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https://www.readbyqxmd.com/read/29095091/an-assessment-of-the-impact-of-pharmacogenomics-on-health-disparities-a-systematic-literature-review
#1
Antony Martin, Jennifer Downing, Michelle Maden, Nigel Fleeman, Ana Alfirevic, Alan Haycox, Munir Pirmohamed
This review assessed evidence of disparities in benefits of pharmacogenomics related to 'model performance' in subgroups of patients and studies which reported impact on health inequalities. 'Model performance' refers to the ability of algorithms including clinical, environmental and genetic information to guide treatment. A total of 4978 abstracts were screened by one reviewer and 30% (1494) were double screened by a second independent reviewer, after which data extraction was performed. Additional forward and backward citation searching of reference lists was conducted...
November 2, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28899946/secondary-prevention-treatment-after-acute-stroke-in-older-south-asian-chinese-and-other-canadians-a-retrospective-data-analysis
#2
Nadia A Khan, Finlay A McAlister, Louise Pilote, Anita Palepu, Hude Quan, Michael D Hill, Jiming Fang, Moira K Kapral
BACKGROUND: Little is known about whether there are differences in medication use between older patients of Chinese descent, those of South Asian descent and other Canadian patients after acute ischemic or primary intracerebral hemorrhagic stroke. The aim of this population-based study was to evaluate potential ethnic differences in secondary prevention pharmacotherapy after acute stroke. METHODS: Using health administrative data, we conducted a retrospective analysis of all patients aged 66 years or more admitted to hospital with acute stroke in Ontario (1997-2011) and British Columbia (1997-2009)...
September 11, 2017: CMAJ Open
https://www.readbyqxmd.com/read/28889200/prevalence-of-common-hereditary-risk-factors-for-thrombophilia-in-somalia-and-identification-of-a-novel-gln544arg-mutation-in-coagulation-factor-v
#3
Abshir Ali Abdi, Abdimajid Osman
Thrombophilia, commonly manifested as venous thromboembolism (VTE), is a worldwide concern but little is known on its genetic epidemiology in many parts of the globe particularly in the developing countries. Here we employed TaqMan genotyping and pyrosequencing to evaluate the prevalence of known common nucleotide polymorphisms associated with thrombophilia in a Somali population in the Puntland region of Somalia. We also employed next generation sequencing (NGS) to investigate other genetic variants in a Somali patient with deep venous thrombosis (DVT)...
November 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/28855770/dual-antiplatelet-therapy-and-the-severity-risk-of-lower-intestinal-bleeding
#4
Neal Carlin, Fady Asslo, Raymund Sison, Hamid Shaaban, Walid Baddoura, Faiza Manji, Joseph Depasquale
BACKGROUND: Dual antiplatelet (Plt) therapy with aspirin and clopidogrel is recommended for up to 1 year following acute coronary syndrome. Many of these cardiac patients are also on anithrombotic therapy like warfarin. Lower gastrointestinal bleeding (LGIB) is the main adverse event of this treatment. AIMS: The main purpose of this study was to analyze the relationship of dual anti-Plt therapy and the risk of LGIB. METHODS: Patients' electronic charts were reviewed to include a total of 19 variables, which included age, sex, ethnicity, daily use aspirin of any dose, daily use of clopidogrel, use of nonsteroidal anti-inflammatory drugs (NSAIDs) at least twice in the last week prior to admission and the daily use of anticoagulants (warfarin, heparin), and were obtained from history and physical examination reports, lab transcripts and procedural reports...
July 2017: Journal of Emergencies, Trauma, and Shock
https://www.readbyqxmd.com/read/28738273/factors-influencing-warfarin-control-in-australia-and-singapore
#5
Nijole Bernaitis, Chi Keong Ching, Siew Chong Teo, Liping Chen, Tony Badrick, Andrew K Davey, Julia Crilly, Shailendra Anoopkumar-Dukie
INTRODUCTION: Warfarin is widely used for patients with non-valvular atrial fibrillation (NVAF). Variations in warfarin control, as measured by time in therapeutic range (TTR), have been reported across different regions and ethnicities, particularly between Western and Asian countries. However, there is limited data on comparative factors influencing warfarin control in Caucasian and Asian patients. Therefore, the aim of this study was to determine warfarin control and potential factors influencing this in patients with NVAF in Australia and Singapore...
