audiologist for consideration of hearing aids. Patients with conductive hearing loss or sensorineural loss that does not improve with hearing aids should be referred to an otolaryngologist. Cochlear implants can be helpful for those with refractory or severe hearing loss.

Operation airway: the first sustainable, multidisciplinary, pediatric airway surgical mission.

OBJECTIVE: This study aimed to describe the development and implementation of the first sustainable, multidisciplinary, pediatric airway surgical mission in an underserved country. METHODS: This prospective, qualitative study was conducted for the first 4 Operation Airway missions in Quito, Ecuador. The major goals of the missions were to assist children with aerodigestive abnormalities, create a sustainable program where the local team could independently provide for their own patient population, develop an educational curriculum and training program for the local team, and cultivate a collaborative approach to provide successful multidisciplinary care. RESULTS: Twenty patients ages 4 months to 21 years were included. Twenty-three bronchoscopies, 5 salivary procedures, 2 tracheostomies, 1 T-tube placement, 1 tracheocutaneous fistula closure, 2 open granuloma excisions, and 6 laryngotracheal reconstructions (LTRs) were performed. All LTR patients were decannulated. A new type of LTR (1.5 stage) was developed to meet special mission circumstances. Two videofluoroscopic swallow studies and 40 bedside swallow evaluations were performed. One local pediatric otolaryngologist, 1 pediatric surgeon, 3 anesthesiologists, 7 intensivists, 16 nurses, and 2 speech-language pathologists have received training. More than 25 hours of lectures were given, and a website was created collaboratively for educational and informational dissemination (http://www.masseyeandear.org/specialties/pediatrics/pediatric-ent/airway/OperationAirway/). CONCLUSION: We demonstrated the successful creation of the first mission stemming from a teaching institution with the goal of developing a sustainable, autonomous surgical airway program.

A Randomized Controlled Trial of Dexamethasone as a Prophylactic Treatment for Subglottic Stenosis in a Rabbit Model.

OBJECTIVE: Iatrogenic injury is a common cause of subglottic stenosis (SGS). We investigated the role of pre-injury dexamethasone as a preventive treatment for iatrogenic subglottic stenosis. METHODS: 16 New Zealand White rabbits were used in an IACUC approved study. Subjects were divided into two groups: intramuscular dexamethasone (DEX) at a dose of 2 mg/kg 15 minutes prior to an endoscopic injury to create SGS, and the same injury creation with a preoperative intramuscular saline (SAL) injection. Three independent, blinded raters evaluated endoscopic images to obtain cross sectional area (CSA) airway measurements. Rabbit airways were measured just prior to injury and at one week post-injury. All subjects were provided as-needed postoperative steroids and buprenorphine for symptoms of respiratory distress. Data analysis was performed using Student t-test. Intraclass correlation coefficients were used to assess inter-rater agreement. RESULTS: All subjects survived to the one-week post-injury airway evaluation. There was no difference in airway size between groups prior to injury (P = .28). Subjects in the DEX group demonstrated an average stenosis of 20.3% (95% CI 10.2-30.5) at one week compared to 60.6% (95% CI 40.3-80.9) in the SAL group (P = .01). Subjects in the control group required significantly more doses of postoperative dexamethasone (P = .02). Inter-rater agreement for between raters was excellent (ICC = .88). CONCLUSION: This is the first study to examine the role of pre-injury glucocorticoids in preventing iatrogenic subglottic stenosis. In our model, a single dose of intramuscular dexamethasone given prior to a subglottic injury resulted in a statistically significant reduction in airway stenosis. This research suggests that administering systemic dexamethasone should be considered prior to any procedure that may injure the subglottis, including traumatic intubation, to prevent iatrogenic subglottic stenosis.

Helicopter Hoist Performance in Novice and Experienced Hoist Operators.

