Development and usability of a virtual reality umbilical venous catheter placement simulator.

PURPOSE: Exposure to procedures varies in the neonatal intensive care unit (NICU). A method to teach procedures should be available without patient availability, expert oversight, or simulation laboratories. To fill this need, we developed a virtual reality (VR) simulation for umbilical vein catheter (UVC) placement and sought to establish its face and content validity and usability. METHODS: Engineers, software developers, graphic designers, and neonatologists developed a VR UVC placement simulator following a participatory design approach. The software was deployed on the Meta Quest 2 head-mounted display (HMD). Neonatal nurse practitioners (NNPs) from a level 4 NICU used the simulator and completed an 11-item questionnaire to establish face and content validity. Participants also completed the validated simulation task load index and system usability scale to assess the usability of the simulator. Group 1 tested the VR simulation, which was optimized based on feedback, prior to Group 2's participation. RESULTS: A total of 14 NNPs with 2-37 years of experience participated in testing. Participants scored the content and face validity of the simulator highly, with most giving scores ≥ 4/5. Usability was established with relatively high average system usability scores for both groups (Group 1: 67.14 ± 7.8, Group 2: 71 ± 14.1) and low SIM-TLX scores indicating manageable load while using the simulator. CONCLUSION: After optimization, Group 2 found the UVC simulator to be realistic and effective. Both groups felt the simulator was easy to use and did not cause physical or cognitive strain. All participants felt the UVC simulator provided a safe environment to make mistakes, and the majority would recommend this experience to trainees.

A Quality Improvement Project to Reduce Antibiotic Exposure in Premature Neonates.

BACKGROUND AND OBJECTIVES: Overuse of antibiotics in NICUs is a problem worldwide. Unnecessary antibiotic exposure leads to resistance, changes in the microbiome, and increases the risk of bronchopulmonary dysplasia, retinopathy of prematurity, periventricular leukomalacia, necrotizing enterocolitis, late-onset sepsis (LOS), and mortality in neonates. We aimed to safely reduce the antibiotic usage rate (AUR) in our level IV unit by 10% by December 2018. METHODS: A multidisciplinary quality improvement project took place as part of a Vermont Oxford Network initiative in 2018. Multiple interventions took place, including identification of variations in practices and subsequent standardization through the creation of early onset and LOS guidelines, mass education, improved visibility of the guidelines, and standardized documentation. The main outcome measure for this project was the AUR for infants born <35 weeks' gestation expressed as antibiotic doses per 1000 patient days. RESULTS: The AUR decreased from a mean of 524 to 394, for a decrease of 24.8%. Results have been sustained for 3 years. Main contributors that led to the sustained success include decreasing the overall use of antibiotics for early onset sepsis, as well as the duration when cultures are negative. The number of LOS courses also decreased slightly. We noted no cases of inadequately treated sepsis resulting in subsequent positive cultures. CONCLUSIONS: Creation of guidelines with mass education and ongoing feedback/monitoring can result in a safe reduction of AUR in the NICU.

Characterization of laboratory coagulation parameters and risk factors for intraventricular hemorrhage in extremely premature neonates.

BACKGROUND: Extremely premature neonates have increased risk for bleeding, perhaps the most devastating version of which being intraventricular hemorrhage (IVH). Limited data are available for coagulation parameters in this vulnerable population. OBJECTIVES: We conducted a prospective cohort study characterizing coagulation laboratory parameters in extremely premature neonates 23-30 weeks gestational age (GA) and determined coagulation parameters and clinical risk factors associated with IVH. PATIENTS/METHODS: One hundred twenty neonates 23-30 weeks GA were enrolled, and umbilical cord blood samples were obtained and processed at the time of birth. Coagulation parameters including prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), and activity assays for factors II, VII, IX, X, XIII, and XIII subunit A antigen were performed by standard methods. Clinical risk factors were analyzed for association with IVH. RESULTS: Of the enrolled neonates, 29 (24.2%) experienced IVH. Persistent pulmonary hypertension (PPHN) independently predicted IVH risk with odds ratio (OR) 5.3 (95% confidence interval [CI] 1.1-24.3), P = .0338; and chronic lung disease (CLD) approached significance with OR 2.3 (95% CI 0.9-5.5), P = .0659. Coagulation parameters were evaluated for association with IVH, and there was no significant difference among coagulation tests in neonates with or without IVH or per GA. Reduced factor XIII subunit A showed significant association with death, P = .003. CONCLUSIONS: We present a large, prospective study of laboratory coagulation parameters in extremely premature neonates, including factor X, factor XIII, and factor XIII subunit A not previously described in this population. These findings may impact clinical practice and should encourage additional study in this vulnerable population.

