Diuretic Tolerance to Repeated-Dose Furosemide in Infants Born Very Preterm with Bronchopulmonary Dysplasia.

OBJECTIVES: To assess the presence and timing of furosemide diuretic tolerance in infants with bronchopulmonary dysplasia (BPD), and to determine if tolerance is modified by thiazide co-administration. STUDY DESIGN: We performed a retrospective cohort study among infants born very preterm with BPD exposed to repeated-dose furosemide for 72 hours, measuring net fluid balance (total intake minus total output) as a surrogate of diuresis in the 3 days before and after exposure. The primary comparison was the difference in fluid balance between the first and third 24 hours of furosemide exposure. We fit a general linear model for within-subject repeated measures of fluid balance over time, with thiazide co-administration as an interaction variable. Secondary analyses included an evaluation of weight trajectories over time. RESULTS: In 83 infants, median fluid balance ranged between + 43.6 and + 52.7 ml/kg/d in the 3 days prior to furosemide exposure. Fluid balance decreased to a median of + 29.1 ml/kg/d in the first 24 hours after furosemide, but then increased to +47.5 ml/kg/d by the third 24-hour interval, consistent with tolerance (P < .001). Thiazides did not modify the change in fluid balance during furosemide exposure for any time-period. Weight decreased significantly in the first 24 hours after furosemide and increased thereafter (P < .001). CONCLUSIONS: The net fluid balance response to furosemide decreases rapidly during repeated-dose exposures in infants with BPD, consistent with diuretic tolerance. Clinicians should consider this finding in the context of an infant's therapeutic goals. Further research efforts to identify safe and effective furosemide dosage strategies are needed.

Do Externalizing and Internalizing Symptoms Moderate Medication Response in Preschool Attention-Deficit/Hyperactivity Disorder? A DBPNet Study.

OBJECTIVES: This study aimed to determine whether parent ratings of attention-deficit/hyperactivity disorder (ADHD) symptom severity or externalizing symptoms (EXT) or internalizing symptoms (INT) moderate response to stimulants (STIM) and alpha-2 adrenergic agonists (A2As) in preschool ADHD. METHODS: Health records for children treated with medication for ADHD and with parent rating scale data available (N = 309; age <72 months) were reviewed at 7 Developmental-Behavioral Pediatric Research Network sites. Severity of ADHD was defined as the number of ADHD symptoms occurring often or very often on DSM-IV-based parent rating scales. EXT or INT from standardized rating scales were categorized as T score <60, 60 to <70, or ≥70. Ordinal logistic regression models predicting response to medication were calculated. RESULTS: The median (interquartile range) age at ADHD diagnosis was 59 (54-65) months. One hundred eighty-three participants had ADHD symptom severity, and 195 had EXT or INT data. ADHD severity was not associated with medication response. Both EXT and INT were associated with medication response but with significant medication class by EXT/INT interactions. Children with higher EXT were less likely to respond to STIM, with percentage of nonresponders for T-score categories <60, 60 to <70, and ≥70 being 3.6%, 25.7%, and 33.3% (p = 0.016) and, for A2As, being 60%, 50%, and 33.3% (p = 0.55), respectively. A similar pattern was observed for INT categories: STIM 19.4%, 22.5%, and 50.0% (p = 0.002) and A2As 42.3%, 30%, and 42.3% (p = 0.48), respectively. CONCLUSION: For preschool ADHD, low ratings of EXT or INT are associated with a high likelihood of response to STIM. By contrast, response rates to STIM and A2As are more similar for children with high levels of EXT or INT.

Adverse Effects of α-2 Adrenergic Agonists and Stimulants in Preschool-age Attention-deficit/Hyperactivity Disorder: A Developmental-Behavioral Pediatrics Research Network Study.