BACKGROUND: Helicopter hoist operators are highly skilled and critical crewmembers in search and rescue. However, hoist operator training programs are relatively underdeveloped in comparison to helicopter pilot training. It is critical that this simulator teaches the necessary skills for high-level performance given the dangers associated with helicopter hoist operation. As a result, we sought to validate and identify critical aspects of skilled hoisting.METHODS: Through expert consultation, we identified several measures of hoist operation, such as mission time, cable plumb, cable tension, cable hand position, and cable displacement. We compared hoist performance between experienced and novice hoist operators in a simulated hoisting mission with two levels of difficulty (with and without wind). The experienced group (eight men/one woman) was composed of nine active or former military hoist operators who were working in commercial search and rescue. The novice group was composed of seven subjects (two men/five women) from the general population and had no previous experience with hoisting operations or the simulator.RESULTS: We found that experienced hoist operators had faster mission time, similar cable plumb, lower tension, and less variable hand position. Further, experienced hoist operators pulled the cable inward in the wind while novice hoist operators pushed the cable away.DISCUSSION: These findings suggests that this simulator captures performance differences between skill levels and, as a result, is a first step supporting the use of this simulator for hoist operator training.King MT, Lenser S, Rogers D, Carnahan H. Helicopter hoist performance in novice and experienced hoist operators. Aerosp Med Hum Perform. 2020; 91(6):496-500.

Randomized Controlled Trial of Balloon Dilation in Treatment of Subglottic Stenosis With a Rabbit Model.

OBJECTIVES: Identify the effects of balloon dilation duration and topical ciprofloxacin-dexamethasone application in treatment of subglottic stenosis. STUDY DESIGN: Randomized controlled trial. SETTING: Animal research facility. SUBJECTS AND METHODS: Forty-four rabbits underwent subglottic injury in an Institutional Animal Care and Use Committee-approved study. One week after injury, the subglottis of each rabbit was measured and treated with endoscopic balloon dilation for 2 rounds of short duration (SBD; 3 seconds), long duration (LBD; 30 seconds), or LBD with topical ciprofloxacin-dexamethasone application (LBD+C). The subglottis of each rabbit was remeasured at the study endpoint: 1 month postdilation or following development of life-threatening respiratory distress. RESULTS: Of 44 rabbits, 35 (80%) survived to endoscopic balloon dilation, with 21 rabbits developing a grade III Cotton-Myer stenosis. Prior to dilation, there was no difference in stenosis rates among groups (all subjects, P = .99; grade III stenosis only, P = .52). Among grade III subjects, improvement in stenosis after dilation was -1% (SD, 21%) for SBD, 27% (SD, 38%) for LBD, and 58% (SD, 29%) for LBD+C (P = .01). Early euthanasia/death rates among grade III subjects were 85% for SBD, 63% for LBD, and 17% for LBD+C (P = .03). Time to early euthanasia/death was 5.0 days for the SBD group and 8.4 days for the LBD group (P = .04). CONCLUSION: SBD was inferior to LBD or LBD+C in multiple metrics. LBD+C offered significant improvements in stenosis size and mortality over the SBD group and had the lowest rate of early mortality. Further research is needed to identify optimal balloon dilation treatment duration.

A Supraglottic Mass in a Pediatric Patient: An Unusual Presentation of Lymphoma.

OBJECTIVE: To present a case of laryngeal lymphoma in a pediatric patient and perform a literature review of this rare entity. PATIENT: A 13-year-old male presented with a rapidly enlarging right neck mass. Work-up of the neck mass included a computed tomography scan of the neck with contrast and revealed a 2.5 cm right level II neck mass and an asymmetric lobulated soft tissue mass in the right pyriform sinus. INTERVENTION: The patient underwent excisional biopsy of the right supraglottic mass. Once his diagnosis was confirmed, he was treated with a standard lymphoma protocol. RESULTS: Intraoperative frozen analysis revealed a small blue cell tumor. Final pathology demonstrated diffuse large B-cell lymphoma of the germinal center B-cell subtype (GC-DLBCL). The patient underwent treatment with primary chemotherapy 12 days after his original procedure with cyclophosphamide, doxorubicin, vincristine, and prednisone. CONCLUSION: Laryngeal lymphoma remains extremely rare in the pediatric population. With appropriate treatment, the 5-year disease-free survival remains excellent for germinal center diffuse large B-cell lymphoma.

