The electronic medication complete communication (EMC2) study: Rationale and methods for a randomized controlled trial of a strategy to promote medication safety in ambulatory care

AbstractBackgroundAdverse drug events (ADEs) affect millions of patients annually and place a significant burden on the healthcare system. The Food and Drug Administration (FDA) has developed patient safety information for high-risk medications that pose serious public health concerns. However, there are currently few assurances that patients receive this information or are able to identify or respond correctly to ADEs.ObjectiveTo evaluate the effectiveness of the Electronic Medication Complete Communication (EMC2) Strategy to promote safe medication use and reporting of ADEs in comparison to usual care.MethodsThe automated EMC2 Strategy consists of: 1) provider alerts to counsel patients on medication risks, 2) the delivery of patient-friendly medication information via the electronic health record, and 3) an automated telephone assessment to identify potential medication concerns or ADEs. The study will take place in two community health centers in Chicago, IL. Adult, English or Spanish-speaking patients (N=1200) who have been prescribed a high-risk medication will be enrolled and randomized to the intervention arm or usual care based upon practice location. The primary outcomes of the study are medication knowledge, proper medication use, and reporting of ADEs; these will be measured at baseline, 4weeks, and three months. Intervention fidelity as well as barriers and costs of implementation will be evaluated.ConclusionsThe EMC2 Strategy automates a patient-friendly risk communication and surveillance process to promote safe medication use while minimizing clinic burden. This trial seeks to evaluate the effectiveness and feasibility of this strategy in comparison to usual care

Identification of a Putative Salmonella enterica Serotype Typhimurium Host Range Factor with Homology to IpaH and YopM by Signature-Tagged Mutagenesis

The genetic basis for the host adaptation of Salmonella serotypes is currently unknown. We have explored a new strategy to identify Salmonella enterica serotype Typhimurium (S. typhimurium) genes involved in host adaptation, by comparing the virulence of 260 randomly generated signature-tagged mutants during the oral infection of mice and calves. This screen identified four mutants, which were defective for colonization of only one of the two host species tested. One mutant, which only displayed a colonization defect during the infection of mice, was further characterized. During competitive infection experiments performed with the S. typhimurium wild type, the mutant was defective for colonization of murine Peyer's patches but colonized bovine Peyer's patches at the wild-type level. No difference in virulence between wild type and mutant was observed when calves were infected orally with 10(10) CFU/animal. In contrast, the mutant possessed a sixfold increase in 50% lethal morbidity dose when mice were infected orally. The transposon in this mutant was inserted in a 2.9-kb pathogenicity islet, which is located between uvrB and yphK on the S. typhimurium chromosome. This pathogenicity islet contained a single gene, termed slrP, with homology to ipaH of Shigella flexneri and yopM of Yersinia pestis. These data show that comparative screening of signature-tagged mutants in two animal species can be used for scanning the S. typhimurium genome for genes involved in host adaptation

Incorporating uncertainty associated with habitat data in marine reserve design

One of the most pervasive forms of uncertainty in data used to make conservation decisions is error associated with mapping of conservation features. Whilst conservation planners should consider uncertainty associated with ecological data to make informed decisions, mapping error is rarely, if ever, accommodated in the planning process. Here, we develop a spatial conservation prioritization approach that accounts for the uncertainty inherent in coral reef habitat maps and apply it in the Kubulau District fisheries management area, Fiji. We use accuracy information describing the probability of occurrence of each habitat type, derived from remote sensing data validated by field surveys, to design a marine reserve network that has a high probability of protecting a fixed percentage (10-90%) of every habitat type. We compare the outcomes of our approach to those of standard reserve design approaches, where habitat-mapping errors are not known or ignored. We show that the locations of priority areas change between the standard and probabilistic approaches, with errors of omission and commission likely to occur if reserve design does not accommodate mapping accuracy. Although consideration of habitat mapping accuracy leads to bigger reserve networks, they are unlikely to miss habitat conservation targets. We explore the trade-off between conservation feature representation and reserve network area, with smaller reserve networks possible if we give up on trying to meet targets for habitats mapped with a low accuracy. The approach can be used with any habitat type at any scale to inform more robust and defensible conservation decisions in marine or terrestrial environments. (C) 2013 Elsevier Ltd. All rights reserved

MYC regulates ribosome biogenesis and mitochondrial gene expression programs through its interaction with host cell factor-1.

