Outcomes After Respiratory Extracorporeal Life Support in Teens and Young Adults: An Extracorporeal Life Support Organization Registry Analysis.

OBJECTIVES: A recent study from Germany found that survival after respiratory extracorporeal life support (ECLS) was lower among patients 10-20 years old than 20-30 years old. The objective of this study was to compare survival between teenage and young adult patients who receive respiratory ECLS. DESIGN: Retrospective cohort study. SETTING: Extracorporeal Life Support Organization registry, an international prospective quality improvement database. PATIENTS: All patients ages 16-30 years cannulated for respiratory indications from 1990 to 2020 were included. Patients were divided into two groups, teens (16-19 yr old) and young adults (20-30 yr old). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary outcome was survival to discharge. Variables were considered for the multivariate logistic regression model if there was both a statistically significant difference (p ≤ 0.05) and a clinically meaningful absolute difference between the groups. A total of 5,751 patients were included, of whom 1,653 (29%) were teens and 4,098 (71%) were young adults. Survival to discharge was higher in young adults than teens, 69% versus 63% (p < 0.001). Severity of illness was higher among teens; however, survival within each stratum defined by Pao2/Fio2 ratio was higher in young adults than in teens. Use of venoarterial ECLS was higher in teens than in young adults, 15% versus 7%, respectively. Teens were more likely to receive high-frequency oscillatory ventilation and this therapy was associated with a longer time from admission to ECLS initiation. After adjusting for variables that differ significantly between the groups, the odds ratio for survival in young adults compared with teens was 1.14 (95% CI, 1.004-1.3). CONCLUSIONS: In this large multicenter retrospective study, mortality was higher in teens than in young adults who received respiratory ECLS. This difference persisted after adjusting for multiple variables and the mechanism underlying these findings remains unclear.

Risk calculator for advanced neonatal resuscitation.

In order to predict which newborns will require advanced resuscitation (ANR), we developed an ANR risk calculator (calculator) using a bootstrap sample size of 52 973 from a case-control study of newborns ≥34 weeks gestation. Multivariable logistic regression coefficients were obtained for the 10 original risk factors and two interaction terms. The area under the receiving-operating characteristic curve predicting ANR was 0.9243. ANR prediction is improved by accounting for perinatal variables, beyond factors known prenatally. Prospective validation of this model is warranted in a clinical setting.

Effect of rotating providers on chest compression performance during simulated neonatal cardiopulmonary resuscitation.

OBJECTIVE: Simulation studies in adults and pediatrics demonstrate improvement in chest compression (CCs) quality as providers rotate every two minutes. There is paucity of studies in neonates on this matter. This study hypothesized that frequent rotation while performing CCs improves provider performance and decreases fatigue. STUDY DESIGN: Prospective randomized, observational crossover study where 51 providers performed 3:1 compression-ventilation CPR as a pair on a term manikin. Participants performed CCs as part of 3 simulation models, rotating every 3, 5 and 10 minutes. Data on various CC metrics were collected. Participant vitals were recorded at multiple points during the simulation and participants reported their level of fatigue at completion of simulation. RESULTS: No statistically significant difference was seen in any of the compression metrics. However, differences in the providers' fatigue scores were statistically significant. CONCLUSION: CC performance metrics did not differ significantly, however, providers' vital signs and self-reported fatigue scores significantly increased with longer CC durations.

Methylated and unmethylated epialleles support variegated epigenetic silencing in Friedreich ataxia.

