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Results: 1 to 5 of 5

Publication Record


Validation of electronic medical record-based phenotyping algorithms: results and lessons learned from the eMERGE network.
Newton KM, Peissig PL, Kho AN, Bielinski SJ, Berg RL, Choudhary V, Basford M, Chute CG, Kullo IJ, Li R, Pacheco JA, Rasmussen LV, Spangler L, Denny JC
(2013) J Am Med Inform Assoc 20: e147-54
MeSH Terms: Algorithms, Computer Communication Networks, Electronic Health Records, Genetic Association Studies, Genetic Research, Humans, Medical Audit, Phenotype, United States, Validation Studies as Topic
Show Abstract · Added May 27, 2014
BACKGROUND - Genetic studies require precise phenotype definitions, but electronic medical record (EMR) phenotype data are recorded inconsistently and in a variety of formats.
OBJECTIVE - To present lessons learned about validation of EMR-based phenotypes from the Electronic Medical Records and Genomics (eMERGE) studies.
MATERIALS AND METHODS - The eMERGE network created and validated 13 EMR-derived phenotype algorithms. Network sites are Group Health, Marshfield Clinic, Mayo Clinic, Northwestern University, and Vanderbilt University.
RESULTS - By validating EMR-derived phenotypes we learned that: (1) multisite validation improves phenotype algorithm accuracy; (2) targets for validation should be carefully considered and defined; (3) specifying time frames for review of variables eases validation time and improves accuracy; (4) using repeated measures requires defining the relevant time period and specifying the most meaningful value to be studied; (5) patient movement in and out of the health plan (transience) can result in incomplete or fragmented data; (6) the review scope should be defined carefully; (7) particular care is required in combining EMR and research data; (8) medication data can be assessed using claims, medications dispensed, or medications prescribed; (9) algorithm development and validation work best as an iterative process; and (10) validation by content experts or structured chart review can provide accurate results.
CONCLUSIONS - Despite the diverse structure of the five EMRs of the eMERGE sites, we developed, validated, and successfully deployed 13 electronic phenotype algorithms. Validation is a worthwhile process that not only measures phenotype performance but also strengthens phenotype algorithm definitions and enhances their inter-institutional sharing.
0 Communities
1 Members
0 Resources
10 MeSH Terms
Formation of 4-hydroxynonenal from cardiolipin oxidation: Intramolecular peroxyl radical addition and decomposition.
Liu W, Porter NA, Schneider C, Brash AR, Yin H
(2011) Free Radic Biol Med 50: 166-78
MeSH Terms: Aldehydes, Animals, Cardiolipins, Cattle, Epoxy Compounds, Hydrogen Peroxide, Intramolecular Oxidoreductases, Oxidation-Reduction, Peroxides, Phosphatidylcholines, Protein Processing, Post-Translational, Rats, Rats, Sprague-Dawley, Validation Studies as Topic
Show Abstract · Added December 10, 2013
We report herein that oxidation of a mitochondria-specific phospholipid tetralinoleoyl cardiolipin (L(4)CL) by cytochrome c and H(2)O(2) leads to the formation of 4-hydroxy-2-nonenal (4-HNE) via a novel chemical mechanism that involves cross-chain peroxyl radical addition and decomposition. As one of the most bioactive lipid electrophiles, 4-HNE possesses diverse biological activities ranging from modulation of multiple signal transduction pathways to the induction of intrinsic apoptosis. However, where and how 4-HNE is formed in vivo are much less understood. Recently a novel chemical mechanism has been proposed that involves intermolecular dimerization of fatty acids by peroxyl bond formation; but the biological relevance of this mechanism is unknown because a majority of the fatty acids are esterified in phospholipids in the cellular membrane. We hypothesize that oxidation of cardiolipins, especially L(4)CL, may lead to the formation of 4-HNE via this novel mechanism. We employed L(4)CL and dilinoleoylphosphatidylcholine (DLPC) as model compounds to test this hypothesis. Indeed, in experiments designed to assess the intramolecular mechanism, more 4-HNE is formed from L(4)CL and DLPC oxidation than 1-palmitoyl-2-linoleoylphosphatydylcholine. The key products and intermediates that are consistent with this proposed mechanism of 4-HNE formation have been identified using liquid chromatography-mass spectrometry. Identical products from cardiolipin oxidation were identified in vivo in rat liver tissue after carbon tetrachloride treatment. Our studies provide the first evidence in vitro and in vivo for the formation 4-HNE from cardiolipin oxidation via cross-chain peroxyl radical addition and decomposition, which may have implications in apoptosis and other biological activities of 4-HNE.
