Prenatal tobacco exposure on brain morphometry partially mediated poor cognitive performance in preadolescent children.

Objectives: To evaluate whether prenatal tobacco exposure (PTE) is related to poorer cognitive performance, abnormal brain morphometry, and whether poor cognitive performance is mediated by PTE-related structural brain differences. Methods: The Adolescent Brain Cognitive Development study dataset was used to compare structural MRI data and neurocognitive (NIH Toolbox®) scores in 9-to-10-year-old children with (n=620) and without PTE (n=10,989). We also evaluated whether PTE effects on brain morphometry mediated PTE effects on neurocognitive scores. Group effects were evaluated using Linear Mixed Models, covaried for socio-demographics and prenatal exposures to alcohol and/or marijuana, and corrected for multiple comparisons using the false-discovery rate (FDR). Results: Compared to unexposed children, those with PTE had poorer performance (all p-values <0.05) on executive function, working memory, episodic memory, reading decoding, crystallized intelligence, fluid intelligence and overall cognition. Exposed children also had thinner parahippocampal gyri, smaller surface areas in the posterior-cingulate and pericalcarine cortices; the lingual and inferior parietal gyri, and smaller thalamic volumes (all p-values <0.001). Furthermore, among children with PTE, girls had smaller surface areas in the superior-frontal (interaction-FDR-p=0.01), precuneus (interaction-FDR-p=0.03) and postcentral gyri (interaction-FDR-p=0.02), while boys had smaller putamen volumes (interaction-FDR-p=0.02). Smaller surface areas across regions of the frontal and parietal lobes, and lower thalamic volumes, partially mediated the associations between PTE and poorer neurocognitive scores (p-values <0.001). Conclusions: Our findings suggest PTE may lead to poorer cognitive performance and abnormal brain morphometry, with sex-specific effects in some brain regions, in pre-adolescent children. The poor cognition in children with PTE may result from the smaller areas and subcortical brain volumes.

Average Volume-assured Pressure Support as Rescue Therapy after CPAP Failure in Pediatric Obstructive Sleep Apnea: A Retrospective Case Series Study.

Background: Continuous positive airway pressure (CPAP) is frequently prescribed for patients with residual obstructive sleep apnea (OSA) following adenotonsillectomy. Objectives: The goal was to examine the efficacy of noninvasive ventilation with average volume-assured pressure support (AVAPS) as a potential option for children with failed CPAP titration. Methods: In a single-center retrospective study, we included children aged 1-17 years, with polysomnographically confirmed OSA who underwent AVAPS titration following failed CPAP titration. In addition to describing the clinical characteristics of the included patients, we compared polysomnographic parameters before and after AVAPS. Results: Nine patients met the inclusion criteria; out of them, 8 (89%) were males with an age range of 6.7 ± 3.9 years and a body mass index percentile of 81.0 ± 28.9. Reasons for failed CPAP titration were: 3 (33%) patients due to inability to control apnea-hypopnea index (AHI), 3 (33%) patients due to sleep-related hypoventilation, 2 (22%) patients due to treatment-emergent central sleep apnea, and 1 (11%) patient due to intolerance to CPAP. AVAPS resulted in a greater reduction in AHI than CPAP (reduction following CPAP = 24.6 ± 29.3, reduction following AVAPS = 42.5 ± 37.6, p = 0.008). All patients had resolution of the problems which caused CPAP failure. Conclusion: In this case a series of children with OSA and with failed CPAP titration, AVAPS resulted in a greater reduction in AHI compared with CPAP as well as resolution of the problems which caused CPAP failure.

Resting-State Cerebral Hemodynamics is Associated With Problem Behaviors in Pediatric Sleep-Disordered Breathing.

