2018 Update on Pediatric Medical Overuse: A Review.

Importance: Efforts to combat medical overuse have gained traction in recent years, but success has been intermittent and shortcomings have been recognized. A commitment to a strong evidence base is needed to more broadly engage clinicians and reduce overuse. Observations: A structured MEDLINE search and a manual review of tables of contents from selected high-impact journals was performed to identify original research published in 2017 relevant to pediatric overuse. Articles were scored from low to high for 3 categories: quality of methods, magnitude of potential harm, and number of patients potentially harmed. The top-scoring articles presented in this review highlight examples of safe reductions in treatment intensity, including in the setting of cancer, appendicitis, acute respiratory tract infection, and elective anesthesia. This year's articles also provide cautionary examples of rational interventions adopted without a full understanding of potential harms, including pharmacologic migraine therapies, docosahexaenoic acid supplementation for preterm neonates, tight glycemic control for individuals with critically illness, and prophylactic antibiotics for children with vesicoureteral reflux. Conclusions and Relevance: The articles represent high-quality, original research from 2017 that may help mitigate overuse. These works should be fundamental to the maturation of the pediatric overuse field.

Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer.

Germline mutations in the BRCA1 tumor suppressor gene often result in a significant increase in susceptibility to breast and ovarian cancers. Although the molecular basis of their effects remains largely obscure, many mutations are known to target the highly conserved C-terminal BRCT repeats that function as a phosphoserine/phosphothreonine-binding module. We report the X-ray crystal structure at a resolution of 1.85 A of the BRCA1 tandem BRCT domains in complex with a phosphorylated peptide representing the minimal interacting region of the DEAH-box helicase BACH1. The structure reveals the determinants of this novel class of BRCA1 binding events. We show that a subset of disease-linked mutations act through specific disruption of phospho-dependent BRCA1 interactions rather than through gross structural perturbation of the tandem BRCT domains.