A5058495115- Colorectal Cancer Treatments and Studies
- Biochemical and Molecular Research
- Pharmacogenetics and Drug Metabolism
- Pancreatic and Hepatic Oncology Research
- Pharmaceutical studies and practices
- Cancer Treatment and Pharmacology
- Cancer therapeutics and mechanisms
- Schizophrenia research and treatment
- Attention Deficit Hyperactivity Disorder
- Genomics and Rare Diseases
- Pharmaceutical Economics and Policy
- Gastric Cancer Management and Outcomes
- Blood disorders and treatments
- Neuroendocrine Tumor Research Advances
- Myasthenia Gravis and Thymoma
- HER2/EGFR in Cancer Research
- Parkinson's Disease and Spinal Disorders
- Pharmacological Effects and Toxicity Studies
- Cancer Genomics and Diagnostics
- Treatment of Major Depression
- Chemical Reactions and Isotopes
- Advanced Breast Cancer Therapies
- BRCA gene mutations in cancer
- Lung Cancer Treatments and Mutations
- Prostate Cancer Treatment and Research
Leiden University Medical Center
2015-2024
Aarhus University
2020-2022
Aarhus University Hospital
2020-2022
Amsterdam UMC Location University of Amsterdam
2017
Sint Franciscus Gasthuis
2017
The Netherlands Cancer Institute
2017
Abstract Despite advances in the field of pharmacogenetics (PGx), clinical acceptance has remained limited. The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate PGx implementation by developing evidence-based guidelines optimize pharmacotherapy. This guideline describes starting dose optimization three anti-cancer drugs (fluoropyrimidines: 5-fluorouracil, capecitabine and tegafur) decrease risk severe, potentially fatal, toxicity (such as diarrhoea, hand-foot syndrome,...
In clinical practice, 25–30% of the patients treated with fluoropyrimidines experience severe fluoropyrimidine‐related toxicity. Extensively clinically validated DPYD genotyping tests are available to identify at risk toxicity due decreased activity dihydropyrimidine dehydrogenase (DPD), rate limiting enzyme in fluoropyrimidine metabolism. April 2020, European Medicines Agency recommended that, as an alternative for genotype‐based testing DPD deficiency, also phenotype based on pretreatment...
DPYD-guided fluoropyrimidine dosing improves patient safety in carriers of DPYD variant alleles. However, the impact on treatment outcome these patients is largely unknown. Therefore, progression-free survival (PFS) and overall (OS) were compared between treated with a reduced dose wild-type controls receiving full retrospective matched-pair analysis.Data from prospective multicenter study (ClinicalTrials.gov identifier: NCT02324452) which received 25% (c.1236G>A c.2846A>T) or 50% (DPYD*2A...
Background: The clinical impact of the functional CYP2C19 and CYP2D6 gene variants on antidepressant treatment in people with depression is not well studied. Here, we evaluate utility pharmacogenetic (PGx) testing psychiatry by investigating association between phenotype status cytochrome P450 (CYP) 2C19/2D6 enzymes one-year risks outcomes patients incident new-use (es)citalopram, sertraline, or fluoxetine. Methods: This study a population-based cohort 17,297 individuals who were born 1981...
Abstract Background The Alpe-DPD study (NCT02324452) demonstrated that prospective genotyping and dose-individualization using four alleles in DPYD ( *2A/rs3918290, c.1236G > A/rs75017182, c.2846A T/rs67376798 c.1679 T G/rs56038477) can mitigate the risk of severe fluoropyrimidine toxicity. However, this could not prevent all toxicities. goal was to identify additional genetic variants, both inside outside , may contribute Methods Biospecimens data from were used. Exon sequencing...
Abstract Pharmacogenetics aims to improve clinical care by studying the relationship between genetic variation and variable drug response. Large population-based datasets could our current understanding of pharmacogenetics from selected study populations. We provide real-world pharmacogenetic frequencies genotypes (combined) phenotypes a large Danish case-cohort sample (iPSYCH2012; data Integrative Psychiatric Research consortium). The genotyped consists 77,684 individuals, which 51,464...
DPYD genotyping prior to fluoropyrimidine treatment is increasingly implemented in clinical care. Without phasing information (i.e., allelic location of variants), current genotype-based dosing guidelines cannot be applied patients carrying multiple variants. The primary aim this study examine diagnostic and therapeutic strategies for A case series variants presented. Different techniques were used determine information. Phenotyping was performed by dihydropyrimidine dehydrogenase (DPD)...
Pharmacogenetics (PGx) aims to improve drug therapy using the individual patients' genetic make-up. Little is known about potential impact of PGx on population level, possibly hindering implementation in clinical care. Therefore, we investigated how many patients use actionable drugs, have genotypes or phenotypes and which could benefit most testing. We included recommendations from two international consortia (Clinical Implementation Consortium (CPIC) Dutch Working Group (DPWG)). Using data...
Abstract Objective To describe life-time use of current actionable pharmacogenetic (PGx) somatic and psychotropic drugs according to international PGx consortia in people with without hospital-diagnosed mental disorders the Danish population. Methods Population- register-based observational drug utilization study 56 065 individuals disorders, i. e. attention-deficit/hyperactivity disorder, autism, bipolar depression schizophrenia, a random, representative sample 29 975 population, born...
Introduction Pharmacogenetics (PGx) studies genetic variance and related differences in drug outcomes. PGx guidelines for psychotropic drugs are available (PGx drugs), but testing is used only limitedly psychiatric clinical practice. Objectives The aim of this study to pinpoint different aspects use the population, support uptake PGx. Methods This utilization investigated prescription 56,065 young individuals with severe mental disorders (SMD) Danish iPSYCH sample (born 1981-2005). We number...
Introduction Pharmacogenetics (PGx) studies genetic variance and related differences in drug outcomes. PGx guidelines for psychotropic drugs are available (PGx drugs). By executing testing a prospective or pre-emptive setting, dose adjustments even change of treatment type can be applied prior to start therapy patients who carry specific geno- phenotype (i.e. actionable phenotypes). doing so, increased efficacy reduced risk adverse events accomplished. In Denmark, broad implementation is...
Introduction Pharmacogenetics (PGx) studies genetic variance and related differences in drug outcomes. The aim of PGx testing is to increase therapy efficacy safety, by applying e.g. dose adjustments patients with a specific geno- or phenotype. guidelines for psychotropic drugs are available (PGx drugs), including atomoxetine used the treatment attention deficit hyperactivity disorder (ADHD). In Denmark, broad implementation currently still low, possibly due lack population-based...