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https://www.readbyqxmd.com/read/28727815/polymorphisms-associated-with-everolimus-pharmacokinetics-toxicity-and-survival-in-metastatic-breast-cancer
#1
Tomas Pascual, María Apellániz-Ruiz, Cristina Pernaut, Cecilia Cueto-Felgueroso, Pablo Villalba, Carlos Álvarez, Luis Manso, Lucia Inglada-Pérez, Mercedes Robledo, Cristina Rodríguez-Antona, Eva Ciruelos
PURPOSE: Metastatic breast cancer (MBC) progressing after endocrine therapy frequently activates PI3K/AKT/mTOR pathway. The BOLERO-2 trial showed that everolimus-exemestane achieves increased progression free survival (PFS) compared with exemestane. However, there is great inter-patient variability in toxicity and response to exemestane-everolimus treatment. The objective of this study was to perform an exploratory study analyzing the implication of single nucleotide polymorphisms (SNPs) on outcomes from this treatment through a pharmacogenetic analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28723867/prediction-of-severe-toxicity-in-adult-patients-under-treatment-with-5-fluorouracil-a-prospective-cohort-study
#2
Carolina Vázquez, María Orlova, Federico Angriman, José N Minatta, Paula Scibona, María A Verzura, Esteban G Jáuregui, Heidy Díaz de Arce, María G Pallotta, Waldo H Belloso
5-Fluorouracil (5-FU) has long been used for the treatment of gastrointestinal tumors harboring interindividual variability in both the pharmacokinetic and the pharmacogenetic profiles, which in turn may lead to life-threatening toxicities. We carried out a prospective cohort study of adult patients initiating treatment with 5-FU between 2013 and 2015. Primary exposures of interest were the methylenetetrahydrofolate reductase single nucleotide polymorphism in exons 4 and 7 and 5'-untranslated region-thymidylate synthase VNTR genotypes, in addition to baseline clinical and demographic variables...
July 18, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28717179/genetic-polymorphisms-and-platinum-based-chemotherapy-treatment-outcomes-in-patients-with-non-small-cell-lung-cancer-a-genetic-epidemiology-study-based-meta-analysis
#3
Li-Ming Tan, Cheng-Feng Qiu, Tao Zhu, Yuan-Xiang Jin, Xi Li, Ji-Ye Yin, Wei Zhang, Hong-Hao Zhou, Zhao-Qian Liu
Data regarding genetic polymorphisms and platinum-based chemotherapy (PBC) treatment outcomes in patients with NSCLC are published at a growing pace, but the results are inconsistent. This meta-analysis integrated eligible candidate genes to better evaluate the pharmacogenetics of PBC in NSCLC patients. Relevant studies were retrieved from PubMed, Chinese National Knowledge Infrastructure and WANFANG databases. A total of 111 articles comprising 18,196 subjects were included for this study. The associations of genetic polymorphisms with treatment outcomes of PBC including overall response rate (ORR), overall survival (OS) and progression-free survival (PFS) were determined by analyzing the relative risk (RR), hazard ration (HR), corresponding 95% confidence interval (CI)...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716797/a-pragmatic-phase-iii-multisite-double-blind-placebo-controlled-parallel-arm-dose-increment-randomised-trial-of-regular-low-dose-extended-release-morphine-for-chronic-breathlessness-breathlessness-exertion-and-morphine-sulfate-beams-study-protocol
#4
David Currow, Gareth John Watts, Miriam Johnson, Christine F McDonald, John O Miners, Andrew A Somogyi, Linda Denehy, Nicola McCaffrey, Danny J Eckert, Philip McCloud, Sandra Louw, Lawrence Lam, Aine Greene, Belinda Fazekas, Katherine C Clark, Kwun Fong, Meera R Agar, Rohit Joshi, Sharon Kilbreath, Diana Ferreira, Magnus Ekström
INTRODUCTION: Chronic breathlessness is highly prevalent and distressing to patients and families. No medication is registered for its symptomatic reduction. The strongest evidence is for regular, low-dose, extended- release (ER) oral morphine. A recent large phase III study suggests the subgroup most likely to benefit have chronic obstructive pulmonary disease (COPD) and modified Medical Research Council breathlessness scores of 3 or 4. This protocol is for an adequately powered, parallel-arm, placebo-controlled, multisite, factorial, block-randomised study evaluating regular ER morphine for chronic breathlessness in people with COPD...
