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Journal of Personalized Medicine

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https://www.readbyqxmd.com/read/29772692/insurance-coverage-policies-for-pharmacogenomic-and-multi-gene-testing-for-cancer
#1
Christine Y Lu, Stephanie Loomer, Rachel Ceccarelli, Kathleen M Mazor, James Sabin, Ellen Wright Clayton, Geoffrey S Ginsburg, Ann Chen Wu
Insurance coverage policies are a major determinant of patient access to genomic tests. The objective of this study was to examine differences in coverage policies for guideline-recommended pharmacogenomic tests that inform cancer treatment. We analyzed coverage policies from eight Medicare contractors and 10 private payers for 23 biomarkers (e.g., HER2 and EGFR ) and multi-gene tests. We extracted policy coverage and criteria, prior authorization requirements, and an evidence basis for coverage. We reviewed professional society guidelines and their recommendations for use of pharmacogenomic tests...
May 16, 2018: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29735935/correction-antoniou-m-et-al-fixed-and-adaptive-parallel-subgroup-specific-design-for-survival-outcomes-power-and-sample-size-j-pers-med-2017-7-19
#2
Miranta Antoniou, Andrea L Jorgensen, Ruwanthi Kolamunnage-Dona
No abstract text is available yet for this article.
May 7, 2018: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29735910/correction-antoniou-m-et-al-biomarker-guided-non-adaptive-trial-designs-in-phase-ii-and-phase-iii-a-methodological-review-j-pers-med-2017-7-1
#3
Miranta Antoniou, Ruwanthi Kolamunnage-Dona, Andrea L Jorgensen
No abstract text is available yet for this article.
May 7, 2018: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29710874/applicability-of-precision-medicine-approaches-to-managing-hypertension-in-rural-populations
#4
Jacqueline R Halladay, Kaitlin C Lenhart, Kimberly Robasky, Wendell Jones, Wayne F Homan, Doyle M Cummings, Crystal W Cené, Alan L Hinderliter, Cassandra L Miller, Katrina E Donahue, Beverly A Garcia, Thomas C Keyserling, Alice S Ammerman, Cam Patterson, Darren A DeWalt, Larry F Johnston, Monte S Willis, Jonathan C Schisler
As part of the Heart Healthy Lenoir Project, we developed a practice level intervention to improve blood pressure control. The goal of this study was: (i) to determine if single nucleotide polymorphisms (SNPs) that associate with blood pressure variation, identified in large studies, are applicable to blood pressure control in subjects from a rural population; (ii) to measure the association of these SNPs with subjects' responsiveness to the hypertension intervention; and (iii) to identify other SNPs that may help understand patient-specific responses to an intervention...
April 30, 2018: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29673183/ten-years-experience-with-the-cyp2d6-activity-score-a-perspective-on-future-investigations-to-improve-clinical-predictions-for-precision-therapeutics
#5
REVIEW
Andrea Gaedigk, Jean C Dinh, Hyunyoung Jeong, Bhagwat Prasad, J Steven Leeder
The seminal paper on the CYP2D6 Activity Score (AS) was first published ten years ago and, since its introduction in 2008, it has been widely accepted in the field of pharmacogenetics. This scoring system facilitates the translation of highly complex CYP2D6 diplotype data into a patient’s phenotype to guide drug therapy and is at the core of all CYP2D6 gene/drug pair guidelines issued by the Clinical Pharmacogenetics Implementation Consortium (CPIC). The AS, however, only explains a portion of the variability observed among individuals and ethnicities...
April 17, 2018: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29659532/genetic-heterogeneity-of-slc22-family-of-transporters-in-drug-disposition
#6
REVIEW
Elisa Lozano, Oscar Briz, Rocio I R Macias, Maria A Serrano, Jose J G Marin, Elisa Herraez
An important aspect of modern medicine is its orientation to achieve more personalized pharmacological treatments. In this context, transporters involved in drug disposition have gained well-justified attention. Owing to its broad spectrum of substrate specificity, including endogenous compounds and xenobiotics, and its strategical expression in organs accounting for drug disposition, such as intestine, liver and kidney, the SLC22 family of transporters plays an important role in physiology, pharmacology and toxicology...
