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Pharmacogenomics review

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https://www.readbyqxmd.com/read/28816643/pharmacometabolomics-informs-quantitative-radiomics-for-glioblastoma-diagnostic-innovation
#1
Theodora Katsila, Minos-Timotheos Matsoukas, George P Patrinos, Dimitrios Kardamakis
Applications of omics systems biology technologies have enormous promise for radiology and diagnostics in surgical fields. In this context, the emerging fields of radiomics (a systems scale approach to radiology using a host of technologies, including omics) and pharmacometabolomics (use of metabolomics for patient and disease stratification and guiding precision medicine) offer much synergy for diagnostic innovation in surgery, particularly in neurosurgery. This synthesis of omics fields and applications is timely because diagnostic accuracy in central nervous system tumors still challenges decision-making...
August 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28815128/a-comparative-study-of-different-methods-for-automatic-identification-of-clopidogrel-induced-bleedings-in-electronic-health-records
#2
Hee-Jin Lee, Min Jiang, Yonghui Wu, Christian M Shaffer, John H Cleator, Eitan A Friedman, Joshua P Lewis, Dan M Roden, Josh Denny, Hua Xu
Electronic health records (EHRs) linked with biobanks have been recognized as valuable data sources for pharmacogenomic studies, which require identification of patients with certain adverse drug reactions (ADRs) from a large population. Since manual chart review is costly and time-consuming, automatic methods to accurately identify patients with ADRs have been called for. In this study, we developed and compared different informatics approaches to identify ADRs from EHRs, using clopidogrel-induced bleeding as our case study...
2017: AMIA Summits on Translational Science Proceedings
https://www.readbyqxmd.com/read/28815127/a-knowledge-based-system-for-intelligent-support-in-pharmacogenomics-evidence-assessment-ontology-driven-evidence-representation-and-retrieval
#3
Chia-Ju Lee, Beth Devine, Peter Tarczy-Hornoch
Pharmacogenomics holds promise as a critical component of precision medicine. Yet, the use of pharmacogenomics in routine clinical care is minimal, partly due to the lack of efficient and effective use of existing evidence. This paper describes the design, development, implementation and evaluation of a knowledge-based system that fulfills three critical features: a) providing clinically relevant evidence, b) applying an evidence-based approach, and c) using semantically computable formalism, to facilitate efficient evidence assessment to support timely decisions on adoption of pharmacogenomics in clinical care...
2017: AMIA Summits on Translational Science Proceedings
https://www.readbyqxmd.com/read/28776467/pharmacogenetics-and-the-treatment-of-asthma
#4
María Isidoro-García, Almudena Sánchez-Martín, Asunción García-Sánchez, Catalina Sanz, Belén García-Berrocal, Ignacio Dávila
Heterogeneity defines both the natural history of asthma as well as patient's response to treatment. Pharmacogenomics contribute to understand the genetic basis of drug response and thus to define new therapeutic targets or molecular biomarkers to evaluate treatment effectiveness. This review is initially focused on different genes so far involved in the pharmacological response to asthma treatment. Specific considerations regarding allergic asthma, the pharmacogenetics aspects of polypharmacy and the application of pharmacogenomics in new drugs in asthma will also be addressed...
August 4, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28766962/clarifying-busulfan-metabolism-and-drug-interactions-to-support-new-therapeutic-drug-monitoring-strategies-a-comprehensive-review
#5
Alan L Myers, Jitesh D Kawedia, Richard E Champlin, Mark A Kramer, Yago Nieto, Romi Ghose, Borje S Andersson
Busulfan (Bu) is an alkylating agent with a limited therapeutic margin and exhibits inter-patient variability in pharmacokinetics (PK). Despite decades of use, mechanisms of Bu PK-based drug-drug interactions (DDIs), as well as the negative downstream effects of these DDIs, have not been fully characterized. Areas covered: This article provides an overview of Bu PK, with a primary focus on how known and potentially unknown drug metabolism pathways influence Bu-associated DDIs. In addition, pharmacogenomics of Bu chemotherapy and Bu-related DDIs observed in the stem cell transplant clinic (SCT) are summarized...
August 2, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28764766/physicians-pharmacogenomics-information-needs-and-seeking-behavior-a-study-with-case-vignettes
#6
Bret S E Heale, Aly Khalifa, Bryan L Stone, Scott Nelson, Guilherme Del Fiol
BACKGROUND: Genetic testing, especially in pharmacogenomics, can have a major impact on patient care. However, most physicians do not feel that they have sufficient knowledge to apply pharmacogenomics to patient care. Online information resources can help address this gap. We investigated physicians' pharmacogenomics information needs and information-seeking behavior, in order to guide the design of pharmacogenomics information resources that effectively meet clinical information needs...
