In this study, we evaluated the performance of a point-of-care device, the CoaguChek XS Plus system, in the determination of prothrombin time and international normalized ratio (INR) based on ...ISO17593: 2007 criteria in Taiwanese patients. The underlying clinical and genetic factors were also investigated.
Fifty patients receiving warfarin therapy were enrolled in this study. The accuracy of the CoaguChek XS Plus system was evaluated with linear regression analysis and bias plot by comparing with the data measured using Sysmex CA-1500. The clinical and genetic factors that may have caused a bias of 0.5 INR were evaluated with Fisher's exact test.
From the 50 patients, 93 INR values were collected by each method. Linear regression analysis indicated a high correlation with r = 0.96, a slope of 1.05, and an intercept of - 0.14. Eight patients showed an INR bias ≥0.5 between the two methods. Only aspartate aminotransferase (AST) >34 U/L (3/8, 37.5% vs. 3/42, 7.1%; p = 0.044) and alanine aminotransferase (ALT) >36 U/L (3/8, 37.5% vs. 3/42, 7.1%; p = 0.044) were significantly different from each other. No differences were observed for hypoalbuminemia, elevated creatinine, anemia, and the polymorphisms of VKORC1 and CYP2C9.
The CoaguChek XS Plus system presented results that were comparable with those obtained using laboratory CA-1500 method. Both methods fell within INR in the range of 2-4.5 defined by ISO17593:2007 and the clinically recognized therapeutic INR range of 2-3.5. Elevated AST and ALT levels might have interfered with the INR results.
Warfarin was first introduced in the 1950s and quickly became themost commonly used oral anticoagulant for the prevention of thromboembolism in patients with deep vein thrombosis, atrial ...fibrillation, or prosthetic heart valve replacement. Warfarin is highly effective in treating these diseases; however, several factors prevent it from even wider use, especially in Asian populations. It is difficult for patients on warfarin to reach desired anticoagulation due to its narrow therapeutic index and highly variable dose response. The major adverse event is bleeding which is associated with overdose of warfarin. Clinical and genetic factors such as polymorphisms in CYP2C9 and VKORC1 associated with an individual’s warfarin maintenance have been identified. More than 20 dose prediction algorithms incorporating both genetic and clinical factors have been developed, and some of them have been tested clinically. However, most of the algorithms were tested in small populations. Several major clinical trials are now underway. This review aims to provide an overview of the field of warfarin which includes information about the drug, genetics of warfarin dose requirements, dosing algorithms developed and the challenges of clinical implementation of warfarin pharmacogenetics.
The imputation of missingness is a key step in Electronic Health Records (EHR) mining, as it can significantly affect the conclusions derived from the downstream analysis in translational medicine. ...The missingness of laboratory values in EHR is not at random, yet imputation techniques tend to disregard this key distinction. Consequently, the development of an adaptive imputation strategy designed specifically for EHR is an important step in improving the data imbalance and enhancing the predictive power of modeling tools for healthcare applications.
We analyzed the laboratory measures derived from Geisinger's EHR on patients in three distinct cohorts-patients tested for
(Cdiff) infection, patients with a diagnosis of inflammatory bowel disease (IBD), and patients with a diagnosis of hip or knee osteoarthritis (OA). We extracted Logical Observation Identifiers Names and Codes (LOINC) from which we excluded those with 75% or more missingness. The comorbidities, primary or secondary diagnosis, as well as active problem lists, were also extracted. The adaptive imputation strategy was designed based on a hybrid approach. The comorbidity patterns of patients were transformed into latent patterns and then clustered. Imputation was performed on a cluster of patients for each cohort independently to show the generalizability of the method. The results were compared with imputation applied to the complete dataset without incorporating the information from comorbidity patterns.
