Citations

ABSTRACTObjectivesThe congenital lung malformation volume ratio (CVR) is a prenatal ultrasound measurement that parameterizes congenital lung malformation (CLM) size. The aims of this study were to use serial measurements to create estimated growth curves of fetal CVR for asymptomatic and symptomatic neonates with CLM and to investigate whether a discriminant prognostic model based on these measurements could predict accurately which fetuses with CLM will require invasive respiratory support at delivery and should therefore be delivered at a tertiary‐care facility.MethodsThis was a retrospective study of fetuses diagnosed prenatally with CLM at three tertiary‐care children's hospitals between 2009 and 2016. Those with two or more sonographic measurements of CVR were included. Serial fetal CVR measurements were used to create estimated growth curves for neonates with and those without respiratory symptoms at delivery, defined as requiring invasive respiratory support for the first 24 h after delivery. A discriminant model based on serial CVR measurements was used to calculate the dynamic probability of the need for invasive respiratory support. The performance of this model overall and in preterm and term neonates was compared with those using maximum CVR thresholds of 1.0 and 1.6.ResultsOf the 147 neonates meeting the inclusion criteria, 16 (10.9%) required postnatal invasive respiratory support. The estimated CVR growth curve models showed different growth trajectories for asymptomatic and symptomatic neonates, with significantly higher CVR in symptomatic neonates, and values peaking late in the second trimester at around 25 weeks' gestation in asymptomatic neonates. All prognostic methods had high accuracy for the prediction of the need for invasive respiratory support in term neonates, but the discriminant model had the best performance overall (area under the receiver–operating characteristics curve (AUC) = 0.88) and in the preterm population (AUC = 0.85).ConclusionsThe estimated CVR growth curves showed different growth patterns in asymptomatic and symptomatic neonates with CLM. The dynamic discriminant model performed well overall and particularly in neonates that were carried to term. Development of an externally validated clinical tool based on this analysis could be useful in determining the site of delivery for fetuses with CLM. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

ABSTRACT Background and purpose: To evaluate the ability of the Well-Being Index (WBI) to stratify distress and well-being (high quality of life [QOL]) in nurse practitioners and physician assistants (NPs and PAs) and identify those whose degree of distress place them at an increased risk for medical error or turnover. Methods: A national sample of NPs and PAs completed a survey that included the WBI and instruments to measure QOL, fatigue, burnout, recent suicidal ideation, medical error, and intent to leave the current job. Conclusions: Overall, 1,576 of 4,106 (38.4%) NPs and PAs completed the survey. Those NPs and PAs with low mental QOL, extreme fatigue, recent suicidal ideation, or burnout had less favorable WBI scores (all p < .0001). Using a prevalence of low overall QOL among APPs of 14.4% as the pretest probability, the WBI score can reduce the posttest probability of low QOL to 2% or increase it to 64.7%. As the WBI score worsened, the posttest probability of high overall QOL decreased from 73% to 8.2%. Also, WBI score stratified the NPs and PAs likelihood of reporting recent medical errors and intent to leave his or her current job. Implications for practice: The WBI is a useful screening tool to stratify distress and well-being in APPs across a variety of domains and identify those NPs and PAs whose degree of distress may increase the risk of medical error or turnover.

Tumor recurrence in glioblastoma multiforme (GBM) is often attributed to acquired resistance to the standard chemotherapeutic agent, temozolomide (TMZ). Promoter methylation of the DNA repair gene MGMT (O6-methylguanine–DNA methyltransferase) has been associated with sensitivity to TMZ, whereas increased expression of MGMT has been associated with TMZ resistance. Clinical studies have observed a downward shift in MGMT methylation percentage from primary to recurrent stage tumors; however, the evolutionary processes that drive this shift and more generally the emergence and growth of TMZ-resistant tumor subpopulations are still poorly understood. Here, we develop a mathematical model, parameterized using clinical and experimental data, to investigate the role of MGMT methylation in TMZ resistance during the standard treatment regimen for GBM—surgery, chemotherapy, and radiation. We first found that the observed downward shift in MGMT promoter methylation status between detection and recurrence cannot be explained solely by evolutionary selection. Next, our model suggests that TMZ has an inhibitory effect on maintenance methylation of MGMT after cell division. Finally, incorporating this inhibitory effect, we study the optimal number of TMZ doses per adjuvant cycle for patients with GBM with high and low levels of MGMT methylation at diagnosis.