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Pharmacogenomics

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https://www.readbyqxmd.com/read/28654958/the-impact-of-whole-genome-sequencing-on-the-primary-care-and-outcomes-of-healthy-adult-patients-a-pilot-randomized-trial
#1
Jason L Vassy, Kurt D Christensen, Erica F Schonman, Carrie L Blout, Jill O Robinson, Joel B Krier, Pamela M Diamond, Matthew Lebo, Kalotina Machini, Danielle R Azzariti, Dmitry Dukhovny, David W Bates, Calum A MacRae, Michael F Murray, Heidi L Rehm, Amy L McGuire, Robert C Green
Background: Whole-genome sequencing (WGS) in asymptomatic adults might prevent disease but increase health care use without clinical value. Objective: To describe the effect on clinical care and outcomes of adding WGS to standardized family history assessment in primary care. Design: Pilot randomized trial. (ClinicalTrials.gov: NCT01736566). Setting: Academic primary care practices. Participants: 9 primary care physicians (PCPs) and 100 generally healthy patients recruited at ages 40 to 65 years...
June 27, 2017: Annals of Internal Medicine
https://www.readbyqxmd.com/read/28654165/using-personalized-medicine-in-the-management-of-diabetes-mellitus
#2
Nina Elk, Otito F Iwuchukwu
Diabetes mellitus is a worldwide problem of immense pharmacoeconomic burden. The multifactorial and complex nature of the disease lends itself to personalized pharmacotherapeutic approaches to treatment. Variability in individual risk and subsequent development of diabetes have been reported, in addition to differences in response to the many oral glucose lowering therapies currently available for diabetes pharmacotherapy. Pharmacogenomic studies have attempted to uncover the heritable components of individual variability in risk susceptibility and response to pharmacotherapy...
June 27, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28654154/commentary-should-pharmacogenomic-evidence-be-considered-in-clinical-decision-making-focus-on-select-cardiovascular-drugs
#3
Michael B Bottorff, David R Bright, David F Kisor
Despite advances in technology and guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC) that focus on how to utilize pharmacogene test results, hurdles remain that have delayed the widespread application of pharmacogenomics in clinical practice. These hurdles include a lack of prospective randomized controlled trials to address the utility of pharmacogenomics on clinical outcomes, what the clinical algorithm for pharmacogenomics should be, and whether or not pharmacogenomics is cost-effective...
June 27, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28653280/clozapine-as-a-model-for-antipsychotic-development
#4
REVIEW
Frederick C Nucifora, Marina Mihaljevic, Brian J Lee, Akira Sawa
Schizophrenia is a devastating illness that affects up to 1% of the population; it is characterized by a combination of positive symptoms, negative symptoms, and cognitive impairment. Currently, treatment consists of one class of medications known as antipsychotics, which include typical (first-generation) and atypical (second-generation) agents. Unfortunately, antipsychotic medications have limited efficacy, with up to a third of patients lacking a full response. Clozapine, the first atypical antipsychotic developed, is the only medication shown to be superior to all other antipsychotics...
June 26, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28640195/pharmacogenomic-variants-may-influence-the-urinary-excretion-of-novel-kidney-injury-biomarkers-in-patients-receiving-cisplatin
#5
Cara Chang, Yichun Hu, Susan L Hogan, Nickie Mercke, Madeleine Gomez, Cindy O'Bryant, Daniel W Bowles, Blessy George, Xia Wen, Lauren M Aleksunes, Melanie S Joy
Nephrotoxicity is a dose limiting side effect associated with the use of cisplatin in the treatment of solid tumors. The degree of nephrotoxicity is dictated by the selective accumulation of cisplatin in renal tubule cells due to: (1) uptake by organic cation transporter 2 (OCT2) and copper transporter 1 (CTR1); (2) metabolism by glutathione S-transferases (GSTs) and γ-glutamyltransferase 1 (GGT1); and (3) efflux by multidrug resistance-associated protein 2 (MRP2) and multidrug and toxin extrusion protein 1 (MATE1)...
