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Pharmacogenomics review

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https://www.readbyqxmd.com/read/29236081/pharmacogenomics-guided-personalization-of-warfarin-and-tamoxifen
#1
REVIEW
Theodore J Wigle, Laura E Jansen, Wendy A Teft, Richard B Kim
The use of pharmacogenomics to personalize drug therapy has been a long-sought goal for warfarin and tamoxifen. However, conflicting evidence has created reason for hesitation in recommending pharmacogenomics-guided care for both drugs. This review will provide a summary of the evidence to date on the association between cytochrome P450 enzymes and the clinical end points of warfarin and tamoxifen therapy. Further, highlighting the clinical experiences that we have gained over the past ten years of running a personalized medicine program, we will offer our perspectives on the utility and the limitations of pharmacogenomics-guided care for warfarin and tamoxifen therapy...
December 13, 2017: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29205206/applications-of-pharmacogenomics-in-regulatory-science-a-product-life-cycle-review
#2
W C Tan-Koi, P C Leow, Y Y Teo
With rapid developments of pharmacogenomics (PGx) and regulatory science, it is important to understand the current PGx integration in product life cycle, impact on clinical practice thus far and opportunities ahead. We conducted a cross-sectional review on PGx-related regulatory documents and implementation guidelines in the United States and Europe. Our review found that although PGx-related guidance in both markets span across the entire product life cycle, the scope of implementation guidelines varies across two continents...
December 5, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29199461/biomarkers-delivering-on-the-expectation-of-molecularly-driven-quantitative-health
#3
Jennifer L Wilson, Russ B Altman
Biomarkers are the pillars of precision medicine and are delivering on expectations of molecular, quantitative health. These features have made clinical decisions more precise and personalized, but require a high bar for validation. Biomarkers have improved health outcomes in a few areas such as cancer, pharmacogenetics, and safety. Burgeoning big data research infrastructure, the internet of things, and increased patient participation will accelerate discovery in the many areas that have not yet realized the full potential of biomarkers for precision health...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29197117/addition-of-allopurinol-for-altering-thiopurine-metabolism-to-optimize-therapy-in-patients-with-inflammatory-bowel-disease
#4
Geoffrey C Wall, Hamid Muktar, Cassandra Effken, Pramod B Mahajan
Thiopurine drugs, including azathioprine and 6-mercaptopurine, are used commonly in patients with inflammatory bowel disease for maintenance of remission. Although generally well tolerated, adverse effects lead to discontinuation in a significant minority of patients. Pharmacogenomic studies have suggested that metabolic breakdown of azathioprine in an individual is genetically determined. Coupled with the fact that certain thiopurine metabolites, notably 6-thioguanine nucleotide and 6-methylmercaptopurine, are associated with antiinflammatory effects and adverse effects, respectively, some investigators have examined intentionally shunting the metabolism of azathioprine toward increasing 6-thioguanine nucleotide levels by using low doses of the xanthine oxidoreductase inhibitor allopurinol to improve efficacy and decrease toxicity of azathioprine in patients with inflammatory bowel disease...
December 1, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/29192598/personalized-medicine-pharmacogenomic-and-companion-biomarker
#5
Hana Manceau, Kawthar Amrani, Katell Peoc'h
The aim of this review is to provide a brief overview of personalized medicine, pharmacogenetics and companion tests. Personalized or stratified medicine is a new paradigm in the management of patients, aimed at better taking into account inter-individual variability. The response to drugs' intake varies considerably, depending on the transport and metabolism of the drugs, the target and the pathophysiological characteristics of the organism. Each stage is very variable and can be modified by endogenous factors (pathophysiology, age, sex, genetics…) or exogenous (environmental: taking other medicines, food, tobacco, alcohol…)...
December 1, 2017: Annales de Biologie Clinique
https://www.readbyqxmd.com/read/29186305/systems-bioinformatics-increasing-precision-of-computational-diagnostics-and-therapeutics-through-network-based-approaches
#6
Anastasis Oulas, George Minadakis, Margarita Zachariou, Kleitos Sokratous, Marilena M Bourdakou, George M Spyrou
Systems Bioinformatics is a relatively new approach, which lies in the intersection of systems biology and classical bioinformatics. It focuses on integrating information across different levels using a bottom-up approach as in systems biology with a data-driven top-down approach as in bioinformatics. The advent of omics technologies has provided the stepping-stone for the emergence of Systems Bioinformatics. These technologies provide a spectrum of information ranging from genomics, transcriptomics and proteomics to epigenomics, pharmacogenomics, metagenomics and metabolomics...
November 27, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/29181807/pharmacogenomic-biomarkers-for-improved-drug-therapy-recent-progress-and-future-developments
#7
Volker M Lauschke, Lili Milani, Magnus Ingelman-Sundberg
Much of the inter-individual variability in drug efficacy and risk of adverse reactions is due to polymorphisms in genes encoding proteins involved in drug pharmacokinetics and pharmacodynamics or immunological responses. Pharmacogenetic research has identified a multitude of gene-drug response associations, which have resulted in genetically guided treatment and dosing decisions to yield a higher success rate of pharmacological treatment. The rapid technological developments for genetic analyses reveal that the number of genetic variants with importance for drug action is much higher than previously thought and that a true personalized prediction of drug response requires attention to millions of rare mutations...
