Extended Work Shifts and Neurobehavioral Performance in Resident-Physicians.

OBJECTIVES: Extended-duration work rosters (EDWRs) with shifts of 24+ hours impair performance compared with rapid cycling work rosters (RCWRs) that limit shifts to 16 hours in postgraduate year (PGY) 1 resident-physicians. We examined the impact of a RCWR on PGY 2 and PGY 3 resident-physicians. METHODS: Data from 294 resident-physicians were analyzed from a multicenter clinical trial of 6 US PICUs. Resident-physicians worked 4-week EDWRs with shifts of 24+ hours every third or fourth shift, or an RCWR in which most shifts were ≤16 consecutive hours. Participants completed a daily sleep and work log and the 10-minute Psychomotor Vigilance Task and Karolinska Sleepiness Scale 2 to 5 times per shift approximately once per week as operational demands allowed. RESULTS: Overall, the mean (± SE) number of attentional failures was significantly higher (P =.01) on the EDWR (6.8 ± 1.0) compared with RCWR (2.9 ± 0.7). Reaction time and subjective alertness were also significantly higher, by ∼18% and ∼9%, respectively (both P <.0001). These differences were sustained across the 4-week rotation. Moreover, attentional failures were associated with resident-physician-related serious medical errors (SMEs) (P =.04). Although a higher rate of SMEs was observed under the RCWR, after adjusting for workload, RCWR had a protective effect on the rate of SMEs (rate ratio 0.48 [95% confidence interval: 0.30-0.77]). CONCLUSIONS: Performance impairment due to EDWR is improved by limiting shift duration. These data and their correlation with SME rates highlight the impairment of neurobehavioral performance due to extended-duration shifts and have important implications for patient safety.

Effect on Patient Safety of a Resident Physician Schedule without 24-Hour Shifts.

BACKGROUND: The effects on patient safety of eliminating extended-duration work shifts for resident physicians remain controversial. METHODS: We conducted a multicenter, cluster-randomized, crossover trial comparing two schedules for pediatric resident physicians during their intensive care unit (ICU) rotations: extended-duration work schedules that included shifts of 24 hours or more (control schedules) and schedules that eliminated extended shifts and cycled resident physicians through day and night shifts of 16 hours or less (intervention schedules). The primary outcome was serious medical errors made by resident physicians, assessed by intensive surveillance, including direct observation and chart review. RESULTS: The characteristics of ICU patients during the two work schedules were similar, but resident physician workload, described as the mean (±SD) number of ICU patients per resident physician, was higher during the intervention schedules than during the control schedules (8.8±2.8 vs. 6.7±2.2). Resident physicians made more serious errors during the intervention schedules than during the control schedules (97.1 vs. 79.0 per 1000 patient-days; relative risk, 1.53; 95% confidence interval [CI], 1.37 to 1.72; P<0.001). The number of serious errors unitwide were likewise higher during the intervention schedules (181.3 vs. 131.5 per 1000 patient-days; relative risk, 1.56; 95% CI, 1.43 to 1.71). There was wide variability among sites, however; errors were lower during intervention schedules than during control schedules at one site, rates were similar during the two schedules at two sites, and rates were higher during intervention schedules than during control schedules at three sites. In a secondary analysis that was adjusted for the number of patients per resident physician as a potential confounder, intervention schedules were no longer associated with an increase in errors. CONCLUSIONS: Contrary to our hypothesis, resident physicians who were randomly assigned to schedules that eliminated extended shifts made more serious errors than resident physicians assigned to schedules with extended shifts, although the effect varied by site. The number of ICU patients cared for by each resident physician was higher during schedules that eliminated extended shifts. (Funded by the National Heart, Lung, and Blood Institute; ROSTERS ClinicalTrials.gov number, NCT02134847.).

Randomized, Placebo-Controlled Trial of Ferrous Sulfate to Treat Insomnia in Children With Autism Spectrum Disorders.