June 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28639505/rationale-and-design-of-the-multiethnic-pharmacogenomics-in-childhood-asthma-consortium
#6
Niloufar Farzan, Susanne J Vijverberg, Anand K Andiappan, Lambang Arianto, Vojko Berce, Natalia Blanca-López, Hans Bisgaard, Klaus Bønnelykke, Esteban G Burchard, Paloma Campo, Glorisa Canino, Bruce Carleton, Juan C Celedón, Fook Tim Chew, Wen Chin Chiang, Michelle M Cloutier, Denis Daley, Herman T Den Dekker, Nicole F Dijk, Liesbeth Duijts, Carlos Flores, Erick Forno, Daniel B Hawcutt, Natalia Hernandez-Pacheco, Johan C de Jongste, Michael Kabesch, Gerard H Koppelman, Vangelis G Manolopoulos, Erik Melén, Somnath Mukhopadhyay, Sara Nilsson, Colin N Palmer, Maria Pino-Yanes, Munir Pirmohamed, Uros Potočnki, Jan A Raaijmakers, Katja Repnik, Maximilian Schieck, Yang Yie Sio, Rosalind L Smyth, Csaba Szalai, Kelan G Tantisira, Steve Turner, Marc P van der Schee, Katia M Verhamme, Anke H Maitland-van der Zee
AIM: International collaboration is needed to enable large-scale pharmacogenomics studies in childhood asthma. Here, we describe the design of the Pharmacogenomics in Childhood Asthma (PiCA) consortium. MATERIALS & METHODS: Investigators of each study participating in PiCA provided data on the study characteristics by answering an online questionnaire. RESULTS: A total of 21 studies, including 14,227 children/young persons (58% male), from 12 different countries are currently enrolled in the PiCA consortium...
June 22, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28639489/healthcare-provider-education-to-support-integration-of-pharmacogenomics-in-practice-the-emerge-network-experience
#7
Carolyn R Rohrer Vitek, Noura S Abul-Husn, John J Connolly, Andrea L Hartzler, Terrie Kitchner, Josh F Peterson, Luke V Rasmussen, Maureen E Smith, Sarah Stallings, Marc S Williams, Wendy A Wolf, Cynthia A Prows
Ten organizations within the Electronic Medical Records and Genomics Network developed programs to implement pharmacogenomic sequencing and clinical decision support into clinical settings. Recognizing the importance of informed prescribers, a variety of strategies were used to incorporate provider education to support implementation. Education experiences with pharmacogenomics are described within the context of each organization's prior involvement, including the scope and scale of implementation specific to their Electronic Medical Records and Genomics projects...
June 22, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28636828/pharmacokinetic-drug-evaluation-of-extended-release-lorcaserin-for-the-treatment-of-obesity
#8
Kathryn Hurren, Marissa W Dunham
Lorcaserin is a serotonin 2C receptor antagonist that was FDA approved in 2012. Lorcaserin is recently available as an extended-release (ER) formulation for the treatment of obesity as an adjunct to lifestyle modification. Areas covered: The pharmacokinetics, pharmacodynamics, efficacy, and safety of lorcaserin ER will be reviewed. Expert opinion: Lorcaserin ER 20mg daily provides drug exposure bioequivalent to lorcaserin immediate release (IR) 10mg twice daily. Lorcaserin IR is associated with 3.3% and 3.0% placebo-subtracted weight loss in patients without and with diabetes, respectively...
June 21, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28632283/the-impact-of-whole-genome-sequencing-on-the-primary-care-and-outcomes-of-healthy-adult-patients-a-pilot-randomized-trial
#9
Jason L Vassy, Kurt D Christensen, Erica F Schonman, Carrie L Blout, Jill O Robinson, Joel B Krier, Pamela M Diamond, Matthew Lebo, Kalotina Machini, Danielle R Azzariti, Dmitry Dukhovny, David W Bates, Calum A MacRae, Michael F Murray, Heidi L Rehm, Amy L McGuire, Robert C Green
Background: Whole-genome sequencing (WGS) in asymptomatic adults might prevent disease but increase health care use without clinical value. Objective: To describe the effect on clinical care and outcomes of adding WGS to standardized family history assessment in primary care. Design: Pilot randomized trial. (ClinicalTrials.gov: NCT01736566). Setting: Academic primary care practices. Participants: 9 primary care physicians (PCPs) and 100 generally healthy patients recruited at ages 40 to 65 years...
