Outcomes of a Comprehensive Ultrasound Guided Peripheral IV Insertion (USGPIV) Training Program in a Pediatric Emergency Department.

INTRODUCTION: Timely and reliable peripheral intravenous cannulation is an imperative skill in a pediatric emergency department. Utilization of point-of-care ultrasound guidance has proven to significantly improve first-attempt peripheral intravenous cannulation insertion rates in pediatric patients. We sought to develop, implement, and evaluate an ultrasound-guided peripheral intravenous training program for emergency nurses in a tertiary care pediatric center. METHODS: Twelve emergency nurses underwent a training program that consisted of an interactive asynchronous learning module followed by 8 hours of training by a vascular access clinical instructor. Data was collected on each ultrasound-guided peripheral intravenous insertion via survey methodology. RESULTS: Complete data for a total of 210 ultrasound-guided peripheral intravenous were recorded over the 9-month period. A total of 65.2% (137/210) of patients who received an ultrasound-guided peripheral intravenous had known difficult intravenous access on history. A total of 89.5% (188/210) of patients had a difficult intravenous access of ≥4. The mean difficult intravenous access score for the patients in which ultrasound-guided peripheral intravenous insertions were attempted was 4.78 (95% confidence interval, 4.55-5.01). A total of 193 of 210 (91.9%) of ultrasound-guided peripheral intravenous were attained successfully. On the first attempt, 86.5% (167/193) ultrasound-guided peripheral intravenous were attained, and 98.96% (191/193) were attained within the first 2 attempts. CONCLUSION: We found that implementing a comprehensive ultrasound-guided peripheral intravenous training program for emergency nurses in a pediatric tertiary care center led to a high first-pass success rate in attaining peripheral intravenous cannulations. It also facilitates vascular access in patients with known difficult intravenous access. Consideration should be made to implementing point-of-care ultrasound intravenous training programs to improve pediatric vascular access in the emergency department, particularly in patients with known difficult intravenous access.

Conversion from tacrolimus to sirolimus as a treatment modality in de novo allergies and immune-mediated disorders in pediatric liver transplant recipients.

De novo PTAID may develop in pediatric solid organ transplant recipients, have a diverse spectrum, and are occasionally treatment resistant. Previous reports showed resolution of immune cytopenias in solid organ transplant recipients following replacement of the calcineurin inhibitor tacrolimus with the mTOR inhibitor sirolimus. Herein we describe a retrospective review (2000-2017) of subjects who developed PTAID in whom immunosuppression was changed to sirolimus. Eight recipients (6 males) of either liver (n = 7) or multivisceral transplant (n = 1) suffered from severe, treatment-resistant PTAID and were switched from tacrolimus to sirolimus. The median age at transplant was 1 year (range 0.5-2.4 years). Six (75%) recipients developed de novo allergy and 2 immune-mediated diseases. The median age at presentation of PTAID was 2.7 (1.4-9) years at a median of 1.3 (0.25-8) years after transplantation. The median time from PTAID presentation to conversion to sirolimus was 1.8 (0.45-10) years. Complete resolution of symptoms was seen in 4 (50%) patients after a median of 12 (range 4-24) months including 2 patients with immune-mediated disease, 1 eczema, and 1 with eosinophilic colitis. One patient with multiple food allergies had a partial response and 3 (38%) had no response. None of the 8 recipients developed sirolimus-attributed adverse events or acute rejection during a median follow-up of 5 (0.6-8) years after the conversion. Immunosuppression conversion from tacrolimus to sirolimus can be an effective therapy in patients suffering severe or treatment-resistant PTAID, suggesting a potential role for tacrolimus in the pathogenesis of PTAID.

Epigenetic Heterogeneity and Mitotic Heritability Prime Endothelial Cell Gene Induction.

Homogeneous populations of mature differentiated primary cell types can display variable responsiveness to extracellular stimuli, although little is known about the underlying mechanisms that govern such heterogeneity at the level of gene expression. In this article, we show that morphologically homogenous human endothelial cells exhibit heterogeneous expression of VCAM1 after TNF-α stimulation. Variability in VCAM1 expression was not due to stochasticity of intracellular signal transduction but rather to preexisting established heterogeneous states of promoter DNA methylation that were generationally conserved through mitosis. Variability in DNA methylation of the VCAM1 promoter resulted in graded RelA/p65 and RNA polymerase II binding that gave rise to a distribution of VCAM1 transcription in the population after TNF-α stimulation. Microarray analysis and single-cell RNA sequencing revealed that a number of cytokine-inducible genes shared this heterogeneous response pattern. These results show that heritable epigenetic heterogeneity is fundamental in inflammatory signaling and highlight VCAM1 as a metastable epiallele.

Pharmacotherapy in bronchiolitis at discharge from emergency departments within the Pediatric Emergency Research Networks: a retrospective analysis.

