Limited therapies exist for neurofibromatosis type 1 (NF1)-associated plexiform neurofibroma (PN). For this reason, the activity of vinblastine (VBL) and methotrexate (MTX) was evaluated in children ...and young adults with NF1 and PN. Patients ≤ 25 years of age with progressive and/or inoperable NF1-PN received VBL 6 mg/m
and MTX 30 mg/m
weekly for 26 weeks, followed by every 2 weeks for 26 weeks. Objective response rate was the primary endpoint. Of 25 participants enrolled, 23 were evaluable. The median age of participants was 6.6 years (range 0.3-20.7). The most frequent toxicities were neutropenia and elevation of transaminases. On two-dimensional (2D) imaging, 20 participants (87%) had stable tumor, with a median time to progression of 41.5 months (95% confidence interval 16.9, 64.9). Two of eight participants (25%) with airway involvement demonstrated functional improvements including decreased positive pressure requirements and apnea-hypopnea index. A post hoc three-dimensional (3D) analysis of PN volumes was completed on 15 participants with amenable imaging; 7 participants (46%) had progressive disease on or by the end of therapy. VBL/MTX was well-tolerated but did not result in objective volumetric response. Furthermore, 3D volumetric analysis highlighted the lack of sensitivity of 2D imaging for PN response evaluation.
Abstract
Study Objectives
Obstructive sleep apnea is associated with neurobehavioral dysfunction, but the relationship between disease severity as measured by the apnea-hypopnea index and ...neurobehavioral morbidity is unclear. The objective of our study is to compare the neurobehavioral morbidity of mild sleep-disordered breathing versus obstructive sleep apnea.
Methods
Children 3–12 years old recruited for mild sleep-disordered breathing (snoring with obstructive apnea-hypopnea index < 3) into the Pediatric Adenotonsillectomy Trial for Snoring were compared to children 5–9 years old recruited for obstructive sleep apnea (obstructive apnea-hypopnea 2–30) into the Childhood Adenotonsillectomy Trial. Baseline demographic, polysomnographic, and neurobehavioral outcomes were compared using univariable and multivariable analysis.
Results
The sample included 453 participants with obstructive sleep apnea (median obstructive apnea-hypopnea index 5.7) and 459 participants with mild sleep-disordered breathing (median obstructive apnea-hypopnea index 0.5). By polysomnography, participants with obstructive sleep apnea had poorer sleep efficiency and more arousals. Children with mild sleep-disordered breathing had more abnormal executive function scores (adjusted odds ratio 1.96, 95% CI 1.30–2.94) compared to children with obstructive sleep apnea. There were also elevated Conners scores for inattention (adjusted odds ratio 3.16, CI 1.98–5.02) and hyperactivity (adjusted odds ratio 2.82, CI 1.83–4.34) in children recruited for mild sleep-disordered breathing.
Conclusions
Abnormal executive function, inattention, and hyperactivity were more common in symptomatic children recruited into a trial for mild sleep-disordered breathing compared to children recruited into a trial for obstructive sleep apnea. Young, snoring children with only minimally elevated apnea-hypopnea levels may still be at risk for deficits in executive function and attention.
Trial Registration
Pediatric Adenotonsillectomy for Snoring (PATS), NCT02562040; Childhood Adenotonsillectomy Trial (CHAT), NCT00560859
It is unknown whether children with primary snoring and children with mild obstructive sleep apnea (OSA) represent populations with substantially different clinical characteristics. Nonetheless, an ...obstructive apnea-hypopnea index (AHI) of 1 or greater is often used to define OSA and plan for adenotonsillectomy (AT).
To assess whether a combination of clinical characteristics differentiates children with primary snoring from children with mild OSA.
Baseline data from the Pediatric Adenotonsillectomy Trial for Snoring (PATS) study, a multicenter, single-blind, randomized clinical trial conducted at 6 academic sleep centers from June 2016 to January 2021, were analyzed. Children aged 3.0 to 12.9 years with polysomnography-diagnosed (AHI <3) mild obstructive sleep-disordered breathing who were considered candidates for AT were included. Data analysis was performed from July 2022 to October 2023.
Logistic regression models were fitted to identify which demographic, clinical, and caregiver reports distinguished children with primary snoring (AHI <1; 311 patients 67.8%) from children with mild OSA (AHI 1-3; 148 patients 32.2%).
A total of 459 children were included. The median (IQR) age was 6.0 (4.0-7.5) years, 230 (50.1%) were female, and 88 (19.2%) had obesity. A total of 121 (26.4%) were Black, 75 (16.4%) were Hispanic, 236 (51.5%) were White, and 26 (5.7%) were other race and ethnicity. Black race (odds ratio OR, 2.08; 95% CI, 1.32-3.30), obesity (OR, 1.80; 95% CI, 1.12-2.91), and high urinary cotinine levels (>5 µg/L) (OR, 1.88; 95% CI, 1.15-3.06) were associated with greater odds of mild OSA rather than primary snoring. Other demographic characteristics, clinical examination findings, and questionnaire reports did not distinguish between primary snoring and mild OSA. A weighted combination of the statistically significant clinical predictors had limited ability to differentiate children with mild OSA from children with primary snoring.