BACKGROUND: Insomnia and low iron stores are common in children with autism spectrum disorders, and low iron stores have been associated with sleep disturbance. METHODS: We performed a randomized placebo-controlled trial of oral ferrous sulfate to treat insomnia in children with autism spectrum disorders and low normal ferritin levels. Twenty participants who met inclusion criteria and whose insomnia did not respond to sleep education were randomized to 3 mg/kg/day of ferrous sulfate (n = 9) or placebo (n = 11) for three months. RESULTS: Iron supplementation was well tolerated, and no serious adverse events were reported. Iron supplementation improved iron status (+18.4 ng/mL active versus -1.6 ng/mL placebo, P = 0.044) but did not significantly improve the primary outcome measures of sleep onset latency (-11.0 minutes versus placebo, 95% confidence interval -28.4 to 6.4 minutes, P = 0.22) and wake time after sleep onset (-7.7 minutes versus placebo, 95% confidence interval -22.1 to 6.6 min, P = 0.29) as measured by actigraphy. Iron supplementation was associated with improvement in the overall severity score from the Sleep Clinical Global Impression Scale (-1.5 points versus placebo, P = 0.047). Changes in measures of daytime behavior did not differ between groups. CONCLUSION: This trial demonstrated no improvement in primary outcome measures of insomnia in subjects treated with ferrous sulfate compared with placebo. Interpretation was limited by low enrollment.

Burden of disease in pediatric narcolepsy: a claims-based analysis of health care utilization, costs, and comorbidities.

BACKGROUND: This study analyzed a privately insured pediatric population with and without narcolepsy to determine the impact of pediatric narcolepsy on comorbidities, health care utilization, and cost. Additional analyses compared narcolepsy type 1 and type 2. METHODS: This retrospective cross-sectional study identified US patients with narcolepsy <18 years of age with ≥2 claims with a diagnosis code of narcolepsy using Truven MarketScan® data 2011 to 2015. Patients were matched to controls without narcolepsy. Comorbid conditions, health care utilization, and costs were measured by calendar year. P values are nominal, and no adjustments for multiplicity or multiple comparisons were made. RESULTS: A total of 1427 pediatric patients with narcolepsy were identified and matched with 4281 controls from 2011 to 2015. Patients with narcolepsy had more comorbid conditions (mean 5.8 vs 2.4, nominal P < 0.001). Respiratory diseases and mood disorders were more common in patients with narcolepsy than controls (57% vs 32% and 56% vs 14%, respectively; both nominal P < 0.001). Compared to controls, patients with narcolepsy underwent more diagnostic tests (electroencephalogram, EEG [0.13 vs 0.0053]) and brain computed tomography, CT/magnetic resonance imaging, MRI (0.26 vs 0.022; both nominal P < 0.001). Mean annual inpatient days (0.71 vs 0.15), emergency department visits (0.51 vs 0.15), and outpatient office visits (8.6 vs 2.3) were higher for patients with narcolepsy than controls (all nominal P < 0.001). Annual mean health care costs were higher for patients with narcolepsy versus controls ($15,797 vs $2449, nominal P < 0.001). CONCLUSION: Pediatric patients with narcolepsy had greater comorbidity, higher health care utilization, and higher costs than patients without narcolepsy.

Nocturnal Hypoxia Activation of the Hedgehog Signaling Pathway Affects Pediatric Nonalcoholic Fatty Liver Disease Severity.