Friedreich ataxia (FRDA) is typically caused by homozygosity for an expanded GAA triplet-repeat in intron 1 of the FXN gene, which results in transcriptional deficiency via epigenetic silencing. Most patients are homozygous for alleles containing > 500 triplets, but a subset (~20%) have at least one expanded allele with < 500 triplets and a distinctly milder phenotype. We show that in FRDA DNA methylation spreads upstream from the expanded repeat, further than previously recognized, and establishes an FRDA-specific region of hypermethylation in intron 1 (~90% in FRDA versus < 10% in non-FRDA) as a novel epigenetic signature. The hypermethylation of this differentially methylated region (FRDA-DMR) was observed in a variety of patient-derived cells; it significantly correlated with FXN transcriptional deficiency and age of onset, and it reverted to the non-disease state in isogenically corrected induced pluripotent stem cell (iPSC)-derived neurons. Bisulfite deep sequencing of the FRDA-DMR in peripheral blood mononuclear cells from 73 FRDA patients revealed considerable intra-individual epiallelic variability, including fully methylated, partially methylated, and unmethylated epialleles. Although unmethylated epialleles were rare (median = 0.33%) in typical patients homozygous for long GAA alleles with > 500 triplets, a significantly higher prevalence of unmethylated epialleles (median = 9.8%) was observed in patients with at least one allele containing < 500 triplets, less severe FXN deficiency (>20%) and later onset (>15 years). The higher prevalence in mild FRDA of somatic FXN epialleles devoid of DNA methylation is consistent with variegated epigenetic silencing mediated by expanded triplet-repeats. The proportion of unsilenced somatic FXN genes is an unrecognized phenotypic determinant in FRDA and has implications for the deployment of effective therapies.

Effect of Nitric Oxide Delivery Device on Tidal Volume Accuracy During Mechanical Ventilation at Small Tidal Volumes.

BACKGROUND: Inhaled nitric oxide (INO) is used in infants as a therapy for elevated pulmonary vascular resistance. When INO is delivered at low tidal volumes, displayed inspiratory and expiratory volumes vary widely. We hypothesize that volume is removed by the sampling line during the ventilation cycle, and this results in a net volume loss at low tidal volumes. This study aimed to measure the volumes delivered and to assess the accuracy of displayed ventilator values using a test lung. METHODS: A test lung was connected to a ventilator and an INO delivery system. All tests were performed with stable mode settings across volumes of 18, 30, 42, and 60 mL. Flow measured with a pneumotachometer attached between the test lung and the circuit assessed the percent error between inspiratory and expiratory volumes measured by the pneumotachometer measured and displayed on the ventilator under various INO/sample line conditions to determine where and how much volume was being displaced. RESULTS: Displayed and measured inspiratory volumes had small variations between the INO/sample line conditions and baseline. However, expiratory volumes, with the sample line connected, exhibited large percent error values that increased (-14, -20, -27, and -34) as tidal volume decreased (60, 42, 30, and 18 mL) and error was significantly larger compared to baseline in all tidal volumes (P < .01) with and without INO delivery. CONCLUSIONS: We concluded that inspiratory volumes were not affected by INO delivery, but additional removal of volume in the expiratory phase of the breath cycle by the sampling line results in a large error in the displayed expiratory volume.

Differences in Endothelin B Receptor Isoforms Expression and Function in Breast Cancer Cells.

The endothelins and their receptors are best known for their regulation of the vascular system. Their widespread expression in epithelial cells and their overexpression in some tumors has prompted investigation into their ability to regulate cancer progression. In this study, we assessed the mRNA expression of the major endothelin B receptor gene (EDNRB) isoforms and found differences in both mRNA and protein expression in normal breast cells and breast cancer cell lines. Knocking down the EDNRB gene in breast cancer cells altered invasiveness toward endothelin 3 (ET3), and we observed EDNRB isoform-specific regulation of breast cancer cell invasion and cell signaling, as well as isoform- and subtype-specific differences in breast cancer patient survival. The results reported in this study emphasize the importance of the endothelin B receptor in breast cancer. To our knowledge, this study is the first to clarify the differential expression and roles of specific EDNRB isoforms in breast cancer.

Structured Curriculum to Improve Pediatric Resident Confidence and Skills in Providing Parenting Advice.

