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Pharmacogenomics review

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https://www.readbyqxmd.com/read/28202365/optimising-the-use-of-medicines-to-reduce-acute-kidney-injury-in-children-and-babies
#1
REVIEW
L Oni, D B Hawcutt, M A Turner, M W Beresford, S McWilliam, C Barton, B K Park, P Murray, B Wilm, I Copple, R Floyd, M Peak, A Sharma, D J Antoine
The majority of medications in children are administered in an unlicensed or off-label manner. Paediatricians are obliged to prescribe using the limited evidence available. The 2007 EU regulation on the use of paediatric drugs means pharmaceutical companies are now obliged to (and receive incentives for) contributing to paediatric drug data and carrying out paediatric clinical trials. This is important, as the efficacy and adverse effect profiles of medicines vary across childhood. Additionally, there are significant age-related changes in the pharmacodynamic and pharmacokinetic activity of many drugs...
February 12, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28183252/pharmacological-profile-and-pharmacogenomics-of-anti-cancer-drugs-used-for-targeted-therapy
#2
Raffaele Di Francia, Angela De Monaco, Mariangela Saggese, Giancarla Iaccarino, Stefania Crisci, Ferdinando Frigeri, Rosaria De Filippi, Massimiliano Berretta, Antonio Pinto
Drugs for targeted therapies are primarily Small Molecules Inhibitors (SMIs), monoclonal antibodies (mAbs), interfering RNA molecules and microRNA. The use of these new agents generates a multifaceted step in the pharmacokinetics (PK) of these drugs. Individual PK variability is often large, and unpredictability observed in the response to the pharmacogenetic profile of the patient (e.g. cytochome P450 enzyme), patient characteristics such as adherence to treatment and environmental factors. Objective This review aims to overview the latest anticancer drugs eligible for targeted therapies and the most recent finding in pharmacogenomics related to toxicity/resistance because either individual gene polymorphisms or acquired mutation in a cancer cell...
February 8, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28162244/pharmacogenetics-of-hypersensitivity-drug-reactions
#3
Simone Negrini, Laurent Becquemont
Adverse drug reactions are a significant cause of morbidity and mortality and represent a major burden on the healthcare system. Some of those reactions are immunologically mediated (hypersensitivity reactions) and can be clinically subdivided into two categories: immediate reactions (IgE-related) and delayed reactions (T-cell-mediated). Delayed hypersensitivity reactions include both systemic syndromes and organ-specific toxicities and can be triggered by a wide range of chemically diverse drugs. Recent studies have demonstrated a strong genetic association between human leukocyte antigen alleles and susceptibility to delayed drug hypersensitivity...
January 3, 2017: Thérapie
https://www.readbyqxmd.com/read/28159880/en-route-to-precision-medicine-through-the-integration-of-biological-sex-into-pharmacogenomics
#4
REVIEW
Lea Gaignebet, Georgios Kararigas
Frequently, pharmacomechanisms are not fully elucidated. Therefore, drug use is linked to an elevated interindividual diversity of effects, whether therapeutic or adverse, and the role of biological sex has as yet unrecognized and underestimated consequences. A pharmacogenomic approach could contribute towards the development of an adapted therapy for each male and female patient, considering also other fundamental features, such as age and ethnicity. This would represent a crucial step towards precision medicine and could be translated into clinical routine...
February 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28117005/pharmacogenomic-challenges-in-cardiovascular-diseases-examples-of-drugs-and-considerations-for-future-integration-in-clinical-practice
#5
Jérôme Chatelin, Maria G Stathopoulou, Alex-Ander Aldasoro Arguinano, Ting Xie, Sophie Visvikis-Siest
Introduction Even if cardiovascular disease (CVD) drugs are supported by high level proofs, the results of CVD treatment present great disparities: there are still patients dying with supposed optimal treatment, patients facing adverse events and CVD remain the primary cause of death in the world. Pharmacogenomics is the basis of personalisation of the treatment able to allow higher medication success rates. In this review, we will present detailed examples of CVD drugs to highlight the complexity of this challenging field and we will discuss novel concepts that should be considered for a fastest integration of pharmacogenomics in clinical practice of CVD...