Chronic intermittent hypoxia and hedgehog (Hh) pathway dysregulation are associated with nonalcoholic fatty liver disease (NAFLD) progression. In this study, we determined the relationship between obstructive sleep apnea (OSA)/nocturnal hypoxia and Hh signaling in pediatric NAFLD. Adolescents with histologic NAFLD (n = 31) underwent polysomnogram testing, laboratory testing, and Sonic Hh (SHh), Indian hedgehog (IHh), glioblastoma-associated oncogene 2 (Gli2), keratin 7 (K7), α-smooth muscle actin (α-SMA), and hypoxia-inducible factor 1α (HIF-1α) immunohistochemistry. Aspartate aminotransferase (AST) correlated with SHh, r = 0.64; Gli2, r = 0.4; α-SMA, r = 0.55; and K7, r = 0.45 (P < 0.01), as did alanine aminotransferase (ALT) (SHh, r = 0.51; Gli2, r = 0.43; α-SMA, r = 0.51; P < 0.02). SHh correlated with NAFLD activity score (r = 0.39), whereas IHh correlated with inflammation (r = -0.478) and histologic grade (r = -0.43); P < 0.03. Subjects with OSA/hypoxia had higher SHh (4.0 ± 2.9 versus 2.0 ± 1.5), Gli2 (74.2 ± 28.0 versus 55.8 ± 11.8), and α-SMA (6.2 ± 3.3 versus 4.3 ± 1.2); compared to those without (P < 0.03). OSA severity correlated with SHh (r = 0.31; P = 0.09) and Gli2 (r = 0.37; P = 0.04) as did hypoxia severity, which was associated with increasing SHh (r = -0.53), Gli2 (r = -0.52), α-SMA (r = -0.61), and K7 (r = -0.42); P < 0.02. Prolonged O2 desaturations <90% also correlated with SHh (r = 0.55) and Gli2 (r = 0.61); P < 0.05. Conclusion: The Hh pathway is activated in pediatric patients with NAFLD with nocturnal hypoxia and relates to disease severity. Tissue hypoxia may allow for functional activation of HIF-1α, with induction of genes important in epithelial-mesenchymal transition, including SHh, and NAFLD progression.

Effects on resident work hours, sleep duration, and work experience in a randomized order safety trial evaluating resident-physician schedules (ROSTERS).

STUDY OBJECTIVES: We compared resident physician work hours and sleep in a multicenter clustered-randomized crossover clinical trial that randomized resident physicians to an Extended Duration Work Roster (EDWR) with extended-duration (≥24 hr) shifts or a Rapidly Cycling Work Roster (RCWR), in which scheduled shift lengths were limited to 16 or fewer consecutive hours. METHODS: Three hundred two resident physicians were enrolled and completed 370 1 month pediatric intensive care unit rotations in six US academic medical centers. Sleep was objectively estimated with wrist-worn actigraphs. Work hours and subjective sleep data were collected via daily electronic diary. RESULTS: Resident physicians worked fewer total hours per week during the RCWR compared with the EDWR (61.9 ± 4.8 versus 68.4 ± 7.4, respectively; p < 0.0001). During the RCWR, 73% of work hours occurred within shifts of ≤16 consecutive hours. In contrast, during the EDWR, 38% of work hours occurred on shifts of ≤16 consecutive hours. Resident physicians obtained significantly more sleep per week on the RCWR (52.9 ± 6.0 hr) compared with the EDWR (49.1 ± 5.8 hr, p < 0.0001). The percentage of 24 hr intervals with less than 4 hr of actigraphically measured sleep was 9% on the RCWR and 25% on the EDWR (p < 0.0001). CONCLUSIONS: RCWRs were effective in reducing weekly work hours and the occurrence of >16 consecutive hour shifts, and improving sleep duration of resident physicians. Although inclusion of the six operational healthcare sites increases the generalizability of these findings, there was heterogeneity in schedule implementation. Additional research is needed to optimize scheduling practices allowing for sufficient sleep prior to all work shifts.Clinical Trial: Multicenter Clinical Trial of Limiting Resident Work Hours on ICU Patient Safety (ROSTERS), https://clinicaltrials.gov/ct2/show/NCT02134847.

Design and recruitment of the randomized order safety trial evaluating resident-physician schedules (ROSTERS) study.

