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Tafireyi Marukutira,1 Shirish Huprikar,2 Nkechi Azie,3 Shun-Ping Quan,3 Herwig-Ulf Meier-Kriesche,3 David L Horn4 1Botswana-Baylor Children’s Clinical Centre of Excellence, Gaborone, Botswana, 2Icahn School of Medicine at Mount Sinai, New York, NY, 3Astellas Scientific and Medical Affairs, Inc, Northbrook, IL, 4David Horn LLC, Doylestown, PA, USA Abstract: This analysis aimed to characterize the epidemiology, diagnosis, treatment, and outcomes of invasive fungal infections (IFIs) in patients with human immunodeficiency virus (HIV). Data were examined for HIV patients enrolled in the Prospective Antifungal Therapy (PATH) Alliance registry, a multicenter, observational study of patients with IFIs in North America from 2004 to 2008. Patient demographics, clinical characteristics, comorbidities, antifungal therapies, and survival were assessed. In total, 320 fungal isolates were identified from 303 HIV patients with IFIs in the PATH Alliance® registry. These included Cryptococcus (50.0%), Candida (33.1%), Histoplasma (9.1%), and Aspergillus (4.4%). Candida infection occurred mainly as candidemia (86.0%); Cryptococcus as central nervous system infection (76.7%); Histoplasma as disseminated infection (74.1%); and Aspergillus as pulmonary infection (81.8%). The CD4 cell count was #200 cells/µL in 91.2% of patients with available data. The majority of patients with Cryptococcus (77.9%), Histoplasma (100.0%), and Aspergillus (71.4%) infections had CD4 cell counts ,50 cells/µL compared with 48.9% of patients with Candida infections. Patients with candidiasis were more likely to have other conditions requiring medical services compared with patients with other IFIs. Survival probability was lower in patients with Aspergillus (0.58) and Candida (0.59) infection than in patients with Histoplasma (0.84) and Cryptococcus (0.81) infection. In the highly active antiretroviral therapy era, traditional opportunistic IFIs such as cryptococcosis and histoplasmosis still mainly occur in HIV patients with CD4 counts ,50 cells/µL. Fungal infections remain a clinical challenge in HIV patients with severe immunosuppression. Our data also suggest that HIV patients with CD4 cell counts .200 cells/µL and other underlying conditions may be susceptible to invasive candidiasis. Keywords: human immunodeficiency virus, invasive fungal infections, Prospective Antifungal Therapy Alliance registry

Rebecca S Campbell,1 Paresh Chaudhari,2 Harlen D Hays,1 Robert J Taylor,1 Brian H Nathanson,3 Samuel A Bozzette,1 David Horn4 1Cerner Research, Culver City, CA, USA; 2Astellas Scientific and Medical Affairs, Inc., Northbrook, IL, USA; 3OptiStatim, LLC, Longmeadow, MA, USA; 4David Horn LLC, Doylestown, PA, USA Background: Lipid-based formulations of amphotericin B (LF-AMB) are indicated for treatment of invasive fungal infections in patients intolerant to conventional amphotericin B (CAB) or with refractory infections. Physicians still may choose to administer CAB to such patients. We described the use of CAB and LF-AMB in this population and quantified differences in post-amphotericin B length of stay (LOS) among survivors and hospital mortality in matched patients. Methods: Data were extracted from Health Facts (Cerner Corporation, Kansas City, MO, USA) for a retrospective cohort analysis. Inpatients aged ≥18 years with evidence of fungal infection and with orders for LF-AMB or CAB on ≥2 days from January 2001 to June 2010 were identified. Patients were required to have renal insufficiency or other relative contraindications to use of CAB, exposure to nephrotoxic agents, or evidence of a CAB-refractory infection. Multilevel (hierarchical) mixed-effects logistic regression was used to determine factors associated with initial exposure to LF-AMB versus CAB. Multivariate adjustment of outcomes was done using propensity score matching. Results: 655 patients were identified: 322 patients initiated therapy with CAB and 333 initiated treatment with LF-AMB. Compared to those initiating CAB, patients initiating LF-AMB had greater acuity and underlying disease severity. In unadjusted analyses, hospital mortality was significantly higher in the LF-AMB group (32.2% versus 23.7%; P = 0.02). After propensity score matching and covariate adjustment, mortality equalized and observed differences in LOS after amphotericin B initiation decreased. Conclusion: Among patients at risk for amphotericin B toxicity, differences between CAB and LF-AMB seen in crude outcomes analyses relate to channeling of sicker patients to initiate treatment with LF-AMB. Failing to account for differences among patients that drive clinical decision-making will result in inaccurate conclusions about the real-world effectiveness of different amphotericin B formulations. Keywords: amphotericin, outcomes, mortality, hospitalization

Objective: To investigate visual-motor integration (VI) skills of prelingually deaf (PLD) children before and after cochlear implantation (CI) and investigate correlations with spoken-language and related processing measures.Design: Study 1 was a longitudinal study in which VI was tested preimplant. Study 2 was a cross sectional study of school-age children who used a CI for >2 years.Method: In study 1, a standardized design-copying task was administered preimplant, and spoken-language data were obtained at intervals up to 4 years postimplantation. Analyses were conducted to determine if preimplant VI scores were predictive of various spoken-language measures. In study 2, standardized design copying and speeded maze tracing tasks were administered along with speech perception, vocabulary, and related processing measures.Results: Whereas preimplant VI scores for children in study 1 fell within the typical range based on age-equivalent norms, postimplant VI standard scores in study 2 were low compared to the normative sample. Postimplant VI scores were inversely related to age at implantation. Preimplant VI scores were robustly predictive of most, but not all, spoken-language outcome scores. Postimplant design copying scores were also correlated with spoken-language and related processing measures whereas maze-tracing scores were less robustly related to these measures.Conclusions: Early auditory and linguistic experience may impact the development of VI skills. VI is a preimplant predictor of later spoken language outcomes. Design copying and speeded maze tracing tasks appear to tap different sets of cognitive resources in PLD children with CIs. [ABSTRACT FROM AUTHOR]