June 27, 2017: Annals of Internal Medicine
https://www.readbyqxmd.com/read/28631723/pharmacogenetic-biomarkers-of-response-in-crohn-s-disease
#10
REVIEW
T M Linares-Pineda, M Cañadas-Garre, A Sánchez-Pozo, M Á Calleja-Hernández
Crohn's disease (CD) is a chronic condition, which affects the immune system. It can also affect any part of the digestive tract and be associated with external manifestations. The causes of the disease remain unknown, although it seems to be the result of a combination of factors, such as genetic predisposition, environment, lifestyle and the composition of the microbiota, among others. The treatment protocol begins with a change in eating and smoking habits, and is continued with different lines of treatment, including corticosteroids, immunomodulators and biologic therapy (infliximab and adalimumab), which have shown differences in response among patients, especially with biologic treatment...
June 20, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28630080/the-potential-of-pharmacogenomics-to-advance-kidney-disease-treatment
#11
EDITORIAL
Kelly A Birdwell, Cecilia P Chung
No abstract text is available yet for this article.
June 19, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28623316/revealing-protein-networks-and-gene-drug-connectivity-in-cancer-from-direct-information
#12
Xian-Li Jiang, Emmanuel Martinez-Ledesma, Faruck Morcos
The connection between genetic variation and drug response has long been explored to facilitate the optimization and personalization of cancer therapy. Crucial to the identification of drug response related genetic features is the ability to separate indirect correlations from direct correlations across abundant datasets with large number of variables. Here we analyzed proteomic and pharmacogenomic data in cancer tissues and cell lines using a global statistical model connecting protein pairs, genes and anti-cancer drugs...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28623161/the-genetics-of-ischemic-heart-disease-from-current-knowledge-to-clinical-implications
#13
Roberto Elosua, Sergi Sayols-Baixeras
Ischemic heart disease continues to cause high morbidity and mortality. Its prevalence is expected to increase due to population aging, and its prevention is a major goal of health policies. The risk of developing ischemic heart disease is related to a complex interplay between genetic, environmental, and lifestyle factors. In the last decade, considerable progress has been made in knowledge of the genetic architecture of this disease. This narrative review provides an overview of current knowledge of the genetics of ischemic heart disease and of its translation to clinical practice: identification of new therapeutic targets, assessment of the causal relationship between biomarkers and disease, improved risk prediction, and identification of responders and nonresponders to specific drugs (pharmacogenomics)...
June 13, 2017: Revista Española de Cardiología
https://www.readbyqxmd.com/read/28619604/clinical-implementation-of-pharmacogenomics-for-personalized-precision-medicine-barriers-and-solutions
#14
REVIEW
Michelle Elizabeth Klein, Md Masud Parvez, Jae-Gook Shin
Clinical implementation of pharmacogenomics (PGx) leads to personalized medicine, which improves the efficacy, safety, and cost-effectiveness of treatments. Although PGx-based research has been conducted for more than a decade, several barriers have slowed down its widespread implementation in clinical practice. Globally, there is an imbalance in programs and solutions required to empower the clinical implementation of PGx between countries. Therefore, we aimed to review these issues comprehensively, determine the major barriers, and find the best solutions...
June 12, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28616427/specific-genes-associated-with-adverse-events-of-methylphenidate-use-in-the-pediatric-population-a-systematic-literature-review
#15
REVIEW
Beinta Joensen, Morten Meyer, Lise Aagaard
The aim of this study was to review empirical studies examining associations between candidate genes and adverse events (AEs) from methylphenidate (MPH) use in children and adolescents. The PubMed, EMBASE, CINAHL, and Web of Science databases were searched from their inception until March 2017. We included empirically based articles on pharmacogenetic studies in 0-17-year-old patients that investigated associations between specific candidate genes, their polymorphisms, and reported AEs. We extracted information about study design, setting, type of AE reporter, studied genes and their polymorphisms, age and gender, administered doses, method of genotyping, outcome measures, and main findings...