BACKGROUND: Clinical guidelines advise against pharmacotherapy in bronchiolitis. However, little is known about global variation in prescribing practices for bronchiolitis at discharge from emergency departments. We aimed to evaluate global variation in prescribing practice (ie, inhaled salbutamol, or oral or inhaled corticosteroids) for infants with bronchiolitis at discharge from emergency departments. METHODS: We did a planned secondary analysis of a multinational, retrospective cohort study of the Pediatric Emergency Research Networks. Previously healthy infants (aged <12 months) who were discharged with bronchiolitis between Jan 1 and Dec 31, 2013 from 38 emergency departments in Australia and New Zealand, Canada, Spain and Portugal, the UK and Ireland, and the USA were included. The primary outcome was pharmacotherapy prescription at discharge from the emergency department. Secondary outcomes were revisits to the emergency department or hospitalisations for bronchiolitis within 21 days of discharge. FINDINGS: Of 1566 infants discharged from the emergency department, 317 (20%) were prescribed pharmacotherapy. Corticosteroid prescriptions were infrequent, ranging from 0% (0 of 68 infants) in Spain and Portugal to 6% (25 of 452) in the USA. Salbutamol prescriptions ranged from 5% (22 of 432) in the UK and Ireland to 32% (146 of 452) in the USA. Compared with the UK and Ireland, the odds of prescription of pharmacotherapy were increased in Spain and Portugal (odds ratio [OR] 9·22, 95% CI 1·70-49·96), the USA (8·20, 2·79-24·11), Canada (5·17, 1·61-16·67), and Australia and New Zealand (1·21, 0·36-4·10). After adjustment for clustering by site, pharmacotherapy at discharge was associated with older age (per 1 month increase; OR 1·23, 95% CI 1·16-1·30), oxygen saturation (per 1% decrease from 100%; 1·09, 1·01-1·18), chest retractions (1·88, 1·26-2·79), network (p=0·00050), and site (p<0·00090). 303 (19%) of 1566 infants returned to the emergency department and 129 (43%) of 303 were hospitalised. Discharge pharmacotherapy was not associated with revisits (p=0·55) or subsequent hospitalisations (p=0·50). INTERPRETATION: Use of ineffective medications in infants with bronchiolitis at discharge from emergency departments is common, with large differences in prescribing practices between countries and emergency departments. Enhanced knowledge translation and deprescribing efforts are needed to optimise and unify the management of bronchiolitis. FUNDING: None.

Impact of Septal Deviation on Recurrent Chronic Rhinosinusitis after Primary Surgery: A Matched Case-Control Study.

OBJECTIVE: To evaluate the impact of untreated deviated nasal septum (DNS) on recalcitrant chronic rhinosinusitis (CRS) among patients undergoing revision endoscopic sinus surgery (ESS). STUDY DESIGN: Case-control study. SETTING: Tertiary academic center. SUBJECTS AND METHODS: We performed a retrospective review of 489 patients undergoing revision ESS for CRS at a tertiary academic center. Patients undergoing septoplasty were matched to nonseptoplasty controls based on age and sex. Preoperative Lund-Mackay score (LMS) was compared between cohorts. Linear regression was used to identify predictors of LMS and ostiomeatal complex (OMC) obstruction. RESULTS: Thirty-six matched pairs (72 patients) were selected for analysis: 36 undergoing septoplasty and revision ESS and 36 undergoing revision ESS alone. Compared with nonseptoplasty controls, the septoplasty group had a significantly higher average LMS (17.8 vs 14.6, P = .02) and a greater rate of OMC obstruction (89% vs 61%, P < .01). The septoplasty group also had significantly higher opacification scores in the maxillary (1.5 vs 1.2, P = .03) and posterior ethmoid (1.8 vs 1.4, P = .02) sinuses. On multivariable analysis, DNS was an independent predictor of LMS ( P = .02) and OMC obstruction ( P < .01). CONCLUSION: Untreated DNS is associated with radiographic markers of CRS severity among patients undergoing revision ESS and may contribute to the multifactorial pathogenesis of persistent CRS.

The Use of Neck Support Pillows and Postural Exercises in the Management of Chronic Neck Pain.

OBJECTIVE: Chronic neck pain is a common problem with a profound effect on quality of life. Identifying evidence-based management strategies is fundamental in improving patient outcomes. This study is a reanalysis of the data from Helewa, et al to further characterize the effects of postural exercises and neck support pillows on neck pain. METHODS: A full factorial model was used. All interactions were analyzed adjusting for the Northwick Park Neck Pain Questionnaire (NPQ) at baseline. RESULTS: Postural exercises significantly decreased NPQ scores at ≥ 3 weeks, and the use of a neck support pillow significantly decreased NPQ scores at ≥ 12 weeks. CONCLUSION: These interventions could be beneficial in reducing neck pain symptoms.

Gene regulation in the vascular endothelium: why epigenetics is important for the kidney.

We now appreciate that the vascular endothelium plays a crucial role in regulating normal blood vessel physiology in the kidney. The gene products responsible are commonly expressed exclusively, or preferentially, in this cell type. However, despite the importance of regulated gene expression in the vascular endothelium, relatively little is known about the mechanisms that restrict endothelial-specific gene expression to this cell type. Even less is known about how gene expression might be restricted to endothelial cells of discrete regions of the kidney, such as the glomerulus or vasa recta. Although significant progress has been made toward understanding the regulation of endothelial genes through cis/trans paradigms, it has become apparent that additional mechanisms also must be operative. Classic models of transcription in vascular endothelial cells, specifically the cis/trans paradigm, have limitations. For instance, how does the environment have chronic effects on gene expression in endothelial cells after weeks or years? When an endothelial cell divides, how is this information transmitted to daughter cells? Chromatin-based mechanisms, including cell-specific DNA methylation patterns and post-translational histone modifications, recently were shown to play important roles in gene expression. This review investigates the involvement of epigenetic regulatory mechanisms in vascular endothelial cell-specific gene expression using endothelial nitric oxide synthase as a prototypical model.