January 23, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28099754/addressing-the-crisis-in-the-treatment-of-osteoporosis-a-path-forward
#6
Sundeep Khosla, Jane A Cauley, Juliet Compston, Douglas P Kiel, Clifford Rosen, Kenneth G Saag, Elizabeth Shane
Considerable data and media attention have highlighted a potential "crisis" in the treatment of osteoporosis. Specifically, despite the availability of several effective drugs to prevent fractures, many patients who need pharmacological therapy are either not being prescribed these medications or if prescribed a medication, are simply not taking it. Although there are many reasons for this "gap" in the treatment of osteoporosis, a major factor is physician and patient concerns over the risk of side effects, especially atypical femur fractures (AFFs) related to bisphosphonate (and perhaps other antiresorptive) drug therapy...
December 29, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28074382/engaging-hmong-adults-in-genomic%C3%A2-and%C3%A2-pharmacogenomic-research-toward-reducing-health-disparities-in-genomic-knowledge-using-a-community-based-participatory-research-approach
#7
Kathleen A Culhane-Pera, Robert J Straka, MaiKia Moua, Youssef Roman, Pachia Vue, Kang Xiaaj, May Xia Lo, Mai Lor
Advancing precision medicine relies in part on examining populations that may exhibit unique genetic variants that impact clinical outcomes. Failure to include diverse populations in genomic-based research represents a health disparity. We implemented a community-based participatory research (CBPR) process with the Hmong community in Minnesota, who were refugees from Laos, in order to assess the feasibility of conducting genomic and pharmacogenomic-based research for genetic variants that are relevant to the Hmong community...
January 10, 2017: Journal of Community Genetics
https://www.readbyqxmd.com/read/28069634/a-review-of-connectivity-map-and-computational-approaches-in-pharmacogenomics
#8
Aliyu Musa, Laleh Soltan Ghoraie, Shu-Dong Zhang, Galina Galzko, Olli Yli-Harja, Matthias Dehmer, Benjamin Haibe-Kains, Frank Emmert-Streib
Large-scale perturbation databases, such as Connectivity Map (CMap) or Library of Integrated Network-based Cellular Signatures (LINCS), provide enormous opportunities for computational pharmacogenomics and drug design. A reason for this is that in contrast to classical pharmacology focusing at one target at a time, the transcriptomics profiles provided by CMap and LINCS open the door for systems biology approaches on the pathway and network level. In this article, we provide a review of recent developments in computational pharmacogenomics with respect to CMap and LINCS and related applications...
January 9, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28068459/does-pharmacogenomic-testing-improve-clinical-outcomes-for-major-depressive-disorder-a-systematic-review-of-clinical-trials-and-cost-effectiveness-studies
#9
Joshua D Rosenblat, Yena Lee, Roger S McIntyre
OBJECTIVE: Pharmacogenomic testing has become scalable and available to the general public. Pharmacogenomics has shown promise for predicting antidepressant response and tolerability in the treatment of major depressive disorder (MDD). In theory, pharmacogenomics can improve clinical outcomes by guiding antidepressant selection and dosing. The current systematic review examines the extant literature to determine the impact of pharmacogenomic testing on clinical outcomes in MDD and assesses its cost-effectiveness...
January 3, 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28057956/nontraditional-career-opportunities-for-pharmacists
#10
Sandra Bai, John B Hertig, Robert J Weber
The changing landscape of health care mirrors that of health-system pharmacy, with pharmacists' scope of practice and provider status being the most significant changes. This creates new roles and opportunities; many of these roles are considered to be nontraditional in today's practice. This article reviews some new roles for pharmacy leaders that provide different career options and pathways. Nontraditional career opportunities discussed include expanded consulting roles in pricing analytics and drug pricing programs (contracting, 340B programs), pharmacogenomics patient consult services and clinics, specialty drug pharmacies, and compounding pharmacy services...
