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Adverse drug reaction active surveillance: developing a national network in Canada's children's hospitals.

https://arctichealth.org/en/permalink/ahliterature150480
Source
Pharmacoepidemiol Drug Saf. 2009 Aug;18(8):713-21
Publication Type
Article
Date
Aug-2009
Author
Bc Carleton
Rl Poole
Ma Smith
Js Leeder
R. Ghannadan
Cjd Ross
Ms Phillips
Mr Hayden
Author Affiliation
Pharmaceutical Outcomes Programme, Children's and Women's Health Centre of British Columbia, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada. bcarleton@popi.ubc.ca
Source
Pharmacoepidemiol Drug Saf. 2009 Aug;18(8):713-21
Date
Aug-2009
Language
English
Publication Type
Article
Keywords
Adverse Drug Reaction Reporting Systems - organization & administration
Analgesics, Opioid - poisoning
Anthracyclines - adverse effects
Antibiotics, Antineoplastic - adverse effects
Breast Feeding
Canada - epidemiology
Case-Control Studies
Child
Child Health Services - organization & administration
Child, Preschool
Cisplatin - adverse effects
Codeine - poisoning
Drug Overdose - genetics - mortality
Female
Genetic markers
Hearing Loss - chemically induced
Heart Diseases - chemically induced
Hospitals, Pediatric - organization & administration
Humans
Infant
Infant, Newborn
National health programs - organization & administration
Pharmacogenetics
Program Development
Time Factors
Abstract
Adverse drug reactions (ADRs) rank as the fifth leading cause of death in the western world. The nature and scope of these ADRs in children are not predictable based on post market surveillance reports that rely heavily on adult drug experience. The genotype-specific approaches to therapy in childhood (GATC) national ADR network was established to identify specific ADRs and to improve drug safety through identification of predictive genomic biomarkers of drug risk.
GATC set out to establish a national network of trained surveillance clinicians in pediatric hospitals across Canada. Surveillance clinicians identified, enrolled, and collected clinical data and biological samples from ADR cases and controls. Surveillance was targeted to three ADRs: anthracycline-induced cardiotoxicity, cisplatin-induced hearing impairment, and codeine-induced mortality in breastfed infants.
The initial surveillance site was established in September 2005, with 10 sites fully operational by 2008. In 3 years, GATC enrolled 1836 ADR cases and 13188 controls. Target numbers were achieved for anthracycline-induced cardiotoxicity. Modified target numbers were nearly attained for cisplatin-induced hearing impairment. Codeine-induced infant mortality in a breastfed infant was discovered by GATC investigators. A case-control study was subsequently conducted.
GATC has demonstrated a model of active and targeted surveillance that builds an important step toward the goal of personalized medicine for children. Effective communication, site-specific solutions and long-term sustainability across the network are critical to maintain participation and productivity. GATC may provide a framework of ADR surveillance that can be adapted by other countries and healthcare systems.
PubMed ID
19507171 View in PubMed
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Adverse reactions to drugs and metabolic problems perceived in northern Canadian Indians and Eskimos.

https://arctichealth.org/en/permalink/ahliterature2199
Source
Progress in Clinical and Biological Research. 1986; 214:77-83.
Publication Type
Article
Date
1986
Author
Schaefer, O.
Author Affiliation
Northern Medical Research Laboratory (Edmonton)
Source
Progress in Clinical and Biological Research. 1986; 214:77-83.
