A Novel Method for Assessing Medication-Related Adverse Outcomes in a Community Hospital

The use of medications for hospitalized patients is universal, and unfortunately medication-related adverse outcomes are common. The accurate assessment of medication-related harm in hospitalized patients is foundational to the development of an effective hospital medication safety program. Every hospital has its own unique fingerprint of harm, accurate determination of the nature of medication-related harm specific to each hospital is necessary to facilitate prevention of that harm with specific and effective interventions. This project has provided a community hospital with its first systematic methodology for assessing medication-related harm. The methodology is adapted from that used in a recent national-level study. Several commonly accepted methods of assessment of medication-related adverse events are in use, but no single method is capable of giving a complete picture of harm at the hospital level. Using a method nearly identical to one employed in large national studies the author examined rates and types of medication-related adverse outcomes in a California community hospital. The hospital had about one-third the national rate of adverse events. An incidental finding was a 4-year pattern of increasing incidence of adverse outcomes followed by 2 years of declining incidence of adverse outcomes. The information gained from the novel assessment method provided a clearer picture of patient harm, a basis for a more effective medication safety plan, and promoted interprofessional collaboration

Characterization of the genomic features and expressed fusion genes in micropapillary carcinomas of the breast

Micropapillary carcinoma ( MPC ) is a rare histological special type of breast cancer, characterized by an aggressive clinical behaviour and a pattern of copy number aberrations ( CNAs ) distinct from that of grade‐ and oestrogen receptor ( ER )‐matched invasive carcinomas of no special type ( IC‐NSTs ). The aims of this study were to determine whether MPCs are underpinned by a recurrent fusion gene(s) or mutations in 273 genes recurrently mutated in breast cancer. Sixteen MPCs were subjected to microarray‐based comparative genomic hybridization ( aCGH ) analysis and Sequenom OncoCarta mutation analysis. Eight and five MPCs were subjected to targeted capture and RNA sequencing, respectively. aCGH analysis confirmed our previous observations about the repertoire of CNAs of MPCs . Sequencing analysis revealed a spectrum of mutations similar to those of luminal B IC‐NSTs , and recurrent mutations affecting mitogen‐activated protein kinase family genes and NBPF10 . RNA ‐sequencing analysis identified 17 high‐confidence fusion genes, eight of which were validated and two of which were in‐frame. No recurrent fusions were identified in an independent series of MPCs and IC‐NSTs . Forced expression of in‐frame fusion genes ( SLC2A1–FAF1 and BCAS4–AURKA ) resulted in increased viability of breast cancer cells. In addition, genomic disruption of CDK12 caused by out‐of‐frame rearrangements was found in one MPC and in 13% of HER2 ‐positive breast cancers, identified through a re‐analysis of publicly available massively parallel sequencing data. In vitro analyses revealed that CDK12 gene disruption results in sensitivity to PARP inhibition, and forced expression of wild‐type CDK12 in a CDK12 ‐null cell line model resulted in relative resistance to PARP inhibition. Our findings demonstrate that MPCs are neither defined by highly recurrent mutations in the 273 genes tested, nor underpinned by a recurrent fusion gene. Although seemingly private genetic events, some of the fusion transcripts found in MPCs may play a role in maintenance of a malignant phenotype and potentially offer therapeutic opportunities. © 2014 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106752/1/path4325.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/106752/2/path4325-sup-0001-AppendixS1.pd