The oncoprotein transcription factor MYC is a major driver of malignancy and a highly validated but challenging target for the development of anticancer therapies. Novel strategies to inhibit MYC may come from understanding the co-factors it uses to drive pro-tumorigenic gene expression programs, providing their role in MYC activity is understood. Here we interrogate how one MYC co-factor, host cell factor (HCF)-1, contributes to MYC activity in a human Burkitt lymphoma setting. We identify genes connected to mitochondrial function and ribosome biogenesis as direct MYC/HCF-1 targets and demonstrate how modulation of the MYC-HCF-1 interaction influences cell growth, metabolite profiles, global gene expression patterns, and tumor growth in vivo. This work defines HCF-1 as a critical MYC co-factor, places the MYC-HCF-1 interaction in biological context, and highlights HCF-1 as a focal point for development of novel anti-MYC therapies

Sustained proliferation in cancer: mechanisms and novel therapeutic targets

Proliferation is an important part of cancer development and progression. This is manifest by altered expression and/or activity of cell cycle related proteins. Constitutive activation of many signal transduction pathways also stimulates cell growth. Early steps in tumor development are associated with a fibrogenic response and the development of a hypoxic environment which favors the survival and proliferation of cancer stem cells. Part of the survival strategy of cancer stem cells may manifested by alterations in cell metabolism. Once tumors appear, growth and metastasis may be supported by overproduction of appropriate hormones (in hormonally dependent cancers), by promoting angiogenesis, by undergoing epithelial to mesenchymal transition, by triggering autophagy, and by taking cues from surrounding stromal cells. A number of natural compounds (e.g., curcumin, resveratrol, indole-3-carbinol, brassinin, sulforaphane, epigallocatechin-3-gallate, genistein, ellagitannins, lycopene and quercetin) have been found to inhibit one or more pathways that contribute to proliferation (e.g., hypoxia inducible factor 1, nuclear factor kappa B, phosphoinositide 3 kinase/Akt, insulin-like growth factor receptor 1, Wnt, cell cycle associated proteins, as well as androgen and estrogen receptor signaling). These data, in combination with bioinformatics analyses, will be very important for identifying signaling pathways and molecular targets that may provide early diagnostic markers and/or critical targets for the development of new drugs or drug combinations that block tumor formation and progression

Convergent Evolution of Escape from Hepaciviral Antagonism in Primates

Escape from antagonism by hepatitis C and related viruses has repeatedly evolved in antiviral factor MAVS via convergent evolution, revealing an ancient history of previous viral encounters in primates

Expression of Xhdsi-1VOC, a novel member of the vicinal oxygen chelate (VOC) metalloenzyme superfamily, is up-regulated in leaves and roots during desiccation in the resurrection plant Xerophyta humilis (Bak) Dur and Schinz

The annotation of novel plant genes is frequently based on sequence and structural similarity to known protein motifs. Understanding the biological function of these genes is dependent on identifying conditions under which they are activated, however. The resurrection plant, Xerophyta humilis is a good model system for identifying and characterizing genes which are important for desiccation tolerance. Desiccation induced-1 (dsi-1VOC), a previously uncharacterized plant gene, is up-regulated during desiccation in leaves, roots, and seeds in X. humilis. The X. humilis desiccation induced-1 gene, Xhdsi-1VOC, shares structural homology with the vicinal oxygen chelate (VOC) metalloenzyme superfamily. Proteins in this superfamily share little sequence similarity, but are characterized by a common βαβββ structural fold. A number of plant orthologues of XhDsi-1VOC have been identified, including Arabidopsis thaliana At1g07645, which is currently annotated as a glyoxalase I-like gene, and many ESTs derived from seed cDNA libraries. Xhdsi-1VOC and its orthologues do not, however, contain the glutathione and zinc binding sites conserved in glyoxalase I genes. Furthermore, expression of Xhdsi-1VOC in yeast failed to rescue a yeast glyoxalase I mutant. Messenger RNA transcripts for At1g07645 accumulate during seed maturation, but are not induced by water loss, salt or mannitol stress in vegetative tissue in Arabidopsis. It is concluded that dsi-1VOC is a seed-specific gene in desiccation-sensitive plants that is activated by water loss in vegetative tissues in the resurrection plant X. humilis and plays an important role in allowing plant tissues to survive loss of 95% of their relative water content

Building an immune-mediated coagulopathy consensus: early recognition and evaluation to enhance post-surgical patient safety

Topical hemostats, fibrin sealants, and surgical adhesives are regularly used in a variety of surgical procedures involving multiple disciplines. Generally, these adjuncts to surgical hemostasis are valuable means for improving wound visualization, reducing blood loss or adding tissue adherence; however, some of these agents are responsible for under-recognized adverse reactions and outcomes. Bovine thrombin, for example, is a topical hemostat with a long history of clinical application that is widely used alone or in combination with other hemostatic agents. Hematologists and coagulation experts are aware that these agents can lead to development of an immune-mediated coagulopathy (IMC). A paucity of data on the incidence of IMC contributes to under-recognition and leaves many surgeons unaware that this clinical entity, originating from normal immune responses to foreign antigen exposure, requires enhanced post-operative vigilance and judicious clinical judgment to achieve best outcomes