CONTEXT: Residents receive little parenting education despite its potential to improve parenting behavior and decrease child maltreatment despite the inclusion of parenting content on board certification examinations. Teaching residents how to discuss parenting and foster positive parent-child relationships is essential to treating the whole person in osteopathic pediatric medicine. OBJECTIVE: To improve pediatric and internal medicine-pediatric residents' knowledge, confidence, and skills in providing parenting advice. METHODS: Four toddler parenting and discipline modules were developed. During continuity clinic, residents viewed and discussed modules with faculty. Residents completed a confidence and knowledge questionnaire before and after the curriculum, provided a self-report of use of skills learned, and completed a feasibility survey. Faculty also completed a feasibility survey. RESULTS: Forty-one of 61 residents (67%) participated in the study. Before participation, the median (interquartile range [IQR]) resident score for confidence in giving advice was 6.0 (4.0-7.0) (on a 10-point scale), increasing to 7.0 (6.0-8.0) for those completing 1 to 3 modules and 8.0 (8.0-9.0) for those completing 4 modules. Median (IQR) score on board-style questions was 8.0 (7.0-9.0) (on a 12-point scale) before participating in the modules and 8.5 (7.5-9.5) for those completing 1 to 3 modules and 9.0 (7.0-9.0) for those completing 4 modules after participation; the increase was not statistically significant. Nine faculty and 29 residents completed the modules and responded to the exit survey regarding feasibility and acceptability of the curriculum. On a 4-point scale (4 being excellent), sessions had an overall mean (SD) rating of 3.7 (0.5) by faculty and 3.5 (0.5) by residents. Most residents (27 [93.1%]) reported interest in more modules, and 28 residents (96.6%) reported using information learned from the modules during clinic visits. CONCLUSION: Confidence delivering parenting advice increased among residents who completed the curriculum modules. Faculty and residents reported high feasibility ratings, and residents endorsed application of skills during clinic visits and interest in more modules.

Impact of electronic cardiac (ECG) monitoring on delivery room resuscitation and neonatal outcomes.

AIM: In 2016, the neonatal resuscitation guidelines suggested electronic cardiac (ECG) monitoring to assess heart rate for an infant receiving positive pressure ventilation immediately after birth. Our aim was to study the impact of ECG monitoring on delivery room resuscitation interventions and neonatal outcomes. METHODS: Observational cohort study compared maternal, perinatal and infant characteristics, before (retrospective cohort, calendar year 2015) and after (prospective cohort, calendar year 2017) implementation of ECG monitoring in the delivery room. Association of ECG monitoring with delivery room resuscitation practice interventions and neonatal outcomes was assessed using unadjusted and adjusted multivariable regression analyses. RESULTS: Of 632 newly born infants who received positive pressure ventilation in the delivery room, ECG monitoring was performed in 369 (the prospective cohort) compared with no ECG monitoring in 263 (the retrospective cohort). Compared to neonates in the retrospective cohort, neonates with ECG monitoring had a significantly lower endotracheal intubation rate (36% vs 48%, P < .005) in the delivery room and higher 5-min Apgar scores (7 [5-8] vs 6 [5-8], P < .05). There was no difference in mortality (31 [8%] vs 23 [9%]), but infants who received ECG monitoring had increased odds of receiving chest compressions with an adjusted odds ratio of 3.6 (95% confidence interval: 1.4-9.5). CONCLUSION: Introduction of ECG monitoring in the delivery room was associated with fewer endotracheal intubations, and an increase use of chest compressions with no difference in mortality.

Pilot Study Comparing Modified Finnegan Scoring Versus Adjusted Scoring System for Infants With Iatrogenic Opioid Abstinence Syndrome After Cardiothoracic Surgery.