April 2017: Journal of Research in Pharmacy Practice
https://www.readbyqxmd.com/read/28612644/methods-to-analyze-big-data-in-pharmacogenomics-research
#16
Ruowang Li, Dokyoon Kim, Marylyn D Ritchie
The scale and scope of pharmacogenomics research continues to expand as the cost and efficiency of molecular data generation techniques advance. These new technologies give rise to enormous opportunity for the identification of important genetic and genomic factors important for drug treatment response. With this opportunity come significant challenges. Most of these can be categorized as 'big data' issues, facing not only pharmacogenomics, but other fields in the life sciences as well. In this review, we describe some of the analysis techniques and tools being implemented for genetic/genomic discovery in pharmacogenomics...
June 14, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28607509/genetic-background-influences-susceptibility-to-chemotherapy-induced-hematotoxicity
#17
D M Gatti, S N Weber, N C Goodwin, F Lammert, G A Churchill
Hematotoxicity is a life-threatening side effect of many chemotherapy regimens. Although clinical factors influence patient responses, genetic factors may also play an important role. We sought to identify genomic loci that influence chemotherapy-induced hematotoxicity by dosing Diversity Outbred mice with one of three chemotherapy drugs; doxorubicin, cyclophosphamide or docetaxel. We observed that each drug had a distinct effect on both the changes in blood cell subpopulations and the underlying genetic architecture of hematotoxicity...
June 13, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28607508/systematic-review-and-meta-analysis-pharmacogenetics-of-anti-tnf-treatment-response-in-rheumatoid-arthritis
#18
REVIEW
S Bek, A B Bojesen, J V Nielsen, J Sode, S Bank, U Vogel, V Andersen
Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects ~1% of the Caucasian population. Over the last decades, the availability of biological drugs targeting the proinflammatory cytokine tumour necrosis factor α, anti-TNF drugs, has improved the treatment of patients with RA. However, one-third of the patients do not respond to the treatment. We wanted to evaluate the status of pharmacogenomics of anti-TNF treatment. We performed a PubMed literature search and all studies reporting original data on associations between genetic variants and anti-TNF treatment response in RA patients were included and results evaluated by meta-analysis...
June 13, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28607507/urinary-lipidomics-evidence-for-multiple-sources-and-sexual-dimorphism-in-healthy-individuals
#19
J Graessler, C S Mehnert, K-M Schulte, S Bergmann, S Strauss, T D Bornstein, J Licinio, M-L Wong, A L Birkenfeld, S R Bornstein
Urinary lipidomics may add new valuable biomarkers to the diagnostic armamentarium for early detection of metabolic and kidney diseases. Sources and composition of urinary lipids in healthy individuals, however, have not been investigated in detail. Shotgun lipidomics was used to quantify lipidomic profiles in native urine samples from 16 individuals (eight men, eight women) collected in five fractions over 24 h. All probands were comprehensively characterized by urinary and clinical indices. The mean total urinary lipid concentration per sample was 0...
June 13, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28607506/cost-effectiveness-of-pharmacogenetic-guided-treatment-are-we-there-yet
#20
REVIEW
M Verbelen, M E Weale, C M Lewis
Pharmacogenetics (PGx) has the potential to personalize pharmaceutical treatments. Many relevant gene-drug associations have been discovered, but PGx-guided treatment needs to be cost-effective as well as clinically beneficial to be incorporated into standard health-care. We reviewed economic evaluations for PGx associations listed in the US Food and Drug Administration (FDA) Table of Pharmacogenomic Biomarkers in Drug Labeling. We determined the proportion of evaluations that found PGx-guided treatment to be cost-effective or dominant over the alternative strategies, and estimated the impact on this proportion of removing the cost of genetic testing...
June 13, 2017: Pharmacogenomics Journal
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