Understanding the Nature of Medication Errors in an ICU with a Computerized Physician Order Entry System

Objectives: We investigated incidence rates to understand the nature of medication errors potentially introduced by utilizing a computerized physician order entry (CPOE) system in the three clinical phases of the medication process: prescription, administration, and documentation. Methods: Overt observations and chart reviews were employed at two surgical intensive care units of a 950-bed tertiary teaching hospital. Ten categories of high-risk drugs prescribed over a four-month period were noted and reviewed. Error definition and classifications were adapted from previous studies for use in the present research. Incidences of medication errors in the three phases of the medication process were analyzed. In addition, nurses' responses to prescription errors were also assessed. Results: Of the 534 prescriptions issued, 286 (53.6%) included at least one error. The proportion of errors was 19.0% (58) of the 306 drug administrations, of which two-thirds were verbal orders classified as errors due to incorrectly entered prescriptions. Documentation errors occurred in 205 (82.7%) of 248 correctly performed administrations. When tracking incorrectly entered prescriptions, 93% of the errors were intercepted by nurses, but two-thirds of them were recorded as prescribed rather than administered. Conclusion: The number of errors occurring at each phase of the medication process was relatively high, despite long experience with a CPOE system. The main causes of administration errors and documentation errors were prescription errors and verbal order processes. To reduce these errors, hospital-level and unit-level efforts toward a better system are needed

Safety and Usability Guidelines of Clinical Information Systems Integrating Clinical Workflow: A Systematic Review.

OBJECTIVES: The usability of clinical information systems (CISs) is known to be an essential consideration in ensuring patient safety as well as integrating clinical flow. This study aimed to determine how usability and safety guidelines of CIS consider clinical workflow through a systematic review in terms of the target systems, methodology, and guideline components of relevant articles. METHODS: A literature search was conducted for articles published from 2000 to 2015 in PubMed, Cochrane, EMBASE, Web of Science, and CINAHL. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement method was employed. Articles containing recommendations, principles, and evaluation items for CIS usability and safety were included. The selected articles were classified according to article type, methodology, and target systems. Taking clinical workflow into consideration, the components of guidelines were extracted and classified. RESULTS: A total of 7,401 articles were identified by keyword search. From the 76 articles remaining after abstract screening, 15 were selected through full-text review. Literature review (n = 7) was the most common methodology, followed by expert opinions (n = 6). Computerized physician order entry (n = 6) was the most frequent system. Four articles considered the entire process of clinical tasks, and two articles considered the principles of the entire process of user interface affecting clinical workflow. Only two articles performed heuristic evaluations of CISs. CONCLUSIONS: The usability and safety guidelines of CISs need improvement in guideline development methodology and with consideration of clinical workflow

Understanding physicians’ behavior toward alerts about nephrotoxic medications in outpatients: a cross-sectional analysis

Background: Although most outpatients are relatively healthy, many have chronic renal insufficiency, and high override rates for suggestions on renal dosing have been observed. To better understand the override of renal dosing alerts in an outpatient setting, we conducted a study to evaluate which patients were more frequently prescribed contraindicated medications, to assess providers’ responses to suggestions, and to examine the drugs involved and the reasons for overrides. Methods: We obtained data on renal alert overrides and the coded reasons for overrides cited by providers at the time of prescription from outpatient clinics and ambulatory hospital-based practices at a large academic health care center over a period of 3 years, from January 2009 to December 2011. For detailed chart review, a group of 6 trained clinicians developed the appropriateness criteria with excellent inter-rater reliability (κ = 0.93). We stratified providers by override frequency and then drew samples from the high- and low-frequency groups. We measured the rate of total overrides, rate of appropriate overrides, medications overridden, and the reason(s) for override. Results: A total of 4120 renal alerts were triggered by 584 prescribers in the study period, among which 78.2% (3,221) were overridden. Almost half of the alerts were triggered by 40 providers and one-third was triggered by high-frequency overriders. The appropriateness rates were fairly similar, at 28.4% and 31.6% for high- and low-frequency overriders, respectively. Metformin, glyburide, hydrochlorothiazide, and nitrofurantoin were the most common drugs overridden. Physicians’ appropriateness rates were higher than the rates for nurse practitioners (32.9% vs. 22.1%). Physicians with low frequency override rates had higher levels of appropriateness for metformin than the high frequency overriders (P = 0.005). Conclusion: A small number of providers accounted for a large fraction of overrides, as was the case with a small number of drugs. These data suggest that a focused intervention targeting primarily these providers and medications has the potential to improve medication safety

National Rules for Drug–Drug Interactions: Are They Appropriate for Tertiary Hospitals?