INTRODUCTION: While the Accreditation Council for Graduate Medical Education limited first year resident-physicians to 16 consecutive work hours from 2011 to 2017, resident-physicians in their second year or higher were permitted to work up to 28 h consecutively. This paper describes the Randomized Order Safety Trial Evaluating Resident-physician Schedules (ROSTERS) study, a clustered-randomized crossover clinical trial designed to evaluate the effectiveness of eliminating traditional shifts of 24 h or longer for second year or higher resident-physicians in pediatric intensive care units (PICUs). METHODS: ROSTERS was a multi-center non-blinded trial in 6 PICUs at US academic medical centers. The primary aim was to compare patient safety between the extended duration work roster (EDWR), which included shifts ≥24 h, and a rapidly cycling work roster (RCWR), where shifts were limited to a maximum of 16 h. Information on potential medical errors was gathered and used for classification by centrally trained physician reviewers who were blinded to the study arm. Secondary aims were to assess the relationship of the study arm to resident-physician sleep duration, work hours and neurobehavioral performance. RESULTS: The study involved 6577 patients with a total of 38,821 patient days (n = 18,749 EDWR, n = 20,072 RCWR). There were 413 resident-physician rotations included in the study (n = 203 EDWR, n = 210 RCWR). Resident-physician questionnaire data were over 95% complete. CONCLUSIONS: Results from data collected in the ROSTERS study will be evaluated for the impact of resident-physician schedule roster on patient safety outcomes in PICUs, and will allow for examination of a number of secondary outcome measures. ClinicalTrials.gov Identifier: NCT02134847.

Treating Obstructive Sleep Apnea and Chronic Intermittent Hypoxia Improves the Severity of Nonalcoholic Fatty Liver Disease in Children.

OBJECTIVE: To determine the effects of treating obstructive sleep apnea/nocturnal hypoxia on pediatric nonalcoholic fatty liver disease (NAFLD) severity and oxidative stress. STUDY DESIGN: Biopsy proven participants (n = 9) with NAFLD and obstructive sleep apnea/hypoxia were studied before and after treatment with continuous positive airway pressure (CPAP) for sleep disordered breathing, including laboratory testing and markers of oxidative stress, urine F(2)-isoprostanes. RESULTS: Adolescents (age 11.5 ± 1.2 years; body mass index, 29.5 ± 3.8 kg/m2) with significant NAFLD (mean histologic necroinflammation grade, 2.3 ± 0.9; fibrosis stage, 1.4 ± 1.3; NAFLD Activity Score summary, 4.8 ± 1.6) had obstructive sleep apnea/hypoxia by polysomnography. At baseline, they had severe obstructive sleep apnea/hypoxia, elevated aminotransferases, the metabolic syndrome, and significant oxidative stress (high F(2)-isoprostanes). Obstructive sleep apnea/hypoxia was treated with home CPAP for a mean 89 ± 62 days. Although body mass index increased, obstructive sleep apnea/hypoxia severity improved on CPAP and was accompanied by reduced alanine aminotransferase, metabolic syndrome markers, and F(2)-isoprostanes. CONCLUSIONS: This study provides strong evidence that treatment of obstructive sleep apnea/nocturnal hypoxia with CPAP in children with NAFLD may reverse parameters of liver injury and reduce oxidative stress. These data also suggest CPAP as a new therapy to prevent progression of NAFLD in those children with obesity found to have obstructive sleep apnea/nocturnal hypoxia.

The Impact of Altitude on Sleep-Disordered Breathing in Children Dwelling at High Altitude: A Crossover Study.