OBJECTIVES: To characterize and compare the type and frequency of a range of common and uncommon adverse effects (AEs) associated with α-2 adrenergic agonist (A2A) and stimulant treatment of attention-deficit/hyperactivity disorder at preschool-age as well as to evaluate the impact of age on common AEs. STUDY DESIGN: This was a retrospective electronic medical record review of children <72 months of age (n = 497) evaluated at outpatient developmental-behavioral pediatric practices at 7 US academic medical centers within the Developmental-Behavioral Pediatrics Research Network. Data on AEs were abstracted for children who had treatment initiated by a developmental-behavioral pediatrician with an A2A or stimulant medication between January 2013 and July 2017; follow-up was complete by February 2019. RESULTS: A2A and stimulants had distinctive AE profiles. A2A compared with stimulants had a greater proportion with daytime sleepiness and headaches; stimulants had significantly greater proportions for most other AE, including moodiness/irritability, difficulty with sleep, appetite suppression, stomachaches, skin picking/repetitive behaviors, withdrawn behavior, and weight loss. Younger age was associated with disruptive behavior and difficulty with sleep. CONCLUSIONS: Stimulants had a greater rate of most AEs compared with A2A. AE profiles, together with efficacy, should inform clinical decision-making. Prospective randomized clinical trials are needed to fully compare efficacy and AE profiles of A2A and stimulants.

Association of Time to Rapid Response Team Activation With Patient Outcomes Using a Range of Physiologic Deterioration Thresholds.

Clinical deterioration of hospitalized patients is common and can lead to critical illness and death. Rapid response teams (RRTs) assess and treat high-risk patients with signs of clinical deterioration to prevent further worsening and subsequent adverse outcomes. Whether activation of the RRT early in the course of clinical deterioration impacts outcomes, however, remains unclear. We sought to characterize the relationship between increasing time to RRT activation after physiologic deterioration and short-term patient outcomes. DESIGN: Retrospective multicenter cohort study. SETTING: Three academic hospitals in Pennsylvania. PATIENTS: We included the RRT activation of a hospitalization for non-ICU inpatients greater than or equal to 18 years old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary exposure was time to RRT activation after physiologic deterioration. We selected four Cardiac Arrest Risk Triage (CART) score thresholds a priori from which to measure time to RRT activation (CART score ≥ 12, ≥ 16, ≥ 20, and ≥ 24). The primary outcome was 7-day mortality-death or discharge to hospice care within 7 days of RRT activation. For each CART threshold, we modeled the association of time to RRT activation duration with 7-day mortality using multivariable fractional polynomial regression. Increased time from clinical decompensation to RRT activation was associated with higher risk of 7-day mortality. This relationship was nonlinear, with odds of mortality increasing rapidly as time to RRT activation increased from 0 to 4 hours and then plateauing. This pattern was observed across several thresholds of physiologic derangement. CONCLUSIONS: Increasing time to RRT activation was associated in a nonlinear fashion with increased 7-day mortality. This relationship appeared most marked when using a CART score greater than 20 threshold from which to measure time to RRT activation. We suggest that these empirical findings could be used to inform RRT delay definitions in further studies to determine the clinical impact of interventions focused on timely RRT activation.

Sustained Improvement in Tracheal Intubation Safety Across a 15-Center Quality-Improvement Collaborative: An Interventional Study From the National Emergency Airway Registry for Children Investigators.