Objective: Candida species are the leading cause of fungal infections in hospitalized patients and are the fourth most common cause of all nosocomial bloodstream infections. Mortality and length of stay (LOS) attributable to candidemia are extremely high; however, less is known about its impact on inpatient care costs. The goal of this study was to determine the inpatient cost of candidemia at a large urban academic tertiary-care hospital.Methods: All patients with a confirmed positive blood culture for Candida at Thomas Jefferson University Hospital, between January 1, 2004, and December 31, 2005, were identified via the microbiology laboratory information system. Data from the hospital's true-cost accounting system were used to calculate costs, LOS, and mortality rates. We determined the added burden of candidemia by comparing the observed costs and LOS for candidemia cases with expected Diagnosis-Related Group (DRG)-adjusted costs and LOS and non-candidemia cases. Differences in costs and LOS were also compared across Candida species.Results: From the 68,526 total hospitalizations during the study period, we identified 287 encounters positive for candidemia, yielding a frequency of 419 cases of candidemia per 100,000 admissions. The mean age of patients with candidemia was 58 years; 52% were female, and 60% were Caucasian. The most commonly identified species were C. albicans (n = 127; 44% of cases) and C. glabrata (n = 75; 26% of patients) . Candidemia was associated with additional costs and LOS of $68,311 (95% CI, $57,513-$79,108) and 23.1 days (95% confidence interval [CI], 19.3-26.8 days), respectively. No statistically significant differences in total costs, LOS, or mortality were found between species.Conclusion: Inpatient candidemia cases are extremely costly, regardless of the involved species. Most of the costs were attributable to the nursing department, with pharmacy costs constituting about 20% of total costs. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to assess relations between fine and gross motor development and spoken language processing skills in pediatric cochlear implant users.Study Design: The authors conducted a retrospective analysis of longitudinal data.Methods: Prelingually deaf children who received a cochlear implant before age 5 and had no known developmental delay or cognitive impairment were included in the study. Fine and gross motor development were assessed before implantation using the Vineland Adaptive Behavioral Scales, a standardized parental report of adaptive behavior. Fine and gross motor scores reflected a given child's motor functioning with respect to a normative sample of typically developing, normal-hearing children. Relations between these preimplant scores and postimplant spoken language outcomes were assessed.Results: In general, gross motor scores were found to be positively related to chronologic age, whereas the opposite trend was observed for fine motor scores. Fine motor scores were more strongly correlated with postimplant expressive and receptive language scores than gross motor scores.Conclusions: Our findings suggest a disassociation between fine and gross motor development in prelingually deaf children: fine motor skills, in contrast to gross motor skills, tend to be delayed as the prelingually deaf children get older. These findings provide new knowledge about the links between motor and spoken language development and suggest that auditory deprivation may lead to atypical development of certain motor and language skills that share common cortical processing resources. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: To determine whether scores from a behavioral assessment of prelingually deafened children who present for cochlear implant surgery are predictive of audiological outcomes.Study Design: Retrospective review of longitudinal data collected from 42 children with prelingual hearing loss who presented for a cochlear implant before age 5 years.Methods: The Vineland Adaptive Behavioral Scales (VABS) was administered during the preimplant workup. Standardized scores reflect daily living skills, socialization, and motor development compared with a normative sample. Regression analyses were conducted to determine whether any subject variables were related to VABS scores. Mixed-model analyses were computed to determine whether preimplant VABS scores were predictive of longitudinal spoken-language data obtained after cochlear implant surgery.Results: Motor scores tended to be higher than nonmotor scores. Nonmotor scores were significantly lower than the normative mean and decreased with testing age. Children with acquired deafness demonstrated lower motor scores than children with congenital causes. Children with higher motor scores demonstrated significantly higher performance on language, vocabulary, and word recognition tests than children with lower motor scores. Nonmotor domains were not as robustly related to spoken-language measures, although similar trends were observed.Conclusion: Profound deafness and language delay may confound the assessment of daily living skills and socialization in the population studied. Motor development appears to proceed normally in prelingually deafened children and is a preimplant predictor of spoken-language outcome in young infants and children with cochlear implants, a finding consistent with the large body of work establishing links between perceptual-motor and language development. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Individual speech and language outcomes of deaf children with cochlear implants (CIs) are quite varied. Individual differences in underlying cognitive functions may explain some of this variance. The current study investigated whether behavioral inhibition skills of deaf children were related to performance on a range of audiologic outcome measures.Design: Retrospective analysis of longitudinal data collected from prelingually and profoundly deaf children who used CIs.Methods: Behavioral inhibition skills were measured using a visual response delay task that did not require hearing. Speech and language measures were obtained from behavioral tests administered at 1-year intervals of CI use.Results: Female subjects showed higher response delay scores than males. Performance increased with length of CI use. Younger children showed greater improvement in performance as a function of device use than older children. No other subject variable had a significant effect on response delay score. A series of multiple regression analyses revealed several significant relations between delay task performance and open set word recognition, vocabulary, receptive language, and expressive language scores.Conclusions: The present results suggest that CI experience affects visual information processing skills of prelingually deaf children. Furthermore, the observed pattern of relations suggests that speech and language processing skills are closely related to the development of response delay skills in prelingually deaf children with CIs. These relations may reflect underlying verbal encoding skills, subvocal rehearsal skills, and verbally mediated self-regulatory skills. Clinically, visual response delay tasks may be useful in assessing behavioral and cognitive development in deaf children after implantation. [ABSTRACT FROM AUTHOR]

Objective: Cochlear implantation of prelingually deaf infants provides auditory input sufficient to develop spoken language; however, outcomes remain variable. Inability to participate in speech perception testing limits testing device efficacy in young listeners. In postlingually implanted adults (aCI), speech perception correlates with spectral resolution an ability that relies independently on frequency resolution (FR) and spectral modulation sensitivity (SMS). The correlation of spectral resolution to speech perception is unknown in prelingually implanted children (cCI). In this study, FR and SMS were measured using a spectral ripple discrimination (SRD) task and were correlated with vowel and consonant identification. It was hypothesized that prelingually deaf cCI would show immature SMS relative to postlingually deaf aCI and that FR would correlate with speech identification., Study Design: Cross-sectional study., Setting: In-person, booth testing., Methods: SRD was used to determine the highest spectral ripple density perceived at various modulation depths. FR and SMS were derived from spectral modulation transfer functions. Vowel and consonant identification was measured; SRD performance and speech identification were analyzed for correlation., Results: Fifteen prelingually implanted cCI and 13 postlingually implanted aCI were included. FR and SMS were similar between cCI and aCI. Better FR was associated with better speech identification for most measures., Conclusion: Prelingually implanted cCI demonstrated adult-like FR and SMS; additionally, FR correlated with speech identification. FR may be a measure of CI efficacy in young listeners., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Loss of function of stereocilin (STRC) is the second most common cause of inherited hearing loss. The loss of the stereocilin protein, encoded by the STRC gene, induces the loss of connection between outer hair cells and tectorial membrane. This only affects the outer hair cells (OHCs) function, involving deficits of active cochlear frequency selectivity and amplifier functions despite preservation of normal inner hair cells. Better understanding of cochlear features associated with mutation of STRC will improve our knowledge of normal cochlear function, the pathophysiology of hearing impairment, and potentially enhance hearing aid and cochlear implant signal processing. Nine subjects with homozygous or compound heterozygous loss of function mutations in STRC were included, age 7-24 years. Temporal and spectral modulation perception were measured, characterized by spectral and temporal modulation transfer functions. Speech-in-noise perception was studied with spondee identification in adaptive steady-state noise and AzBio sentences with 0 and -5 dB SNR multitalker babble. Results were compared with normal hearing (NH) and cochlear implant (CI) listeners to place STRC -/- listeners' hearing capacity in context. Spectral ripple discrimination thresholds in the STRC -/- subjects were poorer than in NH listeners (p < 0.0001) but remained better than for CI listeners (p < 0.0001). Frequency resolution appeared impaired in the STRC -/- group compared to NH listeners but did not reach statistical significance (p = 0.06). Compared to NH listeners, amplitude modulation detection thresholds in the STRC -/- group did not reach significance (p=  0.06) but were better than in CI subjects (p < 0.0001). Temporal resolution in STRC -/- subjects was similar to NH (p = 0.98) but better than in CI listeners (p = 0.04). The spondee reception threshold in the STRC -/- group was worse than NH listeners (p = 0.0008) but better than CI listeners (p = 0.0001). For AzBio sentences, performance at 0 dB SNR was similar between the STRC -/- group and the NH group, 88 % and 97 % respectively. For -5 dB SNR, the STRC -/- performance was significantly poorer than NH, 40 % and 85 % respectively, yet much better than with CI who performed at 54 % at +5 dB SNR in children and 53 % at + 10 dB SNR in adults. To our knowledge, this is the first study of the psychoacoustic performance of human subjects lacking cochlear amplification but with normal inner hair cell function. Our data demonstrate preservation of temporal resolution and a trend to impaired frequency resolution in this group without reaching statistical significance. Speech-in-noise perception compared to NH listeners was impaired as well. All measures were better than those in CI listeners. It remains to be seen if hearing aid modifications, customized for the spectral deficits in STRC -/- listeners can improve speech understanding in noise. Since cochlear implants are also limited by deficient spectral selectivity, STRC -/- hearing may provide an upper bound on what could be obtained with better temporal coding in electrical stimulation., Competing Interests: Declarations of Competing Interest None, (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Early initiation of broad-spectrum antibiotic agents is a cornerstone of the care of necrotizing skin and soft tissue infections (NSTI). However, the optimal duration of antibiotic agents is unclear. We sought to characterize antibiotic prescribing patterns for patients with NSTI, as well as associated complications. Patients and Methods: Using an NSTI registry, we characterized antibiotic use at a quaternary referral center. Kaplan-Meier analyses were used to describe overall antibiotic duration and relative to operative source control, stratified by presence of other infections that independently influenced antibiotic duration. Factors associated with successful antibiotic discontinuation were identified using logistic regression. Results: Between 2015 and 2018, 441 patients received antibiotic agents for NSTI with 18% experiencing a complicating secondary infection. Among those without a complicating infection, the median duration of antibiotic administration was 9.8 days (95% confidence interval [CI], 9.2-10.5) overall, and 7.0 days after the final debridement. Perineal NSTI received fewer days of antibiotic agents (8.3 vs. 10.6) compared with NSTI without perineal involvement. White blood cell (WBC) count and fever were not associated with failure of antibiotic discontinuation, however, a chronic wound as the underlying infection etiology was associated with greater odds of antibiotic discontinuation failure (odds ratio [OR], 4.33; 95% CI, 1.24-15.1). Conclusions: A seven-day course of antibiotic agents after final operative debridement may be sufficient for NSTI without any secondary complicating infections, because clinical characteristics do not appear to be associated with differences in successful antibiotic discontinuation.

