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The article presents a report titled "Gastrointestinal bleeding in hospitalized children in the United States." Topics discussed include chart depicting characteristics of cases with and without a discharge diagnosis of gastrointestinal bleeding, chart presenting morbidity burden, severity of disease, and outcome measures of cases, and the incidence and associated mortality by types including hematemesis, gastric ulcer, and peptic ulcer of gastrointestinal bleed.

Background: Single-center studies suggest an increasing incidence of acute pancreatitis (AP) in children. Our specific aims were to (i) estimate the recent secular trends, (ii) assess the disease burden, and (iii) define the demographics and comorbid conditions of AP in hospitalized children within the United States. Methods: We used the Healthcare Cost and Utilization Project Kids’ Inpatient Database, Agency for Healthcare Research and Quality for the years 2000 to 2009. Extracted data were weighted to generate national-level estimates. We used the Cochrane-Armitage test to analyze trends; cohort-matching to evaluate the association of AP and in-hospital mortality, length of stay, and charges; and multivariable logistic regression to test the association of AP and demographics and comorbid conditions. Results: We identified 55,012 cases of AP in hospitalized children (1–20 years of age). The incidence of AP increased from 23.1 to 34.9 (cases per 10,000 hospitalizations per year; P<0.001) and for all-diagnoses 38.7 to 61.1 (P<0.001). There was an increasing trend in the incidence of both primary and all-diagnoses of AP (P<0.001). In-hospital mortality decreased (13.1 to 7.6 per 1,000 cases, P<0.001), median length of stay decreased (5 to 4 days, P<0.001), and median charges increased ($14,956 to $22,663, P<0.001). Children with AP compared to those without the disease had lower in-hospital mortality (adjusted odds ratio, aOR 0.86, 95% CI, 0.78–0.95), longer lengths of stay (aOR 2.42, 95% CI, 2.40–2.46), and higher charges (aOR 1.62, 95% CI, 1.59–1.65). AP was more likely to occur in children older than 5 years of age (aORs 2.81 to 5.25 for each 5-year age interval). Hepatobiliary disease was the comorbid condition with the greatest association with AP. Conclusions: These results demonstrate a rising incidence of AP in hospitalized children. Despite improvements in mortality and length of stay, hospitalized children with AP have significant morbidity. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) infection of the lower respiratory tract is the leading cause of respiratory failure among infants in the United States of America and annually results in >300,000 deaths worldwide. Despite the importance of RSV, there is no licensed vaccine, and no specific form of therapy. This is largely due to the absence of an appropriate animal model for the evaluation of vaccines and therapeutic agents. We inoculated anesthetized infant (4 wk) baboons (Papio anubis) with a human strain of RSV intranasally or intratracheally. Baboons were monitored daily for clinical changes. Anesthetized baboons were intubated at various intervals, and bronchoalveolar lavage (BAL) was performed for viral culture and determination of leukocyte counts. Sham-infected baboons served as controls. Necropsies were performed on infected baboons on days 1, 3, 5, 8, or 13 after inoculation, with pathological analysis and immunohistochemical staining of lung tissues to detect RSV antigen. Infected baboons developed tachypnea and reduced oxygenation peaking from 4 to 8 days after infection and persisting for ≥14 days. Virus was recoverable in BAL fluid up to 8 days following infection. Necropsy revealed intense interstitial pneumonia, sloughing of the bronchiolar epithelium, and obstruction of the bronchiolar lumen with inflammatory cells and sloughed epithelial cells. RSV antigen was identified in bronchiolar and alveolar epithelium. We conclude that RSV-infected infant baboons develop clinical and pathological changes that parallel those observed in human infants with RSV infection. The infant baboon represents a much-needed model for studying the pathogenesis of RSV infection and evaluating antivirals and vaccines. [ABSTRACT FROM AUTHOR]

