Documentation Burden in Nursing and Its Role in Clinician Burnout Syndrome.

Objectives: The purpose of this study is to understand the relationship between documentation burden and clinician burnout syndrome in nurses working in direct patient care. The Office of the National Coordinator considers documentation burden a high priority problem. However, the presence of documentation burden in nurses working in direct patient care is not well known.

Design and Synthesis of LM146, a Potent Inhibitor of PB1 with an Improved Selectivity Profile over SMARCA2.

PB1 is a bromodomain-containing protein hypothesized to act as the nucleosome-recognition subunit of the PBAF complex. Although PB1 is a key component of the PBAF chromatin remodeling complex, its exact role has not been elucidated due to the lack of potent and selective inhibitors. Chemical probes that target specific bromodomains within the complex would constitute highly valuable tools to characterize the function and therapeutic pertinence of PB1 and of each of its bromodomains.

BET Bromodomain Inhibition Blocks an AR-Repressed, E2F1-Activated Treatment-Emergent Neuroendocrine Prostate Cancer Lineage Plasticity Program.

Purpose: Lineage plasticity in prostate cancer-most commonly exemplified by loss of androgen receptor (AR) signaling and a switch from a luminal to alternate differentiation program-is now recognized as a treatment resistance mechanism. Lineage plasticity is a spectrum, but neuroendocrine prostate cancer (NEPC) is the most virulent example. Currently, there are limited treatments for NEPC.

Nursing Documentation Variation Across Different Medical Facilities Within an Integrated Healthcare System.

The purpose of this study was to demonstrate nursing documentation variation based on electronic health record design and its relationship with different levels of care by reviewing how various flowsheet measures, within the same electronic health record across an integrated healthcare system, are documented in different types of medical facilities. Flowsheet data with information on patients who were admitted to academic medical centers, community hospitals, and rehabilitation centers were used to calculate the frequency of flowsheet entries documented. We then compared the distinct flowsheet measures documented in five flowsheet templates across the different facilities.

The Burden and Burnout in Documenting Patient Care: An Integrative Literature Review.

The implementation of the electronic health record (EHR) across the globe has increased significantly in the last decade. Motivations for this trend include patient safety, regulatory requirements, and healthcare cost containment. However, the impact of regulatory requirements and new EHRs on clinicians has increased the incidence of documentation burden and may lead to burnout syndrome.

A Decade of Experience in Creating and Maintaining Data Elements for Structured Clinical Documentation in EHRs.

Structured clinical documentation is an important component of electronic health records (EHRs) and plays an important role in clinical care, administrative functions, and research activities. Clinical data elements serve as basic building blocks for composing the templates used for generating clinical documents (such as notes and forms). We present our experience in creating and maintaining data elements for three different EHRs (one home-grown and two commercial systems) across different clinical settings, using flowsheet data elements as examples in our case studies.

Prioritization and Refinement of Clinical Data Elements within EHR Systems.

Standardization of clinical data element (CDE) definitions is foundational to track, interpret, and analyze patient states, populations, and costs across providers, settings and time - critical activities to achieve the Triple Aim: improving the experience of care, improving the health of populations, and reducing per capita healthcare costs. We defined and implemented two analytical methods to prioritize and refine CDE definitions within electronic health records (EHRs), taking into account resource restrictions to carry out the analysis and configuration changes: 1) analysis of downstream data needs to identify high priority clinical topics, and 2) gap analysis of EHR CDEs when compared to reference models for the same clinical topics. We present use cases for six clinical topics.

Analysis of Nursing Clinical Decision Support Requests and Strategic Plan in a Large Academic Health System.

Objectives: To understand requests for nursing Clinical Decision Support (CDS) interventions at a large integrated health system undergoing vendor-based EHR implementation. In addition, to establish a process to guide both short-term implementation and long-term strategic goals to meet nursing CDS needs.

Materials And Methods: We conducted an environmental scan to understand current state of nursing CDS over three months.

RVX-297- a novel BD2 selective inhibitor of BET bromodomains.

Bromodomains are epigenetic readers that specifically bind to the acetyl lysine residues of histones and transcription factors. Small molecule BET bromodomain inhibitors can disrupt this interaction which leads to potential modulation of several disease states. Here we describe the binding properties of a novel BET inhibitor RVX-297 that is structurally related to the clinical compound RVX-208, currently undergoing phase III clinical trials for the treatment of cardiovascular diseases, but is distinctly different in its biological and pharmacokinetic profiles.

Pain Documentation: Validation of a Reference Model.

Over the last decade, interoperability of the Electronic Health Record (EHR) is becoming more of a reality. However, inconsistencies in documentation such as pain are considered a barrier to obtaining this goal. In order to be able to remedy this issue, it is necessary to validate reference models that have been created based upon requirements defined by Health Level 7 (HL7), Logical Names and Codes (LOINC) and the Intermountain Clinical Element Model using external published sources and guidelines.