Date
1986
Language
English
Geographic Location
Canada
Publication Type
Article
Physical Holding
Alaska Medical Library
Keywords
Drug reactions
INH inactivator
Nutrition
Diet, traditional
Alcohol metabolism
Sucrose tolerance
Lactose tolerance
Cholinesterase deficiency
Adaptation, Biological
Canada
Comparative Study
Ethanol - metabolism
Humans
Indians, North American
Inuits
Lactose Intolerance - epidemiology
Pharmaceutical Preparations - adverse effects - metabolism
Pharmacogenetics
Phenytoin - metabolism
Succinylcholine - metabolism
Sucrose - adverse effects
Abstract
Eskimos and to a slightly lesser degree Northern Indians are extremely rapid acetylators as tested with isoniazid. They also tend to clear phenytoin rapidly as proven in Greenland Eskimos and supported by clinical observations in Canadian Eskimos. Most "silent gene" cholinesterase cases found in Canada came from the tiny minorities of Northern Indians and Eskimos and an even higher prevalence was found in an isolate of South Western Alaskan Eskimos. We found alcohol metabolism significantly slower in Northern Indians and Eskimos than Caucasians, which is at variance with findings in other Amerindian groups and Asiatic Mongoloids reflecting perhaps quite different physical and nutritional environments over long periods of time. Pecularities of sugar metabolism found in Natives of the Canadian Arctic and Sub-Arctic may also be best explained by the relative deficiency of carbohydrates in their traditional diet.
Notes
From: Fortuine, Robert et al. 1993. The Health of the Inuit of North America: A Bibliography from the Earliest Times through 1990. University of Alaska Anchorage. Citation number 2243.
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Androgen receptor gene CAG repeat length as a modifier of the association between persistent organohalogen pollutant exposure markers and semen characteristics.

https://arctichealth.org/en/permalink/ahliterature77700
Source
Pharmacogenet Genomics. 2007 Jun;17(6):391-401
Publication Type
Article
Date
Jun-2007
Author
Giwercman Aleksander
Rylander Lars
Rignell-Hydbom Anna
Jönsson Bo A G
Pedersen Henning S
Ludwicki Jan K
Lesovoy Vladimir
Zvyezday Valentyna
Spano Marcello
Manicardi Gian-Carlo
Bizzaro Davide
Bonefeld-Jørgensen Eva C
Toft Gunnar
Bonde Jens Peter
Giwercman Charlotte
Tiido Tarmo
Giwercman Yvonne Lundberg
Author Affiliation
Molecular Reproductive Medicine Research Unit, Department of Clinical Sciences, Reproductive Medicine Centre, Malmö University Hospital, Lund University, Malmö, Sweden. aleksander.giwercman@med.lu.se
Source
Pharmacogenet Genomics. 2007 Jun;17(6):391-401
Date
Jun-2007
Language
English
Publication Type
Article
Keywords
Adult
DNA Fragmentation - drug effects
Dichlorodiphenyl Dichloroethylene - blood - toxicity
Endocrine Disruptors - blood - toxicity
Environmental Exposure
Environmental Pollutants - blood - toxicity
Humans
Hydrocarbons, Halogenated - toxicity
Male
Minisatellite Repeats
Pharmacogenetics
Polychlorinated Biphenyls - blood - toxicity
Polymorphism, Genetic
Receptors, Androgen - genetics
Semen - drug effects - metabolism
Sperm Count
Trinucleotide Repeats
Abstract
OBJECTIVES: Exposure to persistent organohalogen pollutants was suggested to impair male reproductive function. A gene-environment interaction has been proposed. No genes modifying the effect of persistent organohalogen pollutants on reproductive organs have yet been identified. We aimed to investigate whether the CAG and GGN polymorphisms in the androgen receptor gene modify the effect of persistent organohalogen pollutant exposure on human sperm characteristics. METHODS: Semen and blood from 680 men [mean (SD) age 34 (10) years] from Greenland, Sweden, Warsaw (Poland) and Kharkiv (Ukraine) were collected. Persistent organohalogen pollutant exposure was assessed by measuring serum levels of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and dichlorodiphenyl dichloroethene (p,p'-DDE). Semen characteristics (volume, sperm concentration, total count, proportion of progressively motile and morphology) and DNA fragmentation index (DFI) were determined. CAG and GGN repeat lengths were determined by direct sequencing of leukocyte DNA. RESULTS: A statistically significant interaction was found between the CB-153 group and CAG repeat category in relation to sperm concentration and total sperm count (P=0.03 and 0.01, respectively). For p,p'-DDE, in the European cohorts a significant interaction was found in relation to DFI (P=0.01). For CAG
PubMed ID
17502831 View in PubMed
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Angiotensinogen and ACE gene polymorphisms and risk of atrial fibrillation in the general population.