November 27, 2017: AAPS Journal
https://www.readbyqxmd.com/read/29171014/the-influence-of-big-clinical-data-and-genomics-on-precision-medicine-and-drug-development
#8
Joshua C Denny, Sara L Van Driest, Wei-Qi Wei, Dan M Roden
Drug development continues to be costly and slow, with medications failing due to lack of efficacy or presence of toxicity. The promise of pharmacogenomic discovery includes tailoring therapeutics based on an individual's genetic makeup, rational drug development, and repurposing medications. Rapid growth of large research cohorts, linked to electronic health record (EHR) data, fuels discovery of new genetic variants predicting drug action, supports Mendelian randomization experiments to show drug efficacy, and suggests new indications for existing medications...
November 24, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29141462/a-safety-review-of-medications-used-for-labour-induction
#9
Lili Sheibani, Deborah A Wing
Induction of labour is a commonly performed procedure around the world. There are various medications used for induction including those commonly used for cervical ripening (prostaglandins) and oxytocin. The ideal agent is one that decreases the time to achieving delivery without compromising maternal or neonatal safety. The 'optimal safe agent' remains undetermined. Areas covered: This article reviews the safety of currently used induction agents. Prostaglandins and oxytocin have proven to be effective in labour induction, and their profiles will be reviewed in this article...
November 15, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29123971/concepts-of-genomics-in-kidney-transplantation
#10
William S Oetting, Casey Dorr, Rory P Remmel, Arthur J Matas, Ajay K Israni, Pamala A Jacobson
Purpose of review: Identification of genetic variants to aid in individualized treatment of solid organ allograft recipients would improve graft survival. We will review the current state of knowledge for associations of variants with transplant outcomes. Recent findings: Many studies have yet to exhibit robust and reproducible results, however, pharmacogenomic studies focusing on cytochrome P450 (CYP) enzymes, transporters and HLA variants have shown strong associations with outcomes and have relevance towards drugs used in transplant...
June 2017: Current Transplantation Reports
https://www.readbyqxmd.com/read/29111156/genetics-of-human-susceptibility-to-active-and-latent-tuberculosis-present-knowledge-and-future-perspectives
#11
REVIEW
Laurent Abel, Jacques Fellay, David W Haas, Erwin Schurr, Geetha Srikrishna, Michael Urbanowski, Nimisha Chaturvedi, Sudha Srinivasan, Daniel H Johnson, William R Bishai
Tuberculosis is an ancient human disease, estimated to have originated and evolved over thousands of years alongside modern human populations. Despite considerable advances in disease control, tuberculosis remains one of the world's deadliest communicable diseases with 10 million incident cases and 1·8 million deaths in 2015 alone based on the annual WHO report, due to inadequate health service resources in less-developed regions of the world, and exacerbated by the HIV/AIDS pandemic and emergence of multidrug-resistant strains of Mycobacterium tuberculosis...
October 27, 2017: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/29103068/antiplatelet-therapy-for-secondary-prevention-of-vascular-disease-complications
#12
REVIEW
Rahul R Goli, Mayur M Contractor, Ashwin Nathan, Sony Tuteja, Taisei Kobayashi, Jay Giri
PURPOSE OF REVIEW: Platelets are activated upon interaction with injured vascular endothelium to form a primary hemostatic plug. Pathogenic thrombosis driven by platelet aggregation can occur in the setting of vascular disease leading to ischemic events. The use of antiplatelet agents has become a mainstay for prevention of the secondary complications of vascular disease. This review summarizes seminal and recent literature related to this area. RECENT FINDINGS: Aspirin is a cornerstone of antiplatelet therapy for coronary artery disease and cerebrovascular disease for prevention of myocardial infarction, stroke, and vascular death...
November 4, 2017: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/29101939/pharmacogenomics-precision-medicine-and-drug-response
#13
REVIEW
Richard M Weinshilboum, Liewei Wang
Pharmacogenomics is the use of genomic and other "omic" information to individualize drug selection and drug use to avoid adverse drug reactions and to maximize drug efficacy. The science underlying pharmacogenomics has evolved rapidly over the 50 years since it was first suggested that genetics might influence drug response phenotypes. That process has occurred in parallel with advances in DNA sequencing and other molecular technologies, with striking increases in our understanding of the human genome. There are now many validated examples of the clinical utility of pharmacogenomics, and this type of clinical genomic information is increasingly being generated in clinical laboratories, incorporated into electronic health records, and used to "tailor" or individualize drug therapy...