April 16, 2018: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29642553/genomic-profiling-on-an-unselected-solid-tumor-population-reveals-a-highly-mutated-wnt-%C3%AE-catenin-pathway-associated-with-oncogenic-egfr-mutations
#7
Jingrui Jiang, Alexei Protopopov, Ruobai Sun, Stephen Lyle, Meaghan Russell
Oncogenic epidermal growth factor receptors (EGFRs) can recruit key effectors in diverse cellular processes to propagate oncogenic signals. Targeted and combinational therapeutic strategies have been successfully applied for treating EGFR-driven cancers. However, a main challenge in EGFR therapies is drug resistance due to mutations, oncogenic shift, alternative signaling, and other potential mechanisms. To further understand the genetic alterations associated with oncogenic EGFRs and to provide further insight into optimal and personalized therapeutic strategies, we applied a proprietary comprehensive next-generation sequencing (NGS)-based assay of 435 genes to systematically study the genomic profiles of 1565 unselected solid cancer patient samples...
April 9, 2018: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29534555/improved-labeling-of-pancreatic-islets-using-cationic-magnetoliposomes
#8
Rita Sofia Garcia Ribeiro, Ashwini Ketkar-Atre, Ting Yin, Karim Louchami, Tom Struys, Ivo Lambrichts, Abdullah Sener, Willy Jean Malaisse, Marcel De Cuyper, Uwe Himmelreich
Pancreatic islets (PIs) transplantation is an alternative approach for the treatment of severe forms of type 1 diabetes (T1D). To monitor the success of transplantation, it is desirable to follow the location of engrafted PIs non-invasively. In vivo magnetic resonance imaging (MRI) of transplanted PIs is a feasible cell tracking method; however, this requires labeling with a suitable contrast agent prior to transplantation. We have tested the feasibility of cationic magnetoliposomes (MLs), compared to commercial contrast agents (Endorem and Resovist), by labeling insulinoma cells and freshly isolated rat PIs...
March 12, 2018: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29495422/a-genome-wide-association-study-of-idiopathic-dilated-cardiomyopathy-in-african-americans
#9
Huichun Xu, Gerald W Dorn, Amol Shetty, Ankita Parihar, Tushar Dave, Shawn W Robinson, Stephen S Gottlieb, Mark P Donahue, Gordon F Tomaselli, William E Kraus, Braxton D Mitchell, Stephen B Liggett
Idiopathic dilated cardiomyopathy (IDC) is the most common form of non-ischemic chronic heart failure. Despite the higher prevalence of IDC in African Americans, the genetics of IDC have been relatively understudied in this ethnic group. We performed a genome-wide association study to identify susceptibility genes for IDC in African Americans recruited from five sites in the U.S. (662 unrelated cases and 1167 controls). The heritability of IDC was calculated to be 33% (95% confidence interval: 19-47%; p = 6...
February 26, 2018: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29462916/gene-environment-interactions-and-predictors-of-colorectal-cancer-in-family-based-multi-ethnic-groups
#10
S Pamela K Shiao, James Grayson, Chong Ho Yu, Brandi Wasek, Teodoro Bottiglieri
For the personalization of polygenic/omics-based health care, the purpose of this study was to examine the gene-environment interactions and predictors of colorectal cancer (CRC) by including five key genes in the one-carbon metabolism pathways. In this proof-of-concept study, we included a total of 54 families and 108 participants, 54 CRC cases and 54 matched family friends representing four major racial ethnic groups in southern California (White, Asian, Hispanics, and Black). We used three phases of data analytics, including exploratory, family-based analyses adjusting for the dependence within the family for sharing genetic heritage, the ensemble method, and generalized regression models for predictive modeling with a machine learning validation procedure to validate the results for enhanced prediction and reproducibility...