September 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28685643/clinical-effect-of-cyp2c9-5-6-genotype-on-a-patient-s-warfarin-dose-requirement
#6
Alison L H Quinn, Ina Liko, James C Lee
We describe a 38-year-old African-American female treated with warfarin for acute bilateral pulmonary emboli who is a carrier of two rare CYP2C9 variant alleles, *5 and *6, along with VKORC1 -1639GG and CYP4F2 433Val/Val genotypes. Warfarin was dosed according to the hospital's Personalized Medicine Program recommendations of 5-6 mg/day for the first 6 days, and reduced to 2.5 mg/day starting on day 8 and continued for the following 3 weeks. This case sheds further light on the cumulative clinical impact of the CYP2C9 variant alleles, *5 and *6, on warfarin dose requirements and practical considerations for warfarin genotyping in a racially and ethnically diverse population...
July 7, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28672100/warfarin-pharmacogenomics-in-diverse-populations
#7
Justin B Kaye, Lauren E Schultz, Heidi E Steiner, Rick A Kittles, Larisa H Cavallari, Jason H Karnes
Genotype-guided warfarin dosing algorithms are a rational approach to optimize warfarin dosing and potentially reduce adverse drug events. Diverse populations, such as African Americans and Latinos, have greater variability in warfarin dose requirements and are at greater risk for experiencing warfarin-related adverse events compared with individuals of European ancestry. Although these data suggest that patients of diverse populations may benefit from improved warfarin dose estimation, the vast majority of literature on genotype-guided warfarin dosing, including data from prospective randomized trials, is in populations of European ancestry...
July 3, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28645443/once-or-twice-daily-non-vitamin-k-antagonist-oral-anticoagulants-in-asian-patients-with-atrial-fibrillation-a%C3%A2-meta-analysis-of-randomized-controlled-trials
#8
Kang-Ling Wang, Chun-Chih Chiu, Doreen Su-Yin Tan, Chun-Yi Lin, En-Yu Lai, Shinya Goto, Robert P Giugliano, Chern-En Chiang
BACKGROUND/PURPOSE: Non-vitamin K antagonist oral anticoagulants (NOACs) have a half-life of around 12 h. We aimed to clarify if there was any effect modification by dosing (once- or twice-daily) regimens in Asian patients. METHODS: Phase III randomized controlled trials of NOACs compared with warfarin in Asian patients with atrial fibrillation (AF) were identified and extracted from PubMed, CENTRAL, and CINAHL databases through November 2016. Outcomes were pooled by dosing regimens with the Mantel-Haenszel fixed-effects model...
June 20, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28639436/a-high-hasbled-score-identifies-poor-warfarin-control-in-patients-treated-for-non-valvular-atrial-fibrillation-in-australia-and-singapore
#9
Nijole Bernaitis, Chi Keong Ching, Liping Chen, Jin Shing Hon, Siew Chong Teo, Tony Badrick, Andrew K Davey, Shailendra Anoopkumar-Dukie
Warfarin reduces stroke risk in atrial fibrillation (AF) patients. The quality of warfarin control, measured by time in therapeutic range (TTR), impacts outcome and adverse events. One tool evaluating risk of adverse events and potential warfarin control would simplify risk-benefit assessment of warfarin. Recently, HASBLED was demonstrated effective for this purpose, but this was in well-controlled patients with deep vein thrombosis. HASBLED as a predictor of warfarin control has not been validated in other populations including differing indications, warfarin control levels and ethnicities...
June 21, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28596457/statin-adherence-is-associated-with-reduced-recurrent-stroke-risk-in-patients-with-or-without-atrial-fibrillation
#10
COMPARATIVE STUDY
Alexander C Flint, Carol Conell, Xiushui Ren, Hooman Kamel, Sheila L Chan, Vivek A Rao, S Claiborne Johnston
BACKGROUND AND PURPOSE: Outpatient statin use reduces the risk of recurrent ischemic stroke among patients with stroke of atherothrombotic cause. It is not known whether statins have similar effects in ischemic stroke caused by atrial fibrillation (AFib). METHODS: We studied outpatient statin adherence, measured by percentage of days covered, and the risk of recurrent ischemic stroke in patients with or without AFib in a 21-hospital integrated healthcare delivery system...