Comparison of Ibuprofen vs Acetaminophen and Severe Bleeding Risk After Pediatric Tonsillectomy: A Noninferiority Randomized Clinical Trial.

Importance: Ibuprofen is an effective analgesic after tonsillectomy alone or tonsillectomy with adenoidectomy, but concerns remain about whether it increases postoperative hemorrhage. Objective: To investigate the effect of ibuprofen compared with acetaminophen on posttonsillectomy bleeding (PTB) requiring surgical intervention in children. Design, Setting, and Participants: A multicenter, randomized, double-blind noninferiority trial was conducted at 4 tertiary medical centers (Massachusetts Eye and Ear Infirmary, Boston; Naval Medical Center, San Diego, California; Naval Medical Center, Portsmouth, Virginia; Madigan Army Medical Center, Tacoma, Washington). A total of 1832 children were assessed for eligibility (presence of sleep-disordered breathing or obstructive sleep apnea, adenotonsillar hypertrophy, or infectious tonsillitis undergoing extracapsular tonsillectomy by electrocautery). Of these, 1091 were excluded because they did not meet eligibility criteria (n = 681) or refused to participate (n = 410); thus, 741 children aged 2 to 18 years undergoing tonsillectomy alone or tonsillectomy with adenoidectomy were enrolled between May 3, 2012, and January 20, 2017. Interventions: Participants were randomized to receive ibuprofen, 10 mg/kg (n = 372), or acetaminophen, 15 mg/kg (n = 369), every 6 hours for the first 9 postoperative days. Main Outcomes and Measures: Rate and severity of posttonsillectomy bleeding were recorded using a postoperative bleeding severity scale: type 1 (bleeds that were observed at home or evaluated in the emergency department without further intervention), type 2 (bleeds that required readmission for observation), and type 3 (bleeds that required a return to the operating room for control of hemorrhage). Type 3 bleeding was the main outcome measure. The noninferiority margin was set at 3%, and modified intention-to-treat analysis was used. Results: Of the 741 children enrolled, 688 children (92.8%) (median [interquartile range] age, 5 [4] years; 366 boys [53.2%]) received the study medication and were included in a modified intention-to-treat analysis. The rate of bleeding requiring operative intervention was 1.2% in the acetaminophen group and 2.9% in the ibuprofen group (difference, 1.7%; 97.5% CI upper limit, 3.8%; P = .12 for noninferiority). There were no significant adverse events or deaths. Conclusions and Relevance: This study could not exclude a higher rate of severe bleeding in children receiving ibuprofen after tonsillectomy alone or tonsillectomy with adenoidectomy. This finding should be considered when selecting a postoperative analgesic regimen. Further studies are needed to understand if bleeding risk is affected when ibuprofen is used for a shorter duration or in combination with acetaminophen for postoperative analgesia. Trial Registration: ClinicalTrials.gov identifier: NCT01605903.

A Simple Endoscopic Technique for Measuring the Cross-Sectional Area of the Upper Airway in a Rabbit Model.