https://arctichealth.org/en/permalink/ahliterature93132
Source
Pharmacogenet Genomics. 2008 Jun;18(6):525-33
Publication Type
Article
Date
Jun-2008
Author
Ravn LS
Benn M
Nordestgaard BG
Sethi AA
Agerholm-Larsen B
Jensen GB
Tybjaerg-Hansen A
Author Affiliation
Department of Cardiology, Danish Arrhythmia Research Center, Copenhagen, Denmark.
Source
Pharmacogenet Genomics. 2008 Jun;18(6):525-33
Date
Jun-2008
Language
English
Publication Type
Article
Keywords
Adult
Aged
Alleles
Amino Acid Sequence
Angiotensinogen - genetics
Atrial Fibrillation - enzymology - genetics
Base Sequence
DNA - genetics
Denmark
Female
Genetic Predisposition to Disease
Heterozygote
Homozygote
Humans
Linkage Disequilibrium
Longitudinal Studies
Male
Middle Aged
Molecular Sequence Data
Peptidyl-Dipeptidase A - genetics
Pharmacogenetics
Polymorphism, Genetic
Renin-Angiotensin System - drug effects - genetics
Risk factors
Sequence Homology, Amino Acid
Sequence Homology, Nucleic Acid
Abstract
OBJECTIVES: The renin-angiotensin system may play a role in the pathogenesis of atrial fibrillation, and renin-angiotensin system blockers reduce the risk of atrial fibrillation. We hypothesized that polymorphisms in the angiotensinogen and angiotensin-converting enzyme (ACE) genes encoding proteins in this system predict risk of atrial fibrillation. METHODS AND RESULTS: We genotyped 9235 individuals from the Danish general population, The Copenhagen City Heart Study, for the a-20c, g-6a, T174M, and M235T polymorphisms in the angiotensinogen gene and the insertion/deletion (I/D) polymorphism in the ACE gene; rare allele frequencies were 0.16, 0.40, 0.12, 0.41, and 0.49, respectively. Participants had sinus rhythm at inclusion. During 26 years of follow-up, 968 individuals developed atrial fibrillation. Multifactorially adjusted hazard ratios for atrial fibrillation for a-20c ac and cc versus aa genotype were 1.1(95% confidence interval: 1.0-1.3; P=0.05) and 1.5(1.1-2.1; P=0.01). Compared with double noncarriers (angiotensinogen -20aa and ACE II), double heterozygotes (ac-I/D genotype), and double homozygotes (cc-DD) had hazard ratios for atrial fibrillation of 1.2(0.9-1.6; P=0.06) and 2.4(1.4-4.1; P=0.001). a-20c cc homozygotes above 70 years of age who were overweight, severely hypertensive, and had heart failure, had an absolute 10-year risk of atrial fibrillation of 61%. CONCLUSION: Angiotensinogen a-20c genotype alone and in combination with ACE I/D genotype predicts an increased risk of atrial fibrillation. Therefore, genetic variation in the renin-angiotensin system may influence effect of renin-angiotensin system blockers on atrial fibrillation.
PubMed ID
18496132 View in PubMed
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Application of principal component analysis to pharmacogenomic studies in Canada.