July 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28527109/erratum-to-clinical-pharmacokinetics-of-sacubitril-valsartan-lcz696-a-novel-angiotensin-receptor-neprilysin-inhibitor
#11
Surya Ayalasomayajula, Thomas Langenickel, Parasar Pal, Sreedevi Boggarapu, Gangadhar Sunkara
Sacubitril/valsartan (LCZ696) is indicated for the treatment of heart failure with reduced ejection fraction. Absorption of sacubitril/valsartan and conversion of sacubitril (prodrug) to sacubitrilat (neprilysin inhibitor) was rapid with maximum plasma concentrations of sacubitril, sacubitrilat, and valsartan (angiotensin receptor blocker) reaching within 0.5, 1.5-2.0, and 2.0-3.0 h, respectively. With a twofold increase in dose, an increase in the area under the plasma concentration-time curve was proportional for sacubitril, ~1...
May 19, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28502675/genotype-guided-dosing-of-warfarin-through-modeling-and-simulation
#12
REVIEW
Jiexin Deng, Valvanera Vozmediano, Monica Rodriguez, Larisa H Cavallari, Stephan Schmidt
Current genotype-guided algorithms for warfarin dosing fail to deliver optimal performance in two aspects: 1) these algorithms are not able to achieve the same level of benefits in non-white populations, since they were developed based on multivariate regression analysis with mostly European/White data and did not include genetic variants found frequently in non-white populations; 2) these algorithms do not account for the dynamic dose/response relationship and were limited in their usefulness to guide dosing during the initiation phase, as the possession of variant VKORC1 and/or CYP2C9 polymorphisms has been associated with a more rapid attainment of target international normalized ratio (INR) and higher risk of over-anticoagulation even in genotype-guided patients...
November 15, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28417439/clinical-pharmacokinetics-of-sacubitril-valsartan-lcz696-a-novel-angiotensin-receptor-neprilysin-inhibitor
#13
REVIEW
Surya Ayalasomayajula, Thomas Langenickel, Parasar Pal, Sreedevi Boggarapu, Gangadhar Sunkara
Sacubitril/valsartan (LCZ696) is indicated for the treatment of heart failure with reduced ejection fraction. Absorption of sacubitril/valsartan and conversion of sacubitril (prodrug) to sacubitrilat (neprilysin inhibitor) was rapid with maximum plasma concentrations of sacubitril, sacubitrilat, and valsartan (angiotensin receptor blocker) reaching within 0.5, 1.5-2.0, and 2.0-3.0 h, respectively. With a two-fold increase in dose, an increase in the area under the plasma concentration-time curve was proportional for sacubitril, ~1...
December 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28224948/predictors-of-warfarin-dose-requirements-in-south-african-patients-attending-an-anticoagulation-clinic
#14
Elise Schapkaitz, Johanna Sithole
INTRODUCTION: Warfarin is the most common oral anticoagulant for the treatment and prevention of thromboembolic disease. However, it has a wide interpatient variability in dose requirements due to various genetic and clinical factors. MATERIALS AND METHODS: This study investigated the effect of clinical and genetic factors on the variability of warfarin dose requirements in 147 South African patients (81 white and 66 black). The study was performed at a University Hospital Anticoagulation Clinic managed by nursing sisters at the Charlotte Maxeke Johannesburg Academic Hospital...
March 2017: Journal of Vascular Nursing: Official Publication of the Society for Peripheral Vascular Nursing
https://www.readbyqxmd.com/read/28178408/epidemiology-risk-factors-and-clinical-features-of-intracerebral-hemorrhage-an-update
#15
REVIEW
Sang Joon An, Tae Jung Kim, Byung-Woo Yoon
Intracerebral hemorrhage (ICH) is the second most common subtype of stroke and a critical disease usually leading to severe disability or death. ICH is more common in Asians, advanced age, male sex, and low- and middle-income countries. The case fatality rate of ICH is high (40% at 1 month and 54% at 1 year), and only 12% to 39% of survivors can achieve long-term functional independence. Risk factors of ICH are hypertension, current smoking, excessive alcohol consumption, hypocholesterolemia, and drugs. Old age, male sex, Asian ethnicity, chronic kidney disease, cerebral amyloid angiopathy (CAA), and cerebral microbleeds (CMBs) increase the risk of ICH...