Due to an increasing trend among states to cut higher education funds, many universities are relying more on private donations and federal funding to keep programs afloat. Scholarship productivity in general has become an integral factor in terms of universities granting tenure to faculty, allocating resources, and supporting program goals due to the fact that more research in a particular area tends to increase the likelihood that one will obtain funding from federal, state, and private sources. In the past, ranking systems have also been used to evaluate programs. However, most ranking systems use methodologies that do not quantify research productivity or evaluate factors that match current university trends. The purpose of this article is to explore current scholarship productivity trends among COAMFTE-accredited doctoral programs through the use of several evaluation methods. Specifically, productivity was examined in regard to the following areas: (a) family therapy journal publications; (b) family science journal publications; (c) historic journal publication trends; and (d) recent journal publication trends. [ABSTRACT FROM AUTHOR]

Thirty faculty in randomly selected Commission on Accreditation for Marriage and Family Therapy Education (COAMFTE) programs representing four geographical regions of the United States were asked to respond to a survey that included seven brief vignettes depicting gatekeeping and remediation challenges supervisors may face when working with therapists-in-training. Research participants were asked to select from among a range of 17 response options and were also asked to provide a rationale for the selection of their responses. The response rate for the mailed survey was 34%. Telephone interviews were conducted with three respondents who had provided especially detailed responses to the open-ended portions of the mailed survey and who also volunteered to be questioned regarding how supervision decisions are made. Results support the conclusion that COAMFTE faculty take their gatekeeping function seriously as they balance commitments to multiple stakeholders. When presented with hypothetical “bare-bones” vignettes, the supervisors in our study consistently recommended talking with the student in order to more fully understand the context of the student’s performance problem before deciding how to proceed. Supervisors recommended a variety of remediation efforts, but reserved the most severe consequences, such as probation, dismissal, and filing an ethics complaint, for the vignette involving dishonesty and lack of personal integrity. [ABSTRACT FROM AUTHOR]

Competing Interests: Declaration of Competing Interest Drs. Chen and Anderson were supported by the Oklahoma Shared Clinical and Translational Resources (U54GM104938) with an Institutional Development Award from National Institute of General Medical Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Competing Interests: Declaration of Competing Interest S.C. and M.P.A. were supported by the Oklahoma Shared Clinical and Translational Resources (U54GM104938) with an Institutional Development Award from National Institute of General Medical Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare no conflicts of interest.

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., Competing Interests: Dr. Thiagarajan’s institution received funding from the U.S. Department of Defense; he received funding from the Extracorporeal Life Support Organization and the Society of Critical Care Medicine. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

This study aimed to create a pediatric sedation scoring system independent of the American Society of Anesthesiology Physical Status (ASA-PS) classification that is predictive of adverse events, facilitates objective stratification, and resource allocation. Multivariable regression and machine learning algorithm analysis of 134,973 sedation encounters logged in to the Pediatric Sedation Research Consortium (PSRC) database between July 2007 and June 2011. Patient and procedure variables were correlated with adverse events with resultant β -regression coefficients used to assign point values to each variable. Point values were then summed to create a risk assessment score. Validation of the model was performed with the 2011 to 2013 PSRC database followed by calculation of ROC curves and positive predictive values. Factors identified and resultant point values are as follows: 1 point: age ≤ 6 months, cardiac diagnosis, asthma, weight less than 5th percentile or greater than 95 th , and computed tomography (CT) scan; 2 points: magnetic resonance cholangiopancreatography (MRCP) and weight greater than 99th percentile; 4 points: magnetic resonance imaging (MRI); 5 points: trisomy 21 and esophagogastroduodenoscopy (EGD); 7 points: cough at the time of examination; and 18 points: bronchoscopy. Sum of patient and procedural values produced total risk assessment scores. Total risk assessment score of 5 had a sensitivity of 82.69% and a specificity of 26.22%, while risk assessment score of 11 had a sensitivity of 12.70% but a specificity of 95.29%. Inclusion of ASA-PS value did not improve model sensitivity or specificity and was thus excluded. Higher risk assessment scores predicted increased likelihood of adverse events during sedation. The score can be used to triage patients independent of ASA-PS with site-specific cut-off values used to determine appropriate sedation resource allocation., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

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., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2020 by Daedalus Enterprises.)