In this analysis of baseline data from the PATS randomized clinical trial, primary snoring and mild OSA were difficult to distinguish without polysomnography. Mild OSA vs snoring alone did not identify a clinical group of children who may stand to benefit from AT for obstructive sleep-disordered breathing.
ClinicalTrials.gov Identifier: NCT02562040.
Lateral sinus thrombosis is a rare intracranial complication of otitis media that is traditionally described in countries with poor access to medical care. Our goal was to describe the clinical ...presentation, management, and outcome of patients diagnosed with lateral sinus thrombosis in a US tertiary care center and to highlight the clinically relevant differences in presentation between these patients and those described in previous reports.
The medical charts of 13 patients diagnosed with otogenic lateral sinus thrombosis were reviewed. These patients were identified from a manual search of 156 subjects with International Classification of Diseases, Ninth Revision codes corresponding with a diagnosis of mastoiditis or thromboembolism over a 10-year period (1997-2007) at the Children's Hospital of Philadelphia.
In contrast to previous reports in the literature, the majority of patients in this series exhibited cranial neuropathies and signs of raised intracranial pressure. Nearly all of the patients had a history of acute otitis media treated with antibiotics in the weeks preceding admission. However, many patients denied high fevers or active otomastoid symptoms, which are classically associated with lateral sinus thrombosis. The diagnosis was made in all of the children by using computed tomography and MRI/venography. Treatment strategies included myringotomy tube placement, simple mastoidectomy, intravenous antibiotics, and anticoagulation. Posthospitalization follow-up data revealed no significant long-term complications.
Despite appropriate antibiotic therapy, lateral sinus thrombosis and other intracranial complications of otitis media are still a threat to children in the modern era. Neurologic, rather than otologic, symptoms may dominate the presentation of otogenic lateral sinus thrombosis. Thus, a high index of suspicion may be critical for ensuring timely diagnosis of this rare condition.
The coronavirus disease 2019 (COVID-19) pandemic requires clinicians to explore alternatives to routine patient management. Otolaryngologists caring for children commonly depend on physical ...examination, laboratory data, and ambulatory surgical procedures. Limiting patient care, mindful allocation of resources, and concern for safety have challenged all aspects of our health care system. This evidence-based clinical consensus is designed to guide practitioners of pediatric otolaryngology for common scenarios during this time.
Peer-reviewed literature, published reports, institutional guidelines, and expert consensus.
A clinical consensus on 6 common scenarios in pediatric otolaryngology developed with evidence-based strategies.
Providers should suspend all in-person nonessential office visits and elective surgical procedures. An emphasis on medical management and caregiver education will provide reasonable approaches to many of the common outpatient concerns. Surgery for chronic otitis media, obstructive sleep apnea, and acute rhinosinusitis should occur only in response to severe complications or failure of medical regimens. The approach to the pediatric neck mass focuses on timely management for oncologic etiologies and cautious surgical intervention for abscess drainage or tissue sampling. Finally, epistaxis and otorrhea must be triaged and addressed without the usual ambulatory procedures.
Adaptation of practice patterns during this unprecedented moment for our health care system requires thoughtful planning. The strategies described allow for safe handling of common pediatric otolaryngology diagnoses. Ultimately, otolaryngologists must be stewards of our global health community while advocating for the care of individual pediatric patients.
MPZL2‐related hearing loss is a rare form of autosomal recessive hearing loss characterized by progressive, mild sloping to severe sensorineural hearing loss. Thirty‐five previously reported patients ...had biallelic truncating variants in MPZL2, with the exception of one patient with a missense variant of uncertain significance and a truncating variant. Here, we describe the clinical characteristics and genotypes of five patients from four families with confirmed MPZL2‐related hearing loss. A rare missense likely pathogenic variant NM_005797.4(MPZL2):c.280C>T,p.(Arg94Trp) located in exon 3 was confirmed to be in trans with a recurrent pathogenic truncating variant that segregated with hearing loss in three of the patients from two unrelated families. This is the first recurrent likely pathogenic missense variant identified in MPZL2. Apparently milder or later‐onset hearing loss associated with rare missense variants in MPZL2 indicates that some missense variants in this gene may cause a milder phenotype than that resulting from homozygous or compound heterozygous truncating variants. This study, along with the identification of truncating loss of function and missense MPZL2 variants in several diverse populations, suggests that MPZL2‐related hearing loss may be more common than previously appreciated and demonstrates the need for MPZL2 inclusion in hearing loss testing panels.
Introduction:
Telemedicine is an increasingly prevalent component of medical practice. In otolaryngology, there is the potential for telemedicine services to be performed in conjunction with device ...use, such as with a nasolaryngoscope. This study evaluates the reliability of remote examinations of the upper airway through an iPhone recording using a coupling device attached to a nasopharyngolaryngoscope (NPL).