January 2017: Journal of Stroke
https://www.readbyqxmd.com/read/28079798/clinical-and-genetic-factors-associated-with-warfarin-maintenance-dose-in-northern-chinese-patients-with-mechanical-heart-valve-replacement
#16
Rui Liu, Jian Cao, Qian Zhang, Xin-Miao Shi, Xiao-Dong Pan, Ran Dong
The effects of genetic variants on warfarin dosing vary among different ethnic groups, especially in the Chinese population. The objective of this study was to recruit patients through a rigorous experimental design and to perform a comprehensive screen to identify gene polymorphisms that may influence warfarin dosing in northern Han Chinese patients with mechanical heart valve replacement. Consenting patients (n = 183) with a stable warfarin dose were included in this study. Ninety-six single nucleotide polymorphisms (SNPs) in 30 genes involved in warfarin pharmacological pathways were genotyped using the Illumina SNP GoldenGate Assay, and their associations with warfarin dosing were assessed using univariate regression analysis with post hoc comparison using least significant difference analysis...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28064291/anticoagulation-use-and-predictors-of-stroke-bleeding-and-mortality-in-multi-ethnic-asian-patients-with-atrial-fibrillation-a-single-centre-experience
#17
P L Chia, X Teoh, C M Hua, M E Ching, D Foo
INTRODUCTION: Atrial fibrillation (AF) is the most common cardiac arrhythmia in singapore. We describe a cohort of multi-ethnic Asian patients with AF, with the aim to evaluate anticoagulation use and to identify factors predictive of stroke, bleeding and all-cause mortality. MATERIALS AND METHODS: this was a single centre, retrospective cohort study. All patients with an admission diagnosis of AF between 1 January 2000 and 31 December 2010 were identified. Of these patients, those who had follow-up data up to 31 December 2012 were included in the study...
October 2016: Medical Journal of Malaysia
https://www.readbyqxmd.com/read/28025970/impact-of-vkorc1-gene-polymorphisms-on-warfarin-maintenance-dosage-a-novel-systematic-review-and-meta-analysis-of-53-studies
#18
REVIEW
Wei Tang, Qing-Ping Shi, Feng Ding, Mei-Ling Yu, Jian Hua, Yong-Xin Wang
OBJECTIVE: To analyze the correlation between <i>VKORC1</i> gene polymorphisms and warfarin maintenance dosage, as well as the correlation of dosage of warfarin with age and ethnicity. METHODS: We retrieved related studies published between January 2000 and March 2016 from PubMed, Embase, the Cochrane Library, Web of Science, VIP, CNKI, and Wan Fang data. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data and crosscheck data...
April 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27927630/inactive-matrix-gla-protein-and-arterial-stiffness-in-type-2-diabetes-mellitus
#19
Mayank Sardana, Izzah Vasim, Swapna Varakantam, Uzma Kewan, Ali Tariq, Maheshwara R Koppula, Amer Ahmed Syed, Melissa Beraun, Nadja E A Drummen, Cees Vermeer, Scott R Akers, Julio A Chirinos
BACKGROUND: Large artery stiffness is increased in diabetes mellitus and causes an excessive pulsatile load to the heart and to the microvasculature. The identification of pathways related to arterial stiffness may provide novel therapeutic targets to ameliorate arterial stiffness in diabetes. Matrix Gla-Protein (MGP) is an inhibitor of vascular calcification. Activation of MGP is vitamin K dependent. We hypothesized that levels of inactive MGP (dephospho-uncarboxylated MGP; dp-ucMGP) are related to arterial stiffness in type 2 diabetes...
February 2017: American Journal of Hypertension
https://www.readbyqxmd.com/read/27887741/evaluation-of-16-genotype-guided-warfarin-dosing-algorithms-in-310-korean-patients-receiving-warfarin-treatment-poor-prediction-performance-in-vkorc1-1173c-carriers
#20
Mina Yang, Rihwa Choi, June Soo Kim, Young Keun On, Oh Young Bang, Hyun-Jung Cho, Soo-Youn Lee
PURPOSE: The purpose of this study was to evaluate the performance of 16 previously published warfarin dosing algorithms in Korean patients. METHODS: The 16 algorithms were selected through a literature search and evaluated using a cohort of 310 Korean patients with atrial fibrillation or cerebral infarction who were receiving warfarin therapy. FINDINGS: A large interindividual variation (up to 11-fold) in warfarin dose was observed (median, 25 mg/wk; range, 7-77 mg/wk)...
December 2016: Clinical Therapeutics
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