Objective: Determine if students with severe-to-profound hearing loss with cochlear implants (CIs) mainstream (transition to general education) more than students with hearing amplification at the population level., Study Design: Cross-sectional secondary analysis of data from the National Center of Education Statistics., Setting: Special education (SpEd) students in the United States who had severe to profound "hearing impairment" and were 6 to 16 years old at enrollment from 2000 to 2001., Methods: We weighted the data to produce national estimates, performed multiple imputations for missingness, and built a multivariate linear regression model, which was cross-validated with a multivariate Poisson regression model. We used a theory-based approach to model-building using a directed acyclic graph to identify the minimally sufficient adjustment set of variables, which included school district urbanicity, student's age when they started SpEd, other disabilities, home language, and caregiver education., Results: We identified 7267 students with CIs and 28,794 students with hearing amplification. CI users mainstreamed more than peers using hearing amplification during secondary school (40.29% less daily time in special education, p = .004) but not during primary school (9.19% less daily time in SpEd, p = .155). Additional significant predictors of mainstreaming varied between the primary and secondary school cohorts and included school district urbanicity and the student's age when they started SpEd., Conclusion: CI status predicts daily time spent in SpEd among a secondary school cohort. These findings do not establish causation. The National Center of Education Statistics should consider linking to clinical databases in future studies., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Objective: To assess the efficacy of interarytenoid injection augmentation (IAIA) and the ability of IAIA to predict response to interarytenoid suture augmentation (IASA) based on diet advancement on video fluoroscopic swallow studies (VFSS)., Methods: Retrospective cohort analysis of patients with persistent pharyngeal dysphagia at a tertiary children's hospital with VFSS pre- and post-IAIA were included between March 2011 and June 2019., Results: Median age of the 229 patients was 2.2 years (5.8 months-19 years). Interarytenoid mucosal height (IAMH) was found to be above the false vocal folds in 112 patients (53.4%) and at true vocal folds in 10 (4.9%) patients. On VFSS post-IAIA, 95 (41.5%) patients were successfully advanced in recommended diet consistency, 115 (50.2%) were stable, and 19 (8.3%) needed thicker consistency. Paired t-tests on pre- and post-operative consistency scores showed significant improvement, p-value of <0.0001, 95% confidence interval (CI; 0.50-0.85). Poisson regression found no covariates with significant association with improvement on IAIA. For IASA patients, 35/60 (58.3%) improved on post-op VFSS. Paired t-tests on pre- and post-operative consistency scores showed significant improvement, p-value of <0.0001, 95% CI (0.63-1.33). Positive predictive value for IAIA predicting response to IASA was 77% with positive likelihood ratio of 2.3. The response to IAIA versus no response to IAIA likelihood ratios were found to have a statistically significant difference (p < 0.05)., Conclusions: Our study suggests IAIA yields objective improvement in swallow function on VFSS in nearly half of our patients and may be a reliable diagnostic tool to predict response to IASA in patients with persistent pharyngeal dysphagia with or without a laryngeal cleft., Level of Evidence: 3 Laryngoscope, 133:1749-1756, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: The Deaf community is an ethnolinguistic minority group. Low sensitivity to Deaf culture contributes to health disparities among Deaf patients. This study determines the level of sensitivity to Deaf culture among otolaryngology-head and neck surgery (OHNS) and audiology trainees., Methods: Cross-sectional survey study of OHNS and audiology trainees from 10 large US institutions. Trainees were queried on their exposure to and comfort with Deaf patients and their education on, attitude toward, and awareness and knowledge of Deaf culture. Sensitivity to Deaf culture was operationalized as awareness and knowledge of Deaf culture. These were assessed using a 35-item instrument that was previously developed using a d/Deaf community-based participatory approach to research. We used T-tests to compare the sample to previous samples of medical students with training in Deaf culture (MS-TDCs) and general practitioners (GPs)., Results: There were 91 completed surveys (response rate 44.5%). Almost all were aware of Deaf culture (97.8%). The mean knowledge score was 55.0% (standard deviation (SD) 13.4%), which was significantly higher than that for GPs at 43.0% (SD 15.0%) (95% confidence interval 8.1%, 15.8%, P  < .0001) but significantly lower than that for MS-TDCs at 69.0% (SD 13.0%)(CI -20.3%, -7.6%, P  < .0001). Knowledge scores were comparable for OHNS and audiology trainees ( P  = .09)., Conclusion: This sample of OHNS and audiology trainees was more sensitive to Deaf culture than GPs but less sensitive than MS-TDCs. Developing specialty-specific education may be warranted., Level of Evidence: 4.

Importance: In the US, most childhood-onset bilateral sensorineural hearing loss is genetic, with more than 120 genes and thousands of different alleles known. Primary treatments are hearing aids and cochlear implants. Genetic diagnosis can inform progression of hearing loss, indicate potential syndromic features, and suggest best timing for individualized treatment., Objective: To identify the genetic causes of childhood-onset hearing loss and characterize severity, progression, and cochlear implant success associated with genotype in a single large clinical cohort., Design, Setting, and Participants: This cross-sectional analysis (genomics) and retrospective cohort analysis (audiological measures) were conducted from 2019 to 2022 at the otolaryngology and audiology clinics of Seattle Children's Hospital and the University of Washington and included 449 children from 406 families with bilateral sensorineural hearing loss with an onset younger than 18 years. Data were analyzed between January and June 2022., Main Outcomes and Measures: Genetic diagnoses based on genomic sequencing and structural variant analysis of the DNA of participants; severity and progression of hearing loss as measured by audiologic testing; and cochlear implant success as measured by pediatric and adult speech perception tests. Hearing thresholds and speech perception scores were evaluated with respect to age at implant, months since implant, and genotype using a multivariate analysis of variance and covariance., Results: Of 406 participants, 208 (51%) were female, 17 (4%) were African/African American, 32 (8%) were East Asian, 219 (54%) were European, 53 (13%) were Latino/Admixed American, and 16 (4%) were South Asian. Genomic analysis yielded genetic diagnoses for 210 of 406 families (52%), including 55 of 82 multiplex families (67%) and 155 of 324 singleton families (48%). Rates of genetic diagnosis were similar for children of all ancestries. Causal variants occurred in 43 different genes, with each child (with 1 exception) having causative variant(s) in only 1 gene. Hearing loss severity, affected frequencies, and progression varied by gene and, for some genes, by genotype within gene. For children with causative mutations in MYO6, OTOA, SLC26A4, TMPRSS3, or severe loss-of-function variants in GJB2, hearing loss was progressive, with losses of more than 10 dB per decade. For all children with cochlear implants, outcomes of adult speech perception tests were greater than preimplanted levels. Yet the degree of success varied substantially by genotype. Adjusting for age at implant and interval since implant, speech perception was highest for children with hearing loss due to MITF or TMPRSS3., Conclusions and Relevance: The results of this cross-sectional study suggest that genetic diagnosis is now sufficiently advanced to enable its integration into precision medical care for childhood-onset hearing loss.

