Surviving Sepsis in a Referral Neonatal Intensive Care Unit: Association between Time to Antibiotic Administration and In-Hospital Outcomes.

OBJECTIVE: To determine if time to antibiotic administration is associated with mortality and in-hospital outcomes in a neonatal intensive care unit (NICU) population. STUDY DESIGN: We conducted a prospective evaluation of infants with suspected sepsis between September 2014 and February 2018; sepsis was defined as clinical concern prompting blood culture collection and antibiotic administration. Time to antibiotic administration was calculated from time of sepsis identification, defined as the order time of either blood culture or an antibiotic, to time of first antibiotic administration. We used linear models with generalized estimating equations to determine the association between time to antibiotic administration and mortality, ventilator-free and inotrope-free days, and NICU length of stay in patients with culture-proven sepsis. RESULTS: Among 1946 sepsis evaluations, we identified 128 episodes of culture-proven sepsis in 113 infants. Among them, prolonged time to antibiotic administration was associated with significantly increased risk of mortality at 14 days (OR, 1.47; 95% CI, 1.15-1.87) and 30 days (OR, 1.47; 95% CI, 1.11-1.94) as well as fewer inotrope-free days (incidence rate ratio, 0.91; 95% CI, 0.84-0.98). No significant associations with ventilator-free days or NICU length of stay were demonstrated. CONCLUSIONS: Among infants with sepsis, delayed time to antibiotic administration was an independent risk factor for death and prolonged cardiovascular dysfunction. Further study is needed to define optimal timing of antimicrobial administration in high-risk NICU populations.

Persistent Basal Cell Hyperplasia Is Associated With Clinical and Endoscopic Findings in Patients With Histologically Inactive Eosinophilic Esophagitis.

BACKGROUND & AIMS: Although eosinophil count is the standard used to monitor disease activity in patients with eosinophilic esophagitis (EoE), there are often disparities between patient-reported symptoms and eosinophil counts. We examined the prevalence of epithelial alterations, namely basal cell hyperplasia (BCH) and spongiosis, among patients with inactive EoE (eosinophil counts below 15 following therapy) and aimed to determine whether maintenance of these changes in epithelial morphology are associated with persistent clinical findings. METHODS: Esophageal biopsies of 243 patients (mean age, 16.9 years) undergoing routine endoscopy at the University of Pennsylvania were evaluated for epithelial BCH and spongiosis. Univariable analysis was used to calculate the association between epithelial changes and symptoms as well as endoscopic findings and peak eosinophil count. We validated our findings using data from a cohort of patients at the University of North Carolina. RESULTS: The discovery and validation cohorts each included patients with inactive EoE, based on histologic factors, but ongoing BCH and spongiosis. Ongoing BCH, but not spongiosis, in patients with inactive EoE was associated with symptoms (odds ratio, 2.14; 95% CI, 1.03-4.42; P = .041) and endoscopic findings (odds ratio, 7.10; 95% CI, 3.12-16.18; P < .001). CONCLUSIONS: In patients with EoE, the presence of BCH might indicate ongoing disease activity, independent of eosinophil count. This might account for the persistent symptoms in patients who are considered to be in remission based on histologic factors.

Efficacy of Epicutaneous Immunotherapy in Children With Milk-Induced Eosinophilic Esophagitis.

BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is caused by an immune response to specific food allergens. There are no approved therapies beyond avoidance of the allergen(s) or treatment of inflammation. Epicutaneous immunotherapy (EPIT) reduces features of eosinophilic gastrointestinal disease in mice and pigs. We performed randomized, placebo-controlled study to determine the safety and efficacy of EPIT with Viaskin milk in children with milk-induced EoE. METHODS: In a double-blind study, 20 children (4-17 years old) with milk-induced EoE were randomly assigned to groups given EPIT with Viaskin milk (n = 15) or placebo (n = 5) for 9 months during a milk-free period, followed by milk-containing diet for 2 months with EPIT. Then, subjects underwent upper endoscopy analysis, biopsies were collected, and maximum esophageal eosinophil counts were determined and was the primary endpoint. After upper endoscopy, patients were given open-label EPIT for 11 months (open-label phase). The subjects were allowed to consume milk if they had maximum values of fewer than 10 eosinophils/high-power field (eos/hpf); otherwise, they remained on a milk-free diet until the last 2 months of the open-label phase. RESULTS: In the intent to treat population, there was no significant difference between the Viaskin milk group in mean eos/hpf (50.1 ± 43.97 eos/hpf) vs the placebo group (48.20 ± 56.98 eos/hpf). However, in the per-protocol population (7 patients given Viaskin milk and 2 patients given placebo), patients given Viaskin milk patients had a significantly lower mean eos/hpf count (25.57 ± 31.19) than patients given placebo (95.00 ± 63.64) (p = .038). At the end of the open-label phase, 9 of 19 evaluable subjects had mean values of fewer than 15 eos/hpf (47% response). The number of adverse events did not differ significantly between the Viaskin milk and placebo groups; there was 1 serious adverse event in the placebo group. CONCLUSIONS: In a pilot study of pediatric patients with EoE given EPIT with Viaskin milk or placebo for 11 months, we found no significant difference between groups for the maximum eosinophil count at the end of the study. However, findings from a per-protocol analysis indicate that Viaskin milk can reduce eos/hpf. At study completion, 47% of patients who continued open-label Viaskin milk for an additional 11 months had mean values of fewer than 15 eos/hpf. ClinicalTrials.gov no: NCT02579876.

Staged Versus Complete Repair in the Symptomatic Neonate With Tetralogy of Fallot.

BACKGROUND: The optimal management of tetralogy of Fallot (TOF) in symptomatic neonates remains unknown. We compared outcomes for those undergoing palliation vs complete repair in the neonatal period. METHODS: In a retrospective cohort study of symptomatic neonates with TOF who had a neonatal complete repair (group 1, n = 112) or staged repair (group 2, n = 26) from 2000 to 2013, we compared outcomes at 4 time points: neonatal complete repair vs palliation (group 1 vs 2A), neonatal vs later complete repair (group 1 vs 2B), the single vs combined admissions to achieve a complete repair (group 1 vs group 2A + 2B), and cumulative events 2 years after complete repair for both groups. RESULTS: Demographics, anatomy, comorbidities, surgical approach, and mortality were similar between groups 1 and 2. Group 1 had a longer duration of cardiopulmonary bypass and deep hypothermic circulatory arrest and more postprocedure cardiac events compared with group 2A; a longer duration of intubation, intensive care, and postprocedure hospital stay compared with groups 2A and 2B; and a longer total hospital stay compared with group 2B. With combined admissions for group 2, there was no difference in the total duration of intensive care, total hospital stay, or reinterventions compared with group 1. CONCLUSIONS: Both management options result in similar survival; however, early morbidity was greater with neonatal complete repair. The impact of increased neonatal exposures, such as cardiopulmonary bypass, deep hypothermic circulatory arrest, and intensive care, on neurocognitive development requires further study but should be considered when choosing an optimal strategy.

Neonatal sepsis registry: Time to antibiotic dataset.

This article describes the process of extracting electronic health record (EHR) data into a format that supports analyses related to the timeliness of antibiotic administration. The de-identified data that accompanies this article were collected from a cohort of infants who were evaluated for possible sepsis in the Neonatal Intensive Care Unit (NICU) at the Children's Hospital of Philadelphia (CHOP). The interpretation of findings from these data are reported in a separate manuscript [1]. For purposes of illustration for interested readers, scripts written in the R programming language related to the creation and use of the dataset have also been provided. Interested researchers are encouraged to contact the research team to discuss opportunities for collaboration.

Development of the Serum α-Fetoprotein Reference Range in Patients with Beckwith-Wiedemann Spectrum.

OBJECTIVE: To establish reference ranges for serum α-fetoprotein (AFP) at various ages in patients with Beckwith-Wiedemann spectrum (BWSp), to better predict the risk for hepatoblastoma in this population. STUDY DESIGN: A retrospective analysis of AFP measurements collected from patients with BWSp was performed. Factors including sex, prematurity, molecular diagnosis of patients, and performing laboratory were evaluated for significant differences. In total, 1372 AFP values were collected from 147 patients and the predictive AFP values at various ages were calculated to establish reference ranges. Mixed-effects polynomial regression models were used to study various potential factors affecting log(AFP) values. RESULTS: Overall, predicted AFP values declined to normal range for age (<10 ng/mL) by 14 months old. Patient sex and performing laboratory were found not to influence values. A significant difference was demonstrated between premature and nonpremature patients, and separate reference values were established. Significant differences in the predicted AFP value were not broadly apparent between molecular subtypes; however, interpretation was limited due to the small sample size of some of these subtypes. CONCLUSIONS: Predictive AFP values were created for premature and nonpremature patients with BWSp to aid with interpretation and monitoring of the risk for hepatoblastoma. Further analysis is needed to determine whether AFP values differ within the less common molecular subtypes of patients with BWSsp.