Copyright © 2010 Elsevier Inc. All rights reserved.
0 Communities
3 Members
0 Resources
14 MeSH Terms
National Lung Cancer Screening Trial American College of Radiology Imaging Network Specimen Biorepository originating from the Contemporary Screening for the Detection of Lung Cancer Trial (NLST, ACRIN 6654): design, intent, and availability of specimens for validation of lung cancer biomarkers.
Patz EF, Caporaso NE, Dubinett SM, Massion PP, Hirsch FR, Minna JD, Gatsonis C, Duan F, Adams A, Apgar C, Medina RM, Aberle DR
(2010) J Thorac Oncol 5: 1502-6
MeSH Terms: Biological Specimen Banks, Biomarkers, Tumor, Early Detection of Cancer, Humans, Lung Neoplasms, Research Design, Validation Studies as Topic
Added March 10, 2014
0 Communities
1 Members
0 Resources
7 MeSH Terms
Analytical validation of protein-based multiplex assays: a workshop report by the NCI-FDA interagency oncology task force on molecular diagnostics.
Rodriguez H, Tezak Z, Mesri M, Carr SA, Liebler DC, Fisher SJ, Tempst P, Hiltke T, Kessler LG, Kinsinger CR, Philip R, Ransohoff DF, Skates SJ, Regnier FE, Anderson NL, Mansfield E, Workshop Participants
(2010) Clin Chem 56: 237-43
MeSH Terms: Biomarkers, Tumor, Humans, Mass Spectrometry, National Cancer Institute (U.S.), Neoplasms, Proteomics, United States, United States Food and Drug Administration, Validation Studies as Topic
Show Abstract · Added March 20, 2014
Clinical proteomics has the potential to enable the early detection of cancer through the development of multiplex assays that can inform clinical decisions. However, there has been some uncertainty among translational researchers and developers as to the specific analytical measurement criteria needed to validate protein-based multiplex assays. To begin to address the causes of this uncertainty, a day-long workshop titled "Interagency Oncology Task Force Molecular Diagnostics Workshop" was held in which members of the proteomics and regulatory communities discussed many of the analytical evaluation issues that the field should address in development of protein-based multiplex assays for clinical use. This meeting report explores the issues raised at the workshop and details the recommendations that came out of the day's discussions, such as a workshop summary discussing the analytical evaluation issues that specific proteomic technologies should address when seeking US Food and Drug Administration approval.
0 Communities
1 Members
0 Resources
9 MeSH Terms
Update on molecular diagnostic tests in head and neck cancer.
Palka KT, Slebos RJ, Chung CH
(2008) Semin Oncol 35: 198-210
MeSH Terms: Biomarkers, Tumor, Carcinoma, Squamous Cell, Chromosome Aberrations, Gene Expression Profiling, Head and Neck Neoplasms, Herpesvirus 4, Human, Humans, Molecular Diagnostic Techniques, Predictive Value of Tests, Prognosis, Protein Array Analysis, Treatment Outcome, Validation Studies as Topic
Show Abstract · Added March 5, 2014
Head and neck cancers (HNCs) include several cancers originating in the upper airways that represent a variety of histologies. The most common type of HNC is squamous cell carcinoma (SCC), which is linked to tobacco and alcohol use and to human papilloma virus (HPV). At present, there are no standard molecular tests that are routinely used in clinics. This overview will discuss the current knowledge on molecular markers with the potential to be developed as diagnostic tests for cancer risk assessment, early detection, clinical response prediction to specific therapies, and prognosis. These markers are usually based on recent findings in tumor biology and genetic defects in HNC, and provide information both independently and in combination with currently available clinical parameters. In practice, many potential markers are difficult to measure due to assay variability, lack of standards for the interpretation of assay results, and incomplete knowledge of the effects on disease biology and response to treatment. However, there is great enthusiasm for the general concept of using molecular knowledge for the clinical management of HNC. Although it will be a great challenge to develop robust and reliable molecular diagnostic tests, the development of promising assays fueled by advances in science and technology will continue and will ultimately reach the goal of improving the care of HNC patients.
0 Communities
1 Members
0 Resources
13 MeSH Terms