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., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

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.

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.

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.

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.

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., Competing Interests: Disclosures At the time of publication Dr Jamie L. Miller was on the speaker's bureau for Chiesi, USA, Inc. The rest of the authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. The authors had full access to all the data and take responsibility for the integrity and accuracy of the data analysis.

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., Competing Interests: Conflict-of-interest statement: David A Fields has received grant funding from Nestle and Mead Johnson.

Objective: This article evaluates postoperative analgesia in pediatric palatoplasty patients using nonopioid oral medications., Design: This study was a retrospective chart review., Setting: The setting for this study was a tertiary-care children's hospital., Participants: Study participants were pediatric patients who underwent palatoplasty procedures performed by a single surgeon., Interventions: Interventions included nonopioid and opioid oral medications for postoperative analgesia., Main Outcome Measures: The adequacy of nonopioid versus opioid oral analgesia was assessed by (1) time to discontinue IV fluid, (2) total IV morphine doses for breakthrough pain, (3) daily IV morphine doses for breakthrough pain, (4) time to discharge from the hospital, and (5) perioperative weight change. Group comparisons of outcome measures were performed using a two one-sided test., Results: A total of 61 patients were identified who received three standard pain regimens: acetaminophen + ibuprofen (12), hydrocodone/acetaminophen (23), and hydrocodone/acetaminophen + ibuprofen (26). There was sufficient evidence to suggest equivalence in outcome measures for acetaminophen + ibuprofen versus hydrocodone/acetaminophen and hydrocodone/acetaminophen + ibuprofen for the following: time to discontinue IV fluid (P = .02, 90% confidence interval [CI] = -0.42 to 0.17; P = .007, 90% CI = -0.28 to 0.34), daily IV morphine doses (P = .023, 90% CI = -0.83 to 0.65; P = .032, 90% CI = -0.92 to 0.28), time to discharge from the hospital (P = .017, 90% CI = -0.40 to 0.27; P = .015, 90% CI = -0.24 to 0.39), and perioperative weight change (P = .002; 90% CI = -0.25 to 0.46; P < .0001; 90% CI = -0.34 to 0.18). There was no sufficient evidence to suggest equivalence for total IV morphine doses (P = .189, 90% CI = -1.51 to 1.78; P = .169, 90% CI = -1.51 to 0.88)., Conclusions: Oral acetaminophen and ibuprofen alone may provide similar analgesia to traditional regimens with reduced risks following pediatric palatoplasty.

Objectives: The primary aim was to compare attainment of goal serum amikacin concentrations using two dosage regimens in patients admitted to a neonatal intensive care unit. Secondary objectives included comparison of percentages of supratherapeutic trough concentrations, and subtherapeutic and supratherapeutic peak concentrations., Methods: This was an Institutional Review Board-approved, retrospective study of neonates receiving amikacin during January-December 2013 (group 1) and January-December 2014 (group 2). Group 1 received amikacin dosage consistent with published recommendations, whereas group 2 was dosed using a modified protocol that was based on postmenstrual and postnatal age. Goal serum amikacin peak concentration was defined as 20 to 35 mg/L; hence, subtherapeutic and supratherapeutic peak concentrations were defined as <20 mg/L and >35 mg/L, respectively. Supratherapeutic trough concentrations were >8 mg/L. Between-group analysis was performed using Wilcoxon-Mann-Whitney test, Student t -test or χ 2 , or Fisher exact analysis as appropriate with a p value <0.05., Results: A total of 278 neonates were included (group 1: n = 144; group 2: n = 134). Most patients were male (60%) and were admitted for prematurity or respiratory distress (77%). The median gestational age in group 1 was 34.4 weeks (range, 30.0-37.9 weeks) versus group 2 at 36.9 weeks (range, 31.4-38.9 weeks), whereas the postnatal age was similar between both groups at 4 days. There was a significant increase in attaining goal peak amikacin concentrations between groups 1 and 2, 34% versus 84%, p < 0.001, and decrease in supratherapeutic peak concentrations, 65% versus 12%, p < 0.001. There was no significant difference in subtherapeutic peak or supratherapeutic trough concentrations., Conclusions: A modified neonatal amikacin dosage protocol resulted in increased peak amikacin serum concentration compared with published dosage recommendations. Future research should focus on determination of the optimal dosage regimen in neonates.