OBJECTIVE: Validate an accurate and reproducible method of measuring the cross-sectional area (CSA) of the upper airway. SUBJECTS AND METHODS: This is a prospective animal study done at a tertiary care medical treatment facility. Control images were obtained using endotracheal tubes of varying sizes. In vivo images were obtained from various timepoints of a concurrent study on subglottic stenosis. Using a 0° rod telescope, an instrument was placed at the level of interest, and a photo was obtained. Three independent and blinded raters then measured the CSA of the narrowest portion of the airway using open source image analysis software. RESULTS: Each blinded rater measured the CSA of 79 photos. The t testing to assess for accuracy showed no difference between measured and known CSAs of the control images ( P = .86), with an average error of 1.5% (SD = 5.5%). All intraclass correlation (ICC) values for intrarater agreement showed excellent agreement (ICC > .75). Interrater reliability among all raters in control (ICC = .975; 95% CI, .817-.995) and in vivo (ICC = .846;, 95% CI, .780-.896) images showed excellent agreement. CONCLUSIONS: We validate a simple, accurate, and reproducible method of measuring the CSA of the airway that can be used in a clinical or research setting.

Reproducing severe acute subglottic stenosis in a rabbit model.

OBJECTIVES: The objectives of this study were to develop an animal model with consistent, severe subglottic stenosis (SGS), and to develop the timeline needed for intervention to limit rabbit mortality. METHODS: Subglottic stenosis was created endoscopically using either a nylon or polypropylene brush in sixteen New Zealand White rabbits. The subglottic cross-sectional area was measured endoscopically using a right-angled probe and an open source image analysis software The cross-sectional areas of the stenotic and native airways were compared to calculate the subglottic stenosis percentage and Myer-Cotton grade classification. RESULTS: The average diameter of the native subglottis was 4.7 mm (SD 0.4). The mean subglottic stenosis percentage was 73% (SD 32) for all rabbits. The three rabbits injured with the nylon brush had 30, 52, and 76% stenosis. Nine of the 12 surviving rabbits (75%) injured with the polypropylene brush had a >86% subglottic stenosis. Four rabbits in the polypropylene brush cohort died from procedural complications. CONCLUSION: This study demonstrates a reliable model using a polypropylene brush to create severe acute subglottic stenosis. Cartilage exposure after creating the injury was associated with more severe stenosis. Mortality rate may have been reduced if endoscopic balloon dilation was performed electively seven days after injury, rather than emergently nine days after injury. LEVEL OF EVIDENCE: 4.

SB-399885 is a potent, selective 5-HT6 receptor antagonist with cognitive enhancing properties in aged rat water maze and novel object recognition models.

SB-399885 (N-[3,5-dichloro-2-(methoxy)phenyl]-4-(methoxy)-3-(1-piperazinyl)benzenesulfonamide) has high affinity for human recombinant and native 5-HT(6) receptors, with pK(i) values 9.11+/-0.03 and 9.02+/-0.05, respectively and is a potent competitive antagonist (pA(2) 7.85+/-0.04). It displays over 200-fold selectivity for the 5-HT(6) receptor over all other receptors, ion channels and enzymes tested to date. SB-399885 inhibited ex vivo [(125)I]SB-258585 (4-Iodo-N-[4-methoxy-3-(4-methyl-piperazin-1-yl)-phenyl]-benzenesulfonamide) binding with an ED(50) of 2.0+/-0.24 mg/kg p.o. in rats. It had a minimum effective dose of 1 mg/kg p.o. in a rat maximal electroshock seizure threshold test and a long duration of action, overall demonstrating an excellent pharmacokinetic-pharmacodynamic correlation. Repeated administration of this agent (10 mg/kg p.o., b.i.d. for 7 days) significantly reversed a scopolamine-induced deficit (0.5 mg/kg i.p.) in a rat novel object recognition paradigm. Moreover, in aged rats (22 months old) SB-399885 (10 mg/kg p.o., b.i.d. for 7 days) fully reversed the age-dependent deficit in water maze spatial learning compared to vehicle-treated age-matched controls and significantly improved recall of the task measured by increases in the searching of the target quadrant on post-training days 1, 3 and 7. In vivo microdialysis in the rat medial prefrontal cortex demonstrated that acute SB-399885 (10 mg/kg p.o.) significantly increased extracellular acetylcholine levels. These data demonstrate that SB-399885 is a potent, selective, brain penetrant, orally active 5-HT(6) receptor antagonist with cognitive enhancing properties that are likely to be mediated by enhancements of cholinergic function. These studies provide further support for the potential therapeutic utility of 5-HT(6) receptor antagonists in disorders characterised by cognitive deficits such as Alzheimer's disease and schizophrenia.