OBJECTIVE: Untreated sleep-disordered breathing (SDB) is associated with problem behaviors in children. The neurological basis for this relationship is unknown. We used functional near-infrared spectroscopy (fNIRS) to assess the relationship between cerebral hemodynamics of the frontal lobe of the brain and problem behaviors in children with SDB. STUDY DESIGN: Cross-sectional. SETTING: Urban tertiary care academic children's hospital and affiliated sleep center. METHODS: We enrolled children with SDB aged 5 to 16 years old referred for polysomnography. We measured fNIRS-derived cerebral hemodynamics within the frontal lobe during polysomnography. We assessed parent-reported problem behaviors using the Behavioral Response Inventory of Executive Function Second Edition (BRIEF-2). We compared the relationships between (i) the instability in cerebral perfusion in the frontal lobe measured fNIRS, (ii) SDB severity using apnea-hypopnea index (AHI), and (iii) BRIEF-2 clinical scales using Pearson correlation (r). A p < .05 was considered significant. RESULTS: A total of 54 children were included. The average age was 7.8 (95% confidence interval, 7.0-8.7) years; 26 (48%) were boys and 25 (46%) were Black. The mean AHI was 9.9 (5.7-14.1). There is a statistically significant inverse relationship between the coefficient of variation of perfusion in the frontal lobe and BRIEF-2 clinical scales (range of r = 0.24-0.49, range of p = .076 to <.001). The correlations between AHI and BRIEF-2 scales were not statistically significant. CONCLUSION: These results provide preliminary evidence for fNIRS as a child-friendly biomarker for the assessment of adverse outcomes of SDB.

Ultrasound versus fine needle aspiration for the initial evaluation of pediatric cervical lymphadenopathy-A systematic review.

OBJECTIVE: Cervical lymphadenopathy is a frequent finding in children that poses diagnostic challenges. We sought to compare the utility of fine needle aspiration (FNA) with ultrasound (US) for evaluating pediatric cervical lymphadenopathy based on published literature. STUDY DESIGN: In October 2019, we performed a comprehensive electronic search of PubMed, OVID (MEDLINE), EMBASE, and Scopus databases. Two authors independently screened and assessed full-text reports of potentially eligible studies. We compared sensitivity, specificity, positive predictive value estimates, and balanced accuracy for determining the underlying etiology of lymphadenopathy. RESULTS: The initial search returned 7736 possible studies, of which 31 met the criteria for inclusion. A total of 25 studies were included in the final analysis, with a total of 4721 patients, of which 52.8% were male. Of these, 9 (36.0%) examined US, and 16 (64%) examined fine needle aspiration. The pooled balanced accuracy for determining etiology was 87.7% for US and 92.9% for FNA. Reactive lymphadenopathy was identified in 47.9%, 9.2% were malignant, 12.6% were granulomatous, and 6.6% were non-diagnostic. CONCLUSIONS: In this systematic review, US was identified as an accurate initial diagnostic imaging modality in children. Fine needle aspiration was found to play a significant role in ruling out malignant lesions and potentially avoiding excisional biopsy.

Secondary Analyses of the Childhood Adenotonsillectomy Trial: A Narrative Review.

Importance: Adenotonsillectomy, performed for approximately 500 000 children annually in the US alone, is the first line of treatment of pediatric obstructive sleep apnea (OSA). The Childhood Adenotonsillectomy Trial (CHAT), the first randomized clinical trial to test the efficacy of adenotonsillectomy, compared the management of pediatric nonsevere OSA by early adenotonsillectomy (eAT) vs watchful waiting with supportive care. Since the publication of the primary article in 2013, the CHAT study data set were made available via the National Sleep Research Resource, which allowed researchers to address a range of additional clinical questions relevant to the care of children with OSA. This review focuses on secondary analyses associated with the CHAT data set as grouped by the outcome of interest. Observations: The results of most secondary analyses suggest that children who underwent eAT experienced the greatest improvements in symptom burden, sleepiness, parent-reported behavior, and quality of life. Changes in other domains, such as cognition, cardiovascular physiology, and metabolic indicators, were modest and selective. The associations between most treatment outcomes and polysomnographic parameters were weak. Symptoms were poor predictors of OSA severity. The results from these secondary analyses benefitted from the rigor of multicenter design and centralized polysomnography interpretation in CHAT. However, the exclusion of younger preschool-aged children and children with primary snoring limited the generalizability of findings. In addition, because caregivers were not masked, some of the parent-reported outcomes may have been inflated. Conclusions and Relevance: The results of this narrative review suggest that CHAT provides a model for future OSA-related studies in children for design, conduct, and subsequent reuse of the study data set, and its findings have advanced our understanding of the pathophysiology and management of pediatric nonsevere OSA. Directions for future research include whether the findings from this landmark study are generalizable to younger children and children with primary snoring and severe OSA. Similar studies may help address practice variability associated with pediatric OSA and help identify children who are most likely to benefit from undergoing eAT.