OBJECTIVES: To compare the modified Finnegan Scoring System (modified Finnegan) with an Adjusted Scoring System Criteria (adjusted Finnegan) for infants after cardiothoracic surgery with iatrogenic opioid abstinence syndrome (IOAS). METHODS: This was a retrospective, observational pilot study. This study was conducted in a tertiary care academic hospital. Infants after cardiothoracic surgery with IOAS transferred between the pediatric intensive care unit and neonatal intensive care unit between January 1, 2014, and January 31, 2016, were included retrospectively. The main outcome variable was to compare the area under the curve for the mean modified Finnegan versus adjusted Finnegan. RESULTS: Twenty-five patients were included in the study. Twenty patients with at least 30 scores were included in the final analysis. Overall, the modified Finnegan scores were at least 2 points higher than the adjusted Finnegan. The difference in area under the curve was 34.6 (p < 0.001). CONCLUSIONS: Use of the modified Finnegan tool for older infants with IOAS could overestimate withdrawal, leading to unnecessary interventions.

Neonatal vocal fold motion impairment after complex aortic arch reconstruction: What should parents expect after diagnosis?

OBJECTIVES: To study the incidence, sequelae, follow up, and recovery rate of vocal fold motion impairment (VFMI) after complex aortic arch reconstruction in neonates. STUDY DESIGN: Retrospective case control study. METHODS: We retrospectively evaluated 105 neonates who underwent complex aortic arch reconstruction from 2014 to 2016. We compared patients that did have VFMI compared to a control group of patients with normal vocal fold movement. Descriptive statistics were computed for all demographic and clinical variables by treatment group. RESULTS: 36% of patients were evaluated for VFMI (n = 38) by an otolaryngologist. The incidence of VFMI was 22% (n = 23). Females were more likely to have VFMI (p = 0.02). Aspiration was more common in patients with VFMI (p = 0.006). The difference in age, weight, incidence of pneumonia, nasogastric tube, gastrostomy, total length of stay, genetic anomaly, and reintubation was not significant between the VFMI group and control group (p > 0.05). Tracheostomy was not performed in any patients with unilateral paralysis. Only 61% of patients followed up in clinic (n = 14). 64% of patients showed improvement or resolution (n = 9). Average time to improvement was 4.8 months. Average time to complete resolution was 10.5 months. CONCLUSIONS: VFMI after complex aortic arch reconstruction is relatively common. Despite increased aspiration in patients with VFMI, pneumonia did not occur at all in either group. Tracheostomy was not necessary in any patients with a unilateral paralysis. Most patients showed an improvement in the VFMI within 5 months of surgery. Our data support the need for otolaryngology follow-up after the diagnosis of VFMI.

Are we validly assessing major depression disorder risk and associated factors among mothers of young children? A cross-sectional study involving home visitation programs.

Failure to account for misclassification error accruing from imperfect case-finding instruments can produce biased estimates of suspected major depression disorder (MDD) risk factor associations. The objective of this study was to estimate the impact of misclassification error on the magnitude of measures of association between suspected risk factors and MDD assessed using the Center of Epidemiological Studies on Depression-Short Form during the prenatal and postnatal periods. Baseline data were collected from 520 mothers participating in two home visitation studies in Oklahoma City between 2010 and 2014. A Bayesian binomial latent class model was used to compare the prevalence proportion ratio (PPR) between suspected risk factors and MDD with and without adjustment for misclassification error and confounding by period of MDD symptom on-set. Adjustment for misclassification error and confounding by period of MDD on-set (prenatal vs postnatal) showed that the association between suspected risk factors and MDD is underestimated (-) and overestimated (+) differentially in different source populations of low-income mothers. The median bias in the magnitude of PPR estimates ranged between -.47 (95% Bayesian Credible Intervals [BCI]: -10.67, 1.90) for intimate partner violence to +.06 (95%BCI: -0.37, 0.47) for race/ethnicity among native-born US residents. Among recent Hispanic immigrants, bias ranged from -.77 (95%BCI: -15.31, 0.96) for history of childhood maltreatment to +.10 (95%BCI: -0.17, 0.39) for adequacy of family resources. Overall, the extent of bias on measures of association between maternal MDD and suspected risk factors is considerable without adjustment for misclassification error and is even higher for confounding by period of MDD assessment. Consideration of these biases in MDD prevention research is warranted.

