Update on pre-ECMO evaluation and treatment for term infants in respiratory failure.

The epidemiology, diagnostic and management approach to severe hypoxemic respiratory failure in the term and near-term neonate has evolved over time, as has the need for extracorporeal membrane oxygenation (ECMO) support in this patient population. Many patients who historically would have required ECMO support now respond to less invasive therapies, with patients requiring ECMO generally representing a higher risk and more heterogenous group of underlying diagnoses. This review will highlight these changes over time and the current available evidence for the diagnosis and management of these infants, as well as the current indications and relative contraindications to ECMO support when oxygen delivery cannot meet demand with less invasive management.

The association of inborn status and resource utilization among neonates who received extracorporeal membrane oxygenation.

BACKGROUND: Many studies have established that extracorporeal membrane oxygenation (ECMO) can be a cost-effective treatment in some populations, but limited data exist on which factors are associated with length of stay (LOS) and total hospital costs. This study aimed to determine if inborn (i.e., cared for in their birth hospitals) neonates who receive ECMO have different resource utilization and outcomes compared to outborn (i.e., not cared for in their birth hospitals) neonates who receive ECMO. METHODS: A retrospective cohort study was conducted using the Healthcare Cost and Utilization Project's Kids' Inpatient Database from 1997-2012. Neonates (infants, <28 days) placed on ECMO were categorized as either inborn or outborn. Salient clinical characteristics were compared between groups. A multivariable analysis was performed to identify the factors associated with length of stay (LOS), total hospital costs, and mortality in these two patient populations. RESULTS: Of 5,152 neonates receiving ECMO, 800 were inborn and 4,352 were outborn. Inborn neonates were more frequently diagnosed with cardiac-related diagnoses (70.5% vs 62.1%, p < 0.001). After adjusting for demographics and hospital-level factors, inborn neonates had longer hospital LOS (13.2 days, 95% CI, 8.7-18.7; p < 0.001), higher total encounter costs ($62,000, 95% CI, 40,000-85,000; p < 0.001) and higher mortality (OR 2.4, 95% CI 1.9-2.9; p < 0.001) compared to outborn neonates. CONCLUSIONS: Inborn neonates placed on ECMO were more frequently diagnosed with cardiac-related diseases or congenital diaphragmatic hernia, had longer LOS, higher total encounter costs, and higher mortality rates relative to their outborn counterparts, and likely represent a higher risk population. These two populations of infants may be inherently different and their differences should be further explored to inform decision making about optimal site of delivery.

Evaluation of Oxygen Saturation Index Compared With Oxygenation Index in Neonates With Hypoxemic Respiratory Failure.

Importance: Oxygenation index (OI), an invasive measurement, is routinely used as a marker of severity of hypoxemic respiratory failure in neonates. Oxygen saturation index (OSI) is a noninvasive measurement and has been shown to be a reliable surrogate marker of OI in children and adults with respiratory failure. Objectives: To evaluate the correlation of OI with OSI and to derive and validate predictive OI from noninvasive OSI measurements for clinically relevant OI values. Design, Setting, and Participants: For this retrospective cohort study, 220 neonates requiring invasive mechanical ventilation for hypoxic respiratory failure during the first 3 days of admission were recruited from a level III neonatal intensive care unit during a 6-year period, from January 1, 2012, to December 31, 2017. Data were analyzed from January 2017 to December 2017. Main Outcomes and Measures: The primary outcome was correlation of OI with OSI, analyzed using Pearson correlation coefficient. The secondary outcome was derivation and validation of OI from OSI. The data were split into derivative samples, from which a predictive equation for OI was derived using generalized linear model, and a validation sample was used to assess the predictive ability of the derived OI. Bland-Altman plot was used to assess agreement between derived OI and measured OI. Results: A total of 1442 paired OI and OSI measurements from 220 infants (190 preterm and 30 term; median [interquartile range] gestational age, 29 [26-33] weeks; mean [SD] birth weight, 1602 [1092] g) were recorded during the study. The median (interquartile range) number of samples was 5 (3-9) per patient. Overall, OI and OSI showed strong correlation (r = 0.89). The correlation was stronger in preterm infants (<28 weeks, r = 0.93; 28-33 weeks, r = 0.93) and within an oxygen saturation range of 85% to 95% (r = 0.94). The predictive derivative equation showed a strong linear association and good agreement in both derivation and validation data sets, with strong accuracy measures of derived OI for OI cutoffs of 5, 10, 15, 20, and 25. Conclusions and Relevance: A strong correlation of OI with OSI was found. Derived OI from OSI was in good agreement and strongly predictive of clinically relevant OI cutoffs from 5 to 25. Oxygenation index derived from noninvasive sources may be useful to reliably assess severity of respiratory failure and response to therapy on a continuous basis.

Associations of parental and peer characteristics with adolescents' social dominance orientation.