Ultrasonographic Guidance to Improve First-Attempt Success in Children With Predicted Difficult Intravenous Access in the Emergency Department: A Randomized Controlled Trial.

STUDY OBJECTIVE: We determine whether ultrasonographically guided intravenous line placement improves the rate of first-attempt success by 20% for children with predicted difficult intravenous access. Secondary objectives included determining whether ultrasonographically guided intravenous line placement reduces the attempt number, improves time to access or parental satisfaction, or affects intravenous line survival and complications. METHODS: This was a prospective, randomized controlled trial conducted in an urban tertiary care pediatric emergency department that enrolled a convenience sample of children requiring an intravenous line and who were predicted to have difficult intravenous access according to a previously validated score. Participants were randomized to traditional or ultrasonographically guided intravenous line placement on first attempt and stratified by aged 0 to 3 versus older than 3 years. RESULTS: One hundred sixty-seven patients were enrolled and randomized to traditional intravenous line or to a care bundle with a multidisciplinary team trained to place ultrasonographically guided intravenous lines. First-attempt success was increased in the ultrasonographically guided intravenous line placement arm (n=83) compared with the traditional intravenous line arm (n=84) (85.4% versus 45.8%; relative risk 1.9; 95% confidence interval [CI] 1.5 to 2.4). There were fewer attempts in the ultrasonographically guided intravenous line placement arm than in the traditional intravenous line arm (median 1 versus 2; median difference 1; 95% CI 0.8 to 1.2) and a shorter time from randomization to intravenous line flush (median 14 minutes [interquartile range 11 to 20] versus 28 minutes [interquartile range 16 to 42]). A Kaplan-Meier survival analysis demonstrated that ultrasonographically guided intravenous lines survived longer than traditional ones (median 7.3 days [95% CI 3.7 to 9.5] versus 2.3 days [95% CI 1.8 to 3.3]). There was no difference in complications between the groups. Parents were more satisfied with ultrasonographically guided intravenous line placement. CONCLUSION: Ultrasonographically guided intravenous line placement in children with predicted difficult intravenous access improved first-attempt success and intravenous line longevity when conducted by a team of trained providers.

Enrollee Characteristics in an Intensive Tobacco Dependence Treatment Program: The Relationship of Race and Sex to Demographic Factors and Tobacco Use Patterns.

Intensive tobacco treatment programs offer many advantages relative to other treatment options, particularly for more complex patients, e.g., highly nicotine dependent, or those with medical and psychiatric symptoms and disorders. Efforts to better understand those who choose to enroll in these programs, particularly regarding the characteristics they possess known to mediate outcomes, are important considerations in tailoring available services. In this study, we examined how participants differed on key descriptive and tobacco use variables within race (i.e., African-American, Caucasian) and sex subgroups. Baseline characteristics from a large group of consecutive program enrollees were examined across targeted subgroups. Strong racial effects and some sex effects were noted for marital status, education, employment and health insurance status, alcohol consumption, presence of medical and psychiatric disorders, as well as participant tobacco use patterns and tobacco use rates of family, friends and coworkers. The differences in participant tobacco use measures across race and sex factors remained significant after adjusting for the confounding effects of all other covariates. These findings have implications for characterizing key patient subgroups who present at tobacco treatment clinics. Such information may contribute to options for tailoring treatment regimens.

Continuous Glucose Monitoring Systems: Are They Useful for Evaluating Glycemic Control in Children with Hyperinsulinism?