The application of appropriate rules for drug–drug interactions (DDIs) could substantially reduce the number of adverse drug events. However, current implementations of such rules in tertiary hospitals are problematic as physicians are receiving too many alerts, causing high override rates and alert fatigue. We investigated the potential impact of Korean national DDI rules in a drug utilization review program in terms of their severity coverage and the clinical efficiency of how physicians respond to them. Using lists of high-priority DDIs developed with the support of the U.S. government, we evaluated 706 contraindicated DDI pairs released in May 2015. We evaluated clinical log data from one tertiary hospital and prescription data from two other tertiary hospitals. The measured parameters were national DDI rule coverage for high-priority DDIs, alert override rate, and number of prescription pairs. The coverage rates of national DDI rules were 80% and 3.0% at the class and drug levels, respectively. The analysis of the system log data showed an overall override rate of 79.6%. Only 0.3% of all of the alerts (n = 66) were high-priority DDI rules. These showed a lower override rate of 51.5%, which was much lower than for the overall DDI rules. We also found 342 and 80 unmatched high-priority DDI pairs which were absent in national rules in inpatient orders from the other two hospitals. The national DDI rules are not complete in terms of their coverage of severe DDIs. They also lack clinical efficiency in tertiary settings, suggesting improved systematic approaches are needed

Large protein complexes retained in the ER are dislocated by non-COPII vesicles and degraded by selective autophagy

Multisubunit protein complexes are assembled in the endoplasmic reticulum (ER). Existing pools of single subunits and assembly intermediates ensure the efficient and rapid formation of complete complexes. While being kinetically beneficial, surplus components must be eliminated to prevent potentially harmful accumulation in the ER. Surplus single chains are cleared by the ubiquitin-proteasome system. However, the fate of not secreted assembly intermediates of multisubunit proteins remains elusive. Here we show by high-resolution double-label confocal immunofluorescence and immunogold electron microscopy that naturally occurring surplus fibrinogen Aα-γ assembly intermediates in HepG2 cells are dislocated together with EDEM1 from the ER to the cytoplasm in ER-derived vesicles not corresponding to COPII-coated vesicles originating from the transitional ER. This route corresponds to the novel ER exit path we have previously identified for EDEM1 (Zuber etal. Proc Natl Acad Sci USA 104:4407-4412, 2007). In the cytoplasm, detergent-insoluble aggregates of fibrinogen Aα-γ dimers develop that are targeted by the selective autophagy cargo receptors p62/SQSTM1 and NBR1. These aggregates are degraded by selective autophagy as directly demonstrated by high-resolution microscopy as well as biochemical analysis and inhibition of autophagy by siRNA and kinase inhibitors. Our findings demonstrate that different pathways exist in parallel for ER-to-cytoplasm dislocation and subsequent proteolytic degradation of large luminal protein complexes and of surplus luminal single-chain proteins. This implies that ER-associated protein degradation (ERAD) has a broader function in ER proteostasis and is not limited to the elimination of misfolded glycoprotein

Lipotoxicity induces hepatic protein inclusions through TANK binding kinase 1â mediated p62/sequestosome 1 phosphorylation

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146331/1/hep29742.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146331/2/hep29742_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146331/3/hep29742-sup-0011-suppinfo.pd

ERADication of EDEM1 occurs by selective autophagy and requires deglycosylation by cytoplasmic peptide N -glycanase

ER degradation-enhancing α-mannosidase-like 1 protein (EDEM1) is involved in the routing of misfolded glycoproteins for degradation in the cytoplasm. Previously, we reported that EDEM1 leaves the endoplasmic reticulum via non-COPII vesicles (Zuber et al. in Proc Natl Acad Sci USA 104:4407-4412, 2007) and becomes degraded by basal autophagy (Le Fourn et al. in Cell Mol Life Sci 66:1434-1445, 2009). However, it is unknown which type of autophagy is involved. Likewise, how EDEM1 is targeted to autophagosomes remains elusive. We now show that EDEM1 is degraded by selective autophagy. It colocalizes with the selective autophagy cargo receptors p62/SQSTM1, neighbor of BRCA1 gene 1 (NBR1) and autophagy-linked FYVE (Alfy) protein, and becomes engulfed by autophagic isolation membranes. The interaction with p62/SQSTM1 and NBR1 is required for routing of EDEM1 to autophagosomes since it can be blocked by short inhibitory RNA knockdown of the cargo receptors. Furthermore, p62/SQSTM1 interacts only with deglycosylated EDEM1 that is also ubiquitinated. The deglycosylation of EDEM1 occurs by the cytosolic peptide N-glycanase and is a prerequisite for interaction and aggregate formation with p62/SQSTM1 as demonstrated by the effect of peptide N-glycanase inhibitors on the formation of protein aggregates. Conversely, aggregation of p62/SQSTM1 and EDEM1 occurs independent of cytoplasmic histone deacetylase. These data provide novel insight into the mechanism of autophagic degradation of the ER-associated protein degradation (ERAD) component EDEM1 and disclose hitherto unknown parallels with the clearance of cytoplasmic aggregates of misfolded proteins by selective autophagy

Tumor suppressive role of sestrin2 during colitis and colon carcinogenesis

The mTOR complex 1 (mTORC1) and endoplasmic reticulum (ER) stress pathways are critical regulators of intestinal inflammation and colon cancer growth. Sestrins are stress-inducible proteins, which suppress both mTORC1 and ER stress; however, the role of Sestrins in colon physiology and tumorigenesis has been elusive due to the lack of studies in human tissues or in appropriate animal models. In this study, we show that human SESN2 expression is elevated in the colon of ulcerative colitis patients but is lost upon p53 inactivation during colon carcinogenesis. In mouse colon, Sestrin2 was critical for limiting ER stress and promoting the recovery of epithelial cells after inflammatory injury. During colitis-promoted tumorigenesis, Sestrin2 was shown to be an important mediator of p53’s control over mTORC1 signaling and tumor cell growth. These results highlight Sestrin2 as a novel tumor suppressor, whose downregulation can accelerate both colitis and colon carcinogenesis