OBJECTIVES: To evaluate the effect of a tracheal intubation safety bundle on adverse tracheal intubation-associated events across 15 PICUs. DESIGN: Multicenter time-series study. SETTING: PICUs in the United States. PATIENTS: All patients received tracheal intubations in ICUs. INTERVENTIONS: We implemented a tracheal intubation safety bundle as a quality-improvement intervention that includes: 1) quarterly site benchmark performance report and 2) airway safety checklists (preprocedure risk factor, approach, and role planning, preprocedure bedside "time-out," and immediate postprocedure debriefing). We define each quality-improvement phase as baseline (-24 to -12 mo before checklist implementation), benchmark performance reporting only (-12 to 0 mo before checklist implementation), implementation (checklist implementation start to time achieving > 80% bundle adherence), early bundle adherence (0-12 mo), and sustained (late) bundle adherence (12-24 mo). Bundle adherence was defined a priori as greater than 80% of checklist use for tracheal intubations for 3 consecutive months. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the adverse tracheal intubation-associated event, and secondary outcomes included severe tracheal intubation-associated events, multiple tracheal intubation attempts, and hypoxemia less than 80%.From January 2013 to December 2015, out of 19 participating PICUs, 15 ICUs (79%) achieved bundle adherence. Among the 15 ICUs, the adverse tracheal intubation-associated event rates were baseline phase: 217/1,241 (17.5%), benchmark reporting only phase: 257/1,750 (14.7%), early 0-12 month complete bundle compliance phase: 247/1,591 (15.5%), and late 12-24 month complete bundle compliance phase: 137/1,002 (13.7%). After adjusting for patient characteristics and clustering by site, the adverse tracheal intubation-associated event rate significantly decreased compared with baseline: benchmark: odds ratio, 0.83 (0.72-0.97; p = 0.016); early bundle: odds ratio, 0.80 (0.63-1.02; p = 0.074); and late bundle odds ratio, 0.63 (0.47-0.83; p = 0.001). CONCLUSIONS: Effective implementation of a quality-improvement bundle was associated with a decrease in the adverse tracheal intubation-associated event that was sustained for 24 months.

Difficult Bag-Mask Ventilation in Critically Ill Children Is Independently Associated With Adverse Events.

OBJECTIVES: Bag-mask ventilation is commonly used prior to tracheal intubation; however, the epidemiology, risk factors, and clinical implications of difficult bag-mask ventilation among critically ill children are not well studied. This study aims to describe prevalence and risk factors for pediatric difficult bag-mask ventilation as well as its association with adverse tracheal intubation-associated events and oxygen desaturation in PICU patients. DESIGN: A retrospective review of prospectively collected observational data from a multicenter tracheal intubation database (National Emergency Airway Registry for Children) from January 2013 to December 2018. SETTING: Forty-six international PICUs. PATIENTS: Children receiving bag-mask ventilation as a part of tracheal intubation in a PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome is the occurrence of either specific tracheal intubation-associated events (hemodynamic tracheal intubation-associated events, emesis with/without aspiration) and/or oxygen desaturation (< 80%). Factors associated with perceived difficult bag-mask ventilation were found using univariate analyses, and multivariable logistic regression identified an independent association between bag-mask ventilation difficulty and the primary outcome. Difficult bag-mask ventilation is reported in 9.5% (n = 1,501) of 15,810 patients undergoing tracheal intubation with bag-mask ventilation during the study period. Difficult bag-mask ventilation is more commonly reported with increasing age, those with a primary respiratory diagnosis/indication for tracheal intubation, presence of difficult airway features, more experienced provider level, and tracheal intubations without use of neuromuscular blockade (p < 0.001). Specific tracheal intubation-associated events or oxygen desaturation events occurred in 40.2% of patients with reported difficult bag-mask ventilation versus 19.8% in patients without perceived difficult bag-mask ventilation (p < 0.001). The presence of difficult bag-mask ventilation is independently associated with an increased risk of the primary outcome: odds ratio, 2.28 (95% CI, 2.03-2.57; p < 0.001). CONCLUSIONS: Difficult bag-mask ventilation is reported in approximately one in 10 PICU patients undergoing tracheal intubation. Given its association with adverse procedure-related events and oxygen desaturation, future study is warranted to improve preprocedural planning and real-time management strategies.

Ketamine Use for Tracheal Intubation in Critically Ill Children Is Associated With a Lower Occurrence of Adverse Hemodynamic Events.