Novel management of an isolated comminuted cricoid cartilage fracture.

Laryngeal trauma is a rare occurrence that can result in significant morbidity and mortality. Isolated cricoid cartilage fractures are exceedingly rare, and their treatment is highly variable. We describe a case of an isolated comminuted, uncalcified cricoid cartilage fracture in a 34-year-old man that responded well to novel management with suture and 2-octylcyanoacrylate tissue adhesive fixation intraoperatively and topical ciprofloxacin/dexamethasone applied to the airway postoperatively. We discuss the novel application of cyanoacrylate glue in laryngeal trauma and the potential benefits of topical ciprofloxacin/dexamethasone application to the airway.

Dystrophic calcification: A rare pediatric parotid mass.

Dystrophic calcification, the ectopic deposition of calcium in previously damaged or inflamed tissues, is an uncommon finding in the head and neck. Only a few cases have been reported in the parotidomasseteric region, and all of them have been located within and adjacent to the masseter. We present a case of dystrophic calcification occurring entirely within the parotid gland in a 7-year-old girl without apparent inciting inflammation, infection, or trauma. Our patient's presentation highlights the diagnostic challenge associated with parotid masses in the pediatric population. To our knowledge, this is the first reported case of dystrophic calcification occurring entirely within the parotid gland in a child.

Collagen Content Limits Optical Coherence Tomography Image Depth in Porcine Vocal Fold Tissue.

OBJECTIVE: Vocal fold scarring, a condition defined by increased collagen content, is challenging to treat without a method of noninvasively assessing vocal fold structure in vivo. The goal of this study was to observe the effects of vocal fold collagen content on optical coherence tomography imaging to develop a quantifiable marker of disease. STUDY DESIGN: Excised specimen study. SETTING: Massachusetts Eye and Ear Infirmary. SUBJECTS AND METHODS: Porcine vocal folds were injected with collagenase to remove collagen from the lamina propria. Optical coherence tomography imaging was performed preinjection and at 0, 45, 90, and 180 minutes postinjection. Mean pixel intensity (or image brightness) was extracted from images of collagenase- and control-treated hemilarynges. Texture analysis of the lamina propria at each injection site was performed to extract image contrast. Two-factor repeated measure analysis of variance and t tests were used to determine statistical significance. Picrosirius red staining was performed to confirm collagenase activity. RESULTS: Mean pixel intensity was higher at injection sites of collagenase-treated vocal folds than control vocal folds (P < .0001). Fold change in image contrast was significantly increased in collagenase-treated vocal folds than control vocal folds (P = .002). Picrosirius red staining in control specimens revealed collagen fibrils most prominent in the subepithelium and above the thyroarytenoid muscle. Specimens treated with collagenase exhibited a loss of these structures. CONCLUSION: Collagen removal from vocal fold tissue increases image brightness of underlying structures. This inverse relationship may be useful in treating vocal fold scarring in patients.

Prevalence of Diagnosed Sleep Disorders and Related Diagnostic and Surgical Procedures in Children with Autism Spectrum Disorders.

