Off-Label Medication use in Children, More Common than We Think: A Systematic Review of the Literature.

CONTENT: Clinician prescribing of off-label medications is common due to a lack of pediatric-specific data regarding the dosing, efficacy and safety of medications regularly prescribed to children. OBJECTIVE: This systematic review summarizes the published incidence of off-label medication use in children from the past 10 years. We also performed a retrospective chart review to determine the incidence of off-label prescriptions for children seen in the OU Physicians clinics. DATA SOURCES: We conducted a literature search of PubMed and OVID Medline from 2007 to 2017. Search terms included off-label use of medications and all child. For the local review, the outpatient electronic medical record (EMR) was queried. STUDY SELECTION: Studies were eligible for inclusion if the study included children < 18 years of age, defined off-label use in the paper, and included the incidence of off-label drug use. DATA EXTRACTION: Each review author extracted the study data from their assigned studies. For the retrospective chart review, the EMR was queried for patients <21 years of age who had a clinic visit and received a new prescription during 2017. RESULTS: We identified 31 studies, with off-label prescription rates from 3.2 % to 95%. The local retrospective chart review included 1,323 prescriptions; 504 were off-label (38.1%) and 819 were approved. The frequency of off-label prescriptions does not differ significantly between the meta-analysis from the systematic review and the local retrospective chart review (30.9% vs 38.1%). CONCLUSIONS: The use of off-label medications in children remains a common practice for pediatric providers.

Loss of function of parathyroid hormone receptor 1 induces Notch-dependent aortic defects during zebrafish vascular development.

OBJECTIVE: Coarctation of the aorta is rarely associated with known gene defects. Blomstrand chondrodysplasia, caused by mutations in the parathyroid hormone receptor 1 (PTHR1) is associated with coarctation of the aorta in some cases, although it is unclear whether PTHR1 deficiency causes coarctation of the aorta directly. The zebrafish allows the study of vascular development using approaches not possible in other models. We therefore examined the effect of loss of function of PTHR1 or its ligand parathyroid hormone-related peptide (PTHrP) on aortic formation in zebrafish. APPROACH AND RESULTS: Morpholino antisense oligonucleotide knockdown of either PTHR1 or PTHrP led to a localized occlusion of the mid-aorta in developing zebrafish. Confocal imaging of transgenic embryos showed that these defects were caused by loss of endothelium, rather than failure to lumenize. Using a Notch reporter transgenic ([CSL:Venus]qmc61), we found both PTHR1 and PTHrP knockdown-induced defective Notch signaling in the hypochord at the site of the aortic defect before onset of circulation, and the aortic occlusion was rescued by inducible Notch upregulation. CONCLUSIONS: Loss of function of either PTHR1 or PTHrP leads to a localized aortic defect that is Notch dependent. These findings may underlie the aortic defect seen in Blomstrand chondrodysplasia, and reveal a link between parathyroid hormone and Notch signaling during aortic development.

Adapting Pediatric Medical Homes for Youth in Foster Care: Extensions of the American Academy of Pediatrics Guidelines.

This article provides recommendations for adapting the pediatric medical home (PMH) model for health care needs of youth in foster care. Recommendations are based on key informant interviews regarding experiences at an established PMH for youth in foster care. Major clinic recommendations include expanding the PMH framework to include proficiency in Medicaid billing, promoting true interdisciplinary care teams, improving care accessibility via phone consultation, providing a stable place for medical records to be housed, delivering services throughout stages of the child welfare case, incorporating all family members, and implementing trauma-informed practice. Preliminary evidence suggests that the PMH model of care may be ideal for addressing the complex and often underserved needs of youth in foster care and their families. The present recommendations provide a logistical framework for establishing a clinic that thoughtfully considers the unique needs of this population. Future research is needed to examine best practices for implementation.

The zebrafish as a novel tool for cardiovascular drug discovery.

The zebrafish is a well established model of vertebrate development, but has recently emerged as a powerful tool for cardiovascular research and in vivo cardiovascular drug discovery. The zebrafish embryo's low cost, small size and permeability to small molecules coupled with the ability to generate thousands of embryos per week, and improved automation of assays of cardiovascular development and performance allow drug screening for a number of cardiovascular effects. Such studies have already led to discovery of novel cardiovascular drugs with potentially clinically beneficial effects. In this review we summarise the advantages and disadvantages of the zebrafish for drug discovery using some patents, previous literature on zebrafish-based drug screening and assess where the zebrafish will fit into existing drug discovery programmes.