OBJECTIVES: Tracheal intubation in critically ill children with shock poses a risk of hemodynamic compromise. Ketamine has been considered the drug of choice for induction in these patients, but limited data exist. We investigated whether the administration of ketamine for tracheal intubation in critically ill children with or without shock was associated with fewer adverse hemodynamic events compared with other induction agents. We also investigated if there was a dose dependence for any association between ketamine use and adverse hemodynamic events. DESIGN: We performed a retrospective analysis using prospectively collected observational data from the National Emergency Airway Registry for Children database from 2013 to 2017. SETTING: Forty international PICUs participating in the National Emergency Airway Registry for Children. PATIENTS: Critically ill children 0-17 years old who underwent tracheal intubation in a PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The association between ketamine exposure as an induction agent and the occurrence of adverse hemodynamic events during tracheal intubation including dysrhythmia, hypotension, and cardiac arrest was evaluated. We used multivariable logistic regression to account for patient, provider, and practice factors with robust SEs to account for clustering by sites. Of 10,750 tracheal intubations, 32.0% (n = 3,436) included ketamine as an induction agent. The most common diagnoses associated with ketamine use were sepsis and/or shock (49.7%). After adjusting for potential confounders and sites, ketamine use was associated with fewer hemodynamic tracheal intubation associated adverse events compared with other agents (adjusted odds ratio, 0.74; 95% CI, 0.58-0.95). The interaction term between ketamine use and indication for shock was not significant (p = 0.11), indicating ketamine effect to prevent hemodynamic adverse events is consistent in children with or without shock. CONCLUSIONS: Ketamine use for tracheal intubation is associated with fewer hemodynamic tracheal intubation-associated adverse events.

Quality Measures, All-Cause Mortality, and Health Care Use in a National Cohort of Veterans With Cirrhosis.

Decompensated cirrhosis is associated with high morbidity and mortality. However, no standardized quality measures (QMs) have yet been adopted widely. The Veterans Affairs (VA) Advanced Liver Disease Technical Advisory Group recently developed a set of six internal QMs to guide quality improvement efforts in cirrhosis in the domains of access to care, hepatocellular carcinoma surveillance, variceal surveillance, quality of inpatient care for upper gastrointestinal bleeding, and cirrhosis-related rehospitalizations. We aimed to (1) quantify adherence to cirrhosis QMs and (2) determine whether adherence was associated with all-cause mortality and health care use within a large national cohort of veterans with cirrhosis. We performed a retrospective study using data from the Veterans Outcomes and Costs Asociated with Liver Disease cohort of 121,129 patients newly diagnosed with cirrhosis from January 1, 2008, to December 31, 2016, at 128 VA facilities. The mean follow-up time was 2.7 years (interquartile range, 1.1-5.1 years). Adherence to outpatient access to specialty care was 71%, variceal surveillance was 32%, and early postdischarge care was 54%. In adjusted analyses, outpatient access to specialty care (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.78-0.82), hepatocellular carcinoma surveillance (HR, 0.92; 95% CI, 0.90-0.95), variceal surveillance (HR, 0.93; 95% CI, 0.89-0.99), and early postdischarge care (HR, 0.57; 95% CI, 0.54-0.60) were associated with lower all-cause mortality. Readmissions after 30 days (HR, 1.53; 1.46-1.60) and 90 days (HR, 1.88; 95% CI, 1.54-1.70) were associated with higher all-cause mortality. Higher adherence to QMs was also associated with lower inpatient health care use. Conclusion: Five of the six proposed VA cirrhosis QMs were measurable using existing data sources, associated with mortality and health care use, and may be used to guide future quality improvement efforts in cirrhosis.

Mortality and Kidney Transplantation Outcomes Among Hepatitis C Virus-Seropositive Maintenance Dialysis Patients: A Retrospective Cohort Study.