August 1, 2017: BMC Medical Informatics and Decision Making
https://www.readbyqxmd.com/read/28762370/impact-of-cyp2d6-polymorphisms-on-endoxifen-concentrations-and-breast-cancer-outcomes
#7
REVIEW
G S Hwang, R Bhat, R D Crutchley, M V Trivedi
We investigated the impact of germline CYP2D6 genotyping done using the non-tumor specimen on endoxifen concentrations and/or clinical outcomes in breast cancer (BC) patients treated with tamoxifen in published studies. We evaluated published data from 13 001 patients in 29 studies. Mean±s.d. endoxifen concentrations were significantly lower in poor metabolizers (PM) versus extensive metabolizers (EM) (8.8±7.2 versus 22.3±11.8 ng ml(-1); P<0.05). The PM status did not influence clinical outcomes in majority of the studies...
August 1, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28761069/evidence-for-treatment-by-biomarker-interaction-for-fda-approved-oncology-drugs-with-required-pharmacogenomic-biomarker-testing
#8
Alexandre Vivot, Isabelle Boutron, Geoffroy Béraud-Chaulet, Jean-David Zeitoun, Philippe Ravaud, Raphaël Porcher
For oncology drugs that were approved by the US Food and Drug Administration (FDA) and required pharmacogenomic biomarker testing, we describe 1) the use of enrichment (biomarker-positive patients) and a randomized controlled design by pre-approval trials and 2) the treatment-by-biomarker interaction. From the 137 drugs included in the FDA table, we selected the 22 oncology drugs with required genetic testing in their labels. These drugs corresponded to 35 approvals supported by 80 clinical studies included in the FDA medical officer reviews of efficacy...
July 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28749586/patient-decisions-to-receive-secondary-pharmacogenomic-findings-and-development-of-a-multidisciplinary-practice-model-to-integrate-results-into-patient-care
#9
J Kevin Hicks, Amy Shealy, Allison Schreiber, Marissa Coleridge, Ryan Noss, Marvin Natowicz, Rocio Moran, Timothy Moss, Angelika Erwin, Charis Eng
Whole exome sequencing (WES) has the potential of identifying secondary findings that are predictive of poor pharmacotherapy outcomes. The purpose of this study was to investigate patients' wishes regarding the reporting of secondary pharmacogenomic findings. WES results (n = 106 patients) were retrospectively reviewed to determine the number of patients electing to receive secondary pharmacogenomic results. Phenotypes were assigned based on Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines...
July 27, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28748348/impact-of-genetic-polymorphisms-on-phenytoin-pharmacokinetics-and-clinical-outcomes-in-the-middle-east-and-north-africa-region
#10
REVIEW
Renée Dagenais, Kyle John Wilby, Hazem Elewa, Mary H H Ensom
BACKGROUND: Genetic polymorphisms are known to influence outcomes with phenytoin yet effects in the Middle East and North Africa region are poorly understood. OBJECTIVES: The objective of this systematic review was to evaluate the impact of genetic polymorphisms on phenytoin pharmacokinetics and clinical outcomes in populations originating from the Middle East and North Africa region, and to characterize genotypic and allelic frequencies within the region for genetic polymorphisms assessed...
July 26, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28745580/pharmacogenomic-considerations-in-the-treatment-of-muscle-invasive-bladder-cancer
#11
Tahlita Cm Zuiverloon, Dan Theodorescu
Recent advances in next-generation sequencing techniques have greatly improved our understanding of the genomic alterations in bladder cancer. Cisplatin-based chemotherapy provides a viable treatment option in the neoadjuvant, adjuvant and metastatic setting in a selected group of patients, but chemoresistance is a major problem. The underlying mechanisms of treatment resistance are poorly understood and elucidating these pathways will subsequently lead to improved patient selection, less unnecessary drug-related toxicity, improved patient outcome and decreased healthcare costs...
August 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28741243/the-pharmacogenomic-and-metabolomic-predictors-of-ace-inhibitor-and-angiotensin-ii-receptor-blocker-effectiveness-and-safety
#12
Hania K Flaten, Andrew A Monte
Hypertension (HTN) is the most common chronic disease in the USA. Hypertensive patients frequently require repeat primary care visits to find an effective drug or drug combination to control their disease. Currently, patients are prescribed drugs for HTN based on race, age, and comorbidities and although the current guidelines are reasonable starting points for prescribing, 50% of hypertensive patients still fail to achieve target blood pressures. Despite numerous strategies to improve compliance, drug effectiveness, and optimization of initial drug choice, effectiveness has remained largely unchanged over the past two decades...
July 24, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28718665/prevalence-of-low-vitamin-d-in-patients-with-breast-cancer-in-a-predominantly-hispanic-population-at-the-american-mexican-border
#13
Safa E Farrag, Alok K Dwivedi, Salman Otoukesh, Nabeel J Badri, Luis A Sanchez, Zeina A Nahleh
INTRODUCTION: Low level of vitamin D (VD) has been linked with a higher risk of cancers. The aim of this study was to assess the prevalence of low VD in patients with breast cancer in a predominantly Mexican Hispanic/Latino patient population, a fast growing and relatively understudied population. MATERIALS/METHODS: We sought to evaluate the serum VD levels in breast cancer patients diagnosed at the Texas Tech University Breast Cancer Center in El Paso, TX, between May 2013 and May2014 via a retrospective chart review of the Electronic Medical Records...