Study Objectives: Sleep-disordered breathing (SDB) is prevalent among children and is associated with adverse health outcomes. Worldwide, approximately 250 million individuals reside at altitudes higher than 2000 meters above sea level (masl). The effect of chronic high-altitude exposure on children with SDB is unknown. This study aims to determine the impact of altitude on sleep study outcomes in children with SDB dwelling at high altitude. Methods: A single-center crossover study was performed to compare results of high-altitude home polysomnography (H-PSG) with lower altitude laboratory polysomnography (L-PSG) in school-age children dwelling at high altitude with symptoms consistent with SDB. The primary outcome was apnea-hypopnea index (AHI), with secondary outcomes including obstructive AHI; central AHI; and measures of oxygenation, sleep quality, and pulse rate. Results: Twelve participants were enrolled, with 10 included in the final analysis. Median altitude was 1644 masl on L-PSG and 2531 masl on H-PSG. Median AHI was 2.40 on L-PSG and 10.95 on H-PSG. Both obstructive and central respiratory events accounted for the difference in AHI. Oxygenation and sleep fragmentation were worse and pulse rate higher on H-PSG compared to L-PSG. Conclusions: These findings reveal a clinically substantial impact of altitude on respiratory, sleep, and cardiovascular outcomes in children with SDB who dwell at high altitude. Within this population, L-PSG underestimates obstructive sleep apnea and central sleep apnea compared to H-PSG. Given the shortage of high-altitude pediatric sleep laboratories, these results suggest a role for home sleep apnea testing for children residing at high altitude.

Family Chaos and Child Functioning in Relation to Sleep Problems Among Children at Risk for Obesity.

This study evaluated the influence of child and family functioning on child sleep behaviors in low-income minority families who are at risk for obesity. A cross-sectional study was utilized to measure child and family functioning from 2013 to 2014. Participants were recruited from Head Start classrooms while data were collected during home visits. A convenience sample of 72 low-income Hispanic (65%) and African American (32%) families of preschool-aged children were recruited for this study. We assessed the association of child and family functioning with child sleep behaviors using a multivariate multiple linear regression model. Bootstrap mediation analyses examined the effects of family chaos between child functioning and child sleep problems. Poorer child emotional and behavioral functioning related to total sleep behavior problems. Chaos associated with bedtime resistance significantly mediated the relationship between Behavioral and Emotional Screening System (BESS) and Bedtime Resistance. Families at high risk for obesity showed children with poorer emotional and behavioral functioning were at higher risk for problematic sleep behaviors, although we found no link between obesity and child sleep. Family chaos appears to play a significant role in understanding part of these relationships. Future longitudinal studies are necessary to establish causal relationships between child and family functioning and sleep problems to further guide obesity interventions aimed at improving child sleep routines and increasing sleep duration.

Knowledge, Attitudes, and Risk for Sudden Unexpected Infant Death in Children of Adolescent Mothers: A Qualitative Study.

OBJECTIVE: To investigate practices, knowledge, attitudes, and beliefs regarding infant sleep among adolescent mothers, a demographic at high risk for sudden unexpected infant death, and to identify novel public health interventions targeting the particular reasons of this population. STUDY DESIGN: Seven targeted focus groups including 43 adolescent mothers were conducted at high school daycare centers throughout Colorado. Focus groups were recorded, transcribed, validated, and then analyzed in NVivo 10. Validation included coding consistency statistics and expert review. RESULTS: Most mothers knew many of the American Academy of Pediatrics recommendations for infant sleep. However, almost all teens reported bedsharing regularly and used loose blankets or soft bedding despite being informed of risks. Reasons for nonadherence to recommendations included beliefs that babies are safest and sleep more/better in bed with them, that bedsharing is a bonding opportunity, and that bedsharing is easier than using a separate sleep space. The most common justifications for blankets were infant comfort and concern that babies were cold. Participants' decision making was often influenced by their own mothers, with whom they often resided. Participants felt that their instincts trumped professional advice, even when in direct contradiction to safe sleep recommendations. CONCLUSIONS: Among focus group participants, adherence with safe sleep practices was poor despite awareness of the American Academy of Pediatrics recommendations. Many mothers expressed beliefs and instincts that infants were safe in various unsafe sleep environments. Future study should investigate the efficacy of alternative educational strategies, including education of grandmothers, who have significant influence over adolescent mothers.

An Official American Thoracic Society Clinical Practice Guideline: Pediatric Chronic Home Invasive Ventilation.