A Practical Approach to Governance and Optimization of Structured Data Elements.

Definition and configuration of clinical content in an enterprise-wide electronic health record (EHR) implementation is highly complex. Sharing of data definitions across applications within an EHR implementation project may be constrained by practical limitations, including time, tools, and expertise. However, maintaining rigor in an approach to data governance is important for sustainability and consistency.

Discovery of a new chemical series of BRD4(1) inhibitors using protein-ligand docking and structure-guided design.

Bromodomains are key transcriptional regulators that are thought to be druggable epigenetic targets for cancer, inflammation, diabetes and cardiovascular therapeutics. Of particular importance is the first of two bromodomains in bromodomain containing 4 protein (BRD4(1)). Protein-ligand docking in BRD4(1) was used to purchase a small, focused screening set of compounds possessing a large variety of core structures.

BET and HDAC inhibitors induce similar genes and biological effects and synergize to kill in Myc-induced murine lymphoma.

The bromodomain and extraterminal (BET) domain family of proteins binds to acetylated lysines on histones and regulates gene transcription. Recently, BET inhibitors (BETi) have been developed that show promise as potent anticancer drugs against various solid and hematological malignancies. Here we show that the structurally novel and orally bioavailable BET inhibitor RVX2135 inhibits proliferation and induces apoptosis of lymphoma cells arising in Myc-transgenic mice in vitro and in vivo.

RVX-208, an inducer of ApoA-I in humans, is a BET bromodomain antagonist.

Increased synthesis of Apolipoprotein A-I (ApoA-I) and HDL is believed to provide a new approach to treating atherosclerosis through the stimulation of reverse cholesterol transport. RVX-208 increases the production of ApoA-I in hepatocytes in vitro, and in vivo in monkeys and humans, which results in increased HDL-C, but the molecular target was not previously reported. Using binding assays and X-ray crystallography, we now show that RVX-208 selectively binds to bromodomains of the BET (Bromodomain and Extra Terminal) family, competing for a site bound by the endogenous ligand, acetylated lysine, and that this accounts for its pharmacological activity.

Cas5d processes pre-crRNA and is a member of a larger family of CRISPR RNA endonucleases.

Small RNAs derived from clustered, regularly interspaced, short palindromic repeat (CRISPR) loci in bacteria and archaea are involved in an adaptable and heritable gene-silencing pathway. Resistance to invasive genetic material is conferred by the incorporation of short DNA sequences derived from this material into the genome as CRISPR spacer elements separated by short repeat sequences. Processing of long primary transcripts (pre-crRNAs) containing these repeats by a CRISPR-associated (Cas) RNA endonuclease generates the mature effector RNAs that target foreign nucleic acid for degradation.

Role of pri-miRNA tertiary structure in miR-17~92 miRNA biogenesis.

MicroRNAs (miRNAs) regulate gene expression in a variety of biological pathways such as development and tumourigenesis. miRNAs are initially expressed as long primary transcripts (pri-miRNAs) that undergo sequential processing by Drosha and then Dicer to yield mature miRNAs. miR-17~92 is a miRNA cluster that encodes 6 miRNAs and while it is essential for development it also has reported oncogenic activity.

Recognition and maturation of effector RNAs in a CRISPR interference pathway.

In bacteria and archaea, small RNAs derived from clustered, regularly interspaced, short palindromic repeat (CRISPR) loci are involved in an adaptable and heritable gene-silencing pathway. Resistance to phage infection is conferred by the incorporation of short invading DNA sequences into the genome as CRISPR spacer elements separated by short repeat sequences. Processing of long primary transcripts (pre-crRNAs) containing these repeats by an RNA endonuclease generates the mature effector RNAs that interfere with phage gene expression.

Structural elucidation of a PRP8 core domain from the heart of the spliceosome.

The spliceosome is a complex ribonucleoprotein (RNP) particle containing five RNAs and more than 100 associated proteins. One of these proteins, PRP8, has been shown to interact directly with the splice sites and branch region of precursor-mRNAs (pre-mRNAs) and spliceosomal RNAs associated with catalysis of the two steps of splicing. The 1.

FRET analysis of in vivo dimerization by RNA-editing enzymes.

Members of the ADAR (adenosine deaminase that acts on RNA) enzyme family catalyze the hydrolytic deamination of adenosine to inosine within double-stranded RNAs, a poorly understood process that is critical to mammalian development. We have performed fluorescence resonance energy transfer experiments in mammalian cells transfected with fluorophore-bearing ADAR1 and ADAR2 fusion proteins to investigate the relationship between these proteins. These studies conclusively demonstrate the homodimerization of ADAR1 and ADAR2 and also show that ADAR1 and ADAR2 form heterodimers in human cells.