OBJECTIVE: Sleep disorders are common and important comorbid conditions in children with autism spectrum disorder (ASD) and can contribute to cognitive and behavioral problems. Sleep-disordered breathing (SDB) is a diagnosable and treatable cause of behavioral problems in children. We aimed to quantify the relative risk for children with ASD versus controls of being diagnosed with sleep disorders including SDB and undergoing related diagnostic and surgical procedures. METHOD: This retrospective case-cohort study included 48,762 children with ASD aged 2 to 18 years enrolled in the military health system (MHS) from 2000 to 2013. Children with ASD were matched 1:5 by birthdate, sex, and enrollment time to children without an ASD diagnosis. The MHS database was queried for International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for sleep disorders or ICD-9-CM and Current Procedural Terminology codes for diagnostic and surgical procedures. Relative risks (RR) and 95% confidence intervals (CI) were determined with binary Poisson regression conditional on the match and adjusting for confounders. RESULTS: Children with ASD were at higher risk of receiving any sleep disorder diagnosis (RR: 1.97 [95% CI, 1.91-2.02]) including SDB (RR: 1.96 [95% CI, 1.88-2.05]). Children with ASD also were at increased risk of undergoing polysomnography (RR: 3.74 [95% CI, 3.56-3.93]) and sleep disorder-related surgery (RR: 1.50 [95% CI, 1.46-1.54]). CONCLUSION: Children with ASD are more likely to be given a sleep disorder diagnosis including SDB and are more likely to undergo related diagnostic and surgical procedures compared with controls without ASD.

Comparison of hybrid laryngotracheal reconstruction to traditional single- and double-stage laryngotracheal reconstruction.

OBJECTIVES: (1) To describe outcomes from and modifications to the hybrid laryngotracheal reconstruction (LTR) technique and (2) to compare this technique to traditional single- and double-stage LTR (ssLTR/dsLTR). STUDY DESIGN: Chart review with case series. SETTING: Tertiary care otolaryngology specialty hospital. SUBJECTS: All patients under 18 years of age who underwent LTR by a single surgeon from July 1, 2009, to December 31, 2013. METHODS: Charts were assessed for age, gender, etiology of stenosis, type of reconstruction, comorbidities, length of stay, complications, and tracheostomy status. Analysis was performed using Kruskal-Wallis and Wilcoxon rank sum analysis. RESULTS: Forty-four patients were identified, with 13 hybrid LTRs, 27 ssLTRs, and 4 dsLTRs. Of the hybrid LTRs, an overall decannulation rate of 76.9% was noted, comparable to those for dsLTR. The hybrid LTR technique offered a significantly shorter period of narcotic use when compared to ssLTR (median 15 vs 21 days, P<.01). No patients in the hybrid LTR group developed supraglottic granulation tissue. There was no statistically significant difference in median length of stay for ssLTRs, dsLTRs, and hybrid LTRs (P=.38). CONCLUSION: The hybrid LTR technique is well tolerated and useful in patients of all ages. Narcotics can be weaned more quickly due to the presence of a secure airway at all times via the existing tracheostomy. Use of a long stent prevents formation of granulation tissue that may be seen with a suprastomal stent. This technique should be considered in patients with high-grade stenosis with a preexisting tracheostomy.

Systemwide change of sedation wean protocol following pediatric laryngotracheal reconstruction.

IMPORTANCE: Pediatric laryngotracheal reconstruction (LTR) remains the standard surgical technique for expanding a stenotic airway and necessitates a multidisciplinary team. Sedation wean following LTR is a critical component of perioperative care. We identified variation and communications deficiencies with our sedation wean practice and describe our experience implementing a standardized sedation wean protocol. OBJECTIVE: To standardize and decrease length of sedation wean in pediatric patients undergoing LTR. DESIGN, SETTING, AND PARTICIPANTS: Using Institute for Healthcare Improvement (IHI) methodology, we implemented systemwide change at a tertiary care center with the goal of improving care based on best practice guidelines. We created a standardized electronic sedation wean communication document and retrospectively examined our experience in 29 consecutive patients who underwent LTR before (n = 16, prewean group) and after (n = 13, postwean group) wean document implementation. INTERVENTIONS: Implementation of a standardized sedation protocol. MAIN OUTCOMES AND MEASURES: Presence of sedation wean document in the electronic medical record, length of sedation wean, and need for continued wean after discharge. RESULTS: The sedation wean document was used in 92.3% patients in the postwean group. With the new process, the mean (SD) length of sedation wean was reduced from 16.19 (11.56) days in the prewean group to 8.92 (3.37) days in the postwean group (P = .045). Fewer patients in the postwean group required continued wean after discharge (81.3% vs 33.3%; P = .02). CONCLUSIONS AND RELEVANCE: We implemented a systemwide process change with the goal of improving care based on best practice guidelines, which significantly decreased the time required for sedation wean following LTR. Our methodological approach may have implications for other heterogeneous patient populations requiring a sedation wean.