Objectives: Spectral resolution correlates with speech understanding in post-lingually deafened adults with cochlear implants (CIs) and is proposed as a non-linguistic measure of device efficacy in implanted infants. However, spectral resolution develops gradually through adolescence regardless of hearing status. Spectral resolution relies on two different factors that mature at markedly different rates: Resolution of ripple peaks (frequency resolution) matures during infancy whereas sensitivity to across-spectrum intensity modulation (spectral modulation sensitivity) matures by age 12. Investigation of spectral resolution as a clinical measure for implanted infants requires understanding how each factor develops and constrains speech understanding with a CI. This study addresses the limitations of the present literature. First, the paucity of relevant data requires replication and generalization across measures of spectral resolution. Second, criticism that previously used measures of spectral resolution may reflect non-spectral cues needs to be addressed. Third, rigorous behavioral measurement of spectral resolution in individual infants is limited by attrition. To address these limitations, we measured discrimination of spectrally modulated, or rippled, sounds at two modulation depths in normal hearing (NH) infants and adults. Non-spectral cues were limited by constructing stimuli with spectral envelopes that change in phase across time. Pilot testing suggested that dynamic spectral envelope stimuli appeared to hold infants' attention and lengthen habituation time relative to previously used static ripple stimuli. A post-hoc condition was added to ensure that the stimulus noise carrier was not obscuring age differences in spectral resolution. The degree of improvement in discrimination at higher ripple depth represents spectral frequency resolution independent of the overall threshold. It was hypothesized that adults would have better thresholds than infants but both groups would show similar effects of modulation depth., Design: Participants were 53 6- to 7-month-old infants and 23 adults with NH with no risk factors for hearing loss who passed bilateral otoacoustic emissions screening. Stimuli were created from complexes with 33- or 100-tones per octave, amplitude-modulated across frequency and time with constant 5 Hz envelope phase-drift and spectral ripple density from 1 to 20 ripples per octave (RPO). An observer-based, single-interval procedure measured the highest RPO (1 to 19) a listener could discriminate from a 20 RPO stimulus. Age-group and stimulus pure-tone complex were between-subjects variables whereas modulation depth (10 or 20 dB) was within-subjects. Linear-mixed model analysis was used to test for the significance of the main effects and interactions., Results: All adults and 94% of infants provided ripple density thresholds at both modulation depths. The upper range of threshold approached 17 RPO with the 100-tones/octave carrier and 20 dB depth condition. As expected, mean threshold was significantly better with the 100-tones/octave compared with the 33-tones/octave complex, better in adults than in infants, and better at 20 dB than 10 dB modulation depth. None of the interactions reached significance, suggesting that the effect of modulation depth on the threshold was not different for infants or adults., Conclusions: Spectral ripple discrimination can be measured in infants with minimal listener attrition using dynamic ripple stimuli. Results are consistent with previous findings that spectral resolution is immature in infancy due to immature spectral modulation sensitivity rather than frequency resolution., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The purpose of this study is to provide updated national estimates on the annual number, educational environments, and secondary school outcomes of students who are D/deaf and hard of hearing (D/HH) receiving special education (SpEd) and related services in the United States., Method: We performed a retrospective cross-sectional descriptive analysis of Individuals with Disabilities Education Act, Part B, Section 618 data from 2012 to 2018. Participants included students 6-21 years old in SpEd with "hearing impairment" reported as their primary disability. The general population of students in secondary school served as a comparator, via Current Population Survey data. We described the annual number of students (a) overall, (b) by educational environment, and (c) by reason for exiting SpEd, including the proportion graduating from and dropping out of secondary school. We described variation over time., Results: The median annual number of students was 67,655, with minimal variation by year. The proportion in general education (GenEd) for ≥ 80% of the day increased by 4.2% over 6 years from 57.8% to 62.0%, whereas the proportions in GenEd for &lt; 40% and 40%-79% of the day decreased by 1.6% and 1.3%, respectively. Proportions in the remainder of the environments changed &lt; 1.0% each. Of exiters, 86.8% of students graduated, whereas 3.9% dropped out, compared to a dropout rate of 5.0% in the general population., Conclusion: From 2012 to 2018, students who are D/HH receiving SpEd in the United States have spent increasingly more time in GenEd, most graduated from high school, and few dropped out, with dropout patterns appearing similar to the general population.

Objective: Suprastomal collapse and granulation are common sequelae of pediatric tracheostomy. We present the first measure of suprastomal obstructive pathology, the Seattle Suprastomal Safety Score (5S), an instrument with 2 domains: collapse and granulation., Study Design: Cross-sectional repeated testing survey., Setting: Electronic survey., Methods: A library of images was assembled from still pictures of the suprastomal area in 50 patients who previously underwent trachea-bronchoscopy at a quaternary children's hospital. Five pediatric otolaryngologists and 2 pediatric pulmonologists reviewed the images in random, blinded fashion and provided 5S scores. Participants repeated this process 2 to 4 weeks later. Interrater agreement was calculated with an intraclass correlation coefficient (ICC) with a 2-way random-effects model and Fleiss's κ. Intrarater agreement was measured with an ICC using a 2-way mixed-effects model as well as with test-retest correlations using Spearman rank coefficient. All measures were performed separately on collapse and granulation domains., Results: ICC for interrater agreement was 0.88 (95% CI, 0.82-0.93) for collapse and 0.97 (95% CI, 0.96-0.98) for granulation, indicating almost perfect agreement. Fleiss's κ demonstrated moderate agreement for collapse and almost perfect agreement for granulation. ICC for intrarater agreement was 0.95 (95% CI, 0.93-0.97) and 0.99 (95% CI, 0.98-0.99) for collapse and granulation, respectively, indicating almost perfect agreement. Spearman rank correlation for test-retest demonstrated substantial agreement for collapse and almost perfect agreement for granulation., Conclusion: The 5S demonstrates excellent interrater and intrarater agreement, making it highly reliable as a novel measure of suprastomal collapse and granulation in tracheostomy-dependent pediatric patients.

Purpose: This review article provides a theoretical overview of the development of spectral resolution in children with normal hearing (cNH) and in those who use cochlear implants (CIs), with an emphasis on methodological considerations. The aim was to identify key directions for future research on spectral resolution development in children with CIs., Method: A comprehensive literature review was conducted to summarize and synthesize previously published behavioral research on spectral resolution development in normal and impaired auditory systems., Conclusions: In cNH, performance on spectral resolution tasks continues to improve through the teenage years and is likely driven by gradual maturation of across-channel intensity resolution. A small but growing body of evidence from children with CIs suggests a more complex relationship between spectral resolution development, patient demographics, and the quality of the CI electrode-neuron interface. Future research should aim to distinguish between the effects of patient-specific variables and the underlying physiology on spectral resolution abilities in children of all ages who are hard of hearing and use auditory prostheses.

Objective: Determine whether variation in the HLA region is associated with the development of post-traumatic sepsis and septic shock., Background: Sepsis-related deaths remain a major source of mortality after traumatic injury. Genetic characteristics may contribute to susceptibility to adverse outcomes including sepsis and septic shock. Recent advances in next-generation sequencing technology now allow comprehensive genotyping of the HLA region., Methods: White adult trauma patients requiring more than 2 days of mechanical ventilation underwent HLA genotyping, and were followed for the development of sepsis and septic shock. Odds ratios (OR) for the associations between our outcomes and HLA variants were estimated, a correction for multiple comparisons was applied, and significant variants were included in regression models adjusting for potential confounders., Results: A total of 1184 patients were included. Patients were severely injured (median injury severity score 33); 33% developed sepsis, 6% septic shock, and in-hospital mortality was 14%. An amino acid variant (156Q) within the HLA-A peptide-binding groove was associated with greater odds of sepsis [OR 1.50, (1.18-1.89)]. HLA-A∗02:01 was associated with lower odds of septic shock [OR 0.52, (0.32-0.82)]. These associations remained significant after adjusting for potential confounders., Conclusions: This is the first study to apply next-generation sequencing techniques to evaluate associations between immunogenetic factors and post-traumatic sepsis and septic shock. Associations with class I HLA variants are novel as they implicate adaptive immunity in post-traumatic sepsis. These findings are a step towards developing a panel of genetic markers assessing risk of infection-related complications as we move towards more personalized medicine., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: β-Hemolytic streptococci are frequently implicated in necrotizing soft-tissue infections (NSTIs). Clindamycin administration may improve outcomes in patients with serious streptococcal infections. However, clindamycin resistance is growing worldwide, and resistance patterns in NSTIs and their impact on outcomes are unknown., Methods: Between 2015 and 2018, patients with NSTI at a quaternary referral center were followed up for the outcomes of death, limb loss, and streptococcal toxic shock syndrome. Surgical wound cultures and resistance data were obtained within 48 hours of admission as part of routine care. Risk ratios for the association between these outcomes and the presence of β-hemolytic streptococci or clindamycin-resistant β-hemolytic streptococci were calculated using log-binomial regression, controlling for age, transfer status, and injection drug use-related etiology., Results: Of 445 NSTIs identified, 85% had surgical wound cultures within 48 hours of admission. β-Hemolytic streptococci grew in 31%, and clindamycin resistance was observed in 31% of cultures. The presence of β-hemolytic streptococci was associated with greater risk of amputation (risk ratio, 1.80; 95% confidence interval, 1.07-3.01), as was the presence of clindamycin resistance among β-hemolytic streptococci infections (1.86; 1.10-3.16)., Conclusions: β-Hemolytic streptococci are highly prevalent in NSTIs, and in our population clindamycin resistance was more common than previously described. Greater risk of limb loss among patients with β-hemolytic streptococci-particularly clindamycin-resistant strains-may portend a more locally aggressive disease process or may represent preexisting patient characteristics that predispose to both infection and limb loss. Regardless, these findings may inform antibiotic selection and surgical management to maximize the potential for limb salvage., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Obstructive sleep apnea affects approximately 1-4% of all children, with increased prevalence amongst overweight and obese children., Objective: To assess the effects of drug-induced sleep endoscopy (DISE)-directed surgery on polysomnography parameters in obese and overweight children., Material/methods: A retrospective case-series was performed on obese and overweight pediatric patients who underwent clinically indicated DISE-directed surgery. Forty children met the inclusion criteria, including: body mass index ≥85%, DISE-study, and pre- and post-DISE polysomnography. Patients were divided into surgically naïve ( n  = 23) and prior adenotonsillectomy ( n  = 17) groups. Demographic and clinical characteristics were examined with chi-square and Wilcoxon rank-sum test. Polysomnography parameters were compared with Wilcoxon signed rank test., Results: Of 40 children with mean BMI 94% and mean age 8 ± 6 years old, 17 (43%) underwent a previous adenotonsillectomy. Overall, significant improvements were observed in the apnea-hypopnea index (AHI; 25.0 to 9.9 events/hour, p  < .01) and oxygen nadir (82.7% to 88.5%, p  < .01). A similar pattern was observed among the surgically naïve (AHI: 35.9 to 12.7 events/hour, p  = .04; oxygen nadir: 79.7% to 86.4%, p  = .2) and post-adenotonsillectomy groups (AHI: 10.4 to 6.2 events/hour, p  = .02; oxygen nadir: 86.7% to 91.2%, p  < .01)., Conclusions/significance: Polysomnography parameters significantly improved following DISE-directed interventions in obese and overweight children with obstructive sleep apnea.