BACKGROUND: Effective treatment and close monitoring in children with congenital hyperinsulinism (HI) are important to prevent hypoglycemic-associated brain damage. The current monitoring approach involves measuring plasma glucose intermittently, but this does not provide a comprehensive assessment of glycemic control and may fail to detect episodes of hypoglycemia. OBJECTIVE: To determine whether Dexcom G5®, a continuous glucose monitoring system (CGMS), is an accurate and effective method for monitoring glycemic control in children with HI. METHODS: Cross-sectional, observational study in 15 children with HI. Participants wore a blinded Dexcom G5® device for 2 weeks. At the end of 2 weeks, data from the Dexcom G5® and home glucose meter were downloaded and analyzed. RESULTS: Fourteen children (15-67 months) completed the study. Using Bland-Altman analysis, the mean (SD) difference between 1,155 paired CGM and glucose meter readings was -8.09 (53.76). The sensitivity and specificity of CGM to detect hypoglycemia (<70 mg/dL) were 86 and 81.4%, respectively. The positive predictive values for hypoglycemia and severe hypoglycemia (<54 mg/dL) detected by CGM were low (50.3 and 14.8%, respectively), while the negative predictive values were high (96.4% for glucose <70 mg/dL and 99.1% for glucose <54 mg/dL). CONCLUSION: Our study showed that CGM is not a reliable method to monitor for hypoglycemia, given the high number of false positive hypoglycemia readings. However, CGM can be useful in preventing unnecessary checks by glucose meter during times of normoglycemia. Therefore, the benefits of using CGM in patients with HI would be in guiding the need to check plasma glucose by glucose meter rather than point accuracy.

Right Ventricular Contractile Reserve Is Impaired in Children and Adolescents With Repaired Tetralogy of Fallot: An Exercise Strain Imaging Study.

BACKGROUND: Pulmonary insufficiency (PI) and right ventricular (RV) dysfunction are long-term complications in patients with repaired tetralogy of Fallot (rTOF). The aim of this study was to investigate RV contractile reserve and changes in PI that occur during exercise in patients with rTOF and the associations of these changes with exercise performance using stress echocardiography. METHODS: Subjects with rTOF (n = 32) and healthy control subjects (n = 10) were prospectively enrolled and underwent rest and peak exercise echocardiography during standard cardiopulmonary exercise test protocol on a cycle ergometer or treadmill. RV contractile reserve was defined as the change in RV global longitudinal strain from rest to peak exercise. PI was assessed with the diastolic-to-systolic time-velocity integral ratio and diastolic/systolic velocity ratio from pulmonary artery Doppler interrogation. Exercise measures included heart rate reserve, percentage predicted maximum oxygen consumption, percentage predicted maximum work, and oxygen pulse. RESULTS: RV contractile reserve was impaired in patients with rTOF compared with control subjects, with a significant drop in the absolute value of RV global longitudinal strain from 17% (range, 8%-27%) at rest to 13% (range, 5%-28%) at peak exercise. Similarly, PI decreased at peak exercise, with decreases in diastolic-to-systolic time-velocity integral and diastolic/systolic velocity ratios. Reduction in PI was directly associated with percentage predicted maximum oxygen consumption, percentage predicted maximum work, and greater oxygen pulse. Heart rate reserve was directly associated with percentage predicted maximum oxygen consumption and percentage predicted maximum work. RV contractile reserve was not associated with any exercise parameters. CONCLUSIONS: Patients with rTOF have an abnormal myocardial response to exercise with impaired RV contractile reserve compared with control subjects. Heart rate reserve and reduction in PI at peak exercise are associated with better exercise performance and appear to be significant contributors to exercise performance in rTOF. Measures to improve chronotropic health in rTOF should be explored.

The Natural History of Inherited Retinal Dystrophy Due to Biallelic Mutations in the RPE65 Gene.

