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Pharmacogenomic

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https://www.readbyqxmd.com/read/27907963/optimizing-medication-outcomes-in-neurocritical-care-focus-on-clinical-pharmacology
#1
Denise H Rhoney, Kathryn Morbitzer, Jimmi Hatton-Kolpek
Drug dosing in neurocritically ill patients presents enormous challenges for clinicians due to the complex pathophysiological alterations. These alterations are dynamic both between and within patients. Unpredictable exposure from standard dosing regimens, which were extrapolated to intensive care unit patients from healthy volunteer studies, may influence medication outcomes. Knowledge of potential alterations in pharmacokinetics/pharmacodynamics in these patients could be applied to maximize the clinical response and minimize adverse effects...
December 2016: Seminars in Neurology
https://www.readbyqxmd.com/read/27905519/the-impact-of-dna-damage-response-gene-polymorphisms-on-therapeutic-outcomes-in-late-stage-ovarian-cancer
#2
F Guffanti, R Fruscio, E Rulli, G Damia
Late stage epithelial ovarian cancer has a dismal prognosis. Identification of pharmacogenomic markers (i.e. polymorphisms) to stratify patients to optimize individual therapy is of paramount importance. We here report the retrospective analysis of polymorphisms in 5 genes (ATM, ATR, Chk1, Chk2 and CDK12) involved in the cellular response to platinum in a cohort of 240 cancer patients with late stage ovarian cancer. The aim of the present study was to evaluate associations between the above mentioned SNPs and patients' clinical outcomes: overall survival (OS) and progression free survival (PFS)...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905415/consistency-in-large-pharmacogenomic-studies
#3
Paul Geeleher, Eric R Gamazon, Cathal Seoighe, Nancy J Cox, R Stephanie Huang
No abstract text is available yet for this article.
November 30, 2016: Nature
https://www.readbyqxmd.com/read/27900865/-treatment-of-dyslipidemia-is-here-still-place-for-cetp-inhibitors
#4
Ján Murín, Miroslav Pernický, Soňa Kiňová
In the treatment of dyslipidemias about 5-6 years back a new class of drugs emerged, CETP (cholesteryl ester transfer protein)-inhibitors. Their benefit was due to an increase of HDL-cholesterol (HDL-C) serum levels. This treatment mode was supported by epidemiological and clinical studies, as people with high serum HDL-C levels suffered less from cardiovascular (CV) events. Three studies with CETP inhibitors (ILLUMINATE with torcetrapib, dal-OUTCOMES with dalcetrapib and ACCELERATE with evacetrapib) were unfortunately negative, and torcetrapib was even harmful to patients due to an increase of aldosterone serum levels...
2016: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27900742/-precision-nursing-individual-based-knowledge-translation
#5
Li-Chi Chiang, Mei-Ling Yeh, Sui-Lung Su
U.S. President Obama announced a new era of precision medicine in the Precision Medicine Initiative (PMI). This initiative aims to accelerate the progress of personalized medicine in light of individual requirements for prevention and treatment in order to improve the state of individual and public health. The recent and dramatic development of large-scale biologic databases (such as the human genome sequence), powerful methods for characterizing patients (such as genomics, microbiome, diverse biomarkers, and even pharmacogenomics), and computational tools for analyzing big data are maximizing the potential benefits of precision medicine...
December 2016: Hu Li za Zhi the Journal of Nursing
https://www.readbyqxmd.com/read/27897269/an-integrated-pharmacokinetic-pharmacogenomic-analysis-of-abcb1-and-slco1b1-polymorphisms-on-edoxaban-exposure
#6
A G Vandell, J Lee, M Shi, I Rubets, K S Brown, J R Walker
Edoxaban and its low-abundance, active metabolite M4 are substrates of P-glycoprotein (P-gp; MDR1) and organic anion transporter protein 1B1 (OATP1B1), respectively, and pharmacological inhibitors of P-gp and OATP1B1 can affect edoxaban and M4 pharmacokinetics (PK). In this integrated pharmacogenomic analysis, genotype and concentration-time data from 458 healthy volunteers in 14 completed phase 1 studies were pooled to examine the impact on edoxaban PK parameters of allelic variants of ABCB1 (rs1045642: C3435T) and SLCO1B1 (rs4149056: T521C), which encode for P-gp and OATP1B1...
November 29, 2016: Pharmacogenomics Journal
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
#7
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
https://www.readbyqxmd.com/read/27897267/increasing-bmi-is-associated-with-reduced-expression-of-p-glycoprotein-abcb1-gene-in-the-human-brain-with-a-stronger-association-in-african-americans-than-caucasians
#8
J Vendelbo, R H Olesen, J K Lauridsen, J Rungby, J E Kleinman, T M Hyde, A Larsen
The efflux pump, p-glycoprotein, controls bioavailability and excretion of pharmaceutical compounds. In the blood-brain barrier, p-glycoprotein regulates the delivery of pharmaceutical substances to the brain, influencing efficacy and side effects for some drugs notably antipsychotics. Common side effects to antipsychotics include obesity and metabolic disease. Polymorphisms in the ABCB1 gene coding for p-glycoprotein are associated with more severe side effects to neuro-pharmaceuticals as well as weight gain, indicating a potential link between p-glycoprotein function and metabolic regulation...