December 2016: Hospital Pharmacy
https://www.readbyqxmd.com/read/28032660/addressing-the-crisis-in-the-treatment-of-osteoporosis-a-path-forward
#11
Sundeep Khosla, Jane A Cauley, Juliet Compston, Douglas P Kiel, Clifford Rosen, Kenneth G Saag, Elizabeth Shane
Considerable data and media attention have highlighted a potential "crisis" in the treatment of osteoporosis. Specifically, despite the availability of several effective drugs to prevent fractures, many patients who need pharmacological therapy are either not being prescribed these medications or if prescribed a medication, are simply not taking it. Although there are many reasons for this "gap" in the treatment of osteoporosis, a major factor is physician and patient concerns over the risk of side effects, especially atypical femur fractures (AFFs) related to bisphosphonate (and perhaps other anti-resorptive) drug therapy...
December 29, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28007021/implementation-of-next-generation-sequencing-into-pediatric-hematology-oncology-practice-moving-beyond-actionable-alterations
#12
Jennifer A Oberg, Julia L Glade Bender, Maria Luisa Sulis, Danielle Pendrick, Anthony N Sireci, Susan J Hsiao, Andrew T Turk, Filemon S Dela Cruz, Hanina Hibshoosh, Helen Remotti, Rebecca J Zylber, Jiuhong Pang, Daniel Diolaiti, Carrie Koval, Stuart J Andrews, James H Garvin, Darrell J Yamashiro, Wendy K Chung, Stephen G Emerson, Peter L Nagy, Mahesh M Mansukhani, Andrew L Kung
BACKGROUND: Molecular characterization has the potential to advance the management of pediatric cancer and high-risk hematologic disease. The clinical integration of genome sequencing into standard clinical practice has been limited and the potential utility of genome sequencing to identify clinically impactful information beyond targetable alterations has been underestimated. METHODS: The Precision in Pediatric Sequencing (PIPseq) Program at Columbia University Medical Center instituted prospective clinical next generation sequencing (NGS) for pediatric cancer and hematologic disorders at risk for treatment failure...
December 23, 2016: Genome Medicine
https://www.readbyqxmd.com/read/27999358/review-of-toxic-epidermal-necrolysis
#13
REVIEW
Victoria Harris, Christopher Jackson, Alan Cooper
Toxic epidermal necrolysis (TEN) is a rare but life threatening mucocutaneous reaction to drugs or their metabolites. It is characterised by widespread keratinocyte apoptosis and sloughing of the skin, erosions of the mucous membranes, painful blistering, and severe systemic disturbance. The pathophysiology of TEN is incompletely understood. Historically, it has been regarded as a drug-induced immune reaction initiated by cytotoxic lymphocytes via a human leukocyte antigen (HLA)-restricted pathway. Several mediators have been identified as contributors to the cell death seen in TEN, including; granulysin, soluble Fas ligand, perforin/granzyme, tumour necrosis factor-α (TNF-α), and TNF-related apoptosis-inducing ligand...
December 18, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27997009/-genomics-of-lung-adenocarcinoma-pathogenetic-significance-and-clinical-applications
#14
Raffaele Palmirotta, Silvana Acquafredda, Antonella Argentiero, Claudia Carella, Laura Lanotte, Nicla Pappagallo, Davide Quaresmini, Franco Silvestris
Diagnostic and therapeutic approaches to non small cell lung cancer (NSCLC), especially adenocarcinoma, have recently undergone dramatic evolution according to the tremendous amount of molecular data collected on this cancer. In fact, the application of oncogenomics has identified novel molecular subtypes of NSCLC and led the way to diagnostic criteria based on the expression of specific genetic alterations that can provide prognostic and specific indications to the molecular targeted therapies. In NSCLC, several genes show "driver" molecular alterations that confer oncogenic potential to progenitor cells through the enrollment of metabolic pathways critical for cell proliferation and tumor development...
December 2016: Recenti Progressi in Medicina
https://www.readbyqxmd.com/read/27992547/the-impact-of-genetic-and-non-genetic-factors-on-warfarin-dose-prediction-in-mena-region-a-systematic-review
#15
Loulia Akram Bader, Hazem Elewa
BACKGROUND: Warfarin is the most commonly used oral anticoagulant for the treatment and prevention of thromboembolic disorders. Pharmacogenomics studies have shown that variants in CYP2C9 and VKORC1 genes are strongly and consistently associated with warfarin dose variability. Although different populations from the Middle East and North Africa (MENA) region may share the same ancestry, it is still unclear how they compare in the genetic and non-genetic factors affecting their warfarin dosing...