February 16, 2018: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29389890/p450-pharmacogenetics-in-indigenous-north-american-populations
#11
REVIEW
Lindsay M Henderson, Katrina G Claw, Erica L Woodahl, Renee F Robinson, Bert B Boyer, Wylie Burke, Kenneth E Thummel
Indigenous North American populations, including American Indian and Alaska Native peoples in the United States, the First Nations, Métis and Inuit peoples in Canada and Amerindians in Mexico, are historically under-represented in biomedical research, including genomic research on drug disposition and response. Without adequate representation in pharmacogenetic studies establishing genotype-phenotype relationships, Indigenous populations may not benefit fully from new innovations in precision medicine testing to tailor and improve the safety and efficacy of drug treatment, resulting in health care disparities...
February 1, 2018: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29385765/pharmacogenomic-impact-of-cyp2c19-variation-on-clopidogrel-therapy-in-precision-cardiovascular-medicine
#12
REVIEW
Sherry-Ann Brown, Naveen Pereira
Variability in response to antiplatelet therapy can be explained in part by pharmacogenomics, particularly of the CYP450 enzyme encoded by CYP2C19 . Loss-of-function and gain-of-function variants help explain these interindividual differences. Individuals may carry multiple variants, with linkage disequilibrium noted among some alleles. In the current pharmacogenomics era, genomic variation in CYP2C19 has led to the definition of pharmacokinetic phenotypes for response to antiplatelet therapy, in particular, clopidogrel...
January 30, 2018: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29382185/genetic-variations-in-sweet-taste-receptor-gene-are-related-to-chocolate-powder-and-dietary-fiber-intake-in-obese-children-and-adolescents
#13
Marina B Pioltine, Maria Edna de Melo, Aritânia S Santos, Alisson D Machado, Ariana E Fernandes, Clarissa T Fujiwara, Cintia Cercato, Marcio C Mancini
Childhood obesity is a major public health problem. It has a direct impact on the quality of life of children and adolescents, as well as on their future risk of developing chronic diseases. Dietary patterns rich in fats and sugars and lacking dietary fibers, vitamins, and minerals, as well as lack of physical exercise have been associated with the rise of obesity prevalence. However, factors that contribute to the preference for foods rich in these nutrients are not well established. Taste is recognized as an important predictor of food choices, and polymorphisms in taste-related genes may explain the variability of taste preference and food intake...
January 29, 2018: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29360800/polymer-therapeutics-biomarkers-and-new-approaches-for-personalized-cancer-treatment
#14
REVIEW
Stuart P Atkinson, Zoraida Andreu, María J Vicent
Polymer therapeutics (PTs) provides a potentially exciting approach for the treatment of many diseases by enhancing aqueous solubility and altering drug pharmacokinetics at both the whole organism and subcellular level leading to improved therapeutic outcomes. However, the failure of many polymer-drug conjugates in clinical trials suggests that we may need to stratify patients in order to match each patient to the right PT. In this concise review, we hope to assess potential PT-specific biomarkers for cancer treatment, with a focus on new studies, detection methods, new models and the opportunities this knowledge will bring for the development of novel PT-based anti-cancer strategies...
January 23, 2018: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29315261/novel-pamam-peg-peptide-conjugates-for-sirna-delivery-targeted-to-the-transferrin-and-epidermal-growth-factor-receptors
#15
Koldo Urbiola, Laura Blanco-Fernández, Manfred Ogris, Wolfgang Rödl, Ernst Wagner, Conchita Tros de Ilarduya
The transferrin (TfR) and epidermal growth factor receptors (EGFR) are known to be overexpressed on the surface of a wide variety of tumor cells. Therefore, the peptides B6 (TfR specific) and GE11 (targeted to the EGFR) were linked to the PAMAM (polyamidoamine) structure via a polyethylenglycol (PEG) 2 kDa chain with the aim of improving the silencing capacity of the PAMAM-based dendriplexes. The complexes showed an excellent binding capacity to the siRNA with a maximal condensation at nitrogen/phosphate (N/P) 2...