https://arctichealth.org/en/permalink/ahliterature149314
Source
Pharmacogenomics J. 2009 Dec;9(6):362-72
Publication Type
Article
Date
Dec-2009
Author
H. Visscher
C J D Ross
M-P Dubé
A M K Brown
M S Phillips
B C Carleton
M R Hayden
Author Affiliation
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
Source
Pharmacogenomics J. 2009 Dec;9(6):362-72
Date
Dec-2009
Language
English
Publication Type
Article
Keywords
African Continental Ancestry Group - genetics
Asian Continental Ancestry Group - genetics
Biotransformation - genetics
Canada
Drug-Related Side Effects and Adverse Reactions
Ethnic Groups - genetics
European Continental Ancestry Group - genetics
Gene Frequency
Genetics, Population
Genome-Wide Association Study
Humans
Pharmacogenetics - methods
Polymorphism, Single Nucleotide
Principal Component Analysis
Abstract
Ethnicity can confound results in pharmacogenomic studies. Allele frequencies of loci that influence drug metabolism can vary substantially between different ethnicities and underlying ancestral genetic differences can lead to spurious findings in pharmacogenomic association studies. We evaluated the application of principal component analysis (PCA) in a pharmacogenomic study in Canada to detect and correct for genetic ancestry differences using genotype data from 2094 loci in 220 key drug biotransformation genes. Using 89 Coriell worldwide reference samples, we observed a strong correlation between principal component values and geographic origin. We further applied PCA to accurately infer the genetic ancestry in our ethnically diverse Canadian cohort of 524 patients from the GATC study of severe adverse drug reactions. We show that PCA can be successfully applied in pharmacogenomic studies using a limited set of markers to detect underlying differences in genetic ancestry thereby maximizing power and minimizing false-positive findings.
PubMed ID
19652663 View in PubMed
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Association between cytochrome P450 3A5 polymorphism and the lung function in Saskatchewan grain workers.

https://arctichealth.org/en/permalink/ahliterature157066
Source
Pharmacogenet Genomics. 2008 Jun;18(6):487-93
Publication Type
Article
Date
Jun-2008
Author
Takayuki Seo
Punam Pahwa
Helen H McDuffie
Keigo Yurube
Masayoshi Egoshi
Yuichiro Umemoto
Sunita Ghosh
Yumi Fukushima
Kazuko Nakagawa
Author Affiliation
Division of Pharmacology and Therapeutics, Graduate School of Medical and Pharmaceutical Science, Kumamoto University, Kumamoto, Japan.
Source
Pharmacogenet Genomics. 2008 Jun;18(6):487-93
Date
Jun-2008
Language
English
Publication Type
Article
Keywords
Adult
Cereals
Cytochrome P-450 CYP3A - genetics
Dust
Forced expiratory volume
Genetic Predisposition to Disease
Genotype
Humans
Longitudinal Studies
Male
Occupational Exposure
Pharmacogenetics
Polymorphism, Genetic
Pulmonary Disease, Chronic Obstructive - enzymology - etiology - genetics - physiopathology
Respiratory Function Tests
Risk factors
Saskatchewan
Smoking - adverse effects
Vital Capacity
Abstract
The activity of the enzymes that metabolize tobacco smoke may affect the susceptibility to chronic obstructive pulmonary disease (COPD). Cytochrome P450 (CYP) 3A5 is expressed selectively over CYP3A4 in human lung, but the association between the CYP3A5 polymorphisms and the airway injury is unknown.
Two hundred and six male Saskatchewan grain workers participated in this longitudinal study, and their lung function values of forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC), respiratory symptoms, smoking status, and the occupational history were analyzed.
A significant interactive effect was observed between the CYP3A5 genotype and current smoking status on FEV1, and the annual decline rates of FEV1 and FVC in current smokers were greater among CYP3A5*1/*3 carriers than CYP3A5*3/*3 carriers (-48.7+/-16.4 vs. -31.5+/-4.7 ml/years, P=0.02; -27.4+/-18.9 vs. -5.8+/-6.5 ml/years, P=0.04). The incidences of chronic cough and COPD were also higher in current smokers with CYP3A5*1/*3 than in nonsmokers and current smokers with CYP3A5*3/*3. The adjusted odds ratios for chronic cough and COPD current smokers with CYP3A5*1/*3 versus nonsmokers with the CYP3A5*3/*3 genotype were 11.4 (P=0.009) and 4.3 (P=0.13), respectively.
The results suggest that CYP3A5*1 may be a novel genetic risk factor for airway injury in smokers, and that CYP3A5 may play a role in airway injury owing to the bioactivation of chemicals in tobacco smoke.
