The hexosamine pathway has been implicated in the pathogenesis of diabetic complications. We determined first that hyperglycemia induced a decrease in glyceraldehyde-3-phosphate dehydrogenase ...activity in bovine aortic endothelial cells via increased production of mitochondrial superoxide and a concomitant 2.4-fold increase in hexosamine pathway activity. Both decreased glyceraldehyde-3-phosphate dehydrogenase activity and increased hexosamine pathway activity were prevented completely by an inhibitor of electron transport complex II (thenoyltrifluoroacetone), an uncoupler of oxidative phosphorylation (carbonyl cyanide m-chlorophenylhydrazone), a superoxide dismutase mimetic manganese (III) tetrakis(4-benzoic acid) porphyrin, overexpression of either uncoupling protein 1 or manganese superoxide dismutase, and azaserine, an inhibitor of the rate-limiting enzyme in the hexosamine pathway (glutamine:fructose-6-phosphate amidotransferase). Immunoprecipitation of Sp1 followed by Western blotting with antibodies to O-linked GlcNAc, phosphoserine, and phosphothreonine showed that hyperglycemia increased GlcNAc by 1.7-fold, decreased phosphoserine by 80%, and decreased phosphothreonine by 70%. The same inhibitors prevented all these changes. Hyperglycemia increased expression from a transforming growth factor-β1promoter luciferase reporter by 2-fold and increased expression from a (-740 to +44) plasminogen activator inhibitor-1 promoter luciferase reporter gene by nearly 3-fold. Inhibition of mitochondrial superoxide production or the glucosamine pathway prevented all these changes. Hyperglycemia increased expression from an 85-bp truncated plasminogen activator inhibitor-1 (PAI-1) promoter luciferase reporter containing two Sp1 sites in a similar fashion (3.8-fold). In contrast, hyperglycemia had no effect when the two Sp1 sites were mutated. Thus, hyperglycemia-induced mitochondrial superoxide overproduction increases hexosamine synthesis and O-glycosylation of Sp1, which activates expression of genes that contribute to the pathogenesis of diabetic complications.
Objective Develop and test web services to retrieve and identify the most precise ICD-10-CM code(s) for a given clinical encounter. Facilitate creation of user interfaces that 1) provide an initial ...shortlist of candidate codes, ideally visible on a single screen; and 2) enable code refinement.
Materials and Methods To satisfy our high-level use cases, the analysis and design process involved reviewing available maps and crosswalks, designing the rule adjudication framework, determining necessary metadata, retrieving related codes, and iteratively improving the code refinement algorithm.
Results The Partners ICD-10-CM Search and Mapping Services (PI-10 Services) are SOAP web services written using Microsoft's.NET 4.0 Framework, Windows Communications Framework, and SQL Server 2012. The services cover 96% of the Partners problem list subset of SNOMED CT codes that map to ICD-10-CM codes and can return up to 76% of the 69 823 billable ICD-10-CM codes prior to creation of custom mapping rules.
Discussion We consider ways to increase 1) the coverage ratio of the Partners problem list subset of SNOMED CT codes and 2) the upper bound of returnable ICD-10-CM codes by creating custom mapping rules. Future work will investigate the utility of the transitive closure of SNOMED CT codes and other methods to assist in custom rule creation and, ultimately, to provide more complete coverage of ICD-10-CM codes.
Conclusions ICD-10-CM will be easier for clinicians to manage if applications display short lists of candidate codes from which clinicians can subsequently select a code for further refinement. The PI-10 Services support ICD-10 migration by implementing this paradigm and enabling users to consistently and accurately find the best ICD-10-CM code(s) without translation from ICD-9-CM.