PURPOSE: To delineate the natural history of visual parameters over time in individuals with biallelic RPE65 mutation-associated inherited retinal dystrophy (IRD); describe the range of causative mutations; determine potential genotype/phenotype relationships; and describe the variety of clinical diagnoses. DESIGN: Global, multicenter, retrospective chart review. METHODS: Study Population: Seventy individuals with biallelic RPE65 mutation-associated IRD. PROCEDURES: Data were extracted from patient charts. MEASUREMENTS: Visual acuity (VA), Goldmann visual field (GVF), optical coherence tomography, color vision testing, light sensitivity testing, and electroretinograms (retinal imaging and fundus photography were collected and analyzed when available). RESULTS: VA decreased with age in a nonlinear, positive-acceleration relationship (P < .001). GVF decreased with age (P < .0001 for both V4e and III4e), with faster GVF decrease for III4e stimulus vs V4e (P = .0114, left eye; P = .0076, right eye). On average, a 1-year increase in age decreased III4e GVF by ∼25 sum total degrees in each eye while V4e GVF decreased by ∼37 sum total degrees in each eye, although individual variability was observed. A total of 78 clinical diagnoses and 56 unique RPE65 mutations were recorded, without discernible RPE65 mutation genotype/phenotype relationships. CONCLUSIONS: The number of clinical diagnoses and lack of a consistent RPE65 mutation-to-phenotype correlation underscore the need for genetic testing. Significant relationships between age and worsening VA and GVF highlight the progressive loss of functional retina over time. These data may have implications for optimal timing of treatment for IRD attributable to biallelic RPE65 mutations.

Determinants of Exercise Performance in Children and Adolescents with Repaired Tetralogy of Fallot Using Stress Echocardiography.

Exercise performance is variable and often impaired in patients with repaired tetralogy of Fallot (rTOF). We sought to identify factors associated with exercise performance by comparing high to low performers on cardiopulmonary exercise testing (CPET) in patients with rTOF. We conducted a cross-sectional study of subjects presenting for CPET who underwent echocardiograms at rest and peak exercise. Patients with pacemakers and arrhythmias were excluded. Right ventricular (RV) global longitudinal strain was used as a measure of systolic function. Pulmonary insufficiency (PI) was assessed with the diastolic systolic ratio and the diastolic systolic time-velocity integral ratio by Doppler interrogation of the pulmonary artery. CPET measures included percent-predicted maximum [Formula: see text][Formula: see text], percent-predicted maximum work and oxygen pulse. High versus low performers were identified as those achieving [Formula: see text] of at least 80% or falling below, respectively. Differences in echocardiographic parameters from rest to peak exercise were examined using mixed-effects regression models. Compared to the low performers (n = 17), high performers (n = 12) were younger (12.8 ± 3.3 years vs. 18.3 ± 4.8 years), had normal chronotropic response (peak heart rate > 185 bpm) with greater heart rate reserve and superior physical working capacity. High performers also had a greater reduction in PI at peak exercise, despite greater PI severity at rest. Oxygen pulse was comparable between groups. For both groups, there was no association of PI severity and RV systolic function at rest with exercise parameters. There was no group difference in the magnitude of change in RV strain and diastolic parameters from rest to peak exercise. Chronotropic response to exercise appears to be an important parameter with which to assess exercise performance in rTOF. Chronotropic health should be taken into consideration in this population, particularly given that RV function and PI severity at rest were not associated with exercise performance.

A Vibrating Cold Device to Reduce Pain in the Pediatric Emergency Department: A Randomized Clinical Trial.

OBJECTIVE: Pain of intravenous (IV) catheter insertion can be mitigated with appropriate analgesia, thereby avoiding unnecessary distress. Our objective was to compare the self-reported pain of IV catheter insertion in children when using a vibrating cold device (VCD) versus standard of care 4% topical lidocaine cream (TL). METHODS: This was a 2-arm randomized controlled noninferiority trial with a convenience sample of 4- to 18-year-olds requiring nonemergent IV catheter insertion. Self-reported pain was measured with the Faces Pain Scale-Revised, anxiety with the Child's Rating of Anxiety scale, and observed pain with the Face, Legs, Activity, Crying, Consolability scale. Caregivers and nurses completed satisfaction surveys. RESULTS: Two hundred twenty-four children were included in the analysis: 114 (90%) of 127 in the VCD group and 110 (89%) of 124 in the TL group. Faces Pain Scale-Revised scores for both groups were equivalent (median, 2.0 cm; interquartile range, 0-5 cm; linear regression difference, 0 [95% confidence interval, -0.82 to 0.82]), as were median Face, Legs, Activity, Crying, Consolability scale scores (difference, 0.33 [95% confidence interval, -0.01 to 0.68]). The time of completion for the IV procedure was significantly shorter for the VCD group compared with the TL group (median, 3.0 vs 40.5 minutes; P < 0.0001). There were no significant differences between groups for self-reported state or trait anxiety, success of IV catheter insertion on first attempt, or satisfaction of caregivers or staff. CONCLUSIONS: A VCD and TL showed equal effectiveness in reducing pain and distress for children undergoing IV catheter insertion. The VCD has the added benefit of quick onset time and an acceptable alternative for caregivers and nurses.