OBJECTIVE: To assess patient opinion on the Patient Protection and Affordable Care Act (PPACA) in an Otolaryngology practice and the factors that influence those opinions. STUDY DESIGN: Observational study. METHODS: An anonymous survey assessing patient opinion on the PPACA, demographic information, political affiliation, medical diagnosis, and insurance status was distributed to patients in three separate Otolaryngology clinics (General, cancer, and Low-income/Indigent) from April to June 2014. A total of 300 surveys were distributed and 207 were used for final analysis. The primary study outcome measures were patient opinion of the PPACA and statistically significant variables affecting that opinion. The association of Support for the PPACA and variables were tested using the Chi-square test. RESULTS: The only variables that showed a significant association with support for the PPACA were Political Party (p<0.0001) and Ethnicity (p=0.0050). Specifically, a higher proportion of Democrats support the PPACA than Republicans and a higher proportion of African Americans and Hispanic/Latinos support the PPACA than Whites and Native Americans. CONCLUSION: Our survey of current Otolaryngology patients mirrors national findings of the division between Republicans and Democrats in their attitudes towards the Affordable Care Act. Political party appears to be the most significant factor in shaping patient opinion on this controversial subject regardless of insurance status or cancer diagnosis and a higher proportion of African Americans and Hispanic/Latinos support the PPACA than Whites and Native Americans. LEVEL OF EVIDENCE: IV.

Friedreich ataxia, the most prevalent inherited ataxia, is caused by an expanded GAA triplet-repeat sequence in intron 1 of the FXN gene. Repressive chromatin spreads from the expanded GAA triplet-repeat sequence to cause epigenetic silencing of the FXN promoter via altered nucleosomal positioning and reduced chromatin accessibility. Indeed, deficient transcriptional initiation is the predominant cause of transcriptional deficiency in Friedreich ataxia. Treatment with 109, a class I histone deacetylase (HDAC) inhibitor, resulted in increased level of FXN transcript both upstream and downstream of the expanded GAA triplet-repeat sequence, without any change in transcript stability, suggesting that it acts via improvement of transcriptional initiation. Quantitative analysis of transcriptional initiation via metabolic labeling of nascent transcripts in patient-derived cells revealed a >3-fold increase (P < 0.05) in FXN promoter function. A concomitant 3-fold improvement (P < 0.001) in FXN promoter structure and chromatin accessibility was observed via Nucleosome Occupancy and Methylome Sequencing, a high-resolution in vivo footprint assay for detecting nucleosome occupancy in individual chromatin fibers. No such improvement in FXN promoter function or structure was observed upon treatment with a chemically-related inactive compound (966). Thus epigenetic promoter silencing in Friedreich ataxia is reversible, and the results implicate class I HDACs in repeat-mediated promoter silencing., (© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Objective: To identify recent tobacco industry influences in the Oklahoma Legislature., Methods: Relevant public records were compiled and published online in searchable databases. Activities related to two contested tobacco-related legislative initiatives were analyzed. Analyses of voting behavior controlled for party affiliation., Results: Legislators receiving the largest amounts of campaign contributions and gifts from tobacco lobbyists performed actions necessary to advance tobacco industry objectives. Several significant associations with voting behavior were observed, the strongest of which was between votes on a pro-tobacco industry bill and gifts from tobacco lobbyists. Most lobbyists'gifts were meals., Conclusions: Tobacco industry influence in the Oklahoma Legislature is enhanced through tobacco lobbyists' campaign contributions and gifts. Greater investments are made in legislative leaders, those serving as champions or spokespersons, and others taking key roles in advancing tobacco industry objectives. Exposing such influences may diminish their effects. Given the egregious and uniquely destructive behavior of the tobacco industry, lawmakers could, as an ethical matter of principle, refuse tobacco lobbyists' money and seek to remedy past harms.