Higher use of maternal and neonatal health (MNH) services may reduce maternal and neonatal mortality in Kenya. This study aims to: 1) prospectively explore women's intentions to use MNH services ...(antenatal care, delivery in a facility, postnatal care, neonatal care) at <20 and 30-35 weeks' gestation and their actual use of these services; 2) identify predictors of intention-behavior discordance among women with positive service use intentions; 3) examine associations between place of delivery, women's reasons for choosing it, and birthing experiences. We used data from a 2012-2013 population-based cohort of pregnant women in the Demographic Surveillance Site in Nyanza province, Kenya. Of 1,056 women completing the study (89.1% response rate), 948 had live-births and 22 stillbirths, and they represent our analytic sample. Logistic regression analysis identified predictors of intention-behavior discordance regarding delivery in a facility and use of postnatal and neonatal care. At <20 and 30-35 weeks' gestation, most women intended to seek MNH services (≥93.9% and ≥87.5%, respectively, for all services assessed). Actual service use was high for antenatal (98.1%) and neonatal (88.5%) care, but lower for delivery in a facility (76.9%) and postnatal care (51.8%). Woman's age >35 and high-school education were significant predictors of intention-behavior discordance regarding delivery in a facility; several delivery-related factors were significantly associated with intention-behavior discordance regarding use of postnatal and neonatal care. Delivery facilities were chosen based on proximity to women's residence, affordability, and service quality; among women who delivered outside a health facility, 16.3% could not afford going to a facility. Good/very good birth experiences were reported by 93.6% of women who delivered in a facility and 32.6% of women who did not. We found higher MNH service utilization than previously documented in Nyanza province. Further increasing the number of facility deliveries and use of postnatal care may improve MNH in Kenya.
Metabolic flux through the hexosamine biosynthetic pathway (HBP) is increased in the presence of high glucose (HG) and potentially stimulates the expression of genes associated with the development ...of diabetic nephropathy. A number of synthetic processes are coupled to the HBP, including enzymatic intracellular O-glycosylation (O-GlcNAcylation), the addition of single O-linked N-acetylglucosamine monosaccharides to serine or threonine residues. Despite much data linking flow through the HBP and gene expression, the exact contribution of O-GlcNAcylation to HG-stimulated gene expression remains unclear. In glomerular mesangial cells, HG-stimulated plasminogen activator inhibitor-1 (PAI-1) gene expression requires the HBP and the transcription factor, Sp1. In this study, the specific role of O-GlcNAcylation in HG-induced PAI-1 expression was tested by limiting this modification with a dominant-negative O-linked N-acetylglucosamine transferase, by overexpression of neutral β-N-acetylglucosaminidase, and by knockdown of O-linked β-N-acetylglucosamine transferase expression by RNA interference. Decreasing O-GlcNAcylation by these means inhibited the ability of HG to increase endogenous PAI-1 mRNA and protein levels, the activity of a PAI-1 promoter-luciferase reporter gene, and Sp1 transcriptional activation. Conversely, treatment with the β-N-acetylglucosaminidase inhibitor, O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate, in the presence of normal glucose increased Sp1 O-GlcNAcylation and PAI-1 mRNA and protein levels. These findings demonstrate for the first time that among the pathways served by the HBP, O-GlcNAcylation, is obligatory for HG-induced PAI-1 gene expression and Sp1 transcriptional activation in mesangial cells.
To create a clinical decision support (CDS) system that is shareable across healthcare delivery systems and settings over large geographic regions.
The enterprise clinical rules service (ECRS) ...realizes nine design principles through a series of enterprise java beans and leverages off-the-shelf rules management systems in order to provide consistent, maintainable, and scalable decision support in a variety of settings.
The ECRS is deployed at Partners HealthCare System (PHS) and is in use for a series of trials by members of the CDS consortium, including internally developed systems at PHS, the Regenstrief Institute, and vendor-based systems deployed at locations in Oregon and New Jersey. Performance measures indicate that the ECRS provides sub-second response time when measured apart from services required to retrieve data and assemble the continuity of care document used as input.
We consider related work, design decisions, comparisons with emerging national standards, and discuss uses and limitations of the ECRS.
ECRS design, implementation, and use in CDS consortium trials indicate that it provides the flexibility and modularity needed for broad use and performs adequately. Future work will investigate additional CDS patterns, alternative methods of data passing, and further optimizations in ECRS performance.
Summary
Background:
The Centers for Medicare & Medicaid Services’ Stage 2 final rule requires that eligible hospitals provide a visit summary electronically at transitions of care in order to qualify ...for “meaningful use” incentive payments. However, Massachusetts state law and Federal law prohibit the transmission of documents containing “sensitive” data unless there is a new patient consent for each transmission.