PubMed ID
18496128 View in PubMed
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Association between inherited CYP2D6/2C19 phenotypes and anticholinergic measures in elderly patients using anticholinergic drugs.

https://arctichealth.org/en/permalink/ahliterature106903
Source
Ther Drug Monit. 2014 Feb;36(1):125-30
Publication Type
Article
Date
Feb-2014
Author
Hege Kersten
Torgeir B Wyller
Espen Molden
Author Affiliation
*Department of Geriatric Medicine, Oslo University Hospital; ‚ĆDepartment of Pharmaceutical Services, The Hospital Pharmacies; ‚Ä°Institute of Clinical Medicine, University of Oslo; §Department of Pharmaceutical Bioscience, School of Pharmacy, University of Oslo; and ¶Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.
Source
Ther Drug Monit. 2014 Feb;36(1):125-30
Date
Feb-2014
Language
English
Publication Type
Article
Keywords
Age Factors
Aged, 80 and over
Aryl Hydrocarbon Hydroxylases - genetics
Cholinergic Antagonists - adverse effects - pharmacokinetics - pharmacology
Cognition - drug effects
Cytochrome P-450 CYP2D6 - genetics
Female
Humans
Male
Mutation
Norway
Nursing Homes
Pharmacogenetics
Phenotype
Radioligand Assay
Statistics, nonparametric
Xerostomia - chemically induced
Abstract
To compare measures of anticholinergic activity between metabolic phenotypes of the polymorphic enzymes cytochrome P450 2D6 (CYP2D6) and CYP2C19 in the elderly patients exposed to anticholinergic agents.
Long-term nursing home patients (n = 80) with an anticholinergic drug scale (ADS) score =3 were recruited from 22 nursing homes in Norway. Based on pharmacogenetic analyses of mutations encoding absent CYP2D6 or CYP2C19 metabolism, patients were divided into subgroups of poor metabolizers (PMs) (n = 8) and extensive metabolizers (n = 72). Serum anticholinergic activity (SAA) was determined by a validated, 96-well format radio receptor assay and adjusted for ADS score. Unadjusted and adjusted SAAs, mouth dryness, and cognitive function (Mini-Mental State Examination and verbal recall tests from Consortium to Establish a Registry for Alzheimer Disease) were compared between the subgroups with Mann-Whitney tests.
The study population was represented by 78% women, 68% had mild to moderate dementia, and mean age was 86 years. More than 80% used more than 1 anticholinergic agent, and their median ADS score was 4. The subpopulation of PMs had significantly higher median SAA than the extensive metabolizers (10.3 versus 4.2 pmol atropine equivalents per milliliter, P = 0.012). This difference remained significant after adjusting for ADS score (P = 0.013). No significant differences in mouth dryness and cognitive function were observed between the subgroups (P > 0.3).
These preliminary findings suggest that elderly CYP2D6/CYP2C19 PMs with a high anticholinergic drug burden are at increased risk of elevated SAA. Whether PMs are also more prone to experience anticholinergic side effects needs to be further studied in larger patient populations.
PubMed ID
24089073 View in PubMed
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[Association of ITGB3, P2RY12, and CYP2C19 gene polymorphisms with platelet functional activity in patients with coronary heart disease during dual antiplatelet therapy].

https://arctichealth.org/en/permalink/ahliterature285325
Source
Ter Arkh. 2017;89(5):74-78
Publication Type
Article
Author
E F Muslimova
S A Afanasiev
T Yu Rebrova
T N Sergienko
A N Repin
Source
Ter Arkh. 2017;89(5):74-78
Language
Russian
Publication Type
Article
Keywords
Alleles
Aspirin - administration & dosage - adverse effects
Blood Platelets - drug effects
Coronary Artery Disease - drug therapy - epidemiology - genetics
Cytochrome P-450 CYP2C19 - genetics
Drug Resistance - genetics
Humans
Integrin beta3 - genetics
Male
Middle Aged
Pharmacogenetics
Platelet Aggregation - drug effects
Platelet Aggregation Inhibitors - administration & dosage - adverse effects
Platelet Function Tests - methods
Polymorphism, Genetic
Receptors, Purinergic P2 - genetics
Siberia - epidemiology
Ticlopidine - administration & dosage - adverse effects - analogs & derivatives
Abstract
To assess the association of CYP2C19 G681A, P2RY12 H1/H2, and ITGB3 T1565C polymorphisms with the extent of platelet aggregation in patients with coronary heart disease (CHD) during antiplatelet therapy.