January 9, 2018: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29301387/pharmacogenetics-of-vascular-risk-factors-in-alzheimer-s-disease
#16
REVIEW
Ramón Cacabelos, Arun Meyyazhagan, Juan C Carril, Pablo Cacabelos, Óscar Teijido
Alzheimer's disease (AD) is a polygenic/complex disorder in which genomic, epigenomic, cerebrovascular, metabolic, and environmental factors converge to define a progressive neurodegenerative phenotype. Pharmacogenetics is a major determinant of therapeutic outcome in AD. Different categories of genes are potentially involved in the pharmacogenetic network responsible for drug efficacy and safety, including pathogenic, mechanistic, metabolic, transporter, and pleiotropic genes. However, most drugs exert pleiotropic effects that are promiscuously regulated for different gene products...
January 3, 2018: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29301385/ethical-considerations-related-to-return-of-results-from-genomic-medicine-projects-the-emerge-network-phase-iii-experience
#17
Robyn Fossey, David Kochan, Erin Winkler, Joel E Pacyna, Janet Olson, Stephen Thibodeau, John J Connolly, Margaret Harr, Meckenzie A Behr, Cynthia A Prows, Beth Cobb, Melanie F Myers, Nancy D Leslie, Bahram Namjou-Khales, Hila Milo Rasouly, Julia Wynn, Alexander Fedotov, Wendy K Chung, Ali Gharavi, Janet L Williams, Lynn Pais, Ingrid Holm, Sharon Aufox, Maureen E Smith, Aaron Scrol, Kathleen Leppig, Gail P Jarvik, Georgia L Wiesner, Rongling Li, Mary Stroud, Jordan W Smoller, Richard R Sharp, Iftikhar J Kullo
We examined the Institutional Review Board (IRB) process at 9 academic institutions in the electronic Medical Records and Genomics (eMERGE) Network, for proposed electronic health record-based genomic medicine studies, to identify common questions and concerns. Sequencing of 109 disease related genes and genotyping of 14 actionable variants is being performed in ~28,100 participants from the 9 sites. Pathogenic/likely pathogenic variants in actionable genes are being returned to study participants. We examined each site's research protocols, informed-consent materials, and interactions with IRB staff...
January 3, 2018: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29283396/pharmacogenomics-of-cyp2c9-functional-and-clinical-considerations
#18
REVIEW
Ann K Daly, Allan E Rettie, Douglas M Fowler, John O Miners
CYP2C9 is the most abundant CYP2C subfamily enzyme in human liver and the most important contributor from this subfamily to drug metabolism. Polymorphisms resulting in decreased enzyme activity are common in the CYP2C9 gene and this, combined with narrow therapeutic indices for several key drug substrates, results in some important issues relating to drug safety and efficacy. CYP2C9 substrate selectivity is detailed and, based on crystal structures for the enzyme, we describe how CYP2C9 catalyzes these reactions...
December 28, 2017: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29244735/development-of-the-precision-link-biobank-at-boston-children-s-hospital-challenges-and-opportunities
#19
REVIEW
Florence T Bourgeois, Paul Avillach, Sek Won Kong, Michelle M Heinz, Tram A Tran, Ramkrishna Chakrabarty, Jonathan Bickel, Piotr Sliz, Erin M Borglund, Susan Kornetsky, Kenneth D Mandl
Increasingly, biobanks are being developed to support organized collections of biological specimens and associated clinical information on broadly consented, diverse patient populations. We describe the implementation of a pediatric biobank, comprised of a fully-informed patient cohort linking specimens to phenotypic data derived from electronic health records (EHR). The Biobank was launched after multiple stakeholders' input and implemented initially in a pilot phase before hospital-wide expansion in 2016...
December 15, 2017: Journal of Personalized Medicine
https://www.readbyqxmd.com/read/29236081/pharmacogenomics-guided-personalization-of-warfarin-and-tamoxifen
#20
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
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