Prospective validation of a brief questionnaire for predicting the severity of pediatric obstructive sleep apnea.

INTRODUCTION: Pediatric obstructive sleep apnea (OSA) is diagnosed and stratified by polysomnography. However, due to cost and inaccessibility, up to 90% of children undergo tonsillectomy and adenoidectomy (T&A) solely based on clinical criteria. We previously developed a data-driven brief screening questionnaire ('Selected Features,' SF) that predicted OSA severity than alternatives. The SF asks the parent whether a child: (i) has had breath-holding spells at night over the past 4 weeks, (ii) is a mouth-breather during the day, (iii) has stopped growing at a normal rate any time since birth, and (iv) is overweight. This study sought prospectively validate the SF questionnaire. METHODS: We conducted a prospective assessment of the predictive accuracy of SF compared to the Pediatric Sleep Questionnaire-Sleep Related Breathing Disorder (PSQ-SRBD) scale in otherwise healthy children with sleep disordered breathing referred for T&A. We compared the model fits of PSQ-SRDB and SF for (i) a linear regression model for the prediction of OSA, and (ii) a logistic regression model for severe OSA, defined as apnea hypopnea index (AHI) > 10. P < 0.05 was significant. RESULTS: A total of 124 patients were included. The average age was 7.3 years (95% confidence interval, 6.6-8.0) and 66 (54%) were male. The racial composition was 54 (44%) black, 41 (33%) white, and 28 (23%) other. The median AHI was 4.8 (interquartile range 12) and 43 (35%) of patients had severe OSA. In linear and logistic regression models, SF outperformed the PSQ-SRBD and null models as measured by Akaike Information Criteria. The overall accuracy in predicting AHI >10 for PSQ-SRBD was 0.65 (0.56-0.73, P = 0.54) compared to 0.73 (0.64-0.80, P = 0.04) for SF. CONCLUSION: By eliminating redundancy, we have developed a questionnaire with improved prediction of OSA and its severity, in children with high pre-test probability of the condition. While multi-site validation is necessary, SF demonstrates value in screening children prior to T&A in resource-limited environments.

The impact of sleep events on weight gain following early adenotonsillectomy compared to supportive care for pediatric OSA.

OBJECTIVES: Children with obstructive sleep apnea (OSA) who undergo adenotonsillectomy (AT) often experience post-operative weight gain, although the mechanism remains unclear. Our aim is to understand how changes in sleep events impact changes in weight in children with OSA following adenotonsillectomy compared to watchful waiting with supportive care. METHODS: We performed a secondary analysis of the Childhood adenotonsillectomy trial (CHAT) dataset in which children with OSA were randomized to undergo early adenotonsillectomy (eAT) or watchful waiting with supportive care (WWSC). The primary outcome measures included changes in body mass index (BMI) percentile, apnea-hypopnea index (AHI) and arousal index (AI) during rapid eye movement (REM) sleep. The change in BMI percentile attributable to changes in AHI and AI during REM sleep was determined using causal mediation analysis. RESULTS: Of the 453 children with OSA randomized to eAT or WWSC, 397 children were included in the analysis. Children in the eAT arm experienced a greater increase in their weight as measured by BMI percentile, compared to children who received WWSC (WWSC 4.12 (2.70, 5.55) vs. eAT 6.62 (4.87, 8.38), Cohen's d = 0.22 (0.02, 0.42), p = 0.02). A significant proportion of the weight gain was attributable to decreases in apneic events (proportion mediated 19% (2-97%), p = 0.03) and arousals (proportion mediated 20% (5-78%), p = 0.01) during REM sleep. CONCLUSION: A significant proportion of post-adenotonsillectomy weight gain in children with OSA is attributable to polysomnographic changes during REM sleep, potentially due to the mitigation of REM-related sleep fragmentation and subsequent reduction in metabolic expenditure.