November 29, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27897005/strategies-for-equitable-pharmacogenomic-guided-warfarin-dosing-among-european-and-african-american-individuals-in-a-clinical-population
#9
Laura K Wiley, Jacob P Vanhouten, David C Samuels, Melinda C Aldrich, Dan M Roden, Josh F Peterson, Joshua C Denny
The blood thinner warfarin has a narrow therapeutic range and high inter- and intra-patient variability in therapeutic doses. Several studies have shown that pharmacogenomic variants help predict stable warfarin dosing. However, retrospective and randomized controlled trials that employ dosing algorithms incorporating pharmacogenomic variants under perform in African Americans. This study sought to determine if: 1) including additional variants associated with warfarin dose in African Americans, 2) predicting within single ancestry groups rather than a combined population, or 3) using percentage African ancestry rather than observed race, would improve warfarin dosing algorithms in African Americans...
2016: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/27884289/psoriasis-therapy-breakthroughs-in%C3%A2-pharmacogenomics-or-in-pharmacology
#10
Mark Lebwohl
As the cost of psoriasis therapies skyrockets, it becomes increasingly important to find biomarkers that predict which patients will respond to expensive medications. The ability to predict response to a specific therapy is particularly important for medications that are effective in only a small portion of the population. As we develop medications that clear most patients, the need for a predictive biomarker diminishes. Nevertheless, the importance of pharmacogenomics is likely to increase as the cost of drugs continues to rise...
December 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27883291/pharmacogenomics-of-second-line-drugs-used-for-treatment-of-unresponsive-or-relapsed-osteosarcoma-patients
#11
Claudia M Hattinger, Serena Vella, Elisa Tavanti, Marilù Fanelli, Piero Picci, Massimo Serra
Second-line treatment of high-grade osteosarcoma (HGOS) patients is based on different approaches and chemotherapy protocols, which are not yet standardized. Although several drugs have been used in HGOS second-line protocols, none of them has provided fully satisfactory results and the role of rescue chemotherapy is not well defined yet. This article focuses on the drugs that have most frequently been used for second-line treatment of HGOS, highlighting the present knowledge on their mechanisms of action and resistance and on gene polymorphisms with possible impact on treatment sensitivity or toxicity...
November 24, 2016: Pharmacogenomics
https://www.readbyqxmd.com/read/27881428/genome-transcriptome-and-proteome-the-rise-of-omics-data-and-their-integration-in-biomedical-sciences
#12
Claudia Manzoni, Demis A Kia, Jana Vandrovcova, John Hardy, Nicholas W Wood, Patrick A Lewis, Raffaele Ferrari
Advances in the technologies and informatics used to generate and process large biological data sets (omics data) are promoting a critical shift in the study of biomedical sciences. While genomics, transcriptomics and proteinomics, coupled with bioinformatics and biostatistics, are gaining momentum, they are still, for the most part, assessed individually with distinct approaches generating monothematic rather than integrated knowledge. As other areas of biomedical sciences, including metabolomics, epigenomics and pharmacogenomics, are moving towards the omics scale, we are witnessing the rise of inter-disciplinary data integration strategies to support a better understanding of biological systems and eventually the development of successful precision medicine...
November 22, 2016: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/27878205/iterative-development-and-evaluation-of-a-pharmacogenomic-guided-clinical-decision-support-system-for-warfarin-dosing
#13
Brittany L Melton, Alan J Zillich, Jason Saleem, Alissa L Russ, James E Tisdale, Brian R Overholser
OBJECTIVE: Pharmacogenomic-guided dosing has the potential to improve patient outcomes but its implementation has been met with clinical challenges. Our objective was to develop and evaluate a clinical decision support system (CDSS) for pharmacogenomic-guided warfarin dosing designed for physicians and pharmacists. METHODS: Twelve physicians and pharmacists completed 6 prescribing tasks using simulated patient scenarios in two iterations (development and validation phases) of a newly developed pharmacogenomic-driven CDSS prototype...
November 23, 2016: Applied Clinical Informatics
https://www.readbyqxmd.com/read/27871989/quality-by-design-qbd-approach-of-pharmacogenomics-in-drug-designing-and-formulation-development-for-optimization-of-drug-delivery-systems
#14
REVIEW
Sumeet Gupta, Vikas Jhawat
Conventional approaches of drug discovery are very complex, costly and time consuming. But after the completion of human genome project, applications of pharmacogenomics in this area completely revolutionize the drug discovery and development process to produce a quality by design (QbD) approach based products. The applications of two areas of pharmacogenomics i.e. structural and functional pharmacogenomics excel the drug discovery process by employing genomic data in drug target identification and evaluation, lead optimization via high throughput screening, evaluation of drug metabolizing enzymes, drug transporters and drug receptors using computer aided technique and bioinformatics library data base...