Firearm storage method is a potentially modifiable risk factor for suicide. Using data from a large, multi-state survey, we sought to determine whether there is an association between mental health and household firearm storage practices, and characterize that association by state of residence. Participants who endorsed the presence of a household firearm and answered the mental health questions in the 2016-2017 Behavioral Risk Factor Surveillance System from eight states were included (n=26,949). Exposures were recent poor mental health (≥14 vs. 0-13 days/past month), and diagnosis of depression. Outcomes were household firearm storage practices (loaded, and both loaded and unlocked). Using Poisson regression, we calculated adjusted prevalence ratios (aPR) overall and stratified by state of residence. Of adults endorsing a household firearm, 35.1% reported storing a firearm loaded, and of those, 53.4% reported that the firearm was both loaded and unlocked. Neither recent poor mental health nor depression was associated with loaded (aPR 1.14 [95% CI: 0.95-1.37] and aPR 0.94 [95% CI 0.80-1.09], respectively) or loaded and unlocked (aPR 1.08 [95% CI 0.88-1.42] and aPR 1.04 [95% CI 0.88-1.22], respectively) firearm storage. In the setting of highly prevalent loaded firearm storage, no differences in storage practices by mental health indicators were observed across eight states despite disparate firearm policies and local culture. The lack of difference in storage practices by mental health indicators across several states highlights an opportunity to improve means safety counseling practices, and the need for dedicated evaluation of state-level firearm storage policies., (Published by Elsevier Inc.)

Background: Following trauma, persistent inflammation, immunosuppression, and catabolism may characterize delayed recovery or failure to recover. Understanding the metabolic response associated with these adverse outcomes may facilitate earlier identification and intervention. We characterized the metabolic profiles of trauma victims who died or developed chronic critical illness (CCI) and hypothesized that differences would be evident within 1-week postinjury., Methods: Venous blood samples from trauma victims with shock who survived at least 7 days were analyzed using mass spectrometry. Subjects who died or developed CCI (intensive care unit length of stay of ≥14 days with persistent organ dysfunction) were compared with subjects who recovered rapidly (intensive care unit length of stay, ≤7 days) and uninjured controls. We used partial least squares discriminant analysis, t tests, linear mixed effects regression, and pathway enrichment analyses to make broad comparisons and identify differences in metabolite concentrations and pathways., Results: We identified 27 patients who died or developed CCI and 33 who recovered rapidly. Subjects were predominantly male (65%) with a median age of 53 years and Injury Severity Score of 36. Healthy controls (n = 48) had similar age and sex distributions. Overall, from the 163 metabolites detected in the samples, 56 metabolites and 21 pathways differed between injury outcome groups, and partial least squares discriminant analysis models distinguished injury outcome groups as early as 1-day postinjury. Differences were observed in tryptophan, phenylalanine, and tyrosine metabolism; metabolites associated with oxidative stress via methionine metabolism; inflammatory mediators including kynurenine, arachidonate, and glucuronic acid; and products of the gut microbiome including indole-3-propionate., Conclusions: The metabolic profiles in subjects who ultimately die or develop CCI differ from those who have recovered. In particular, we have identified differences in markers of inflammation, oxidative stress, amino acid metabolism, and alterations in the gut microbiome. Targeted metabolomics has the potential to identify important metabolic changes postinjury to improve early diagnosis and targeted intervention., Level of Evidence: Prognostic/epidemiologic, level III., (Copyright © 2020 American Association for the Surgery of Trauma.)

Objectives: Cochlear implant depth of insertion affects audiologic outcomes and can be measured in adults using plain films obtained in the "cochlear view." The objective of this study was to assess interrater and intrarater reliability of measuring depth of insertion using cochlear view radiography., Study Design: Prospective, observational., Setting: Tertiary referral pediatric hospital., Subjects and Methods: Patients aged 11 months to 20 years (median, 4 years; interquartile range [IQR], 1-8 years) undergoing cochlear implantation at our institution were studied over 1 year. Children underwent cochlear view imaging on postoperative day 1. Films were deidentified and 1 image per ear was selected. Two cochlear implant surgeons and 2 radiologists evaluated each image and determined angular depth of insertion. Images were re-reviewed 6 weeks later by all raters. Inter- and intrarater reliability were calculated with intraclass correlation coefficients (ICCs)., Results: Fifty-seven ears were imaged from 42 children. Forty-nine ears (86%) had successful cochlear view x-rays. Median angular depth of insertion was 381° (minimum, 272°; maximum, 450°; IQR, 360°-395°) during the first round of measurement. Measurements of the same images reviewed 6 weeks later showed median depth of insertion of 382° (minimum, 272°; maximum, 449°; IQR, 360°-397°). Interrater and intrarater reliability ICCs ranged between 0.81 and 0.96, indicating excellent reliability., Conclusions: Postoperative cochlear view radiography is a reliable tool for measurement of cochlear implant depth of insertion in infants and children. Further studies are needed to determine reliability of intraoperatively obtained cochlear view radiographs in this population.

Purpose: Drug-induced sleep endoscopy (DISE) is useful in children with obstructive sleep apnea (OSA) that persists after adenotonsillectomy (AT), but its utility in surgically naïve children is unclear. We report polysomnography outcomes of surgically naïve children who underwent DISE-directed intervention because they were considered high risk for persistent OSA after adenotonsillectomy., Methods: This study is a case series of 62 surgically naïve children with OSA who were considered high risk for persistence after AT and underwent DISE-directed intervention with pre- and postoperative polysomnography between 2012 and 2016. Analysis was performed with the paired t test., Results: Children were on average 5.9 (± 5.5, 0.2-18.6) years old at the time of surgery, 68% male, 18% obese, and 60% white. Thirty-eight percent had a syndromic diagnosis: 19% trisomy 21, 11% hypotonic neuromuscular disorder, and 8% craniofacial condition. The remaining 62% were non-syndromic but underwent DISE because they had at least one risk factor for OSA persistence after AT (age > 7 years, black race, 1+ tonsils, obesity, and/or severe OSA). Forty-two percent underwent AT, while 58% underwent treatment other than AT, including 18% who had multilevel surgery. Children improved significantly in 4 out of 5 polysomnography parameters tested, including obstructive apnea-hypopnea index (oAHI; 22.2 to 7.2, p < 0.01) and oxygen nadir (82 to 87, p < 0.01). Thirty-eight (61%) had a postoperative oAHI < 5; 16 (21%) had a postoperative oAHI < 2., Conclusion: DISE resulted in intervention other than AT in 58% of surgically naïve children at high risk for persistent OSA after AT. DISE-directed intervention resulted in significant mean improvement in postoperative OSA.