Use of Intravenous Acetaminophen in Children for Analgesia After Spinal Fusion Surgery: A Randomized Clinical Trial.

OBJECTIVES: Opioid pharmacotherapy is the cornerstone of postoperative analgesia. Despite its effectiveness, it has a variety of potential adverse effects. Therefore, a multimodal approach with non-opioid analgesics would be optimal. The aim of this study was to determine if intravenous (IV) acetaminophen would reduce opioid requirements and improve clinical outcomes in children after surgery. METHODS: A single-center, randomized, double-blind study was conducted in 57 children (10-18 years old) undergoing posterior spine fusion surgery between July 2011 to May 2014. All subjects received either acetaminophen or placebo at the end of surgery, followed by repeated doses every 6 hours for a total of 8 doses. RESULTS: In the first 24 postoperative hours, the average opioid consumption was lower for the active group compared with the placebo group (p = 0.02). The total unadjusted time to patient controlled analgesia (PCA) discontinuation was also longer in the placebo group than the active group (90 hours vs. 73 hours, p = 0.02); however, this was not statistically significant after normalizing for body weight. Additionally, time to first solid intake was longer without the use of acetaminophen (69 hours vs. 49 hours, p = 0.01). CONCLUSIONS: Postoperative use of IV acetaminophen was associated with earlier time to diet advancement and discontinuation of IV analgesics and may result in lower opioid consumption.

Predictors of Length of Hospital Stay After Complete Repair for Tetralogy of Fallot: A Prospective Cohort Study.

BACKGROUND: We sought to identify patient and surgical factors associated with time to hospital discharge in patients undergoing complete repair for tetralogy of Fallot. METHODS AND RESULTS: We performed a prospective cohort study of patients with tetralogy of Fallot admitted for complete repair between May 1, 2012 and June 2, 2017 at Children's Hospital of Philadelphia with detailed demographic, clinical, and operative characteristics. The primary outcome was time to hospital discharge. Cox proportional hazards models were used to identify patient and operative predictors of time to hospital discharge. We enrolled 151 subjects, 62.8% male, 65.6% non-Hispanic white, and 9.9% non-Hispanic black. The median time to hospital discharge was 7 days (interquartile range 4, 12). Five patients died in the hospital, all of whom underwent tetralogy of Fallot repair beyond the neonatal period. Greater birth weight was associated with higher rate of hospital discharge (hazard ratio [HR]=1.35, 95% confidence interval (CI) =1.11, 1.64), while absent pulmonary valve versus pulmonary stenosis (HR=0.27, 95% CI=0.08, 0.91), pulmonary valve atresia versus pulmonary stenosis (HR=0.57, 95% CI=0.33, 0.97), presence of aortopulmonary collaterals (HR=0.44, 95% CI=0.24, 0.84), complete repair performed in the neonatal period (<30 days of life) (HR=0.45, 95% CI=0.27, 0.75), more than 1 cardiopulmonary bypass run (HR=0.33, 95% CI=0.18, 0.61), and longer aortic cross-clamp time (HR [per 10 minutes]=0.88, 95% CI=0.79, 0.97) were associated with lower rate of hospital discharge. CONCLUSIONS: Postoperative hospital stay after complete repair of tetralogy of Fallot is in part determined by patient and operative factors. Some (eg, surgical strategy for the symptomatic neonate) may be modifiable. These results may impact patient counseling, choice of surgical approach, and postoperative care.

Longitudinal Changes in Right Ventricular Function in Tetralogy of Fallot in the Initial Years after Surgical Repair.