2016: PloS One
https://www.readbyqxmd.com/read/27987157/incorporating-pharmacogenomics-into-health-information-technology-electronic-health-record-and-decision-support-system-an-overview
#16
Abdullah Alanazi
As the adoption of information technology in healthcare is rising, the potentiality of moving Pharmacogenomics from benchside to bedside is aggravated. This paper reviews the current status of Pharmacogenomics (PGx) information and the attempts for incorporating them into the Electronic Health Record (EHR) system through Decision Support Systems (DSSs). Rigorous review strategies of PGx information and providing context-relevant recommendations in form of action plan- dose adjustment, lab tests rather than just information- would be ideal for making clinical recommendations out of PGx information...
February 2017: Journal of Medical Systems
https://www.readbyqxmd.com/read/27978982/pharmacogenomics-in-the-age-of-personalized-medicine
#17
REVIEW
Leslie J Dickmann, Joseph A Ware
The aim of personalized medicine is to offer the right treatment to the right person at the right dose, thus maximizing efficacy and minimizing toxicity for each individual patient. Pharmacogenomic approaches attempt to refine the aim of personalized medicine by utilizing an individual's germline and somatic DNA signatures to guide treatment. In this review, we highlight the current use of pharmacogenomic based biomarker information in drug labeling. We also present several case studies on the implementation of pharmacogenomic strategies in drug discovery and development...
September 2016: Drug Discovery Today. Technologies
https://www.readbyqxmd.com/read/27957864/drug-metabolism-and-liver-disease-a-drug-gene-environment-interaction
#18
Nathalie K Zgheib, Robert A Branch
Despite the central role of the liver in drug metabolism, surprisingly there is lack of certainty in anticipating the extent of modification of the clearance of a given drug in a given patient. The intent of this review is to provide a conceptual framework in considering the impact of liver disease on drug disposition and reciprocally the impact of drug disposition on liver disease. It is proposed that improved understanding of the situation is gained by considering the issue as a special example of a drug-gene-environment interaction...
January 23, 2017: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/27942231/cyp2d6-polymorphisms-and-their-influence-on-risperidone-treatment
#19
REVIEW
Apichaya Puangpetch, Natchaya Vanwong, Nopphadol Nuntamool, Yaowaluck Hongkaew, Monpat Chamnanphon, Chonlaphat Sukasem
Cytochrome P450 enzyme especially CYP2D6 plays a major role in biotransformation. The interindividual variations of treatment response and toxicity are influenced by the polymorphisms of this enzyme. This review emphasizes the effect of CYP2D6 polymorphisms in risperidone treatment in terms of basic knowledge, pharmacogenetics, effectiveness, adverse events, and clinical practice. Although the previous studies showed different results, the effective responses in risperidone treatment depend on the CYP2D6 polymorphisms...
2016: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/27897268/germline-polymorphisms-as-biomarkers-of-tumor-response-in-colorectal-cancer-patients-treated-with-anti-egfr-monoclonal-antibodies-a-systematic-review-and-meta-analysis
#20
E K Morgen, H-J Lenz, D J Jonker, D Tu, G Milano, F Graziano, J Zalcberg, C S Karapetis, A Dobrovic, C J O'Callaghan, G Liu
Studies of germline polymorphisms as predictors of tumor response to anti-epidermal growth factor receptor (EGFR) monoclonal antibody agents in metastatic colorectal cancer have reported inconsistent results. We performed a systematic review of studies from 1990 to September 2015, followed by random-effects meta-analyses for polymorphisms examined in at least three studies. Of 87 studies, 40 passed the criteria for systematic review and 23 for meta-analysis. The polymorphisms suitable for meta-analysis were CCND1 (rs17852153), COX2 (rs20417), EGF (rs4444903), EGFR (rs712829, rs11543848, 3'UTR CA repeat), FCGR2A (rs1801274), FCGR3A (rs396991), IL8 (rs4073), KRAS (rs61764370) and VEGFA (rs3025039)...
November 29, 2016: Pharmacogenomics Journal
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