BACKGROUND: Children with chronic invasive ventilator dependence living at home are a diverse group of children with special health care needs. Medical oversight, equipment management, and community resources vary widely. There are no clinical practice guidelines available to health care professionals for the safe hospital discharge and home management of these complex children. PURPOSE: To develop evidence-based clinical practice guidelines for the hospital discharge and home/community management of children requiring chronic invasive ventilation. METHODS: The Pediatric Assembly of the American Thoracic Society assembled an interdisciplinary workgroup with expertise in the care of children requiring chronic invasive ventilation. The experts developed four questions of clinical importance and used an evidence-based strategy to identify relevant medical evidence. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to formulate and grade recommendations. RESULTS: Clinical practice recommendations for the management of children with chronic ventilator dependence at home are provided, and the evidence supporting each recommendation is discussed. CONCLUSIONS: Collaborative generalist and subspecialist comanagement is the Medical Home model most likely to be successful for the care of children requiring chronic invasive ventilation. Standardized hospital discharge criteria are suggested. An awake, trained caregiver should be present at all times, and at least two family caregivers should be trained specifically for the child's care. Standardized equipment for monitoring, emergency preparedness, and airway clearance are outlined. The recommendations presented are based on the current evidence and expert opinion and will require an update as new evidence and/or technologies become available.

Greater risk of hospitalization in children with Down syndrome and OSA at higher elevation.

BACKGROUND: Children with Down syndrome (DS) are at high risk for OSA. Increasing elevation is known to exacerbate underlying respiratory disorders and worsen sleep quality in people without DS, but whether altitude modulates the severity of OSA in DS is uncertain. In this study, we evaluate the impact of elevation (≤ 1,500 m vs > 1,500 m) on the proportion of hospitalizations involving OSA in children with and without DS. METHODS: Merging the 2009 Kids' Inpatient Database with zip-code linked elevation data, we analyzed differences in the proportion of pediatric hospitalizations (ages 2-20 years) involving OSA, pneumonia, and congenital heart disease (CHD), with and without DS. We used multivariable logistic regression to evaluate the association of elevation with hospitalizations involving OSA and DS, adjusting for key comorbidities. RESULTS: Proportionately more DS encounters involved OSA, CHD, and pneumonia within each elevation category than non-DS encounters. However, the risk difference for hospitalizations involving OSA and DS increased disproportionately at higher elevations (DS: 16.2% [95% CI, 9.2%-23.2%]; non-DS: 0.1% [95% CI, -0.4% to 0.7%]). Multivariable estimates of relative risk indicate increased risk for hospitalization involving OSA at higher elevations for people with DS and in children aged 2 to 4 years or with two or more chronic conditions. CONCLUSIONS: At elevations > 1,500 m, children with DS and OSA have a disproportionately higher risk for hospitalization than children with OSA without DS. This finding has not been described previously. With further validation, this finding suggests the need for greater awareness and earlier screening for OSA and its complications in patients with DS living at higher elevations.

Comparative meta-analysis of prazosin and imagery rehearsal therapy for nightmare frequency, sleep quality, and posttraumatic stress.

STUDY OBJECTIVE: In this meta-analysis, we compare the short-term efficacy of prazosin vs. IRT on nightmares, sleep quality, and posttraumatic stress symptoms (PTSS). METHODS: Reference databases were searched for randomized controlled trials using IRT or prazosin for nightmares, sleep disturbance, and/or PTSS. Effect sizes were calculated by subtracting the mean posttest score in the control group from the mean posttest score in the treatment group, and dividing the result by the pooled standard deviation of both groups. Mixed effects models were performed to evaluate effects of treatment characteristics, as well as sample characteristics (veteran vs. civilian) on treatment efficacy. RESULTS: Four studies used prazosin, 10 used IRT alone or in combination with another psychological treatment, and 1 included a group receiving prazosin and another group receiving IRT. Overall effect sizes of both treatments were of moderate magnitude for nightmare frequency, sleep quality, and PTSS (p < 0.01). Effect size was not significantly different with type of treatment (psychological vs. pharmacological) on nightmare frequency (p = 0.79), sleep quality (p = 0.65), or PTSS, (p = 0.52). IRT combined with CBT for insomnia showed more improvement in sleep quality compared to prazosin (p = 0.03), IRT alone (p = 0.03), or IRT combined with another psychological intervention, (p < 0.01). CONCLUSION: Although IRT interventions and prazosin yield comparable acute effects for the treatment of nightmares, adding CBT for insomnia to IRT seems to enhance treatment outcomes pertaining to sleep quality and PTSS. More randomized clinical trials with long-term follow-up are warranted. COMMENTARY: A commentary on this article appears in this issue on page 9.