We analyzed a total of 67,445 patients (11,230 IBD patients, 10,000 OA patients, and 46,215 patients tested for
infection). We extracted 495 LOINC and 11,230 diagnosis codes for the IBD cohort, 8160 diagnosis codes for the Cdiff cohort, and 2042 diagnosis codes for the OA cohort based on the primary/secondary diagnosis and active problem list in the EHR. Overall, the most improvement from this strategy was observed when the laboratory measures had a higher level of missingness. The best root mean square error (RMSE) difference for each dataset was recorded as -35.5 for the Cdiff, -8.3 for the IBD, and -11.3 for the OA dataset.
An adaptive imputation strategy designed specifically for EHR that uses complementary information from the clinical profile of the patient can be used to improve the imputation of missing laboratory values, especially when laboratory codes with high levels of missingness are included in the analysis.
This document is an update to the 2011 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2C9 and VKORC1 genotypes and warfarin dosing. Evidence from the published literature ...is presented for CYP2C9, VKORC1, CYP4F2, and rs12777823 genotype‐guided warfarin dosing to achieve a target international normalized ratio of 2–3 when clinical genotype results are available. In addition, this updated guideline incorporates recommendations for adult and pediatric patients that are specific to continental ancestry.
In the post-genomic era, the rapid evolution of high-throughput genotyping technologies and the increased pace of production of genetic research data are continually prompting the development of ...appropriate informatics tools, systems and databases as we attempt to cope with the flood of incoming genetic information. Alongside new technologies that serve to enhance data connectivity, emerging information systems should contribute to the creation of a powerful knowledge environment for genotype-to-phenotype information in the context of translational medicine. In the area of pharmacogenomics and personalized medicine, it has become evident that database applications providing important information on the occurrence and consequences of gene variants involved in pharmacokinetics, pharmacodynamics, drug efficacy and drug toxicity will become an integral tool for researchers and medical practitioners alike. At the same time, two fundamental issues are inextricably linked to current developments, namely data sharing and data protection. Here, we discuss high-throughput and next-generation sequencing technology and its impact on pharmacogenomics research. In addition, we present advances and challenges in the field of pharmacogenomics information systems which have in turn triggered the development of an integrated electronic ‘pharmacogenomics assistant’. The system is designed to provide personalized drug recommendations based on linked genotype-to-phenotype pharmacogenomics data, as well as to support biomedical researchers in the identification of pharmacogenomics-related gene variants. The provisioned services are tuned in the framework of a single-access pharmacogenomics portal.
Clinical Application of Pharmacogenomics Lee, Ming Ta Michael; Mahasirimongkol, Surakameth; Zhang, Yanfei ...
Public health genomics,
01/2014, Letnik:
17, Številka:
5/6
Journal Article
Recenzirano
Pharmacogenomics is gradually becoming more and more indispensable in modern medicine. In several cases, a pharmacogenomics test may alleviate serious drug-induced adverse reactions, if it precedes ...drug prescription. In this article, we provide an overview of the well-established HLA-based carbamazepine- and allopurinol-induced adverse reactions, as one of the most characteristic examples of the clinical application of pharmacogenomics, highlighting its regional impact in Southeast Asian populations in preventing adverse reactions of certain drug/allele pairs. This example provides useful insights towards evidence generation for policy implementation, including economic evaluation analysis, the implementation of pharmacogenomics testing procedures and monitoring of policy effectiveness, hence serving, per se or in the context of international collaborative efforts, as a model for similar cases in several national healthcare systems worldwide.
To clarify whether the activities of multiple CYPs associated with warfarin metabolism would be correlated with each other.
Oral clearances (CLpo) of warfarin enantiomers were estimated in 378 ...Chinese, Caucasians and African-Americans. The partial metabolic clearances (CLm) for 7-hydroxywarfarin enantiomers were also measured. In addition, CLpo and CLm were determined in a patient on warfarin and rifampicin.
Correlations between CLpo for warfarin enantiomers existed across the three populations. In addition, there was a significant correlation between the CLm for 7-hydroxylation of warfarin enantiomers. Under induced conditions by rifampicin, there were significant correlations between the enantio- and regio-selective metabolisms of warfarin.
Metabolic activities of CYP2C9, CYP1A2 and CYP3A4 may be regulated by common transcriptional mechanism(s).
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