166 male patients with CHD, living in the Western Siberian Region, were examined. All the patients underwent a test for platelet aggregation induced by ADP (2.5 and 5.0 µm) and epinephrine (0.2 µm). Genotyping was performed using an allele-specific polymerase chain reaction technique.
The polymorphic variants of the P2RY12 and ITGB3 genes were ascertained to have no impact on the extent of platelet aggregation in patients receiving clopidogrel and acetylsalicylic acid. An association was found between CYP2C19 681A allele carriage and the increased extent of platelet aggregation induced by ADP.
The carriage of the cytochrome P450 CYP2C19 681A allele rather than platelet receptor gene polymorphisms determines a risk for clopidogrel resistance in patients with CHD.
PubMed ID
28631703 View in PubMed
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The Canadian Pharmacogenomics Network for Drug Safety: a model for safety pharmacology.

https://arctichealth.org/en/permalink/ahliterature142605
Source
Thyroid. 2010 Jul;20(7):681-7
Publication Type
Article
Date
Jul-2010
Author
Colin J D Ross
Henk Visscher
Johanna Sistonen
Liam R Brunham
Kusala Pussegoda
Tenneille T Loo
Michael J Rieder
Gideon Koren
Bruce C Carleton
Michael R Hayden
Author Affiliation
Department of Medical Genetics, Faculty of Medicine, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada.
Source
Thyroid. 2010 Jul;20(7):681-7
Date
Jul-2010
Language
English
Publication Type
Article
Keywords
Adult
Adverse Drug Reaction Reporting Systems
Antithyroid Agents - adverse effects
Biomarkers, Pharmacological
Canada - epidemiology
Child
Cisplatin - adverse effects
Codeine - poisoning
Drug-Related Side Effects and Adverse Reactions - epidemiology - genetics - mortality - prevention & control
Genetic Association Studies
Genetic markers
Genetic Testing - methods
Humans
Individualized Medicine - methods
International Cooperation
Pharmacogenetics - methods
Population Surveillance - methods
Sentinel Surveillance
Abstract
Adverse drug reactions (ADRs) rank as one of the top 10 leading causes of death in the developed world, and the direct medical costs of ADRs exceed $100 billion annually in the United States alone. Pharmacogenomics research seeks to identify genetic factors that are responsible for individual differences in drug efficacy and susceptibility to ADRs. This has led to several genetic tests that are currently being used to provide clinical recommendations. The Canadian Pharmacogenomics Network for Drug Safety is a nation-wide effort established in Canada to identify novel predictive genomic markers of severe ADRs in children and adults. A surveillance network has been established in 17 of Canada's major hospitals to identify patients experiencing specific ADRs and to collect biological samples and relevant clinical history for genetic association studies. To identify ADR-associated genetic markers that could be incorporated into predictive tests that will reduce the occurrence of serious ADRs, high-throughput genomic analyses are conducted with samples from patients that have suffered serious ADRs and matched control patients.
ADRs represent a significant unmet medical problem with significant morbidity and mortality, and Canadian Pharmacogenomics Network for Drug Safety is a nation-wide network in Canada that seeks to identify genetic factors responsible for interindividual differences in susceptibility to serious ADRs.
Active ADR surveillance is necessary to identify and recruit patients who suffer from serious ADRs. National and international collaborations are required to recruit sufficient patients for these studies. Several pharmacogenomics tests are currently in clinical use to provide dosing recommendations, and the number of pharmacogenomics tests is expected to significantly increase in the future.
PubMed ID
20578893 View in PubMed
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82 records – page 1 of 9.