Evaluation of a new pediatric positive airway pressure mask.

STUDY OBJECTIVES: The choice and variety of pediatric masks for continuous positive airway pressure (CPAP) is limited in the US. Therefore, clinicians often prescribe modified adult masks. Until recently a mask for children aged < 7 years was not available. This study evaluated apnea-hypopnea index (AHI) equivalence and acceptability of a new pediatric CPAP mask for children aged 2-7 years (Pixi; ResMed Ltd, Sydney, Australia). METHODS: Patients aged 2-7 years were enrolled and underwent in-lab baseline polysomnography (PSG) using their previous mask, then used their previous mask and the VPAP III ST-A flow generator for ≥ 10 nights at home. Thereafter, patients switched to the Pixi mask for ≥ 2 nights before returning for a PSG during PAP therapy via the Pixi mask. Patients then used the Pixi mask at home for ≥ 21 nights. Patients and their parents/guardians returned to the clinic for follow-up and provided feedback on the Pixi mask versus their previous mask. RESULTS: AHI with the Pixi mask was 1.1 ± 1.5/h vs 2.6 ± 5.4/h with the previous mask (p = 0.3538). Parents rated the Pixi mask positively for: restfulness of the child's sleep, trouble in getting the child to sleep, and trouble in having the child stay asleep. The Pixi mask was also rated highly for leaving fewer or no marks on the upper lip and under the child's ears, and being easy to remove. CONCLUSIONS: The Pixi mask is suitable for children aged 2-7 years and provides an alternative to other masks available for PAP therapy in this age group.

Obstructive sleep apnea and hypoxemia are associated with advanced liver histology in pediatric nonalcoholic fatty liver disease.

OBJECTIVE: To determine whether obstructive sleep apnea (OSA) and/or nocturnal hypoxemia are associated with the severity of liver injury in patients with pediatric nonalcoholic fatty liver disease (NAFLD). STUDY DESIGN: Obese children aged 10-18 years with liver biopsy-proven NAFLD were enrolled. Demographic, clinical, and laboratory data were collected, polysomnography was performed, and liver histology was scored. Subjects were divided into those with OSA/hypoxemia and those without OSA/hypoxemia for analysis. RESULTS: Of 25 subjects with NAFLD, OSA/hypoxemia was present in 15 (60%) (mean age, 12.8 ± 1.9 years; 68% male; 88% Hispanic; mean body mass index z-score, 2.3 ± 0.3). Subjects with and without OSA/hypoxemia had similar levels of serum aminotransferases, serum lipids, and inflammatory and insulin resistance markers. Although there were no differences between groups in the histological severity of steatosis, inflammation, ballooning degeneration, NAFLD activity score, or histological grade, subjects with OSA/hypoxemia had significantly more severe hepatic fibrosis. Moreover, oxygen saturation nadir during polysomnography was related to hepatic fibrosis stage (r = -0.49; P = .01) and aspartate aminotransferase level (r = 0.42; P < .05). Increasing percentage of time with oxygen saturation ≤90% was related to NAFLD inflammation grade (r = 0.44; P = .03), degree of hepatic steatosis (r = -0.50; P = .01), NAFLD activity score (r = 0.42; P = .04), aspartate aminotransferase level (r = 0.56; P = .004), and alanine aminotransferase level (r = 0.44; P = .03). CONCLUSION: Moderate OSA/hypoxemia is common in pediatric patients with biopsy-proven NAFLD. OSA and the severity/duration of hypoxemia are associated with biochemical and histological measures of NAFLD severity.