COVID-19 is a rapidly growing global pandemic caused by a novel coronavirus. With no vaccine or definitive treatment, public health authorities have recommended a strategy of "social distancing," reducing individual interaction, canceling elective procedures, and limiting nonessential services. Health care providers must determine what procedures are considered "elective," balancing risk of treatment delays with that of coronavirus exposure to patient, family, and providers. Given critical periods for language development and the long-term impact of auditory deprivation, some audiologic and otologic services should be considered essential. In this article, we describe the experience of a quaternary referral pediatric hospital in Seattle, the epicenter of COVID-19 in the United States, and share strategies for risk minimization employed by Seattle Children's Hospital. We hope that this work can be a reference for other centers continuing care for children who are deaf and hard of hearing during the COVID-19 and future resource-limiting crises.

Background: Necrotizing soft tissue infections (NSTI) represent a heterogeneous group of rapidly progressive skin and soft tissue infections associated with significant morbidity and mortality. Efforts to identify factors associated with death have produced mixed results, and little or no data is available for other adverse outcomes. We sought to determine whether admission variables were associated with mortality, limb loss, and discharge disposition in patients with NSTI., Methods: We analyzed prospectively collected data of adult patients with surgically confirmed NSTI from an NSTI registry maintained at a quaternary referral center. Factors independently associated with mortality, amputation, and skilled nursing facility discharge were identified using logistic regression., Results: Between 2015 and 2018, 446 patients were identified. The median age was 55 years (interquartile range, 43-62). The majority of patients were male (65%), white (77%), and transferred from another facility (90%). The perineum was most commonly involved (37%), followed by the lower extremity (34%). The median number of operative debridements was 3 (interquartile range, 2-4). Overall mortality was 15%, and 21% of extremity NSTI patients required amputation. Age greater than 60 years; creatinine greater than 2 mg/dL; white blood cell count greater than 30 x 10^ /μl, platelets less than 150 × 10/μL, and clostridial involvement were independently associated with greater odds of death; perineal involvement was associated with lower odds of death. Age greater than 60 years; sex, male; nonwhite race; diabetes; chronic wound as etiology; leg involvement; transfer status; and sodium, less than 130 mEq/L were independently associated with amputation. Age greater than 60 years; sex, female; nonwhite race; perineal involvement; and amputation were associated with skilled care facility discharge., Conclusion: Necrotizing soft tissue infections are a heterogeneous group of infections involving significantly different patient populations with different outcomes; efforts to differentiate and predict adverse outcomes in NSTI should include laboratory data, comorbidities, infection site, and/or etiology to improve predictions and better account for this heterogeneity., Level of Evidence: Prognostic, Level III.

Coronavirus disease 2019 (COVID-19) is a novel coronavirus resulting in high mortality in the adult population but low mortality in the pediatric population. The role children and adolescents play in COVID-19 transmission is unclear, and it is possible that healthy pediatric patients serve as a reservoir for the virus. This article serves as a summary of a single pediatric institution's response to COVID-19 with the goal of protecting both patients and health care providers while providing ongoing care to critically ill patients who require urgent interventions. A significant limitation of this commentary is that it reflects a single institution's joint effort at a moment in time but does not take into consideration future circumstances that could change practice patterns. We still hope dissemination of our overall response at this moment, approximately 8 weeks after our region's first adult case, may benefit other pediatric institutions preparing for COVID-19.

Objective: The U.S. Food and Drug Administration guidelines for cochlear implantation (CI) include age greater than 12 months. Studies have suggested that implantation in children younger than 12 months with congenital deafness may be associated with better spoken language outcomes. Compare auditory comprehension (AC) outcomes for children with congenital deafness who received CI less than 12 months of age to those implanted at 12 to 24 months of age., Methods: Retrospective review of prospectively collected data in consecutively implanted patients under 2 years of age who received CI and had post-CI Preschool Language Scale (PLS)-AC scores. Receptive language was assessed with the AC subtest of the PLS. Patients without pre-CI PLS-AC scores were excluded. The association between age at implantation and post-CI PLS-AC scores up to 2 years after CI surgery was modeled using a linear mixed-effects model. Time from CI surgery, number of implants, risk factors for language delay, pre-CI PLS-AC score, and sex were included in the model. Patients implanted less than 12 months of age were compared to those implanted between 12 and 24 months., Results: Twenty-nine patients who had CI surgery by 12 months and 82 who had CI surgery between 12 and 24 months were included in the analysis. Younger age at implantation and better pre-CI PLS-AC scores were significantly associated with better post-CI PLS-AC scores., Conclusion: Cochlear implantation in children with congenital deafness less than 12 months of age was associated with better PLS-AC than in children implanted over 12 months of age up to 2 years after implantation., Level of Evidence: 4 Laryngoscope, 130:776-781, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Spectral ripple discrimination tasks are commonly used to probe spectral resolution in cochlear implant (CI), normal-hearing (NH), and hearing-impaired individuals. In addition, these tasks have also been used to examine spectral resolution development in NH and CI children. In this work, stimulus sine-wave carrier density was identified as a critical variable in an example spectral ripple-based task, the Spectro-Temporally Modulated Ripple (SMR) Test, and it was demonstrated that previous uses of it in NH listeners sometimes used values insufficient to represent relevant ripple densities. Insufficient carry densities produced spectral under-sampling that both eliminated ripple cues at high ripple densities and introduced unintended structured interference between the carriers and intended ripples at particular ripple densities. It was found that this effect produced non-monotonic psychometric functions for NH listeners that would cause systematic underestimation of thresholds with adaptive techniques. Studies of spectral ripple detection in CI users probe a density regime below where this source of aliasing occurs, as CI signal processing limits dense ripple representation. While these analyses and experiments focused on the SMR Test, any task in which discrete pure-tone carriers spanning frequency space are modulated to approximate a desired pattern must be designed with the consideration of the described spectral aliasing effect.

Objectives/hypothesis: The optimal surgical treatment to improve sleep apnea in children with small tonsils is not known. Drug-induced sleep endoscopy (DISE) may be useful in selecting effective surgical procedures for this patient population. This study compared polysomnography (PSG) measures before and after DISE-directed surgery in children with small tonsils. We hypothesize that DISE-directed surgery improves PSG measures in children with small tonsils. We also aimed to identify the most common surgery performed in this population., Study Design: Retrospective chart review., Methods: A retrospective review was performed of subjects who underwent DISE at a single pediatric tertiary care center over a 6-year period. Inclusion criteria were 1+ tonsils and PSG performed before and after DISE-directed surgery. Exclusion criteria were previous tonsillectomy and tonsils score 2+ or greater. Pre- and postoperative PSG parameters were compared using paired t tests., Results: Average age was 7 ± 4 years old at the time of surgery. The most common DISE-directed intervention was supraglottoplasty (n = 23). DISE-directed surgery significantly improved mean apnea-hypopnea index (AHI) from 14.4 to 8.0 (P = .02). Although improvements were seen in mean obstructive AHI (12.5 to 5.5), O 2 nadir (87.0 to 88.3), and ODI (10.6 to 5.8), these measures did not reach statistical significance., Conclusions: DISE-directed surgery significantly improves AHI in children with small tonsils. The most common intervention performed on these children was supraglottoplasty. Interestingly, adenotonsillectomy was rarely performed in this cohort. Additionally, supraglottic collapse, prompting supraglottoplasty, is difficult to accurately assess in an awake child, supporting use of a DISE-directed approach in this patient population., Level of Evidence: 4 Laryngoscope, 129:2771-2774, 2019., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: The clinical significance of the interarytenoid mucosal height (IAMH) in pediatric dysphagia, ranging from normal anatomy to a laryngeal cleft, is unknown. This study seeks to evaluate a cohort of patients who underwent evaluation of their IAMH during microdirect laryngoscopy (MDL) for associations between IAMH and dysphagia as diagnosed on preoperative videofluoroscopic swallow study (VFSS)., Methods: A retrospective case series of 1,351 patients who underwent MDL between 2011 and 2016 were reviewed for intraoperative evaluation of IAMH using our interarytenoid assessment protocol. After exclusions, 182 patients were divided into three groups: 1) thickened diet: VFSS with recommendation for thickened liquids (n = 82 of 182; 45.1%), 2) normal diet: VFSS with allowance of thin liquids (n = 19 of 182; 10.4%), and 3) control: no VFSS performed (n = 81 of 182; 44.5%)., Results: There was no difference in IAMH between groups (P = 0.35). Power analysis was able to achieve > 80% power to detect an effect size of ≥ 0.5 (1-5 mucosal height scale). The majority of patients in each group had an IAMH above the false vocal folds (thickened diet: 57.3%, normal diet: 57.9%, control: 64.2%). There were similar percentages of patients in each group with an IAMH at or below the true vocal folds (thickened diet: 4.9%, normal diet: 5.3%, control: 6.1%)., Conclusion: There was no significant association between IAMH and preoperative thickened liquid recommendation in this cohort. This data fails to support the hypothesis that the IAMH is an independent etiological factor for pediatric pharyngeal dysphagia. Further studies comparing IAMH with outcomes after feeding therapy and surgery may better clarify this relationship between anatomy and physiology., Level of Evidence: 4. Laryngoscope, 129:2588-2593, 2019., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To assess the reliability and construct validity of the Penetration-Aspiration Scale in children., Study Design: This was a retrospective cohort study of pre- and postoperative video modified barium swallow studies from children who underwent interarytenoid injection augmentation for unexplained persistent pharyngeal dysphagia. Two pediatric speech and language pathologists reviewed each study twice in a blinded and randomized fashion., Setting: Tertiary academic pediatric hospital., Subjects and Methods: Thirty children were identified with adequate pre- and postoperative modified barium swallow studies within 4 weeks of intervention. Children were separated into clinical outcome groups based on ability to advance to thinner diet consistencies postoperatively. Construct validity was assessed with a mixed linear model to test the hypothesis that only the clinically improved group would receive better Penetration-Aspiration Scale scores after surgery. Reliability was assessed by calculating chance-corrected agreement between raters (interrater) and raters' repeat evaluations (intrarater)., Results: Inter- and intrarater reliabilities (Cohen's κ) were both excellent. Results of the mixed model revealed a significant interaction between outcome group and pre- and postoperative time interval. As hypothesized, this involved a significant improvement in Penetration-Aspiration Scale score only in the improved group., Conclusions: These findings suggest that the Penetration-Aspiration Scale is a reliable and valid measure of clinical response to interarytenoid injection augmentation in children.