A Neck Mass of Thymic Origin in a Pediatric Patient.

In this study, we present the case of a 10-year-old boy with a left-sided neck mass. Although most neck masses in children are non-cancerous, their etiology can be complex, especially in neck masses of congenital origin. The workup of a pediatric neck mass includes imaging and cytopathology. In this case, the histopathology of the excised mass revealed thymic tissue, which helped establish the diagnosis of a thymopharyngeal duct cyst. Thymophayngeal duct cysts, although rare, can be diagnosed preoperatively by characteristic tapering toward the mediastinum. Cytopathology may demonstrate Hassall corpuscles. These unique features can help disentangle the differential diagnoses, which commonly include thyroglossal duct cysts, venolymphatic malformations, and branchial cleft cysts.

Baseline apnea-hypopnea index threshold and adenotonsillectomy consideration in children with OSA.

OBJECTIVES: Adenotonsillectomy (AT) is the first line of treatment for pediatric obstructive sleep apnea (OSA). In some treatment guidelines, children with moderate to severe OSA, defined as apnea-hypopnea index (AHI) ≥ 5, may be recommended AT regardless of symptoms. The differences in outcomes between children randomized to watchful waiting with supportive care (WWSC) or AT were compared based on baseline OSA severity threshold of AHI≥ 5. METHODS: A secondary analysis of the Childhood Adenotonsillectomy Trial, a randomized controlled trial of children with OSA aged 5-9 years who underwent AT or WWSC, was performed. The primary outcome was the change in neurocognition measured by Developmental Neuropsychological Assessment (NEPSY). Secondary outcomes included changes in behavior, symptoms of OSA, and quality of life. Outcomes were measured at baseline and the seven-month follow-up after grouping children based on whether their AHI was greater than or equal to 5. Comparisons were performed using two-way analysis of covariance (ANCOVA) while controlling for age, sex and race. Differences in treatment effect were measured using Cohen's d. RESULTS: Of the 397 children included, 203 received WWSC and 194 underwent AT. The treatment effects on post-randomization changes in neurocognition, measured by NEPSY in children with AHI ≥5 (Cohen's d = 0.1 [95% CI, -0.1 to 0.4]) was not significantly different from children with AHI <5 (Cohen's d = 0.1 [95% CI, -0.1 to 0.4]). Furthermore, among children in the AT group alone, the effects of AT on post-treatment changes in NEPSY did not differ based on AHI threshold (Cohen's d = -0.06 [95% CI, -0.3 to 0.2]). Additionally, the treatment effects on post-randomization changes in behavior, symptoms, and quality of life did not vary based on AHI threshold. CONCLUSION: The outcomes of neurocognition, behavior, symptoms, and quality of life did not differ between children with OSA randomized to WWSC or AT based on OSA severity threshold alone. Additionally, the effects of AT on post-treatment outcomes did not differ based on AHI threshold.

Tracheostomy on infants born in the periviable period: Outcomes at discharge from the neonatal intensive care unit (NICU).