Objectives:
To describe the implementation and evaluation of a rule-based decision support system used to screen transition of care documents for sensitive data.
Methods:
We implemented a rule-based document screening system to identify transition of care documents that might contain sensitive data. The transmission of detected documents is withheld until a new patient consent is obtained. The documents that were flagged as containing sensitive data were reviewed in two different time periods to verify that the decision support system was not missing documents or withholding more documents than necessary.
Results:
The rule-based screening system has been in regular production use for the past 18 months. During the first evaluation period, 3% of 5,841 documents were identified as containing sensitive data (true-positive rate of 44%). After additional enhancements to the rules, the system was evaluated a second time and 4.5% of 6,935 documents were identified as containing sensitive data (true-positive rate of 98.4%).
Conclusion:
The analysis of the system demonstrates that production rules can be used to automatically screen the content of transition of care documents for sensitive data. The utilization of the rule-based decision support system enabled our hospitals to achieve meaningful use and, at the same time, remain compliant with state and federal laws.
Objective Clinical data warehouses have accelerated clinical research, but even with available open source tools, there is a high barrier to entry due to the complexity of normalizing and importing ...data. The Office of the National Coordinator for Health Information Technology's Meaningful Use Incentive Program now requires that electronic health record systems produce standardized consolidated clinical document architecture (C-CDA) documents. Here, we leverage this data source to create a low volume standards based import pipeline for the Informatics for Integrating Biology and the Bedside (i2b2) clinical research platform. We validate this approach by creating a small repository at Partners Healthcare automatically from C-CDA documents.
Materials and methods We designed an i2b2 extension to import C-CDAs into i2b2. It is extensible to other sites with variances in C-CDA format without requiring custom code. We also designed new ontology structures for querying the imported data.
Results We implemented our methodology at Partners Healthcare, where we developed an adapter to retrieve C-CDAs from Enterprise Services. Our current implementation supports demographics, encounters, problems, and medications. We imported approximately 17 000 clinical observations on 145 patients into i2b2 in about 24 min. We were able to perform i2b2 cohort finding queries and view patient information through SMART apps on the imported data.
Discussion This low volume import approach can serve small practices with local access to C-CDAs and will allow patient registries to import patient supplied C-CDAs. These components will soon be available open source on the i2b2 wiki.
Conclusions Our approach will lower barriers to entry in implementing i2b2 where informatics expertise or data access are limited.
Highlights • We describe use of CDS services in a trial of blunt head trauma prediction rules. • We evaluate the execution characteristics of the system at two emergency departments. • The CDS ...service was the source of recommendations in 60% of real-time workflows. • The CDS service was the source of recommendations in all near-real-time workflows. • Evolving CDS services facilitate sharing of CDS in selected clinical settings.
For children who present to emergency departments (EDs) due to blunt head trauma, ED clinicians must decide who requires computed tomography (CT) scanning to evaluate for traumatic brain injury ...(TBI). The Pediatric Emergency Care Applied Research Network (PECARN) derived and validated two age-based prediction rules to identify children at very low risk of clinically-important traumatic brain injuries (ciTBIs) who do not typically require CT scans. In this case report, we describe the strategy used to implement the PECARN TBI prediction rules via electronic health record (EHR) clinical decision support (CDS) as the intervention in a multicenter clinical trial.
Thirteen EDs participated in this trial. The 10 sites receiving the CDS intervention used the Epic(®) EHR. All sites implementing EHR-based CDS built the rules by using the vendor's CDS engine. Based on a sociotechnical analysis, we designed the CDS so that recommendations could be displayed immediately after any provider entered prediction rule data. One central site developed and tested the intervention package to be exported to other sites. The intervention package included a clinical trial alert, an electronic data collection form, the CDS rules and the format for recommendations.
The original PECARN head trauma prediction rules were derived from physician documentation while this pragmatic trial led each site to customize their workflows and allow multiple different providers to complete the head trauma assessments. These differences in workflows led to varying completion rates across sites as well as differences in the types of providers completing the electronic data form. Site variation in internal change management processes made it challenging to maintain the same rigor across all sites. This led to downstream effects when data reports were developed.
The process of a centralized build and export of a CDS system in one commercial EHR system successfully supported a multicenter clinical trial.
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