Establishment of a normative cepstral pediatric acoustic database.

IMPORTANCE: Few studies have used objective measures to evaluate the development of the normal pediatric voice. Cepstral analysis of continuous speech samples is a reliable method for gathering acoustic data; however, it has not been used to examine the changes that occur with voice development. OBJECTIVE: To establish and characterize acoustic patterns of the normal pediatric voice using cepstral analysis of voice samples from a normal pediatric voice database. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of 218 children aged 4 to 17 years, for whom English was the primary language spoken at home, conducted at a pediatric otolaryngology practice and pediatric practice in a tertiary hospital (April 2012-May 2014). INTERVENTIONS AND EXPOSURES: Sustained vowel utterances and continuous speech samples (4 Consensus Auditory-Perceptual Evaluation of Voice [CAPE-V] and 2 sentences from the rainbow passage) were recorded and analyzed from children with normal voices. MAIN OUTCOMES AND MEASURES: Normal values were collected for the acoustic measures studied (ie, fundamental frequency, cepstral peak fundamental frequency, cepstral peak prominence [CPP], low-to-high spectral ratio [L/H ratio], and cepstral-spectral index of dysphonia in recorded phrases) and compiled into a normative acoustic database. RESULTS: Significant changes in fundamental frequency were observed with a distinct shift in slope at ages 11 and 14 years in boys for sustained vowel (ages 4-11 years, -6.83 Hz/y [P < .001]; 11-14 years, -27.62 Hz/y [P < .001]; and 14-17 years, -5.68 Hz/y [P = .001]), all voiced (ages 4-11 years, -4.19 Hz/y [P = .002]; 11-14 years, -29.42 Hz/y [P < .001]; and 14-17 years, -4.63 Hz/y [P < .001]), glottal attack (ages 4-11 years, -4.51 Hz/y; 11-14 years, -27.23 Hz/y; and 14-17 years, -1.70 Hz/y [P < .001 for all]), and rainbow (ages <14 years, -20.68 Hz/y [P < .001]; and 14-17 years, -4.50 Hz/y [P = .001]) recordings. A decreasing linear trend in fundamental frequency among all recordings (vowel, all voiced, easy onset, glottal attack, plosives, and rainbow) was found in girls (-2.56 Hz/y [P < .001], -3.48 Hz/y [P < .001], -2.82 Hz/y [P < .001], -3.49 Hz/y [P < .001], -2.30 Hz/y [P < .001], and -2.98 Hz/y [P = .01], respectively). A linear increase in CPP was seen with age in boys, with significant changes seen in recordings for vowel (0.10 dB/y [P = .05]), all voiced (0.2 dB/y [P < .001]), easy onset (0.13 dB/y [P < .001]), glottal attack (0.12 dB/y [P < .001]), plosives (0.15 dB/y [P < .001]), and rainbow (0.17 dB/y [P = .006]). A significant linear increase in CPP for girls was only seen in all voiced (0.13 dB/y [P < .001]). L/H ratio showed a linear increase with age among all speech samples (vowel, all voiced, easy onset, glottal attack, plosives, and rainbow) in boys (1.14 dB/y [P < .001], 0.92 dB/y [P < .001], 1.19 dB/y [P < .001], 0.79 dB/y [P < .001], 0.69 dB/y [P < .001], and 0.54 dB/y [P = .002], respectively) and girls (0.96 dB/y, 0.60 dB/y, 0.75 dB/y, 0.37 dB/y, 0.44 dB/y, and 0.58 dB/y, respectively [P ≤ .001 for all]). CONCLUSIONS AND RELEVANCE: This represents the first pediatric voice database using frequency-based acoustic measures. Our goal was to characterize the changes that occur in both male and female voices as children age. These findings help illustrate how acoustic measurements change with development and may aid in our understanding of the developing voice, pathologic changes, and response to treatment.