RATIONALE & OBJECTIVE: Hepatitis C virus (HCV) infection is common among maintenance dialysis patients. Few studies have examined both dialysis survival and transplantation outcomes for HCV-seropositive patients because registry data sets lack information for HCV serostatus. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adult long-term dialysis patients treated by a US national dialysis provider between January 1, 2004, and December 31, 2014. EXPOSURE: HCV antibody serostatus obtained as part of clinical data from a national dialysis provider. OUTCOMES: Mortality on dialysis therapy, entry onto the kidney transplant waiting list, kidney transplantation, and estimated survival benefit from kidney transplantation versus remaining on the waitlist. ANALYTICAL APPROACH: After linking clinical data with data from the Organ Procurement and Transplantation Network, Cox and cause-specific hazards regression were implemented to estimate the associations between HCV seropositivity and mortality, as well as entry onto the kidney transplant waitlist. Cox regression was also used to estimate the survival benefit from transplantation versus dialysis among HCV-seropositive individuals. RESULTS: Among 442,171 dialysis patients, 31,624 (7.2%) were HCV seropositive. HCV seropositivity was associated with a small elevation in the rate of death (adjusted HR [aHR], 1.09; 95% CI, 1.07-1.11) and a substantially lower rate of entry onto the kidney transplant waitlist (subdistribution HR [sHR], 0.67; 95% CI, 0.61-0.74). Once wait-listed, the kidney transplantation rate was not different for HCV-seropositive (sHR 1.10; 95% CI, 0.96-1.27) versus HCV-seronegative patients. HCV-seropositive patients lived longer with transplantation (aHR at 3 years, 0.42; 95% CI, 0.27-0.63). Receiving an HCV-seropositive donor kidney provided a survival advantage at the 2-year posttransplantation time point compared to remaining on dialysis therapy waiting for an HCV-negative kidney. LIMITATIONS: No data for HCV viral load or liver biopsy. CONCLUSIONS: HCV-seropositive patients experience reduced access to the kidney transplantation waitlist despite deriving a substantial survival benefit from transplantation. HCV-seropositive patients should consider foregoing HCV treatment while accepting kidneys from HCV-infected donors to facilitate transplantation and prolong survival.

Common Use of Stimulants and Alpha-2 Agonists to Treat Preschool Attention-Deficit Hyperactivity Disorder: A DBPNet Study.

OBJECTIVE: To describe the use of stimulants and alpha-2 agonists (A2As) for the treatment of preschool-aged children with attention-deficit hyperactivity disorder (ADHD) at 2 Developmental-Behavioral Pediatrics Research Network sites. METHODS: Demographic information, diagnoses, and medications prescribed by developmental-behavioral pediatricians (DBPs) were extracted from the electronic health record for all outpatient visits from January 1, 2010, to December 31, 2011. The subset of visits for children aged 2 to 5 years who had a diagnosis of ADHD was included in this analysis. Multivariable models were constructed to identify factors associated with prescribing stimulants and A2As. RESULTS: Over the 2-year period, 984 children with a diagnosis of ADHD were seen at 1779 visits. Of the 984 children, 342 (34.8%) were prescribed a stimulant, and 243 (24.7%) were prescribed an A2A. Both medications were prescribed at the same visit at least once during the 2-year period for 97 children (9.9%). Alpha-2 agonists were prescribed more often at site 2 than site 1 (OR [odds ratio] = 1.62, p = 0.015). Stimulants were more likely to be prescribed for older preschool-aged children (OR = 1.66, p < 0.001), and A2As were more likely to be prescribed for younger children (OR = 0.82, p = 0.02). Both stimulants and A2As were more likely to be prescribed to children with ADHD and comorbid conditions. CONCLUSION: Alpha-2 agonists are commonly used by some DBPs for preschool ADHD. Variation in the use of A2As across sites may indicate a lack of consensus on when to use these medications and suggests a need for comparative effectiveness research to better define the relative benefits and side effects of A2As and stimulants for the treatment of preschool ADHD.