The work-up and management of sensorineural hearing loss in children has been an area of rapid evolution. With the availability of genetic and cytomegalovirus testing, the diagnostic process is continuously refined. Aural rehabilitation should be provided to children in a timely manner. At present, the main surgical options for the treatment of sensorineural hearing loss are bone conduction sound processors and cochlear implants. Investigations into modalities such as auditory brainstem implants are ongoing. With further technological and medical advancements, the evaluation and management of pediatric sensorineural hearing loss will undoubtedly continue to change., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The goal of this study was to determine if temporal modulation cutoff frequency was mature in three-month-old infants. Normal-hearing infants and young adults were tested in a single-interval forced-choice observer-based psychoacoustic procedure. Two parameters of the temporal modulation transfer function (TMTF) were estimated to separate temporal resolution from amplitude modulation sensitivity. The modulation detection threshold (MDT) of a broadband noise amplitude modulated at 10 Hz estimated the y-intercept of the TMTF. The cutoff frequency of the TMTF, measured at a modulation depth 4 dB greater than the MDT, provided an estimate of temporal resolution. MDT was obtained in 27 of 33 infants while both MDT and cutoff frequency was obtained in 15 infants and in 16 of 16 adults. Mean MDT was approximately 10 dB poorer in infants compared to adults. In contrast, mean temporal modulation cutoff frequency did not differ significantly between age groups. These results suggest that temporal resolution is mature, on average, by three months of age in normal hearing children despite immature sensitivity to amplitude modulation. The temporal modulation cutoff frequency approach used here may be a feasible way to examine development of temporal resolution in young listeners with markedly immature sensitivity to amplitude modulation.

Objective: This study interviewed youth with unilateral hearing, utilizing their responses to generate candidate items for a condition-specific patient-reported instrument., Study Design: Mixed methods, cross-sectional., Setting: Tertiary care children's hospital., Participants and Methods: Youth with unilateral hearing loss and normal hearing in the contralateral ear were identified and recruited for participation through query of an audiometric database and through hearing loss clinics. Interviews with the youth were qualitatively analyzed to identify common themes and generate items related to functional impact. A multi-institutional expert panel reviewed items with prespecified item selection criteria. Participants rated items for impact on daily life. For preliminary criterion validity assessment, statistical analyses explored correlations between functional scores and type and severity of hearing loss., Results: Thirty-nine youth aged 9 to 18 years with unilateral hearing loss participated; 31% used a hearing device. Fifteen youth participated in interviews; thematic analysis, item crafting, and expert panel item review resulted in 41 items. Twenty-six youth responded to the items, reporting low functional scores in the domains of sound localization, ear positioning, and noise environment. They reported better levels of function in carrying out group conversations, focusing on schoolwork, and feeling safe during activities. Multivariate linear regression found that youth scored 0.4 points (or approximately 8%) lower on the functional impact scale with every 20-dB HL increase in pure tone average in the abnormal ear., Conclusion: Youth with unilateral hearing loss report functional impact, particularly related to sound localization, ear positioning, and noise environment; therefore, they may benefit from a condition-specific functional assessment instrument.

Background: Children with Down Syndrome (DS) and obstructive sleep apnea (OSA) are difficult to treat, as first line therapies may not lead to significant improvement. Drug-induced sleep endoscopy (DISE) directed surgery may be particularly beneficial for these patients., Objective: To assess change in polysomnography (PSG) measures of patients with DS who underwent DISE-directed surgery., Methods: Retrospective chart review was performed on patients with DS who underwent DISE-directed surgery and had pre- and post-surgery PSG. Patients were analyzed in groups defined by previous adenotonsillectomy. Two-sided t-tests with equal variances were used to assess statistical significance., Results: Of 24 patients reviewed, 14 were surgically naïve and 10 had undergone prior adenotonsillectomy. The primary outcome was change in PSG parameters including apnea hypopnea index, obstructive apnea hypopnea index, oxygen nadir, oxygen desaturation index, and mean carbon dioxide level. While improvement was seen in all PSG parameters, only improvement in oxygen nadir in children who had undergone prior adenotonsillectomy was statistically significant (88.5% to 90.9%, p = .04)., Conclusions and Significance: DISE-directed surgery may be beneficial for children with DS and OSA, with improvement in the means of main PSG measures observed. A larger, prospective study is warranted to further explore DISE utility.

Objective: To investigate the epidemiology, treatment, length of stay (LOS) and costs for neonatal and pediatric inpatients with invasive candidiasis (IC)., Methods: The Cerner Health Facts Database was used to assess inpatients (2005-2014) identified by positive blood or cerebrospinal fluid (CSF) Candida cultures. Log-transformed LOS and cost were examined in candidemia-only patients (n = 191) using multivariable linear regression., Results: A total of 202 patients had a positive culture (blood: n = 192; CSF: n = 10; both: n = 2). The most prevalent species were C. parapsilosis (n = 70, 34.7%), and C. albicans (n = 66, 32.7%). Mean (SD) age was 5 (5.5) years; 30 (14.9%) patients were <4 months. Comorbidities included sepsis (n = 85, 42.1%), coagulation disorders (n = 57, 28.2%), cancer (n = 64, 31.7%), and low birthweight (n = 26, 12.9%). Antifungals (AFs) included azoles (57.4%), polyenes (28.7%), and echinocandins (35.1%); 20.8% of patients received no AF during their encounter. The mean (SD) cost per encounter was $97,392 ($149,253), with a mean (SD) LOS of 45.6 (59.5) days and 9.9% mortality at discharge. Results were similar across Candida species. In regression analysis, intensive care unit (ICU) exposure, central catheter, sepsis, AF >48 hours prior to index culture, and age <4 months were associated with increased LOS; treatment at a non-teaching hospital was associated with reduced LOS (p < .05). AF use >48 hours before index, in-hospital mortality, Midwest region and ventricular shunt were associated with increased cost (p ≤ .05)., Conclusions: This analysis confirms the association between pediatric candidemia and increased resource utilization and LOS. Given high observed rates of potential under-treatment, an opportunity may exist to improve AF therapy in this population.