Respiratory and polysomnographic values in 3- to 5-year-old normal children at higher altitude.

STUDY OBJECTIVES: To determine polysomnographic parameter differences in children living at higher altitude to children living near sea level. DESIGN AND SETTING: Prospective study of non-snoring, normal children recruited from various communities around Denver, CO. In-lab, overnight polysomnograms were performed at a tertiary care children's hospital. All children required residence for greater than one year at an elevation around 1,600 meters. PARTICIPANTS: 45 children (62% female), aged 3-5 years, 88.9% non-Hispanic white with average BMI percentile for age of 47.8% ± 30.7%. MEASUREMENTS AND RESULTS: Standard sleep indices were obtained and compared to previously published normative values in a similar population living near sea level (SLG). In the altitude group (AG), the apnea-hypopnea index was 1.8 ± 1.2 and the central apnea-hypopnea index was 1.7 ± 1.1, as compared to 0.9 ± 0.8 and 0.8 ± 0.7, respectively, (P ≤ 0.005) in SLG. Mean end-tidal CO2 level in AG was 42.3 ± 3.0 mm Hg and 40.6 ± 4.6 mm Hg in SLG (P = 0.049). The ≥ 4% desaturation index was 3.9 ± 2.0 in AG compared to 0.3 ± 0.4 in SLG (P < 0.001). Mean periodic limb movement in series index was 10.1 ± 12.3 in AG and 3.6 ± 5.4 in SLG (P = 0.001). CONCLUSION: Comparison of altitude and sea level sleep studies in healthy children reveals significant differences in central apnea, apneahypopnea, desaturation, and periodic limb movement in series indices. Clinical providers should be aware of these differences when interpreting sleep studies and incorporate altitude-adjusted normative values in therapeutic-decision making algorithms.

Heterogeneous pulmonary phenotypes associated with mutations in the thyroid transcription factor gene NKX2-1.

BACKGROUND: Mutations in the gene encoding thyroid transcription factor, NKX2-1, result in neurologic abnormalities, hypothyroidism, and neonatal respiratory distress syndrome (RDS) that together are known as the brain-thyroid-lung syndrome. To characterize the spectrum of associated pulmonary phenotypes, we identified individuals with mutations in NKX2-1 whose primary manifestation was respiratory disease. METHODS: Retrospective and prospective approaches identified infants and children with unexplained diffuse lung disease for NKX2-1 sequencing. Histopathologic results and electron micrographs were assessed, and immunohistochemical analysis for surfactant-associated proteins was performed in a subset of 10 children for whom lung tissue was available. RESULTS: We identified 16 individuals with heterozygous missense, nonsense, and frameshift mutations and five individuals with heterozygous, whole-gene deletions of NKX2-1. Neonatal RDS was the presenting pulmonary phenotype in 16 individuals (76%), interstitial lung disease in four (19%), and pulmonary fibrosis in one adult family member. Altogether, 12 individuals (57%) had the full triad of neurologic, thyroid, and respiratory manifestations, but five (24%) had only pulmonary symptoms at the time of presentation. Recurrent respiratory infections were a prominent feature in nine subjects. Lung histopathology demonstrated evidence of disrupted surfactant homeostasis in the majority of cases, and at least five cases had evidence of disrupted lung growth. CONCLUSIONS: Patients with mutations in NKX2-1 may present with pulmonary manifestations in the newborn period or during childhood when thyroid or neurologic abnormalities are not apparent. Surfactant dysfunction and, in more severe cases, disrupted lung development are likely mechanisms for the respiratory disease.