Objectives: The objective was to estimate emergency department (ED) visits for Clostridium difficile infection in the United States for the years 2006 through 2010., Methods: Estimates of ED visits for C. difficile infection were calculated in patients 18 years and older using the Nationwide Emergency Department Sample., Results: During the calendar years 2006 through 2010, there were an estimated total of 491,406,018 ED visits. Of these, 462,160 ED visits were associated with a primary International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis of C. difficile. The C. difficile infection ED visit rate (visits/100,000 census population) increased from 34.1 in 2006 to 42.3 in 2010, an increase of 24% (p < 0.01). There was also a significant overall increased trend in the number of ED visits for C. difficile from 2006 through 2010 (p < 0.01). The highest ED visit rate for C. difficile was observed for patients 65 years and older (163.18 per 100,000), while the lowest visit rate was for patients aged 18 to 24 years (5.10 per 100,000). The greatest increase in C. difficile infection visits occurred in the age group 18 to 24 years., Conclusions: These results indicate an increased trend of ED visits for C. difficile in the period 2006 through 2010 with an overall population-adjusted increase of 24%. This represents important complementary data to previous studies reporting an increase in the rate of C. difficile infections in the U.S. hospitalized population., (© 2014 by the Society for Academic Emergency Medicine.)

Background: The purpose of this study was to determine how proximal (home) and distal (neighborhood) environmental characteristics interact to influence obesity in early and middle adolescents., Methods: This was a descriptive, cross-sectional study using the 2007 National Survey of Children's Health (NCSH). Participants were 39,542 children ages 11 to 17 years. Logistic regressions were used to examine the relationship between adolescent obesity and environmental factors, the relative strength of these factors, and the influence of age and gender., Results: Proximal environmental factors were stronger correlates of adolescent obesity than distal environmental factors. Sedentary behavior related to TV watching time at home was the strongest correlate of adolescent obesity overall (OR 1.13, 95% CI 1.11-1.15). Parks and playgrounds (OR 0.86, 95% CI 0.08-0.92), as well as recreation centers (OR 0.91, 95% CI 0.85-0.97) were significant distal environmental factor correlates. Girls and middle adolescents were at less risk for obesity than boys and early adolescents (OR 0.51, 95% CI 0.68-0.82; OR 0.75, 95% CI 0.68-0.96)., Conclusion: The results of this study reveal the importance of proximal environmental characteristics on adolescent obesity relative to distal environmental characteristics. Obesity intervention strategies for adolescents should target sedentary behavior and opportunities for physical activity with a focus on early adolescents and boys.

DNA barcodes are short strands of 255-700 nucleotide bases taken from the cytochrome c oxidase subunit 1 (COI) region of the mitochondrial DNA. It has been proposed that these barcodes may be used as a method of differentiating between biological species. Current methods of species classification utilize distance measures that are heavily dependent on both evolutionary model assumptions as well as a clearly defined "gap" between intra- and interspecies variation. Such distance measures fail to measure classification uncertainty or to indicate how much of the barcode is necessary for classification. We propose a sequential naïve Bayes classifier for species classification to address these limitations. The proposed method is shown to provide accurate species-level classification on real and simulated data. The method proposed here quantifies the uncertainty of each classification and addresses how much of the barcode is necessary.