Race, Risk, and Willingness of End-Stage Renal Disease Patients Without Hepatitis C Virus to Accept an HCV-Infected Kidney Transplant.

BACKGROUND: Despite effective antiviral treatment, hundreds of kidneys from deceased donors with hepatitis C virus (HCV) are discarded annually. Little is known about the determinants of willingness to accept HCV-infected kidneys among HCV-negative patients. METHODS: At 2 centers, 189 patients undergoing initial or reevaluation for transplant made 12 hypothetical decisions about accepting HCV-infected kidneys in which we systematically varied expected HCV cure rate, allograft quality, and wait time for an uninfected kidney. RESULTS: Only 29% of the participants would accept an HCV-infected kidney under all scenarios, whereas 53% accepted some offers and rejected others, and 18% rejected all HCV-infected kidneys. Higher cure rate (odds ratio [OR], 3.49; 95% confidence interval [CI], 2.33-5.24 for 95% vs 75% probability of HCV cure), younger donor (OR, 2.34; 95% CI, 1.91-2.88 for a 20-year-old vs a 60-year-old hypertensive donor), and longer wait for an uninfected kidney (OR, 1.43; 95% CI, 1.22-1.67 for 5 years vs 2 years) were associated with greater willingness to accept an HCV-infected kidney. Black race modified the effect of HCV cure rate, such that willingness to accept a kidney increased less for blacks versus whites as the cure rate improved. Patients older than 60 years and prior kidney recipients showed greater willingness to accept an HCV-infected organ. CONCLUSIONS: Most patients will consider an HCV-infected kidney in some situations. Future trials using HCV-infected kidneys may enhance enrollment by targeting older patients and prior transplant recipients, but centers should anticipate that black patients' acceptance of HCV-infected kidneys will be reduced compared with white patients.

A Social Media Peer Group for Mothers To Prevent Obesity from Infancy: The Grow2Gether Randomized Trial.

BACKGROUND: Few studies have addressed obesity prevention among low-income families whose infants are at increased obesity risk. We tested a Facebook peer-group intervention for low-income mothers to foster behaviors promoting healthy infant growth. METHODS: In this randomized controlled trial, 87 pregnant women (Medicaid insured, BMI ≥25 kg/m2) were randomized to the Grow2Gether intervention or text message appointment reminders. Grow2Gether participants joined a private Facebook group of 9-13 women from 2 months before delivery until infant age 9 months. A psychologist facilitated groups featuring a curriculum of weekly videos addressing feeding, sleep, parenting, and maternal well-being. Feasibility was assessed using the frequency and content of participation, and acceptability using surveys. Maternal beliefs and behaviors and infant growth were assessed at birth, 2, 4, 6, and 9 months. Differences in infant growth between study arms were explored. We conducted intention-to-treat analyses using quasi-least-squares regression. RESULTS: Eighty-eight percent (75/85) of intervention participants (42% (36/85) food insecure, 88% (75/85) black) reported the group was helpful. Participants posted 30 times/group/week on average. At 9 months, the intervention group had significant improvement in feeding behaviors (Infant Feeding Style Questionnaire) compared to the control group (p = 0.01, effect size = 0.45). Intervention group mothers were significantly less likely to pressure infants to finish food and, at age 6 months, give cereal in the bottle. Differences were not observed for other outcomes, including maternal feeding beliefs or infant weight-for-length. CONCLUSIONS: A social media peer-group intervention was engaging and significantly impacted certain feeding behaviors in families with infants at high risk of obesity.

Management of Attention-Deficit/Hyperactivity Disorder by Developmental-Behavioral Pediatricians: A DBPNet Study.