OBJECTIVES: Advances in neonatal intensive care have allowed successful resuscitation of children born at the border of viability. However, there has been little change in the incidence of bronchopulmonary dysplasia (BPD) and anatomical upper airway obstruction which may require a tracheostomy in that group. The benefits of the procedure are accompanied by sequelae that impact outcomes. Information about these issues can assist caregivers in making decisions and planning care after discharge from the neonatal intensive care unit (NICU). The objectives of this study were to describe the clinical characteristics of neonates born in the periviable period (≤25 weeks gestation) requiring tracheotomy and to highlight their hospital course, complications and status upon NICU discharge. METHODS: Retrospective analysis at four tertiary care academic children's hospitals. Medical records of neonates born ≤25 weeks gestation who required tracheotomy between January 1, 2012 and December 31, 2018 were reviewed. Demographics, medical comorbidities, and tracheostomy related complications were studied. Feeding, ventilation, and neurodevelopmental outcomes at time of transfer from NICU were evaluated. RESULTS: Fifty-two patients were included. The mean gestational age was 24.3 (95% confidence interval, 24.1 to 24.5) weeks. The mean birth weight was 635 (95% CI: 603 to 667) grams and 50 (96.2%) children had BPD. At time of discharge from the NICU, 47 (90.4%) required mechanical ventilation, four (7.7%) required supplemental oxygen and one (1.9%) was weaned to room air. Forty-two (80.8%) were discharged with a gastrostomy tube, seven (28%) with a nasogastric tube, and three (5.8%) were on oral feeds. Two (3.8%) suffered hypoxic ischemic encephalopathy, 27 (51.9%) had neurodevelopmental delay, seven (13.5%) were diagnosed with another anomaly, and 16 (30.8%) were considered normal. Complications related to the procedure were observed in 28 (53.8%) neonates. Granulation tissue was seen in 17 (32.7%), wound break down or cellulitis in three (5.8%), one (1.9%) with tracheostomy plugging, three (5.8%) with dislodgement of the tracheostomy tube and four (7.7%) developed tracheitis. CONCLUSIONS: Tracheostomy in infants born in the periviable period is primarily performed for BPD and portends extended ventilatory dependence. It is associated with non-oral alimentation at the time of discharge from the NICU and developmental delay. Mortality directly related to the procedure is rare. Minor complications are common but do not require surgical intervention. These data may aid in counseling caregivers about the procedure in this vulnerable population.

Predictors of Postoperative Complications After Paramedian Forehead Flaps.

Importance: The predictors of postoperative complications after paramedian forehead flaps (PMFF) are unknown. Objective: To determine whether preoperative factors can predict post-PMFF complications. Design, Setting, Participants: A retrospective review of 1438 adults from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database who underwent PMFF between 2010 and 2018. Main Outcomes and Measures: Surgical complications, medical complications, and all-cause mortality. Results: Of the 1438 patients, 75 experienced postoperative complications (5.2%). Of these, 36 developed isolated surgical complications (2.5%), 29 developed isolated medical complications (2.0%), and 8 developed concurrent surgical and medical complications (0.5%). Of the three mortalities (0.2%), one patient developed concurrent surgical and medical complications. A dirty or infected wound classification was the strongest predictor of postoperative complications (odds ratio [OR] 13.5; confidence interval [95% CI] 3.4-49.5). In contrast, the likelihood of postoperative complications decreased significantly with outpatient procedures (OR 0.4; 95% CI 0.2-0.8). Conclusions and Relevance: A dirty or infected wound classification is the strongest predictor of postoperative complications after PMFF.

Association Between Habitual Snoring and Cognitive Performance Among a Large Sample of Preadolescent Children.