Assessment of Outcomes With a Sedation Protocol During Laser Photocoagulation in Preterm Infants With Retinopathy of Prematurity.

OBJECTIVES: To evaluate the success of a sedation protocol of fentanyl and midazolam infusions for infants undergoing laser photocoagulation for retinopathy of prematurity. METHODS: This retrospective study included infants receiving a sedation protocol for laser photocoagulation during a 4-year period. The primary objective was protocol success, defined as completion without interruption, absence of protocol dose deviations, and absence of interventions. Secondary objectives compared outcomes between those with and without opioid/benzodiazepine exposure. A logistic regression was used to assess the effect of prior opioid/benzodiazepine exposure on requirement for fentanyl infusion increases. RESULTS: Twenty-six infants were included. Seven (26.9%) had protocol success. Sixteen (61.5%) had protocol success, excluding dose deviations. Seventeen (65.4%) experienced ≥1 cardiopulmonary adverse events. Photocoagulation was completed in all cases. CONCLUSIONS: Most achieved protocol success, when eliminating dosing deviations. These data indicate that flexibility is needed in fentanyl and midazolam infusion titration, based on clinical response.

Vitamin D and associated perinatal-neonatal outcomes among extremely low-birth-weight infants.

OBJECTIVE: To evaluate vitamin D inadequacy among extremely low-birth-weight (ELBW, <1000 g) infants and the association between circulating vitamin D concentrations and perinatal-neonatal outcomes. STUDY DESIGN: Prospective cohort study of ELBW infants in the neonatal ICU. Blood was collected within the first 3 days after birth after obtaining informed consent. Circulating 25-hydroxyvitamin D concentrations (25(OH)D) were quantified using liquid chromatography-tandem mass spectroscopy and classified as vitamin D deficient, insufficient, or adequate ( < 20, 20-30, or > 30 ng/mL, respectively). Associations between 25(OH)D and perinatal-neonatal outcomes were determined by multivariable regression, adjusted for covariates that differ in the bivariate analysis. RESULTS: Of the 60 ELBW infants enrolled, 13 (22%) were vitamin D deficient, 15 (25%) were insufficient, and 32 (53%) were adequate. 25(OH)D levels were positively associated with fetal growth restriction and prolonged rupture of the membranes. CONCLUSIONS: Vitamin D inadequacy was frequent among ELBW infants. Circulating vitamin D concentrations were significantly associated with perinatal outcomes in this contemporary cohort.

Distinguishing neurocysticercosis epilepsy from epilepsy of unknown etiology using a minimal serum mass profiling platform.

Neurocysticercosis is associated with epilepsy in pig-raising communities with poor sanitation. Current internationally recognized diagnostic guidelines for neurocysticercosis rely on brain imaging, a technology that is frequently not available or not accessible in areas endemic for neurocysticercosis. Minimally invasive and low-cost aids for diagnosing neurocysticercosis epilepsy could improve treatment of neurocysticercosis. The goal of this study was to test the extent to which patients with neurocysticercosis epilepsy, epilepsy of unknown etiology, idiopathic headaches and among different types of neurocysticercosis lesions could be distinguished from each other based on serum mass profiling. For this, we collected sera from patients with neurocysticercosis-associated epilepsy, epilepsy of unknown etiology, recovered neurocysticercosis, and idiopathic headaches then performed binary group comparisons among them using electrospray ionization mass spectrometry. A leave one [serum sample] out cross validation procedure was employed to analyze spectral data. Sera from neurocysticercosis patients was distinguished from epilepsy of unknown etiology patients with a p-value of 10-28. This distinction was lost when samples were randomized to either group (p-value = 0.22). Similarly, binary comparisons of patients with neurocysticercosis who has different types of lesions showed that different forms of this disease were also distinguishable from one another. These results suggest neurocysticercosis epilepsy can be distinguished from epilepsy of unknown etiology based on biomolecular differences in sera detected by mass profiling.

Safety of Ibuprofen for Postoperative Pain After Palatoplasty: A Pilot Study.