BACKGROUND: Right ventricular (RV) dysfunction is associated with adverse long-term outcomes in patients with tetralogy of Fallot. Little is known about RV function in the first years after surgical repair. The aim of this study was to investigate perioperative changes in myocardial deformation using global longitudinal strain. METHODS: A retrospective analysis of patients with surgically repaired tetralogy of Fallot was performed. Global longitudinal peak systolic RV strain was measured on early postoperative echocardiograms, two subsequent postoperative echocardiograms through 2 years postoperatively, and preoperative echocardiograms, when available. Preoperative and late follow-up strain was compared with strain in 0- to 8-month-old and 1- to 4-year-old control subjects, respectively. RESULTS: Forty-seven patients were included. Compared with postoperative strain (7 ± 7 days postoperatively), strain at follow-up 1 (8.3 ± 4 months postoperatively) was significantly improved (-12.3 ± 3.3% vs -18.8 ± 2.5%, P < .001), with no additional improvement 23.2 ± 6 months postoperatively (-18.8 ± 2.5% vs -19.8 ± 3.1%, P = .12). Postoperative strain was worse than preoperative strain (n = 25, -12.5 ± 3.6% vs -18.4 ± 2.9%, P < .001). Compared with control subjects, preoperative strain was similar (-19.3 ± 3.8% vs -18.4 ± 2.9%, P = .30), though late follow-up strain was significantly worse (-27.7 ± 2.8% vs -19.8 ± 3.1%, P < .001). CONCLUSIONS: RV global longitudinal strain worsens in the early postoperative period following surgical repair of tetralogy of Fallot but recovers through 2 postoperative years. Despite recovery to preoperative values, the presence of RV dysfunction compared with control subjects suggests that long-term dysfunction may begin early. The trajectory of RV dysfunction through the later years needs further study.

22q11.2 Deletion Status and Perioperative Outcomes for Tetralogy of Fallot with Pulmonary Atresia and Multiple Aortopulmonary Collateral Vessels.

Deletion of 22q11.2 (del22q11) is associated with adverse outcomes in patients with tetralogy of Fallot (TOF). We sought to investigate its contribution to perioperative outcome in patients with a severe form of TOF characterized by pulmonary atresia (PA) or severe pulmonary stenosis (PS) and major aortopulmonary collateral arteries (MAPCAS). We conducted a retrospective review of patients with TOF/MAPCAS who underwent staged surgical reconstruction between 1995 and 2006. Groups were compared according to 22q11.2 deletion status using t-tests or the Wilcoxon Rank sum test. We included 26 subjects, 24 of whom survived the initial operation. Of those, 21 subjects had known deletion status and constitute the group for this analysis [15 with no deletion present (ND) and 6 del22q11 subjects]. There was no difference with respect to occurrence of palliative procedure prior to initial operation, or to timing of closure of the ventricular septal defect (VSD). Other than higher prevalence of prematurity (50%) in the del22q11 group versus no prematurity in the ND, the groups were comparable in terms of pre-operative characteristics. The intra- and post-operative course outcomes (length of cardiopulmonary bypass, use of vasopressors, duration of intensive care and length of hospital stay, tube-feeding) were also comparable. Although the del22q11 had longer mechanical ventilation than the ND, this difference was not significant [68 h (range 4-251) vs. 45 h (range 3-1005), p = 0.81]. In this detailed comparison of a small patient cohort, 22q11.2 deletion syndrome was not associated with adverse perioperative outcomes in patients with TOF, PA, and MAPCAS when compared to those without 22q11.2 deletion syndrome. These results are relevant to prenatal and neonatal pre-operative counseling and planning.

Right ventricular function mirrors clinical improvement with use of prostacyclin analogues in pediatric pulmonary hypertension.

Pulmonary hypertension (PH) causes significant morbidity and mortality in children due to right ventricular (RV) failure. We sought to determine the effect of prostacyclin analogues on RV function assessed by echocardiography in children with PH. We conducted a retrospective cohort study of children with PH treated with a prostacyclin analogue (epoprostenol or treprostinil) between January 2001 and August 2015 at our center. Data were collected before initiation of treatment (baseline) and at 1-3 and 6-12 months after. Protocolized echocardiogram measurements including tricuspid annular plane systolic excursion (TAPSE) and RV global longitudinal strain were made with blinding to clinical information. Forty-nine individuals (65% female), aged 0-29 years at the time of prostacyclin initiation were included. Disease types included pulmonary arterial hypertension (idiopathic [35%], heritable [2%], and congenital heart disease-associated [18%]), developmental lung disease (43%), and chronic thromboembolic PH (2%). Participants received intravenous (IV) epoprostenol (14%) and IV/subcutaneous (SQ) (67%) or inhaled (18%) treprostinil. Over the study period, prostacyclin analogues were associated with improvement in TAPSE ( P = 0.007), RV strain ( P < 0.001), and qualitative RV function ( P = 0.037) by echocardiogram, and BNP ( P < 0.001), functional class ( P = 0.047) and 6-min walk distance ( P = 0.001). TAPSE and strain improved at early follow up ( P = 0.05 and P = 0.002, respectively) despite minimal RV pressure change. In children with PH, prostacyclin analogues are associated with an early and sustained improvement in RV function measured as TAPSE and strain as well as clinical markers of PH severity. RV strain may be a sensitive marker of RV function in this population.

