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.

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.

Apnea induction for invasive lung function testing in infant olive baboons: Comparison of intravenous propofol versus hyperventilation.

BACKGROUND: In various types of pulmonary research, pulmonary function testing (PFT) is performed to quantify the severity of lung disease. Induction of apnea and positive pressure ventilation are required for accurate PFT measurements in non-cooperative subjects. We compared two methods of apnea induction in infant olive baboons (Papio anubis). METHODS: Pulmonary function testing results were compared during apnea induced by hyperventilation (CO2 washout) vs. intravenous propofol (1 dose 10 mg/kg). PFT was evaluated using a hot-wire pneumotachometer incorporated within an Avea ventilator in nine 1-month-old baboons. RESULTS: Propofol induced apnea faster and more reliably. In both groups, PFT values passed the statistical equivalence test and were not significantly different (Student's t-test). There was a trend toward less data variability after propofol administration. CONCLUSIONS: Intravenous propofol was non-inferior to CO2 washout for apnea induction in infant olive baboons. Propofol induced apnea faster and more reliably and yielded less variable PFT results.

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.

Reversal of epigenetic promoter silencing in Friedreich ataxia by a class I histone deacetylase inhibitor.

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.

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.

A Comparison of Nonopioid and Opioid Oral Analgesia Following Pediatric Palatoplasty.

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.

Macronutrient and micronutrient intakes of children in Oklahoma child-care centres, USA.

OBJECTIVE: To determine macronutrients and micronutrients in foods served to and consumed by children at child-care centres in Oklahoma, USA and compare them with Dietary Reference Intakes (DRI). DESIGN: Observed lunch nutrients compared with one-third of the age-based DRI (for 1-3 years-olds and 4-8-year-olds). Settings Oklahoma child-care centres (n 25), USA. SUBJECTS: Children aged 3-5 years (n 415). RESULTS: Regarding macronutrients, children were served 1782 (sd 686) kJ (426 (sd 164) kcal), 22·0 (sd 9·0) g protein, 51·5 (sd 20·4) g carbohydrate and 30·7 (sd 8·7) % total fat; they consumed 1305 (sd 669) kJ (312 (sd 160 kcal), 16·0 (sd 9·1) g protein, 37·6 (sd 18·5) g carbohydrate and 28·9 (sd 10·6) % total fat. For both age-based DRI: served energy (22-33 % of children), protein and carbohydrate exceeded; consumed energy (7-13 % of children) and protein exceeded, while carbohydrate was inadequate. Regarding micronutrients, for both age-based DRI: served Mg (65·9 (sd 24·7) mg), Zn (3·8 (sd 11·8) mg), vitamin A (249·9 (sd 228·3) µg) and folate (71·9 (sd 40·1) µg) exceeded; vitamin E (1·4 (sd 2·1) mg) was inadequate; served Fe (2·8 (sd 1·8) mg) exceeded only in 1-3-year-olds. Consumed folate (48·3 (sd 38·4) µg) met; Ca (259·4 (sd 146·2) mg) and Zn (2·3 (sd 3·0) mg) exceeded for 1-3-year-olds, but were inadequate for 4-8-year-olds. For both age-based DRI: consumed Fe (1·9 (sd 1·2) mg) and vitamin E (1·0 (sd 1·7) mg) were inadequate; Mg (47·2 (sd 21·8) mg) and vitamin A (155·0 (sd 126·5) µg) exceeded. CONCLUSIONS: Lunch at child-care centres was twice the age-based DRI for consumed protein, while energy and carbohydrate were inadequate. Areas of improvement for micronutrients pertain to Fe and vitamin E for all children; Ca, Zn, vitamin E and folate for older pre-schoolers. Adequate nutrients are essential for development and the study reveals where public health nutrition experts, policy makers and care providers should focus to improve the nutrient density of foods.

Patient Opinion on the Affordable Care Act in an Otolaryngology Practice: the Ideological Divide.

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.

A sequential naïve Bayes classifier for DNA barcodes.

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.

Team cohesiveness, team size and team performance in team-based learning teams.