We investigated the volume of endoscopic retrograde cholangiopancreatographies (ERCPs) performed in hospitalized children in the United States using a nationwide healthcare administrative database for the years 2000 to 2009. A total of 22,153 cases of ERCP were identified: 6372 diagnostic and 17,314 therapeutic (1533 cases were recorded as undergoing both types during a single hospitalization). The number of ERCPs increased from 5337 to 6733 per year; diagnostic ERCPs decreased 43% and therapeutic increased 69% (significant decreasing trends for diagnostic and increasing for therapeutic ERCPs, P<0.001 for each analysis). Our results define a recent increase in the use of therapeutic ERCPs in hospitalized children.

Background: Opioids are commonly used in the neonatal intensive care unit (NICU). Negative neurodevelopmental effects in the short-term setting have been associated with opioids ; however, long-term studies have been limited., Objective: The primary objective was to determine if there is a dose relationship between fentanyl and neurodevelopmental outcomes, as measured by Bayley Scales of Infant and Toddler Development (Bayley-III) composite scores for language, cognition, and motor skills. Secondary objectives included comparison of Bayley-III scores and neurodevelopmental impairment classification based on fentanyl exposure., Methods: A retrospective evaluation of 147 very-low-birth-weight infants with Bayley-III scores obtained at a chronological age of 6 months to 2 years at clinic follow-up was conducted. Univariate and multivariable linear regression analyses were used to determine if there was a dose-related association between fentanyl and neurodevelopmental outcomes. To evaluate secondary outcomes, patients were divided based on cumulative fentanyl dose ("high-dose" versus "low/no-dose")., Results: The univariate analysis found a statistically significant decrease in cognition (P = .034) and motor skills scores (P = .006). No association was found in the multi-variable regression between fentanyl cumulative dose and Bayley-III scores. There was a significant decrease in the motor skills score between the high-dose versus low/no-dose group, 94 ± 20 versus 102 ± 15, respectively (P = .026); however, no statistical differences were noted for language or cognition scores or neurological impairment classification., Conclusions: When controlling for other variables, the cumulative fentanyl dose did not correlate with neurodevelopmental outcomes. Further evaluation of benefits and risks of opioids in premature infants are needed.

Purpose: To determine whether medical student intubation proficiency with a neonatal mannequin differs according to weekly or consecutive day practice sessions during a six-week pediatric clerkship., Method: From July 2010 through June 2011, the authors prospectively randomized 110 third-year medical students into three neonatal intubation practice groups: standard (control; no practice sessions), weekly (practice once/week for four consecutive weeks), or consecutive day (practice once/day for four consecutive days). At baseline, students performed intubation during individual sessions using a neonatal mannequin (SimNewB). Two reviewers, blinded to practice group, viewed videotapes of intubations and independently scored students on equipment selection, procedural skill steps, length of intubation attempts (in seconds), and the number of attempts (up to three) needed for a successful intubation. Videotaped individual final assessment intubation sessions during week six were evaluated in the same manner., Results: Students in the weekly and consecutive day practice groups performed better at the final assessment on all variables than students in the standard group (P < .001), but over six weeks, the authors detected no differences between the two distributed practice formats for any outcomes of interest., Conclusions: Practice improved all aspects of neonatal intubation performance, including choosing the correct equipment, properly performing the skill steps, length of time to successful intubation, and success rate, for novice health care providers in a simulation setting. Over six weeks, neither practice format proved superior, but it remains unclear whether one format is superior for learning and skill retention over the long term or in actual practice.