July 17, 2017: BMJ Open
https://www.readbyqxmd.com/read/28712653/neural-circuit-specialized-astrocytes-transcriptomic-proteomic-morphological-and-functional-evidence
#5
Hua Chai, Blanca Diaz-Castro, Eiji Shigetomi, Emma Monte, J Christopher Octeau, Xinzhu Yu, Whitaker Cohn, Pradeep S Rajendran, Thomas M Vondriska, Julian P Whitelegge, Giovanni Coppola, Baljit S Khakh
Astrocytes are ubiquitous in the brain and are widely held to be largely identical. However, this view has not been fully tested, and the possibility that astrocytes are neural circuit specialized remains largely unexplored. Here, we used multiple integrated approaches, including RNA sequencing (RNA-seq), mass spectrometry, electrophysiology, immunohistochemistry, serial block-face-scanning electron microscopy, morphological reconstructions, pharmacogenetics, and diffusible dye, calcium, and glutamate imaging, to directly compare adult striatal and hippocampal astrocytes under identical conditions...
July 11, 2017: Neuron
https://www.readbyqxmd.com/read/28705252/efficacy-of-prospective-pharmacogenetic-testing-in-the-treatment-of-major-depressive-disorder-results-of-a-randomized-double-blind-clinical-trial
#6
Víctor Pérez, Ariana Salavert, Jordi Espadaler, Miquel Tuson, Jerónimo Saiz-Ruiz, Cristina Sáez-Navarro, Julio Bobes, Enrique Baca-García, Eduard Vieta, José M Olivares, Roberto Rodriguez-Jimenez, José M Villagrán, Josep Gascón, Josep Cañete-Crespillo, Montse Solé, Pilar A Saiz, Ángela Ibáñez, Javier de Diego-Adeliño, José M Menchón
BACKGROUND: A 12-week, double-blind, parallel, multi-center randomized controlled trial in 316 adult patients with major depressive disorder (MDD) was conducted to evaluate the effectiveness of pharmacogenetic (PGx) testing for drug therapy guidance. METHODS: Patients with a CGI-S ≥ 4 and requiring antidepressant medication de novo or changes in their medication regime were recruited at 18 Spanish public hospitals, genotyped with a commercial PGx panel (Neuropharmagen®), and randomized to PGx-guided treatment (n = 155) or treatment as usual (TAU, control group, n = 161), using a computer-generated random list that locked or unlocked psychiatrist access to the results of the PGx panel depending on group allocation...
July 14, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/28701180/influence-of-genetic-variants-on-toxicity-to-anti-tubercular-agents-a-systematic-review-and-meta-analysis-protocol
#7
Marty Richardson, Jamie Kirkham, Kerry Dwan, Derek Sloan, Geraint Davies, Andrea Jorgensen
BACKGROUND: Tuberculosis patients receiving anti-tuberculosis treatment may experience serious adverse drug reactions, such as hepatotoxicity. Genetic risk factors, such as polymorphisms of the NAT2, CYP2E1 and GSTM1 genes, may increase the risk of experiencing such toxicity events. Many pharmacogenetic studies have investigated the association between genetic variants and anti-tuberculosis drug-related toxicity events, and several meta-analyses have synthesised data from these studies, although conclusions from these meta-analyses are conflicting...
July 13, 2017: Systematic Reviews
https://www.readbyqxmd.com/read/28699646/review-of-opioid-pharmacogenetics-and-considerations-for-pain-management
#8
Aniwaa Owusu Obeng, Issam Hamadeh, Michael Smith
Opioid analgesics are the standards of care for the treatment of moderate to severe nociceptive pain, particularly in the setting of cancer and surgery. Their analgesic properties mainly emanate from stimulation of the μ receptors, which are encoded by the OPRM1 gene. Hepatic metabolism represents the major route of elimination, which, for some opioids, namely codeine and tramadol, is necessary for their bioactivation into more potent analgesics. The highly polymorphic nature of the genes coding for phase I and phase II enzymes (pharmacokinetics genes) that are involved in the metabolism and bioactivation of opioids suggests a potential interindividual variation in their disposition and, most likely, response...