November 2017: Mayo Clinic Proceedings
https://www.readbyqxmd.com/read/29099060/clinical-pharmacogenetics-of-cytochrome-p450-associated-drugs-in-children
#14
Ida Aka, Christiana J Bernal, Robert Carroll, Angela Maxwell-Horn, Kazeem A Oshikoya, Sara L Van Driest
Cytochrome P450 (CYP) enzymes are commonly involved in drug metabolism, and genetic variation in the genes encoding CYPs are associated with variable drug response. While genotype-guided therapy has been clinically implemented in adults, these associations are less well established for pediatric patients. In order to understand the frequency of pediatric exposures to drugs with known CYP interactions, we compiled all actionable drug-CYP interactions with a high level of evidence using Clinical Pharmacogenomic Implementation Consortium (CPIC) data and surveyed 10 years of electronic health records (EHR) data for the number of children exposed to CYP-associated drugs...
November 2, 2017: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29095091/an-assessment-of-the-impact-of-pharmacogenomics-on-health-disparities-a-systematic-literature-review
#15
Antony Martin, Jennifer Downing, Michelle Maden, Nigel Fleeman, Ana Alfirevic, Alan Haycox, Munir Pirmohamed
This review assessed evidence of disparities in benefits of pharmacogenomics related to 'model performance' in subgroups of patients and studies which reported impact on health inequalities. 'Model performance' refers to the ability of algorithms including clinical, environmental and genetic information to guide treatment. A total of 4978 abstracts were screened by one reviewer and 30% (1494) were double screened by a second independent reviewer, after which data extraction was performed. Additional forward and backward citation searching of reference lists was conducted...
November 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/29089781/pharmacogenomics-of-sickle-cell-disease-steps-toward-personalized-medicine
#16
REVIEW
Marium Husain, Amber D Hartman, Payal Desai
Sickle cell disease (SCD) is a monogenetic disease but has a wide range of phenotypic expressions. Some of these differences in phenotype can be explained by genetic polymorphisms in the human globin gene. These polymorphisms can result in different responses to typical treatment, sometimes leading to inadequate therapeutics. Research is revealing more polymorphisms, and therefore, new targets for intervention to improve outcomes in SCD. This area of pharmacogenomics is continuing to develop. We provide a brief review of the current literature on pharmacogenomics in SCD and possible targets for intervention...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/29078708/a-clinical-pharmacy-pilot-within-a-precision-medicine-program-for-cancer-patients-and-review-of-related-pharmacist-clinical-practice
#17
Justin R Arnall, Robin Petro, Jai N Patel, LeAnne Kennedy
Purpose The implementation, benefits, and challenges of clinical pharmacist services within a Precision Medicine Program for cancer patients are described. By relating the practice model that was developed, this report may further encourage pharmacists at cancer centers nationally to be involved and lead precision-based care in the oncology setting. Summary A clinical pharmacist was integrated into a Precision Medicine Program for oncology patients using somatic testing to identify actionable mutations and apply targeted therapy to malignancies...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29075194/pharmacogenomics-dna-biomarkers-in-colorectal-cancer-current-update
#18
REVIEW
Nurul-Syakima Ab Mutalib, Najwa F Md Yusof, Shafina-Nadiawati Abdul, Rahman Jamal
Colorectal cancer (CRC) remains as one of the most common cause of worldwide cancer morbidity and mortality. Improvements in surgical modalities and adjuvant chemotherapy have increased the cure rates in early stage disease, but a significant portion of the patients will develop recurrence or advanced disease. The efficacy of chemotherapy of recurrence and advanced CRC has improved significantly over the last decade. Previously, the historical drug 5-fluorouracil was used as single chemotherapeutic agent. Now with the addition of other drugs such as capecitabine, irinotecan, oxaliplatin, bevacizumab, cetuximab, panitumumab, vemurafenib, and dabrafenib, the median survival of patients with advanced CRC has significantly improved from less than a year to the current standard of almost 2 years...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29068423/comprehensive-analysis-of-cancer-proteogenome-to-identify-biomarkers-for-the-early-diagnosis-and-prognosis-of-cancer
#19
REVIEW
Hem D Shukla
During the past century, our understanding of cancer diagnosis and treatment has been based on a monogenic approach, and as a consequence our knowledge of the clinical genetic underpinnings of cancer is incomplete. Since the completion of the human genome in 2003, it has steered us into therapeutic target discovery, enabling us to mine the genome using cutting edge proteogenomics tools. A number of novel and promising cancer targets have emerged from the genome project for diagnostics, therapeutics, and prognostic markers, which are being used to monitor response to cancer treatment...
October 25, 2017: Proteomes
https://www.readbyqxmd.com/read/29032303/current-strategies-to-streamline-pharmacotherapy-for-older-adults
#20
REVIEW
Jan-F Schlender, Valvanera Vozmediano, Adam G Golden, Monica Rodriguez, Tanay S Samant, Chakradhar V Lagishetty, Thomas Eissing, Stephan Schmidt
Although the term "personalized medicine" has been associated in many cases with pharmacogenomics, its definition embraces the use of specific biomarkers and covariates to help in the selection of medical treatments and procedures which are best for each patient. While several efforts have been performed for the tailored selection of therapies and dosing regimens in the general population, developing personalized medicine initiatives for elderly patients remains understudied. The personalized drug therapy for older patients requires the consideration of anatomical, physiological and functional alterations in a multimorbid setting requiring multiple medications...
October 12, 2017: European Journal of Pharmaceutical Sciences
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