OBJECTIVES: The purpose of this study was to explore the relationships among variables associated with teams in team-based learning (TBL) settings and team outcomes. METHODS: We administered the National Board of Medical Examiners (NBME) Psychiatry Subject Test first to individuals and then to teams of Year three students at four medical schools that used TBL in their psychiatry core clerkships. Team cohesion was analysed using the Team Performance Scale (TPS). Bivariate correlation and linear regression analysis were used to analyse the relationships among team-level variables (mean individual TPS scores for each team, mean individual NBME scores of teams, team size, rotation and gender make-up) and team NBME test scores. A hierarchical linear model was used to test the effects of individual TPS and individual NBME test scores within each team, as well as the effects of the team-level variables of team size, team rotation and gender on team NBME test scores. Individual NBME test and TPS scores were nested within teams and treated as subsampling units. RESULTS: Individual NBME test scores and individual TPS scores were positively and statistically significantly (p < 0.01) associated with team NBME test scores, when team rotation, team size and gender make-up were controlled for. Higher team NBME test scores were associated with teams rotating later in the year and larger teams (p < 0.01). Gender make-up was not significantly associated. CONCLUSIONS: The results of an NBME Psychiatry Subject Test administered to TBL teams at four medical schools suggest that larger teams on later rotations score higher on a team NBME test. Individual NBME test scores and team cohesion were positively and significantly associated with team NBME test scores. These results suggest the need for additional studies focusing on team outcomes, team cohesion, team size, rotation and other factors as they relate to the effective and efficient performance of TBL teams in health science education.

Instrumental activities of daily living performance and role satisfaction in people with and without mild cognitive impairment: a pilot project.

OBJECTIVE: We investigated differences in observed performance of instrumental activities of daily living (IADLs) and self-reported satisfaction with social role performance between people with amnestic mild cognitive impairment (a-MCI) and age- and gender-matched control participants. METHOD: We measured observed performance of 14 IADLs using the Independence, Safety, and Adequacy domains of the Performance Assessment of Self-Care Skills (PASS) and the Patient-Reported Outcomes Measurement Information Systems (PROMIS) to examine satisfaction with social role performance. RESULTS: Total PASS scores were significantly lower in participants with a-MCI (median=40.6) than in control participants (median=44.2; p=.006). Adequacy scores were also significantly lower. No significant differences were found between groups on the PROMIS measures. CONCLUSION: IADL differences between groups were related more to errors in adequacy than to safety and independence. Occupational therapy practitioners can play a key role in the diagnosis and treatment of subtle IADL deficits in people with MCI.

Tobacco Industry Influences in the Oklahoma Legislature.

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.

Changes in cardiac function and cerebral blood flow in relation to peri/intraventricular hemorrhage in extremely preterm infants.

OBJECTIVE: To investigate whether changes in cardiac function and cerebral blood flow (CBF) precede the occurrence of peri/intraventricular hemorrhage (P/IVH) in extremely preterm infants. STUDY DESIGN: In this prospective observational study, 22 preterm infants (gestational age 25.9 ± 1.2 weeks; range 23-27 weeks) were monitored between 4 and 76 hours after birth. Cardiac function and changes in CBF and P/IVH were assessed by ultrasound every 12 hours. Changes in CBF were also followed by continuous monitoring of cerebral regional oxygen saturation (rSO2) and by calculating cerebral fractional oxygen extraction. RESULTS: Five patients developed P/IVH (1 patient grade II and 4 patients grade IV). Whereas measures of cardiac function and CBF remained unchanged in neonates without P/IVH, patients with P/IVH tended to have lower left ventricular output and had lower left ventricle stroke volume and cerebral rSO2 and higher cerebral fractional oxygen extraction during the first 12 hours of the study. By 28 hours, these variables were similar in the 2 groups and myocardial performance index was lower and middle cerebral artery mean flow velocity higher in the P/IVH group. P/IVH was detected after these changes occurred. CONCLUSIONS: Cardiac function and CBF remain stable in very preterm neonates who do not develop P/IVH during the first 3 postnatal days. In very preterm neonates developing P/IVH during this period, lower systemic perfusion and CBF followed by an increase in these variables precede the development of P/IVH. Monitoring cardiac function and cerebral rSO2 may identify infants at higher risk for developing P/IVH before the bleeding occurs.

Association of fentanyl with neurodevelopmental outcomes in very-low-birth-weight infants.

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.

Trends in endoscopic retrograde cholangiopancreatography in children within the United States, 2000-2009.

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.