July 18, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28717926/clinical-evaluation-of-modified-release-and-immediate-release-tacrolimus-formulations
#14
Simon Tremblay, Rita R Alloway
The science of drug delivery has evolved considerably and has led to the development of multiple sustained release formulations. Each of these formulations can present particular challenges in terms of clinical evaluation and necessitate careful study to identify their optimal use in practice. Tacrolimus is an immunosuppressive agent that is widely used in organ transplant recipients. However, it is poorly soluble, has an unpredictable pharmacokinetic profile subject to important genetic polymorphisms and drug-drug interactions, and has a narrow therapeutic index...
July 17, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28698977/pharmacogenetics-and-pharmacogenomics-of-targeted-therapeutics-in-chronic-myeloid-leukemia
#15
REVIEW
Aritro Nath, Jacqueline Wang, R Stephanie Huang
The advent of targeted therapeutics has greatly improved outcomes of chronic myeloid leukemia (CML) patients. Despite increased efficacy and better clinical responses over cytotoxic chemotherapies, many patients receiving targeted drugs exhibit a poor initial response, develop drug resistance, or undergo relapse after initial success. This inter-individual variation in response has heightened the interest in studying pharmacogenetics and pharmacogenomics (PGx) of cancer drugs. In this review, we discuss the influence of various germline and somatic factors on targeted drug response in CML...
July 11, 2017: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/28696417/harnessing-low-density-lipoprotein-receptor-protein-6-lrp6-genetic-variation-and-wnt-signaling-for-innovative-diagnostics-in-complex-diseases
#16
REVIEW
Z-M Wang, J-Q Luo, L-Y Xu, H-H Zhou, W Zhang
Wnt signaling regulates a broad variety of processes in both embryonic development and various diseases. Recent studies indicated that some genetic variants in Wnt signaling pathway may serve as predictors of diseases. Low-density lipoprotein receptor protein 6 (LRP6) is a Wnt co-receptor with essential functions in the Wnt/β-catenin pathway, and mutations in LRP6 gene are linked to many complex human diseases, including metabolic syndrome, cancer, Alzheimer's disease and osteoporosis. Therefore, we focus on the role of LRP6 genetic polymorphisms and Wnt signaling in complex diseases, and the mechanisms from mouse models and cell lines...
July 11, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28695285/the-role-of-hla-genes-in-pharmacogenomics-unravelling-hla-associated-adverse-drug-reactions
#17
REVIEW
Patricia T Illing, Anthony W Purcell, James McCluskey
Genetic polymorphism in the genes encoding the human leukocyte antigen (HLA) molecules enables presentation of a wide range peptide ligands thus maximising immune surveillance of pathogens. A consequence of the diversification of the HLA Ag-binding pocket is the enhanced opportunity for off-target binding of small drugs by HLA molecules, with subsequent immune reactivity. These potential off-target interactions are 'set up' to generate T cell-mediated adverse drug reactions even though the precise mechanisms of most HLA-drug interactions are still poorly understood...
July 10, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28682531/florida-best-practice-psychotherapeutic-medication-guidelines-for-adults-with-major-depressive-disorder
#18
REVIEW
Roger S McIntyre, Trisha Suppes, Rajiv Tandon, Michael Ostacher
OBJECTIVE: Herein we provide the 2015 update for the Florida Best Practice Psychotherapeutic Medication Guidelines (FPG) for major depressive disorder (MDD). The FPG represent evidence-based decision support for practitioners providing care to adults with MDD. PARTICIPANTS: The consensus meeting included representatives from the Florida Agency for Health Care Administration (FAHCA), advocacy members, academic experts in MDD, and multidisciplinary mental health clinicians, as well as health policy experts...
June 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28672074/collaborative-counseling-considerations-for-pharmacogenomic-tests
#19
Heather A Zierhut, Colleen A Campbell, Allison G Mitchell, Amy A Lemke, Rachel Mills, Jeffrey R Bishop
Increased use of pharmacogenomic (PGx) testing in the clinical setting has revealed a number of challenges to the provision of this service. PGx is an important component of precision medicine which brings together the fields of genetics and clinical pharmacology. A model that incorporates a multi-disciplinary approach to implementation and information delivery may be the most beneficial to patients and providers. In this review, translational considerations in the provision of PGx testing and counseling services are described...
July 3, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28657381/safety-profile-of-biological-therapies-for-treating-rheumatoid-arthritis
#20
Juan D Cañete, Mª Victoria Hernández, Raimon Sanmartí
Biological agents such as tumor necrosis factor inhibitors (TNFi), abatacept, rituximab and tocilizumab have proven efficacy in RA. However, these agents are also associated with adverse events so further data is essential to detect them at the earliest stage possible. Areas covered: Herein, the authors review the safety profile of biological therapy, including TNFi and non-TNF agents including abatacept (ABA), rituximab (RTX) and tocilizumab (TCZ). The authors analyze both published articles and congress communications including clinical trials, meta-analyses, observational studies, data from registries and spontaneous clinical reports...
July 17, 2017: Expert Opinion on Biological Therapy
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