Incidence and characteristics of positive pressure ventilation delivered to newborns in a US tertiary academic hospital.

INTRODUCTION: The Neonatal Resuscitation Program (NRP) guidelines recommend positive pressure ventilation (PPV) in the first 60s of life to support perinatal transition in non-breathing newborns. Our aim was to describe the incidence and characteristics of newborn PPV using real-time observation in the delivery unit. METHODS: Prospective, observational, quality improvement study conducted at a tertiary academic hospital. Deliveries during randomized weekday/evening 8-h shifts were attended by a trained observer. Intervention data were recorded for all newborns with gestational age (GA) ≥34wks that received PPV. Descriptive summaries and Kruskal-Wallis test for continuous variables and Fisher's exact test for categorical variables were used to compare characteristics. RESULTS: Of 1135 live deliveries directly observed over 18mos, 64 (6%) newborns with a mean GA 39±2wks received PPV: Median time from birth to warmer was 20s (IQR 15-22s); PPV was initiated within 60s of life in 29 (45%) and between 60 and 90s of life in 17 (27%). PPV duration was <120s in 38 (60%). Seven/21 (33%) newborns that received PPV after vaginal delivery were not pre-identified and resuscitation team was alerted after delivery. We found no association between PPV start time and duration of PPV (p=0.86). CONCLUSION: We observed that most (94%) term newborns spontaneously initiate respirations. In over half observed deliveries receiving PPV, time to initiation of PPV was greater than 60s (longer than recommended). Compliance with current NRP guidelines is difficult, and it's not clear whether it is the recommendations or the training to achieve PPV recommendations that should be modified.

Improved Retention of Chest Compression Psychomotor Skills With Brief "Rolling Refresher" Training.

INTRODUCTION: High-quality cardiopulmonary resuscitation (CPR) is critical to improve survival from cardiac arrest. However, cardiopulmonary resuscitation knowledge and psychomotor skill proficiency are transient. We hypothesized that brief, in situ refresher training will improve chest compression (CC) psychomotor skill retention for bedside providers. METHODS: Nurses completed a baseline skill evaluation of CC quality 6 months after traditional basic life support recertification. Data collected using ResusciAnne with SkillReporter included the following: CC depth, rate, complete release, and correct hand position. Total compliance was defined as 100% CC with depth of 50 mm or greater, rate of 100/min or greater, and more than 90% complete release. After the baseline evaluation, the subjects completed "Rolling Refresher" (RR) CC psychomotor training using audiovisual feedback every 2 to 3 months for 12 months until 30 seconds of CCs fulfilling total compliance criteria was achieved. Chest compression quality evaluations were repeated twice ("RR 6 month" and "RR 12 month" evaluation) after implementation of RR program. RESULTS: Thirty-seven providers enrolled and completed the baseline evaluation. Mean depth was 36.3 (9.7) mm, and 8% met criteria for depth, 35% for rate, and 5% for total compliance. After RRs were implemented, CC quality improved significantly at RR 6-month evaluation: odds ratio for meeting criteria were the following: depth of 35.1 (95% confidence interval = 2.5496, P = 0.009) and total compliance of 22.3 (95% confidence interval = 2.1239, P = 0.010). There was no difference in CC quality at RR 12-month versus RR 6-month evaluation. CONCLUSIONS: Retention of CC psychomotor skill quality is limited to 6 months after traditional basic life support recertification. Rolling Refresher CC training can significantly improve retention of CC psychomotor skills. Whether CC skills are improved, maintained, or deteriorate after 12 months of Refresher training and optimal frequency of Refreshers is unknown.