OBJECTIVE: To determine the safety of ibuprofen used for postoperative pain control following palatoplasty in pediatric patients. DESIGN: Retrospective chart review. SETTING: Tertiary care, pediatric hospital. PARTICIPANTS: Patients who received ibuprofen for postoperative pain control after palatoplasty. MAIN OUTCOME MEASURES: Number of doses of ibuprofen given during hospitalization and the presence of postoperative primary or secondary bleeding following palatoplasty. Detection of postoperative hemorrhage was obtained from (1) chart review from inpatient hospitalization after palatoplasty, (2) chart review of each patient's 3-week postoperative clinic visit, and (3) phone call to caretakers from primary author. RESULTS: Thirty-two patients underwent palatoplasty who received ibuprofen for control of postoperative pain. Mean number of inpatient doses given was 4.8 (range: 1-17). None (0%) experienced hemorrhage in the hospital before discharge. Thirty-two (100%) patients were seen at a 3-week follow-up and no (0%) episodes of postoperative hemorrhage were noted. Seventeen (53%) caretakers of patients responded to contact by phone and confirmed no subsequent bleeding. CONCLUSIONS: Ibuprofen may not increase postoperative hemorrhage after palatoplasty. Further studies will be needed to evaluate safety on a larger scale.

Abdominal obesity adversely affects bone mass in children.

AIM: To determine the effect of childhood obesity and insulin resistance on bone health. METHODS: We conducted a cross sectional study in pubertal adolescents and young adults 13-20 years old who were either overweight/obese or normal weight. Participants were Tanner 3 or above for pubertal stage, and had fasting blood work done to measure glucose, insulin, C-reactive protein and lipid levels. Homeostatic model of insulin resistance (HOMA-IR) was calculated using the formula (Fasting Blood Glucose *Insulin/405). Body composition and bone mineral density were measured using dual energy X-ray absorptiometry (DXA; Hologic QDR 4500, Waltham, MA, United Kingdom). RESULTS: Percent trunk fat was associated inversely with whole body bone mineral content (BMC), whereas HOMA-IR was associated positively with whole body BMC. CONCLUSION: Our results suggest that abdominal adiposity may have an adverse effect on whole body bone parameters and that this effect is not mediated by insulin resistance.

The Relationship Between Pediatric Residents' Experiences Being Parented and Their Provision of Parenting Advice.

Background: Factors surrounding pediatricians' parenting advice and training on parenting during residency have not been well studied. The Resident Parenting Questionnaire (RPQ) was developed to assess (a) the relationship between pediatric residents' upbringing and their parenting advice style and (b) factors associated with confidence and resource use when delivering parenting advice. Methods: Three hundred and one pediatric residents from 15 United States residency programs completed the RPQ with upbringing and advice responses categorized using Baumrind's parenting model (authoritative, authoritarian, permissive). Chi-square/Fisher's exact tests, Bowker's test of symmetry, and regression analyses assessed associations between residents' upbringing, parenting advice style/content, and confidence in providing parenting advice. Results: Most participants indicated being raised authoritatively (68%) and giving authoritative parenting advice (83%), but advice differed based on how they perceived their upbringing (p < 0.001). Residents noting authoritative upbringing were more likely to give authoritative advice (85%) while others tended to give advice differing from upbringing (e.g., those perceiving authoritarian upbringing were more likely to give authoritative/permissive). Analyses suggest resident race, acculturation, future plans, and resident level are associated with parenting advice type. Confidence in giving parenting advice decreased significantly as patient age increased and increased with resident level advancement. Residents reported consulting attending physicians for parenting advice guidance more than any other evidence-based resources. Conclusion: Most pediatric residents appear to be aware of appropriate authoritative parenting advice regardless of upbringing, especially as they advance through residency. Residents may benefit from opportunities to reflect upon their upbringing, particularly if raised in authoritarian or permissive styles. Targeted training of residents on evidence-based parenting strategies, particularly for older pediatric patients, appears warranted.