July 12, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28698977/pharmacogenetics-and-pharmacogenomics-of-targeted-therapeutics-in-chronic-myeloid-leukemia
#9
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/28696420/a-cost-effectiveness-analysis-of-maternal-cyp2d6-genetic-testing-to-guide-treatment-for-postpartum-pain-and-avert-infant-adverse-events
#10
M E Moretti, D F Lato, H Berger, G Koren, S Ito, W J Ungar
Mothers with a CYP2D6 ultrarapid metabolizer phenotype may expose their infants to risk of adverse events when taking codeine while breastfeeding, by producing more of the active metabolite, morphine. Pharmacogenetic testing may be a valuable tool to identify such mothers, but testing can be costly. The objective of the study was to determine the incremental costs of genotyping to avert neonatal adverse events during maternal pharmacotherapy. A cost-effectiveness analysis, using a decision model, was performed with a hypothetical cohort of prenatal subjects...
July 11, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28696418/associations-between-functional-polymorphisms-and-response-to-biological-treatment-in-danish-patients-with-psoriasis
#11
N D Loft, L Skov, L Iversen, R Gniadecki, T N Dam, I Brandslund, H J Hoffmann, M R Andersen, R B Dessau, A C Bergmann, N M Andersen, P S Andersen, S Bank, U Vogel, V Andersen
Biological agents including anti-tumor necrosis factor (anti-TNF; adalimumab, infliximab, etanercept) and anti-interleukin-12/13 (IL12/23; ustekinumab) are essential for treatment of patients with severe psoriasis. However, a significant proportion of the patients do not respond to a specific treatment. Pharmacogenetics might be a way to predict treatment response. Using a candidate gene approach, 62 mainly functional single-nucleotide polymorphisms (SNPs) in 44 different genes were evaluated in 478 Danish patients with psoriasis undergoing 376 series of anti-TNF treatment and 230 series of ustekinumab treatment...
July 11, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28696414/pharmacogenetics-of-oral-antidiabetes-drugs-evidence-for-diverse-signals-at-the-irs1-locus
#12
S Prudente, R Di Paola, S Pezzilli, M Garofolo, O Lamacchia, T Filardi, G C Mannino, L Mercuri, F Alberico, M G Scarale, G Sesti, S Morano, G Penno, M Cignarelli, M Copetti, V Trischitta
To investigate the role of IRS1 locus on failure to oral antidiabetes drugs (OADs) we genotyped single-nucleotide polymorphisms (SNPs), rs2943641, rs7578326 (tagging all SNPs genome-wide associated with type 2 diabetes (T2D) and related traits at this locus) and rs1801278 (that is, the loss-of-function IRS1 G972R amino acid substitution) in 2662 patients with T2D. Although no association with OAD failure was observed for rs2943641 and rs7578326 SNPs (odds ratio (OR): 1.04, 95% confidence interval (CI): 0.93-1...
July 11, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28690699/feasibility-of-clinical-pharmacist-led-cyp2c19-genotyping-for-patients-receiving-non-emergent-cardiac-catheterization-in-an-integrated-health-system
#13
Samuel G Johnson, Paul B Shaw, Thomas Delate, Deanna L Kurz, Dylon Gregg, John C Darnell, Christina L Aquilante
OBJECTIVE: To assess the feasibility of clinical pharmacist-led CYP2C19 genotype-guided P2Y12 inhibitor antiplatelet drug therapy recommendations to cardiologists in an outpatient cardiology practice. METHODS: This was a prospective, open-labeled, single-arm study conducted in an integrated healthcare delivery system between March 1, 2013 and January 23, 2014. Patients requiring non-emergent cardiac catheterization were included. A clinical pharmacist provided interpretation and recommendations from genotyping results...