Background: The incidence and prevalence of pediatric inflammatory bowel disease (IBD) seems to be increasing in North America and Europe. Our objective was to evaluate hospitalization rates in children with IBD in the United States during the decade 2000 to 2009., Methods: We analyzed cases with a discharge diagnosis of Crohn disease (CD) and ulcerative colitis (UC) within the Healthcare Cost and Utilization Project Kids' Inpatient Database, Agency for Healthcare Research and Quality., Results: We identified 61,779 pediatric discharges with a diagnosis of IBD (CD, 39,451 cases; UC, 22,328 cases). The number of hospitalized children with IBD increased from 11,928 to 19,568 (incidence, 43.5-71.5 cases per 10,000 discharges per year; P < 0.001). For CD, the number increased from 7757 to 12,441 (incidence, 28.3-45.0; P < 0.001) and for UC, 4171 to 7127 (15.2-26.0; P < 0.001). Overall, there was a significant increasing trend for pediatric hospitalizations with IBD, CD, and UC (P < 0.001). In addition, there was an increase in IBD-related complications and comorbid disease burden (P < 0.01)., Conclusion: There was a significant increase in the number and incidence of hospitalized children with IBD in the United States from 2000 to 2009.

Background: Children with inflammatory bowel disease (IBD), similar to adults, are at increased risk of acquiring a Clostridium difficile infection (CDI). Our objective was to characterize the health care burden associated with CDI in hospitalized pediatric patients with IBD., Methods: We extracted and analyzed cases with a discharge diagnosis of IBD or CDI from the U.S. Healthcare Cost and Utilization Project Kids' Inpatient Database., Results: In our primary analysis, we evaluated pediatric cases with a principal diagnosis of IBD or CDI. For the year 2009, we identified 12,610 weighted cases with IBD of which 3.5% had CDI. In children with IBD, CDI was independently associated with lengthier hospital stays (8.0 versus 6.0 days; adjusted regression coefficient, 2.1 days; 95% confidence interval [CI], 1.4-2.8), higher charges ($45,126 versus $34,703; adjusted regression coefficient, $11,506; 95% CI, 6192-16,820), and greater need for parenteral nutrition (15.9% versus 12.1%; adjusted odds ratio, 1.5; 95% CI, 1.1-2.0) and blood transfusion (17.7% versus 9.8%; adjusted odds ratio, 1.8; 95% CI, 1.4-2.4). There were no deaths. We made similar observations in a subanalysis of cases with principal or secondary diagnoses of IBD or CDI. The incidence of CDI in patients with IBD increased between 2000 and 2009 from 21.7 to 28.0 cases per 1000 IBD cases per year (P < 0.001). There was a significant increase in CDI complicating ulcerative colitis (28.1 versus 42.2, P < 0.001) but not for Crohn's disease (18.3 versus 20.3)., Conclusions: CDI represents a significant health care burden in hospitalized children with IBD.

Background: Cardiovascular disease is seen at a younger age and at a higher prevalence in patients with type 1 diabetes than in the general population. It is well described that women with type 1 diabetes have a higher relative risk of cardiovascular disease than men with type 1 diabetes, unlike that seen in the general population. The pathophysiology behind this is unknown., Objective: We performed a cross-sectional study to examine sex differences in cardiovascular disease risk factors in adolescents with type 1 diabetes between ages 13 and 20 years, compared with children of a similar age without type 1 diabetes., Methods: All patients underwent a dual energy x-ray absorptiometry scan to measure body composition and a pulse wave test measure of arterial elasticity. Fasting serum lipid levels, apolipoprotein B, and apolipoprotein C-III levels were measured in each patient. Twenty-nine children with type 1 diabetes (10 girls, 19 boys) and 37 healthy children (18 girls, 19 boys) participated., Results: Although no sex differences for body mass index (P = 0.91) and glycosylated hemoglobin (P = 0.69) were seen, girls with type 1 diabetes had a significantly higher percent trunk fat compared with boys (P = 0.004). No sex differences were found (P > 0.05) for percent trunk fat in adolescents without diabetes. There was no sex difference among any other cardiovascular risk factors in either children with or without diabetes., Conclusions: Female adolescents with type 1 diabetes have more centrally distributed fat, which may contribute to their relatively higher cardiovascular disease risk. Attenuation of the central distribution of fat through exercise and dietary modifications may help ameliorate their subsequent cardiovascular disease burden., (Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.)