Objective: To determine whether the degree of lateral pharyngeal wall (LPW) obstruction on pediatric drug-induced sleep endoscopy (DISE) correlates with preprocedure tonsillar hypertrophy score on physical examination, and to determine if clinically small tonsils are obstructive., Methods: Retrospective review of 154 patients who underwent DISE at a single pediatric tertiary care center over a 4-year period. Inclusion criteria were documentation of Brodsky tonsil score on preoperative physical examination. Exclusion criteria were previous tonsillectomy, adenoidectomy, or adenotonsillectomy. Lateral pharyngeal wall obstruction was graded for each patient from 0 (no obstruction) to 3 (severe obstruction) using a validated pediatric DISE scoring system known as the Chan-Parikh scoring system (C-P). Data were analyzed using multivariate linear regression controlling for age at time of DISE and presence of comorbid conditions., Results: One hundred fifteen patients met criteria for analysis. Median age at DISE was 5.1 years. A moderate positive correlation was calculated between Brodsky score and DISE score, Spearman correlation coefficient 0.55, P = < 0.001. Linear regression modeling determined that for every 1-point increase in tonsil score, there was a 0.7-point increase in C-P LPW score (95% confidence interval [0.45, 0.92]). Sensitivity analysis did not detect a difference in correlation between children with comorbid conditions and children who were otherwise in good health. Of the 65 children with a pre-DISE Brodsky tonsil score of 1, 39 (60%) had a LPW score of 0 (no obstruction); nine (14%) had a score of 1 (< 50% obstruction); 11 (17%) had a score of 2 (> 50% obstruction); and six (9%) had a score of 3 (100% obstruction)., Conclusion: There is a positive correlation between Brodsky Score and DISE LPW score. The majority of children with sleep-disordered breathing with a Brodsky score of 1 did not demonstrate LPW obstruction. These children may benefit from DISE for identification of alternative sites of upper airway obstruction., Level of Evidence: 4. Laryngoscope, 127:1943-1949, 2017., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: To investigate the risk of hearing loss progression in each ear among children with unilateral hearing loss associated with ipsilateral bony cochlear nerve canal (BCNC) stenosis., Setting: Tertiary pediatric referral center., Patients: Children diagnosed with unilateral hearing loss who had undergone temporal bone computed tomography imaging and had at least 6 months of follow-up audiometric testing were identified from a prospective audiological database., Interventions: Two pediatric radiologists blinded to affected ear evaluated imaging for temporal bone anomalies and measured bony cochlear canal width independently. All available audiograms were reviewed, and air conduction thresholds were documented., Main Outcome Measure: Progression of hearing loss was defined by a 10 dB increase in air conduction pure-tone average., Results: One hundred twenty eight children met inclusion criteria. Of these, 54 (42%) had a temporal bone anomaly, and 22 (17%) had ipsilateral BCNC stenosis. At 12 months, rates of progression in the ipsilateral ear were as follows: 12% among those without a temporal bone anomaly, 13% among those with a temporal bone anomaly, and 17% among those with BCNC stenosis. Children with BCNC stenosis had a significantly greater risk of progression in their ipsilateral ear compared with children with no stenosis: hazard ratio (HR) 2.17, 95% confidence interval (CI) (1.01, 4.66), p value 0.046. When we compared children with BCNC stenosis to those with normal temporal bone imaging, we found that the children with stenosis had nearly two times greater risk estimate for progression, but this difference did not reach significance, HR 1.9, CI (0.8, 4.3), p = 0.1. No children with BCNC stenosis developed hearing loss in their contralateral year by 12 months of follow-up., Conclusion: Children with bony cochlear nerve canal stenosis may be at increased risk for progression in their ipsilateral ear. Audiometric and medical follow-up for these children should be considered.

The immune responses of humans and animals to insults ( i.e ., infections, traumas, tumoral transformation and radiation) are based on an intricate network of cells and chemical messengers. Abnormally high inflammation immediately after insult or abnormally prolonged pro-inflammatory stimuli bringing about chronic inflammation can lead to life-threatening or severely debilitating diseases. Mesenchymal stem cell (MSC) transplant has proved to be an effective therapy in preclinical studies which evaluated a vast diversity of inflammatory conditions. MSCs lead to resolution of inflammation, preparation for regeneration and actual regeneration, and then ultimate return to normal baseline or homeostasis. However, in clinical trials of transplanted MSCs, the expectations of great medical benefit have not yet been fulfilled. As a practical alternative to MSC transplant, a synthetic drug with the capacity to boost endogenous MSC expansion and/or activation may also be effective. Regarding this, IMT504, the prototype of a major class of immunomodulatory oligonucleotides, induces in vivo expansion of MSCs, resulting in a marked improvement in preclinical models of neuropathic pain, osteoporosis, diabetes and sepsis. IMT504 is easily manufactured and has an excellent preclinical safety record. In the small number of patients studied thus far, IMT504 has been well-tolerated, even at very high dosage. Further clinical investigation is necessary to demonstrate the utility of IMT504 for resolution of inflammation and regeneration in a broad array of human diseases that would likely benefit from an immunoprotective/immunoregenerative therapy., Competing Interests: Conflict-of-interest statement: López RA and Zorzopulos J are shareholders of Immunotech, the company that provided funding for several of the studies partially described in this review; Horn DL is the owner and CEO of David Horn, LLC, which owns all the IMT504 patents [Patents numbers: EP1511845B1. Immunostimulatory oligonucleotides and uses thereof. International application number: PCT/EP2003/005691. International publication number: WO2003/101375. US7943316(B2)]. There are no further patents, products in development, or marketed products to declare. These statements do not alter the authors’ adherence to all the BPG policies on sharing data and material.

Objectives: Spectral resolution is a correlate of open-set speech understanding in postlingually deaf adults and prelingually deaf children who use cochlear implants (CIs). To apply measures of spectral resolution to assess device efficacy in younger CI users, it is necessary to understand how spectral resolution develops in normal-hearing children. In this study, spectral ripple discrimination (SRD) was used to measure listeners' sensitivity to a shift in phase of the spectral envelope of a broadband noise. Both resolution of peak to peak location (frequency resolution) and peak to trough intensity (across-channel intensity resolution) are required for SRD., Design: SRD was measured as the highest ripple density (in ripples per octave) for which a listener could discriminate a 90° shift in phase of the sinusoidally-modulated amplitude spectrum. A 2 × 3 between-subjects design was used to assess the effects of age (7-month-old infants versus adults) and ripple peak/trough "depth" (10, 13, and 20 dB) on SRD in normal-hearing listeners (experiment 1). In experiment 2, SRD thresholds in the same age groups were compared using a task in which ripple starting phases were randomized across trials to obscure within-channel intensity cues. In experiment 3, the randomized starting phase method was used to measure SRD as a function of age (3-month-old infants, 7-month-old infants, and young adults) and ripple depth (10 and 20 dB in repeated measures design)., Results: In experiment 1, there was a significant interaction between age and ripple depth. The infant SRDs were significantly poorer than the adult SRDs at 10 and 13 dB ripple depths but adult-like at 20 dB depth. This result is consistent with immature across-channel intensity resolution. In contrast, the trajectory of SRD as a function of depth was steeper for infants than adults suggesting that frequency resolution was better in infants than adults. However, in experiment 2 infant performance was significantly poorer than adults at 20 dB depth suggesting that variability of infants' use of within-channel intensity cues, rather than better frequency resolution, explained the results of experiment 1. In experiment 3, age effects were seen with both groups of infants showing poorer SRD than adults but, unlike experiment 1, no significant interaction between age and depth was seen., Conclusions: Measurement of SRD thresholds in individual 3 to 7-month-old infants is feasible. Performance of normal-hearing infants on SRD may be limited by across-channel intensity resolution despite mature frequency resolution. These findings have significant implications for design and stimulus choice for applying SRD for testing infants with CIs. The high degree of variability in infant SRD can be somewhat reduced by obscuring within-channel cues.

Spectral resolution limits speech perception with a cochlear implant (CI) in post-lingually deaf adults. However, the development of spectral resolution in pre-lingually deaf implanted children is not well understood. Acoustic spectral resolution was measured as a function of age (school-age versus adult) in CI and normal-hearing (NH) participants using spectral ripple discrimination (SRD). A 3-alternative forced-choice task was used to obtain SRD thresholds at five ripple depths. Effects of age and hearing method on SRD and spectral modulation transfer function (SMTF) slope (reflecting frequency resolution) and x-intercept (reflecting across-channel intensity resolution) were examined. Correlations between SRD, SMTF parameters, age, and speech perception in noise were studied. Better SRD in NH than CI participants was observed at all depths. SRD thresholds and SMTF slope correlated with speech perception in CI users. When adjusted for floor performance, x-intercept did not correlate with SMTF slope or speech perception. Age and x-intercept correlations were positive and significant in NH but not CI children suggesting that across-channel intensity resolution matures during school-age in NH children. No evidence for maturation of spectral resolution beyond early school-age in pre-lingually deaf implanted CI users was found in the present study.