OBJECTIVE: To describe practice patterns for developmental-behavioral pediatricians (DBPs) practicing within Developmental-Behavioral Pediatrics Research Network (DBPNet) academic medical centers providing follow-up for children with attention-deficit/hyperactivity disorder (ADHD) and determine how well they adhere to American Academy of Pediatrics ADHD Clinical Practice Guidelines. METHODS: Seventy-eight DBPs at 12 academic medical centers participating in the DBPNet were asked to complete follow-up encounter surveys for patients with ADHD or autism spectrum disorder seen from 12/2011 through 6/2012. Data regarding patient characteristics, comorbid conditions, and medication management were obtained at the time of each visit. RESULTS: Fifty-seven DBPs completed 301 ADHD follow-up encounter surveys; 75.3% of patients were male with mean age 9.57 years (SD = 3.3). Race/ethnicity was primarily white/non-Hispanic with similar numbers on private insurance (41.5%) versus Medicaid (45.5%). DBPs identified comorbid learning disorders in 27.6% of children ≥6 years. Only 58.3% of children <6 years received counseling/behavioral therapy or had it recommended during the visit. DBPs primarily (90.6%) prescribed medications FDA-approved for ADHD treatment and growth was monitored for >98% of visits during which stimulants were prescribed. Parent- and teacher-completed rating scales were reviewed/completed during 43.9% and 37.8% of visits, respectively. There were no child or physician factors consistently associated with variation in practice patterns. CONCLUSION: Developmental-behavioral pediatricians practicing within DBPNet medical centers adhere to the recommended medication prescribing practices for ADHD, including use of FDA-approved medications and monitoring growth. However, DBPs within DBPNet do not consistently review ADHD rating scales or recommend behavioral counseling for children <6 years of age as recommended.

Evolution of Obstructive Sleep Apnea in Infants with Cleft Palate and Micrognathia.

STUDY OBJECTIVES: Children with craniofacial anomalies are a heterogeneous group at high risk for obstructive sleep apnea (OSA). However, the prevalence and structural predictors of OSA in this population are unknown. We hypothesized that infants with micrognathia would have more significant OSA than those with isolated cleft palate ± cleft lip (ICP), and those with ICP would have more significant OSA than controls. We postulated that OSA severity would correlate with reduced mandibular size, neurodevelopmental scores, and growth. METHODS: Prospective cohort study. 15 infants with ICP, 19 with micrognathia, and 9 controls were recruited for polysomnograms, neurodevelopmental testing, cephalometrics (ICP and micrognathia groups) at baseline and a follow-up at 6 mo. RESULTS: Baseline apnea-hypopnea index (AHI) [median (range)] of the micrognathia group [20.1 events/h (0.8, 54.7)] was greater than ICP [3.2 (0.3, 30.7)] or controls [3.1 (0.5, 23.3)] (p = 0.001). Polysomnographic findings were similar between ICP and controls. Controls had a greater AHI than previously reported in the literature. Cephalometric measures of both midface hypoplasia and micrognathia correlated with OSA severity. Neurodevelopment was similar among groups. OSA improved with growth in participants with ICP and postoperatively in infants with micrognathia. CONCLUSIONS: Micrognathia, but not ICP, was associated with more significant OSA compared to controls. Both midface and mandibular hypoplasia contribute to OSA in these populations. OSA improved after surgical correction in most infants with micrognathia, and improved without intervention before palate repair in infants with ICP.

Early Electroencephalographic Background Features Predict Outcomes in Children Resuscitated From Cardiac Arrest.