Studies with adults of social dominance orientation (SDO), a preference for inequality among social groups, have found correlations with various prejudices and support for discriminatory practices. This study explores the construct among adolescents at an age when they are beginning to recognize the social groups in their environment, particularly adolescent crowds. The relationship of SDO and perceptions of parents' responsiveness and demandingness were also investigated. Subjects were in grades 9-12 (N = 516, 53% female, 96% White). Mother's and father's responsiveness significantly predicted adolescent's SDO scores, with greater perceived responsiveness associated with lower SDO. To analyze the multiple crowd memberships of the 76% belonging to more than one crowd, two-step cluster analysis was used to identify patterns, resulting in 8 clusters of distinct, heterogeneous composition. SDO differed significantly among males in different clusters, but not females. The importance of membership was positively associated with SDO among high-status crowds and negatively associated with SDO among the academic and normal crowds. The findings have implications for prejudices that may be developing in adolescence and indicate a need for further research into the social context of SDO and its development.

The role of hRev7, the accessory subunit of hPolζ, in translesion synthesis past DNA damage induced by benzo[a]pyrene diol epoxide (BPDE).

BACKGROUND: DNA polymerase zeta (Polζ) is a specialized DNA polymerase that, unlike classical replicative polymerases, is capable of replicating past DNA lesions, i.e. of performing translesion synthesis (TLS). The catalytic subunit of hPolζ, hRev3, has been shown to play a critical role in DNA damage-induced mutagenesis in human cells, but less is known about the role of hRev7, the accessory subunit of hPolζ, in such mutagenesis. To address this question, we recently generated human fibroblasts with very significantly reduced levels of hRev7 protein and demonstrated that hRev7 is required to protect cells from ultraviolet(254 nm) (UV) radiation-induced cytotoxicity and mutagenesis (McNally et al., DNA Repair 7 (2008) 597-604). The goal of the present study was to determine whether hRev7 is similarly involved in the tolerance of DNA damage induced by benzo[a]pyrene diol epoxide (BPDE), the reactive form of the widespread environmental carcinogen benzo[a]pyrene. METHODS: To determine whether hRev7 also plays a role in protecting human cells from the cytotoxicity and mutagenesis induced by benzo[a]pyrene diol epoxide (BPDE), cell strains with reduced hRev7 were compared to their parental strain and a vector control strain for the effect of BPDE on cell survival, induction of mutations, and the ability to progress through the cell cycle. RESULTS: The results show that cell strains with reduced hRev7 are more sensitive to the cytotoxic effect of BPDE than the control strains, and progress through S-phase at a slower rate than the control cells following BPDE treatment, indicating that hRev7, and likely hPolζ, is required for efficient bypass of BPDE-induced DNA lesions. However, neither the frequency nor kinds of mutations induced by BPDE in cells with reduced hRev7 differ significantly from those induced in the control strains, suggesting that hPolζ is not essential for inserting nucleotides opposite BPDE-induced DNA damage. CONCLUSIONS: Taken together, our results which show that hRev7 is required for TLS past BPDE-induced DNA lesions but that it is not essential for inserting nucleotides opposite such lesions suggest a role for hPolζ in the extension step of translesion synthesis.

The challenge of adolescent crowd research: defining the crowd.

As research on adolescent crowds has increased over the past several decades, researchers appear to be confident in their claims of the consequences of crowd membership, even suggesting targeted interventions. This review of the various methods used to identify adolescents' crowd membership suggests that this confidence may be misplaced. There are diverse methodologies used in this research area that examine different samples of adolescents belonging to each crowd. Social-type rating methods, self-identification methods, grouping by adolescent behaviors or characteristics, and ethnographic or other qualitative methods should be accompanied by greater specificity in terminology to alert researchers to the various phenomena being studied (i.e., "reputational crowd," "interactional crowd," "behavioral crowd," "affiliation crowd"). Additionally, studies comparing the various self-identification approaches and peer ratings are needed, along with reliability studies of peer ratings. More attention to specific methodology to determine crowd membership and its stability will aid the design of theoretical models of adolescent crowds and contribute to developmental outcome research.

Effects of verbal and physical prompts on external strategy use in children with and without mild mental retardation.

Effects of type of prompt on the use of external strategies were examined. Participants were 7-, 9-, 11-, and 17-year-old children without mental retardation and 11- and 17-year-old children with mental retardation (N = 272). They were given a task requiring memory for object placement and assigned to one of four conditions: no prompt, verbal prompt, physical prompt, verbal and physical prompt. In the physical and verbal prompt condition, 17-year-old children with mental retardation used strategies at the same rate as 17-year-old children without mental retardation. Eleven-year-old children with mental retardation used similar types of strategies as the 7-year-old children without mental retardation. Thus, strategy use of older children with mental retardation may be activated to the same level of children without mental retardation with prompts.