Uncertain, Not Unimportant: Callosal Dysgenesis and Variants of Uncertain Significance in ROBO1.

Congenital anomalies affect 3% to 5% of births and remain the leading cause of infant death in the United States. As whole exome and genome sequencing are increasingly used to diagnose underlying genetic disease, the patient's clinical presentation remains the most important context for interpreting sequencing results, including frequently reported variants of uncertain significance (VUS). Classification of a variant as VUS acknowledges limits on evidence to establish whether a variant can be classified as pathogenic or benign according to the American College of Medical Genetics guidelines. Importantly, the VUS designation reflects limits on the breadth of evidence linking the genetic variant to a disease. However, available evidence, although limited, may be surprisingly relevant in an individual patient's case. Accordingly, a VUS result should be approached neither as nondiagnostic genetic result nor as automatically "uncertain" in its potential to guide clinical decision-making. In this article, we discuss a case of an infant born at 29 weeks 4 days without a corpus callosum, whose whole genome sequencing yielded compound heterozygous variants both classified as VUS in ROBO1, a gene encoding for a receptor involved in a canonical signaling mechanism that guides axons across midline. Approaching the VUS result as potentially pathogenic, we found the infant ultimately had pituitary dysfunction and renal anomalies consistent with other reported ROBO1 variants and basic science literature. Accordingly, we highlight resources for variant interpretation available to clinicians to evaluate VUS results, particularly as they inform the diagnosis of individually rare but collectively common rare diseases.

Risk factors associated with intraventricular hemorrhage in extremely premature neonates.

: Intraventricular hemorrhage (IVH) is a significant cause of morbidity in extremely premature infants despite many advances in neonatal intensive care. We conducted an institutional retrospective review aimed to correlate risk factors associated with IVH. Clinical variables reported to the Vermont-Oxford Network on less than 30 weeks gestational age infants over a 5-year period were evaluated with Pearson's chi-square and multivariate logistic regression. Of 618 infants born less than 30-week gestational age, 178 (28.8%) experienced IVH. Of those less than 1000 g, 105 (36.5%) of 288 infants experienced IVH. Multivariate analysis revealed that thrombocytopenia [odds ratio (OR) 2.03, 95% confidence interval (CI) 1.30-3.19, P = 0.0020] and cardiopulmonary resuscitation (CPR) ±â€Šintubation at delivery (OR 1.84, 95% CI 1.12-3.02, P = 0.0162) were independently associated with IVH. Among infants less than 1000 g, thrombocytopenia (OR 2.09, 95% CI 1.22-3.60, P = 0.0077) and CPR ±â€Šintubation at delivery (OR 2.01, 95% CI 1.10-3.68, P = 0.0229) were also significantly associated with IVH. IVH is a complex phenomenon with many contributing risk factors. In our study, infants less than 30-week gestational age and less than 1000 g revealed thrombocytopenia and CPR ±â€Šintubation in delivery room were independently associated with IVH. These data should alert clinicians to those neonates most likely to suffer IVH.

Endothelial colony forming cells and mesenchymal stem cells are enriched at different gestational ages in human umbilical cord blood.

Endothelial progenitor cells (EPCs) are used for angiogenic therapies and as biomarkers of cardiovascular disease. Human umbilical cord blood (UCB) is a rich source of endothelial colony forming cells (ECFCs), which are EPCs with robust proliferative potential that may be useful for clinical vascular regeneration. Previous studies show that hematopoietic progenitor cells are increased in premature UCB compared with term controls. Based on this paradigm, we hypothesized that premature UCB would be an enriched source of ECFCs. Thirty-nine UCB samples were obtained from premature infants (24-37 wk gestational age (GA)) and term controls. ECFC colonies were enumerated, clonally isolated, and identified by expression of endothelial cell surface antigens and functional analysis. GA of 33-36 wk UCB yielded predominantly ECFC colonies at equivalent numbers to term infants. UCB from 24 to 28 wk GA infants had significantly fewer ECFCs. Surprisingly, 24-28 wk GA UCB yielded predominantly mesenchymal stem cell (MSC) colonies, capable of differentiating into adipocytes, chondrocytes, and osteocytes. MSCs were rarely identified in 37-40 wk GA UCB. These studies demonstrate that circulating MSCs and ECFCs appear at different GA in the human UCB, and that 24-28 wk GA UCB may be a novel source of MSCs for therapeutic use in human diseases.