Methods:
A prospective, blinded study was performed for pediatric patients requiring an NPL during an office visit. The NPL was performed using a coupling device attached to a smartphone to record the examination. A second, remote otolaryngologist then evaluated the recorded examination. Both otolaryngologists evaluated findings of anatomic sites including nasopharynx, oropharynx, base of tongue, larynx including subsites of epiglottis, arytenoids, aryepiglottic folds, false vocal cords, true vocal cords, patency of airway, and diagnostic impression, all of which were documented through a survey. Results of the survey were evaluated through inter-rater agreement using the κ statistic.
Results:
Forty-five patients underwent an NPL, all of which were included in the study. The average age was 4.9 years. The most common complaint requiring NPL was noisy breathing (n = 16). The inter-rater agreement for overall diagnosis was 0.74 with 80% percent agreement, rated as “good.” Other anatomic subsites with “good” or better inter-rater agreement were nasopharynx (0.75), oropharynx (0.75), and true vocal cords (0.71), with strong percentage agreement of 89%, 91%, and 87%, respectively. Both users of the adaptor found the recording setup to run smoothly.
Conclusion:
A telemedicine device for NPL use demonstrates strong diagnostic accuracy across providers and good overall evaluation. It holds potential for use in remote settings.
Caregivers frequently report poor quality of life (QOL) in children with sleep-disordered breathing (SDB). Our objective is to assess the correlation between caregiver- and child-reported QOL in ...children with mild SDB and identify factors associated with differences between caregiver and child report.
Analysis of baseline data from a multi-institutional randomized trial SETTING: Pediatric Adenotonsillectomy Trial for Snoring, where children with mild SDB (obstructive apnea-hypopnea index <3) were randomized to observation or adenotonsillectomy.
The Pediatric Quality of Life Inventory (PedsQL) assessed baseline global QOL in participating children 5 to 12 years old and their caregivers. Caregiver and child scores were compared. Multivariable regression assessed whether clinical factors were associated with differences between caregiver and child report.
PedsQL scores were available for 309 families (mean child age, 7.0 years). The mean caregiver-reported PedsQL score was higher at 75.2 (indicating better QOL) than the mean child-reported score of 67.9 (P < .001). The agreement between caregiver and child total PedsQL scores was poor, with intraclass correlation coefficients of 0.03 (95% CI, -0.09 to 0.15) for children 5 to 7 years old and 0.21 (95% CI, 0.03-0.38) for children 8 to 12 years old. Higher child age and health literacy were associated with closer agreement between caregiver and child report.
Caregiver- and child-reported global QOL in children with SDB was weakly correlated, more so for young children. In pediatric SDB, child-perceived QOL may be poorer than that reported by caregivers. Further research is needed to assess whether similar trends exist for disease-specific QOL metrics.
Children with snoring and mild sleep-disordered breathing may be at increased risk for neurocognitive deficits despite few obstructive events. We hypothesized that actigraphy-based sleep duration and ...continuity associate with neurobehavioral functioning and explored whether these associations vary by demographic and socioeconomic factors.
298 children enrolled in the Pediatric Adenotonsillectomy Trial, ages 3 to 12.9 years, 47.3% from racial or ethnic minority groups, with habitual snoring and an apnea-hypopnea index < 3 were studied with actigraphy (mean 7.5 ± 1.4 days) and completed a computerized vigilance task (Go-No-Go) and a test of fine motor control (9-Hole Pegboard). Caregivers completed the Behavior Rating Inventory of Executive Function. Regression analyses evaluated associations between sleep exposures (24-hour and nocturnal sleep duration, sleep fragmentation index, sleep efficiency) with the Behavior Rating Inventory of Executive Function Global Executive Composite index, pegboard completion time (fine motor control), and vigilance (d prime on the Go-No-Go), adjusting for demographic factors and study design measures.
Longer sleep duration, higher sleep efficiency, and lower sleep fragmentation were associated with better executive function; each additional hour of sleep over 24 hours associated with more than a 3-point improvement in executive function (
= .002). Longer nocturnal sleep (
= .02) and less sleep fragmentation (
= .001) were associated with better fine motor control. Stronger associations were observed for boys and children less than 6 years old.
Sleep quantity and continuity are associated with neurocognitive functioning in children with mild sleep-disordered breathing, supporting efforts to target these sleep health parameters as part of interventions for reducing neurobehavioral morbidity.
Registry: ClinicalTrials.gov; Name: Pediatric Adenotonsillectomy for Snoring (PATS); URL: https://clinicaltrials.gov/ct2/show/NCT02562040; Identifier: NCT02562040.
Robinson KA, Wei Z, Radcliffe J, et al. Associations of actigraphy measures of sleep duration and continuity with executive function, vigilance, and fine motor control in children with snoring and mild sleep-disordered breathing.
. 2023;19(9):1595-1603.
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