Importance: Previous studies have identified an association between habitual snoring and lower cognitive performance in children. However, whether and to what extent this association is confounded by pertinent demographic, anthropometric, and socioeconomic characteristics is unknown. Objective: To assess the extent to which potential confounding factors modify the association between parent-reported habitual snoring and cognitive outcomes among a large and diverse sample of typically developing preadolescent children. Design, Setting, and Participants: This cross-sectional analysis used a baseline data set (version 2.0.1) from children enrolled in the ongoing Adolescent Brain Cognitive Development study between September 1, 2016, and October 15, 2018. Children aged 9 to 10 years without serious psychiatric or neurological comorbidities were recruited at 21 research sites in the US. Study recruitment was designed to approximate the racial and socioeconomic diversity of the US population. Data were analyzed from February 1 to March 31, 2020. Exposures: Parent-reported habitual snoring in children that occurs 3 or more nights per week. Main Outcomes and Measures: Associations between habitual snoring and cognitive performance were assessed using the Sleep Disturbance Scale for Children and the National Institutes of Health Toolbox Cognition Battery, which includes 7 domain-specific and 3 composite (total cognitive function, fluid cognition, and crystallized cognition) standard scores that are uncorrected for covariates. Cognitive performance was examined before and after adjustment for covariates, which included age, sex, body mass index percentile, annual household income before taxes, and highest educational level of caregiver. The extent of confounding was assessed by the effect size, represented by Cohen d, before and after inclusion of covariates using linear mixed-effects models. Results: A total of 11 873 children aged 9 to 10 years (6187 boys [52.1%]; 6174 White [52.0%]) with available data were included in the study. Of those, habitual snoring (≥3 nights per week) was reported in 810 children (6.8%), and nonhabitual snoring (1-2 nights per week) was reported in 4058 children (34.2%). In the unadjusted models, the total cognitive function composite score among children who habitually snored was significantly lower compared with children who never snored (Cohen d, 0.35; 95% CI, 0.28-0.42). Differences were also identified in the crystallized cognition (Cohen d, 0.34; 95% CI, 0.26-0.41) and fluid cognition (Cohen d, 0.28; 95% CI, 0.21-0.35) composite scores. The association between habitual snoring and cognitive performance was substantially attenuated after adjustment for covariates (Cohen d, 0.16 [95% CI, 0.09 to 0.24] for total cognitive function, 0.14 [95% CI, 0.07 to 0.21] for crystallized cognition, and 0.13 [95% CI, 0.06 to 0.21] for fluid cognition). Similar mitigation was also observed for all domain-specific scores. Conclusions: In this cross-sectional study, when adjusted for baseline demographic, anthropometric, and socioeconomic characteristics, the association between parent-reported habitual snoring and cognitive performance was substantially attenuated among children aged 9 to 10 years.

Recovery After Adenotonsillectomy-Do Steroids Help? Outcomes From a Randomized Controlled Trial.

OBJECTIVES: The primary objective was to compare pain control following adenotonsillectomy (AT) in children with and without a single postoperative dose of oral dexamethasone in addition to standard analgesic medication. The secondary objective was to compare changes in caregiver-reported snoring, return to normal diet and baseline function, and the number of phone calls and emergency department (ED) visits. STUDY DESIGN: Prospective randomized controlled trial. SETTING: Tertiary care university hospital. METHODS: Children aged 3 to 10 years with sleep-disordered breathing who were scheduled to undergo AT were randomized to receive standard analgesia with or without dexamethasone (0.6 mg/kg) administered on the third postoperative day. Standard analgesia was defined as alternating weight-based doses of ibuprofen and acetaminophen. A nurse practitioner blinded to the study condition performed telephone surveys postoperatively, and the electronic medical record was reviewed. RESULTS: Enrollment comprised 149 children, of whom 119 were included. When compared with the control group (n = 61, 51%), children who received dexamethasone (n = 58, 49%) had a greater decrease in reported pain score on day 4 (mean ± SD, 2.5 ± 3.1 vs 1.1 ± 3.5, P < .001). Additionally, steroid use was associated with fewer caregiver phone calls (18 [29.5%] vs 6 [10%]) and ED visits (6 [10%] vs 1 [2%]). CONCLUSION: A single dose of dexamethasone administered on day 3 after adenotonsillectomy significantly improved pain control. There were fewer phone calls and ED visits in the steroid arm. These results support the use of oral steroids as an adjunct for postoperative pain control in children undergoing AT.