April 2017: Pharmacy Practice
https://www.readbyqxmd.com/read/28686143/pharmacogenetics-of-inflammatory-bowel-disease-a-focus-on-crohn-s-disease
#14
Sara Rufini, Cinzia Ciccacci, Giuseppe Novelli, Paola Borgiani
Crohn's disease is an inflammatory bowel disease showing a high heterogeneity in phenotype and a strong genetic component. The treatment is complex, due to different severity of clinical parameters and to the fact that therapies only permit to control symptoms and to induce remission for short periods. Moreover, all categories of drugs present a great interindividual variability both in terms of efficacy and side effects appearance. For this reason, the identification of specific genomic biomarkers involved in drugs response will be of great clinical utility in order to foresee drug's efficacy and to prevent adverse reactions, permitting a more personalized therapeutic approach...
July 7, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28686141/educating-patients-and-providers-through-comprehensive-pharmacogenetic-test-reports
#15
Susanne B Haga
No abstract text is available yet for this article.
July 7, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28686075/pharmacogenetics-and-the-treatment-of-functional-gastrointestinal-disorders
#16
Houssam Halawi, Michael Camilleri
The diagnosis and management of functional gastrointestinal disorders (FGIDs) remain very challenging. In the era of precision medicine, it is important to individualize the treatment of these conditions by providing targeted and effective therapies while minimizing the risk of medication side effects. By using genetic information that predicts and affects the responses to specific medications, it is anticipated that the science of pharmacogenetics in FGIDs will advance the practice of precision medicine. The pathophysiology of FGIDs is complex, involving the interaction between predisposing genetic and environmental factors...
July 7, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28685055/identification-of-genetic-variants-in-pharmacogenetic-genes-associated-with-type-2-diabetes-in-a-mexican-mestizo-population
#17
Nidia Samara Rodríguez-Rivera, Patricia Cuautle-Rodríguez, Fernando Castillo-Nájera, Juan Arcadio Molina-Guarneros
Type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic pathologies in the world. In developing countries, such as Mexico, its prevalence represents an important public health and research issue. Determining factors triggering T2DM are environmental and genetic. While diet, exercise and proper weight control are the first measures recommended to improve the quality of life and life expectancy of patients, pharmacological treatment is usually the next step. Within every population there are variations in interindividual drug response, which may be due to genetic background...
July 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28682948/skeletal-muscle-metabolic-dysfunction-in-patients-with-malignant-hyperthermia-susceptibility
#18
Sara J Thompson, Sheila Riazi, Natalia Kraeva, Michael D Noseworthy, Tammy E Rayner, Jane E Schneiderman, Barbara Cifra, Greg D Wells
BACKGROUND: Malignant hyperthermia (MH), a pharmacogenetic disorder of skeletal muscle, presents with a potentially lethal hypermetabolic reaction to certain anesthetics. However, some MH-susceptible patients experience muscle weakness, fatigue, and exercise intolerance in the absence of anesthetic triggers. The objective of this exploratory study was to elucidate the pathophysiology of exercise intolerance in patients tested positive for MH with the caffeine-halothane contracture test...
July 4, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28681659/the-relationship-of-genetics-nursing-practice-and-informatics-tools-in-6-mercaptopurine-dosing-in-pediatric-oncology
#19
Wendy J Haylett
An antileukemic agent prescribed for pediatric oncology patients during the maintenance phase of therapy for acute lymphoblastic leukemia, 6-mercaptopurine (6-MP), is highly influenced by genetic variations in the thiopurine S-methyltransferase enzyme. As such, 6-MP must be dosed so that patients with 1 or 2 inactive thiopurine S-methyltransferase alleles will not incur an increased risk for myelosuppression or other toxicities. Informatics tools such as clinical decision support systems are useful for the application of this and similar pharmacogenetics information to the realm of nursing and clinical practice for safe and effective patient care...
July 1, 2017: Journal of Pediatric Oncology Nursing: Official Journal of the Association of Pediatric Oncology Nurses
https://www.readbyqxmd.com/read/28680777/proposal-for-a-pharmacogenetic-decision-algorithm
#20
EDITORIAL
Saeed K Alzghari, Lori Blakeney, Kerry Anne Rambaran
Personalized medicine is playing an ever-increasing role in patient care. Over the past decade, awareness of the role of pharmacogenetics and its benefits is leading to its growing acceptance among providers. Though providers are using pharmacogenetics in practice, the decision-making process of when to use this tool can be ambiguous. Herein, we propose an algorithm to help guide providers on when to use pharmacogenetics for patient care.
May 30, 2017: Curēus
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