Purpose: To investigate the relationship between postmenstrual age of onset of retinopathy of prematurity (ROP) and the need for treatment, while examining the effects of two different neonatal oxygen saturation protocols on this relationship., Methods: A retrospective chart review was conducted for eligible inborn infants born before and after the institution of a new oxygen protocol adjusting target oxygen saturation from 90%-99% to 85%-93%. Early versus late-onset ROP was defined as first presence of any stage disease on examination at <36 versus ≥ 36 weeks' postmenstrual age, respectively., Results: The median birth weight/postmentrual age of infants was 840 g per 26.1 weeks (early-onset ROP) versus 952.5 g per 28 weeks (late-onset ROP; P < 0.01 vs P < 0.01). ROP developed in 119 of 369 (32.2%) of high oxygen target infants, and 100 of 373 (26.8%) infants in the low-target group (P = 0.11). Cumulatively, 35 of 144 (24.3%) of early-onset and 8 of 69 (11.6%) of late-onset patients required treatment (P = 0.03). Maximal severity of disease after treatment, including retinal detachment frequency, was similar in early- and late-onset patients, independent of the oxygen protocol (P = 1.00)., Conclusions: The clinical behavior of type 1 ROP is similar in early-and late-onset disease, regardless of oxygen saturation targets. Type 1 ROP disease occurred in 11.6% of patients with late-onset ROP., (Copyright © 2012 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.)

Objective: To investigate the association of Clostridium difficile infection (CDI) with the outcomes of hospitalized patients with end-stage renal disease (ESRD)., Methods: We extracted all adult cases with a discharge diagnosis of ESRD or CDI from the United States Nationwide Inpatient Sample 2009 database. Outcome variables (mortality, length of hospital stay [LOS], and hospitalization charges), demographic information, and comorbidity data were collected. Data were evaluated by univariate and multiple regression analyses., Results: We identified 184,139 cases with ESRD of which 2.8% had CDI. Comparison of patients with ESRD + CDI to those with only ESRD revealed in-hospital mortality (13.2% vs 5.3%; P < 0.001), LOS (17.3 vs 7.1 days; P < 0.001), and charges ($124,846 vs $56,663; P < 0.001) to be more than 2-fold greater. In the ESRD cohort (ESRD only and ESRD + CDI), CDI was independently associated with greater mortality (adjusted odds ratio, 2.15; 95% CI, 2.07-2.24; P < 0.001), longer LOS (mean difference, 9.4 days; 95% CI, 9.2-9.5; P < 0.001), and higher charges (mean difference, $62,824; 95% CI, 61,615-64,033; P < 0.001)., Conclusions: Clostridium difficile infection is associated with significantly worse outcomes in hospitalized patients with ESRD.

Objective: To determine whether patients receiving higher doses of caffeine have increased alkaline phosphatase (ALP) levels, as a biomarker for osteopenia., Methods: This descriptive, retrospective study included 152 extremely low-birth-weight infants (ie, <1 kg) admitted from January 1, 2007, to September 30, 2009, who received caffeine for >2 weeks. Patients were divided into a low-dose (<7.5 mg/kg/day) and high-dose (≥7.5 mg/kg/day) group based on maximum caffeine dose received. The primary objective was to compare peak ALP levels between groups. Secondary objectives included a comparison of caffeine regimens and risk factors for osteopenia between groups and identification of factors significantly related to increase in ALP. Between-group analysis was performed using the chi-squared or Fisher exact test and Wilcoxon Mann-Whitney median test or t-tests where appropriate. A linear regression model was used, with peak ALP as the dependent variable., Results: A majority of the patients (n=122) were included in the high-dose caffeine group. No significant difference in maximum ALP level between groups (median, 599.5, versus 602.5 units/L, p=0.72). Gestational age and birth weight were inversely related to ALP, whereas parenteral nutrition duration was directly related. No significant relationship between caffeine dose and ALP was identified., Conclusions: In this preliminary study, using ALP as a biochemical marker for bone turnover, there does not appear to be a dose-related effect between ALP and caffeine dose.