Predictors of Behavioral Changes After Adenotonsillectomy in Pediatric Obstructive Sleep Apnea: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Adenotonsillectomy (AT) is associated with improved behavior in children with obstructive sleep apnea (OSA). However, it is unknown whether polysomnographic parameters are superior to the parent-reported severity of sleep-disordered breathing (SDB) in predicting behavioral changes after AT. Objective: To ascertain whether polysomnographic parameters vs parent-reported severity of SDB are better predictors of treatment-related behavioral changes in children with OSA. Design, Setting, and Participants: This ad hoc secondary analysis of the Childhood Adenotonsillectomy Trial (CHAT) downloaded and analyzed data from January 1 to January 31, 2020. Children aged 5 to 9 years with a polysomnographic diagnosis of OSA were enrolled in the CHAT and subsequently randomized to undergo either early AT or watchful waiting with supportive care. All outcome measures were obtained at baseline and at follow-up (7 months after randomization). Interventions: Early AT vs watchful waiting with supportive care. Main Outcomes and Measures: Postrandomization changes between the baseline and follow-up periods were derived from (1) T scores in 4 validated behavioral assessments (Conners Global Index parent and teacher versions, Behavior Rating Inventory of Executive Function metacognition index, and Child Behavior Checklist of total, internalizing, and externalizing behavior subscales); (2) 8 aggregated polysomnographic parameters representing the severity of obstruction, hypoxemia, sleep quality, and structure; and (3) the parent-reported severity of SDB measured by the Pediatric Sleep Questionnaire-Sleep-Related Breathing Disorder (PSQ-SRBD) scale. The treatment-related changes in each of the behavioral outcomes attributable to changes in SDB severity (represented by the subjective PSQ-SRBD score and objective polysomnographic parameters) were measured and compared using mediation analysis. Results: A total of 453 children were assessed at baseline, of whom 234 were girls (52%) and the mean (SD) age was 6.6 (1.4) years. The postrandomization changes in 7 of 8 behavioral outcome measures between the baseline and follow-up periods were partially mediated by the changes in PSQ-SRBD scores (range of nonzero causally mediated effects, 2.4-3.5), without contribution from any of the polysomnographic parameters. Conclusions and Relevance: This secondary analysis of a national randomized clinical trial found that most treatment-related behavioral changes in children with OSA were mediated by the changes in parent-reported SDB severity alone. These findings suggest that polysomnographic parameters provide clinicians with limited means to predict the improvement in neurobehavioral morbidity in OSA. Trial Registration: ClinicalTrials.gov Identifier: NCT00560859.

Machine Learning Prediction of Extracapsular Extension in Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma.

OBJECTIVE: To determine whether machine learning (ML) can predict the presence of extracapsular extension (ECE) prior to treatment, using common oncologic variables, in patients with human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). STUDY DESIGN: Retrospective database review. SETTING: National Cancer Database study. METHODS: All patients with HPV-associated OPSCC treated surgically between January 1, 2010, and December 31, 2015, were selected from the National Cancer Database. Patients were excluded if surgical pathology reports did not include information regarding primary tumor stage, number of metastatic regional lymph nodes, size of largest metastatic regional lymph node, and tumor grade. The data were split into a random distribution of 80% for training and 20% for testing with ML methods. RESULTS: A total of 3753 adults with surgically treated HPV-associated OPSCC met criteria for inclusion in the study. Approximately 38% of these patients treated with surgical management demonstrated ECE. ML models demonstrated modest accuracy in predicting ECE, with the areas under the receiver operating characteristic curves ranging from 0.58 to 0.68. The conditional inference tree model (0.66) predicted the metastatic lymph node number to be the most important predictor of ECE. CONCLUSION: Despite a large cohort and the use of ML algorithms, the power of clinical and oncologic variables to predict ECE in HPV-associated OPSCC remains limited.

Predicting polysomnographic severity thresholds in children using machine learning.

BACKGROUND: Approximately 500,000 children undergo tonsillectomy and adenoidectomy (T&A) annually for treatment of obstructive sleep disordered breathing (oSDB). Although polysomnography is beneficial for preoperative risk stratification in these children, its expanded use is limited by the associated costs and resources needed. Therefore, we used machine learning and data from potentially wearable sensors to identify children needing postoperative overnight monitoring based on the polysomnographic severity of oSDB. METHODS: Children aged 2-17 years undergoing polysomnography were included. Six machine learning models were created using (i) clinical parameters and (ii) nocturnal actigraphy and oxygen desaturation index. The prediction performance for polysomnography-derived severity of oSDB measured by apnea hypopnea index (AHI) >2 and >10 were evaluated. RESULTS: One hundred and ninety children were included. One hundred and eight were male (57%), mean age was 6.7 years [95% confidence interval; 6.1, 7.2], and mean AHI was 10.6 [7.8, 13.4]. Predictive performance utilizing clinical parameters was poor for both AHI > 2 (accuracy range: 48-56% for all models) and AHI > 10 (50-61%). Combining oximetry and actigraphy improved the accuracy to 87-89% for AHI > 2 and 95-96% for AHI > 10. CONCLUSIONS: Machine learning with oximetry and actigraphy identifies most children needing overnight monitoring as determined by polysomnographic severity of oSDB, supporting a potential resource-conscious screening pathway for children undergoing T&A. IMPACT: We provide proof of principle for the utility of machine learning, oximetry, and actigraphy to screen for severe obstructive sleep apnea syndrome (OSAS) in children. Clinical parameters perform poorly in predicting the severity of OSAS, which is confirmed in the current study. The predictive accuracy for severe OSAS was improved by a smaller subset of quantifiable physiologic parameters, such as oximetry. The results of this study support a lower cost, patient-friendly screening pathway to identify children in need of in-hospital observation after surgery.