Effects of Nucleus Basalis Magnocellularis Lesions in Rats on Delayed Matching and Non-Matching to Position Tasks.

The effects of quisqualic acid lesions of the nucleus basalis magnocellularis on short-term memory capacities of the rat have been investigated using the delayed matching and non-matching to position tasks. The lesions do not disrupt performance of either task by pretrained animals, but do disrupt the ability to acquire the non-matching contingency, and to reverse to the non-matching task when trained on the matching task. The unidirectional nature of the reversal deficit has been replicated. The generalized disruption of performance of either task by the muscarinic antagonist scopolamine was comparable in lesioned and control rats. The lesions were associated with extensive loss of acetylcholinesterase staining in the basal forebrain and in the neocortex, and 55% depletions of choline acetyltransferase activity in the neocortex but not in the hippocampus. These observations demonstrate that the cholinergic projection from nucleus basalis to the neocortex is not critical for normal short-term memory, but that lesions involving this system do disrupt specific types of conditional discrimination learning.

Pharmacological profile of SB-357134: a potent, selective, brain penetrant, and orally active 5-HT(6) receptor antagonist.

N-(2,5-Dibromo-3-fluorophenyl)-4-methoxy-3-piperazin-1-ylbenzenesulfonamide (SB-357134) potently inhibited [125I]SB-258585 and [3H]LSD binding in a HeLa cell line expressing human 5-HT(6) receptors (pK(i)=8.6 and 8.54, respectively). Furthermore, SB-357134 inhibited [125I]SB-258585 binding in human caudate--putamen and in rat and pig striatum membranes (pK(i)=8.82, 8.44, and 8.61, respectively). SB-357134 displayed over 200-fold selectivity for the 5-HT(6) receptor versus 72 other receptors and enzymes. 5-HT-stimulated cyclic AMP (cAMP) accumulation in human 5-HT(6) receptors was competitively antagonised by SB-357134 (pA(2)=7.63). SB-357134 inhibited ex vivo [125I]SB-258585 binding in the rat with an ED(50) of 4.9 +/- 1.3 mg/kg po, 4 h postdose. In the rat maximal electroshock seizure threshold (MEST) test, SB-357134 produced a potent and dose-dependent increase in seizure threshold, with a minimum effective dose of 0.1 mg/kg po. At 10 mg/kg po, maximum activity occurred between 4 and 6 h postdose. Good exposure was observed with SB-357134 at 10 mg/kg po, reaching maximal blood and brain concentrations of 4.3 +/- 0.2 and 1.3 +/- 0.06 microM, respectively, 1 h postdose. In addition, SB-357134 (10 mg/kg po) enhanced memory and learning following chronic administration (twice a day for 7 days) in the rat water maze. Overall, these studies demonstrate that SB-357134 is a potent, selective, brain penetrant, and orally active 5-HT(6) receptor antagonist.

Use of botulinum toxin in pediatric otolaryngology and laryngology.

The use of botulinum toxin in adult otolaryngology has been commonly used in conditions such as spasmodic dysphonia, cricopharyngeal spasm, palatal myoclonus, sialorrhea, and for cosmetic reasons. The current use of botulinum toxin in pediatric otolaryngology and laryngology has primarily been off label and in children older than 2 years of age. This review discusses the different applications of botulinum toxin in pediatric patients and its effectiveness in treating different pediatric conditions.