OBJECTIVES: To determine 1) whether early electroencephalographic background features were associated with survival and neurologic outcomes among children resuscitated from cardiac arrest and not treated with therapeutic hypothermia and 2) if addition of electroencephalographic background to commonly used clinical criteria is more predictive of outcome than clinical criteria alone. DESIGN: Retrospective study. SETTING: PICU and Cardiac ICUs of a tertiary children's hospital. PATIENTS: Patients resuscitated from in-hospital or out-of-hospital cardiac arrest who underwent clinically indicated electroencephalographic monitoring and were not treated with therapeutic hypothermia. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One-hundred twenty-eight patients underwent electroencephalographic monitoring within 1 day of return of spontaneous circulation. Background category was normal in four subjects (3%), slow-disorganized in 58 subjects (45%), discontinuous-burst suppression in 24 subjects (19%) and attenuated-flat in 42 subjects (33%). Forty-six subjects (36%) had a reactive electroencephalography. Twenty subjects (15%) had a seizure during electroencephalographic monitoring. Absence of reactivity (p < 0.001) and seizures (p = 0.04) were associated with worse electroencephalographic background category. After controlling for covariates, for each incrementally worse background score, the odds of death was 3.63 (95% CI, 2.18-6.0; p < 0.001) and the odds of unfavorable neurologic outcome was 4.38 (95% CI, 2.51-7.17; p = 0.001). CONCLUSIONS: Worse electroencephalographic background early after resuscitation from both in-hospital and out-of-hospital cardiac arrest is associated with increased odds of death and unfavorable neurologic outcomes at hospital discharge. These electroencephalographic background patterns may be used in addition to clinical criteria to support prognostic decision making.

Perinatal Risk Factors Associated with the Obstructive Sleep Apnea Syndrome in School-Aged Children Born Preterm.

STUDY OBJECTIVES: The obstructive sleep apnea syndrome (OSAS) is more prevalent in ex-preterm children compared to the general pediatric population. However, it is unknown whether OSAS in ex-preterm children is associated with specific perinatal risk factors. This multicenter cohort study aimed to determine perinatal factors associated with OSAS at school age. METHODS: 197 ex-preterm (500-1,250 g) children aged 5-12 y who participated as neonates in a double-blind, randomized clinical trial of caffeine versus placebo (Caffeine for Apnea of Prematurity) underwent comprehensive ambulatory polysomnography. A negative binomial regression model was used to identify perinatal risk factors associated with OSAS. RESULTS: 19 children had OSAS (9.6%). Chorioamnionitis and multiple gestation were positively associated with OSAS with P values of 0.014 and 0.03, respectively. Maternal white race (P = 0.047) and maternal age (P = 0.002) were negatively associated with OSAS. Other risk factors, such as birth weight, Apgar score at 5 min, antenatal corticosteroids, delivery route, and sex were not significant. CONCLUSIONS: OSAS is very frequent, and is associated with chorioamnionitis and multiple gestation in ex-preterm children. Those born to older white mothers appear to be protected. We speculate that the former may be due to systemic inflammation and the latter to a higher socio-economic status. COMMENTARY: A commentary on this article appears in this issue on page 721.

Change over time in brain serotonin transporter binding in major depression: effects of therapy measured with [(123) I]-ADAM SPECT.

Several studies have reported low brain serotonin transporter (SERT) binding in individuals with major depression. We hypothesized that the SERT standardized uptake ratio (SUR) values using [(123) I]-ADAM single photon emission computed tomography would increase in depressed subjects who responded to cognitive behavior therapy (CBT) compared to CBT nonresponders. [(123) I]-ADAM scans were acquired before and after 12 weeks of CBT from 20 depressed subjects and on two occasions 12 weeks apart from 10 nondepressed, healthy volunteers. The primary outcome measure was change over time in SUR values in the midbrain, medial temporal lobe, and basal ganglia regions. Depressed subjects demonstrated low pretreatment mean SUR values that significantly increased over time in the midbrain (P = .011), right medial temporal lobe (P = .008), and left medial temporal lobe (P = .000) regions. Treatment responders showed a significant increase over time in SUR values in left medial temporal lobe (P = .029) and right medial temporal lobe (P = .007) regions. Partial and nonresponder subjects also showed a significant increase over time in SUR values in the left medial temporal region (P = .040) (vs. healthy volunteers), but to a lesser degree. The findings suggest that low pretreatment SERT binding may increase over time in some depressed individuals who experience symptom improvement.