Treatment-Related Changes in Heart Rate Variability in Children with Sleep Apnea.

OBJECTIVE: Heart rate variability (HRV), a noninvasive indicator of autonomic regulation of cardiac rhythm, may represent the physiologic burden of obstructive sleep apnea (OSA). We hypothesized that the treatment-related effects of OSA on HRV in children are causally attributable to the improvement in OSA severity. STUDY DESIGN: Secondary analysis of outcomes from the Childhood Adenotonsillectomy Trial (CHAT). SETTING: Analysis of database. SUBJECTS AND METHODS: Time- and frequency-domain HRV parameters along with polysomnographic (PSG) and demographic variables were obtained from the CHAT study, which compared early adenotonsillectomy (eAT) to watchful waiting (WW) in children with OSA. The relative contributions of PSG variables and covariates to each HRV parameter were quantified. The proportion of changes in HRV parameters causally attributable to changes in OSA severity, measured by the apnea-hypopnea index (AHI) and oxygen desaturation index (ODI), was estimated. RESULTS: In total, 404 children aged 5 to 10 years were included. The median (interquartile range) age was 6 (3-9) years. The median body mass index percentile was 82 (53), 195 (48%) children were male, and 147 (36%) were African American. The average heart rate during PSG was the strongest independent predictor of each HRV parameter (P < .001). Although eAT resulted in statistically significant changes in the majority of HRV parameters, these effects were not causally attributable to treatment-related changes in AHI or ODI. CONCLUSIONS: The average heart rate strongly modulates HRV in children with OSA. Although eAT results in discernible changes in HRV, it appears to not be causally attributable to specific treatment-related changes in AHI or ODI.

Tracheostomy in the Extremely Premature Neonate: A Multi-Institutional Study.

OBJECTIVE: (1) To describe characteristics associated with tracheostomy placement and (2) to describe associated in-hospital morbidity in extremely premature infants. STUDY DESIGN: Pooled retrospective analysis of charts. SETTING: Academic children's hospitals. SUBJECTS AND METHODS: The patient records of premature infants (23-28 weeks gestational age) who underwent tracheostomy between January 1, 2012, and December 31, 2017, were reviewed from 4 academic children's hospitals. Demographics, procedural morbidity, feeding, respiratory, and neurodevelopmental outcomes at the time of transfer from the neonatal intensive care unit (NICU) were obtained. The contribution of baseline characteristics to mortality, neurodevelopmental, and feeding outcomes was also assessed. RESULTS: The charts of 119 infants were included. The mean gestational age was 25.5 (95% confidence interval, 25.2-25.7) weeks. The mean birth weight was 712 (671-752) g. Approximately 50% was African American. The principal comorbidity was chronic lung disease (92.4%). Overall, 60.5% of the infants had at least 1 complication. At the time of transfer, most remained mechanically ventilated (94%) and dependent on a feeding tube (90%). Necrotizing enterocolitis increased the risk of feeding impairment (P = .002) and death (P = .03). CONCLUSIONS: Tracheostomy in the extremely premature neonate is primarily performed for chronic lung disease. Complications occur frequently, with skin breakdown being the most common. Placement of a tracheostomy does not seem to mitigate the systemic morbidity associated with extreme prematurity.