November 19, 2016: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27864206/educational-strategies-to-enable-expansion-of-pharmacogenomics-based-care
#15
Kristin Wiisanen Weitzel, Christina L Aquilante, Samuel Johnson, David F Kisor, Philip E Empey
PURPOSE: The current state of pharmacogenomics education for pharmacy students and practitioners is discussed, and resources and strategies to address persistent challenges in this area are reviewed. SUMMARY: Consensus-based pharmacist competencies and guidelines have been published to guide pharmacogenomics knowledge attainment and application in clinical practice. Pharmacogenomics education is integrated into various pharmacy school courses and, increasingly, into Pharm...
December 1, 2016: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/27864205/evidence-and-resources-to-implement-pharmacogenetic-knowledge-for-precision-medicine
#16
Kelly E Caudle, Roseann S Gammal, Michelle Whirl-Carrillo, James M Hoffman, Mary V Relling, Teri E Klein
PURPOSE: The current state of pharmacogenetic data curation and dissemination is described, and evidence-based resources for applying pharmacogenetic data in clinical practice are reviewed. SUMMARY: Implementation of pharmacogenetics in clinical practice has been relatively slow despite substantial scientific progress in understanding linkages between genetic variation and variability of drug response and effect. One factor that has inhibited the adoption of genetic data to guide medication use is a lack of knowledge of how to translate genetic test results into clinical action based on currently available evidence...
December 1, 2016: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/27864204/integrating-pharmacogenomics-into-electronic-health-records-with-clinical-decision-support
#17
J Kevin Hicks, Henry M Dunnenberger, Karl F Gumpper, Cyrine E Haidar, James M Hoffman
PURPOSE: Existing pharmacogenomic informatics models, key implementation steps, and emerging resources to facilitate the development of pharmacogenomic clinical decision support (CDS) are described. SUMMARY: Pharmacogenomics is an important component of precision medicine. Informatics, especially CDS in the electronic health record (EHR), is a critical tool for the integration of pharmacogenomics into routine patient care. Effective integration of pharmacogenomic CDS into the EHR can address implementation challenges, including the increasing volume of pharmacogenomic clinical knowledge, the enduring nature of pharmacogenomic test results, and the complexity of interpreting results...
December 1, 2016: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/27864203/implementation-of-a-multidisciplinary-pharmacogenomics-clinic-in-a-community-health-system
#18
Henry M Dunnenberger, Matthew Biszewski, Gillian C Bell, Annette Sereika, Holley May, Samuel G Johnson, Peter J Hulick, Janardan Khandekar
PURPOSE: The development and implementation of a multidisciplinary pharmacogenomics clinic within the framework of an established community-based medical genetics program are described. SUMMARY: Pharmacogenomics is an important component of precision medicine that holds considerable promise for pharmacotherapy optimization. As part of the development of a health system-wide integrated pharmacogenomics program, in early 2015 Northshore University Health-System established a pharmacogenomics clinic run by a multidisciplinary team including a medical geneticist, a pharmacist, a nurse practitioner, and genetic counselors...
December 1, 2016: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/27861439/trends-in-tramadol-pharmacology-metabolism-and-misuse
#19
Karen Miotto, Arthur K Cho, Mohamed A Khalil, Kirsten Blanco, Jun D Sasaki, Richard Rawson
Tramadol is a unique analgesic medication, available in variety of formulations, with both monoaminergic reuptake inhibitory and opioid receptor agonist activity increasingly prescribed worldwide as an alternative for high-affinity opioid medication in the treatment of acute and chronic pain. It is a prodrug that is metabolized by cytochrome P450 (CYP) enzymes CYP2D6 and CYP3A4 to its more potent opioid analgesic metabolites, particularly the O-demethylation product M1. The opioid analgesic potency of a given dose of tramadol is influenced by an individual's CYP genetics, with poor metabolizers experiencing little conversion to the active M1 opioid metabolite and individuals with a high metabolic profile, or ultra-metabolizers, experiencing the greatest opioid analgesic effects...
November 17, 2016: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/27854302/severe-cutaneous-adverse-reactions-the-pharmacogenomics-from-research-to-clinical-implementation
#20
REVIEW
Shih-Chi Su, Shuen-Iu Hung, Wen-Lang Fan, Ro-Lan Dao, Wen-Hung Chung
Severe cutaneous adverse reactions (SCARs), previously thought to be idiosyncratic or unpredictable, are a deadly form of adverse drug reactions with skin manifestations. Current pharmacogenomic studies of SCARs have made important strides, as the prevention of SCARs, to some extent, appears attainable with the identification of genetic variants for genes encoding drug-metabolizing enzymes and human leukocyte antigens (HLAs). Despite the improvement of incidence, a treatment guideline for this devastating condition is still unavailable, highlighting the inadequacy of contemporary accepted therapeutic interventions...
November 15, 2016: International Journal of Molecular Sciences
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