Pharmacogenetics and pharmacogenomics: practical applications in routine medical practice

A report of the 3rd joint European Science Foundation and University of Barcelona Conference in Biomedicine, San Feliu de Guixols, Catalonia, Spain, 6-11 June 2010

Современные представления о супружеских конфликтах и супружеской дезадаптации

Рассмотрены современные данные о семейных конфликтах и связанной с ними супружеской дезадаптации. Сделан вывод о необходимости дальнейшей разработки этой проблемы.Modern data about family conflicts and the associated spouse deadaptation are discussed. The author concludes about the necessity of further investigation of the issue

Pharmacogenomic insights into treatment and management of statin-induced myopathy

Although statins are generally well tolerated, the most common adverse drug reaction from statin therapy is myopathy. This article reviews the current pharmacogenomic knowledge of statin-induced myopathy. Furthermore, we will discuss the importance of recent pharmacogenetic advances for the treatment and management of statin-induced myopathy. Variation in the SLCO1B1 gene is associated with increased incidence of statin-induced myopathy, particularly with simvastatin and less so with other statins. If different pharmacokinetic enzymes and transporters are responsible for susceptibility to myopathy, this may explain differences in the occurrence of statin-induced myopathy in individual patients. Genotyping in patients suffering from statin-induced myopathy may help to personalize the choice of statin for the lowest chance of developing myopathy

Довідкові регіональні видання з геральдики

Одним з джерел інформації про наявність історичних гербів міст України та новотворів 60-х–80-х рр. ХХ ст. виступає «Алфавитный каталог городов, поселков, сел, губерний и областей России, СНГ, бывших союзных республик СССР, имеющих старые и современные гербы». Автор рецензії проаналізував принципи укладання подібних джерел інформації, зробив свої зауваження та висловив побажання щодо їх вдосконалення.«Alphabetical catalogue of towns, settlements, villages, provinces and regions of Russia, Commonwealth of Independent States, former Soviet Republics of the USSR, which have old and present-day coat of arms» is one of the sources that gives information about historical coat of arms and newly formed emblems of Ukraine during 60th – 80th of XX century. The author of the review analysed the structure of similar sources and made her remarks and suggestion regarding to its improvement

Mining treatment patterns of glucose-lowering medications for type 2 diabetes in the Netherlands

Rationale and objectives Different classes of glucose-lowering medications are used for patients with type 2 diabetes mellitus (T2DM) management. It is unclear how often these medications are prescribed in clinical practice. In this study, we aimed to describe treatment patterns of glucose-lowering medications in patients with T2DM in the Netherlands. Methods We studied a cohort of 73 819 patients with T2DM, aged ≥45 years with a first prescription for oral glucose-lowering medication between 2011 and 2017. We used the NControl database with dispensing data from 800 pharmacies in the Netherlands. Prevalence of each glucose-lowering medication class during 6 years after the index date was calculated. Using SQL Server, we identified stepwise patterns of medication prescription in this population. Findings During the study period, prevalence of biguanides (BIGU) decreased from 95.6% to 80.8% and use of sulfonylureas (SU) increased from 27.3% to 42.3%. 55.2% of all patient

Economic evaluation of a pharmacogenetic dosing algorithm for coumarin anticoagulants in The Netherlands

AIM: To investigate the cost-effectiveness of a pharmacogenetic dosing algorithm versus a clinical dosing algorithm for coumarin anticoagulants in The Netherlands. MATERIALS & METHODS: A decision-analytic Markov model was used to analyze the cost-effectiveness of pharmacogenetic dosing of phenprocoumon and acenocoumarol versus clinical dosing. RESULTS: Pharmacogenetic dosing increased costs by €33 and quality-adjusted life-years (QALYs) by 0.001. The incremental cost-effectiveness ratios were €28,349 and €24,427 per QALY gained for phenprocoumon and acenocoumarol, respectively. At a willingness-to-pay threshold of €20,000 per QALY, the pharmacogenetic dosing algorithm was not likely to be cost effective compared with the clinical dosing algorithm. CONCLUSION: Pharmacogenetic dosing improves health only slightly when compared with clinical dosing. However, availability of low-cost genotyping would make it a cost-effective option

Characteristics and quality of oral anticoagulation treatment in pediatric patients in the Netherlands based on the CAPS cohort

Essentials: The knowledge of quality and safety of acenocoumarol and phenprocoumon use in children is limited. We used data from a multicenter retrospective follow-up study in children in the Netherlands. The quality of anticoagulation control in the first month of use was low, but improved thereafter. No thromboembolic events occurred, however bleeding events occurred in 1-3 out of 10 patients. Summary: Background: The use of vitamin-K antagonists in pediatric patients is rare and information on the quality and safety of treatment with acenocoumarol and phenprocoumon is limited. Objectives: To assess the quality, safety and effectiveness during the first year of acenocoumarol and phenprocoumon treatment in pediatric patients in the Netherlands. Methods: The Children Anticoagulation and Pharmacogenetics Study (C

FCER2 T2206C variant associated with FENO levels in asthmatic children using inhaled corticosteroids: The PACMAN study

Background: The FCER2 gene, via encoding of the CD23 receptor, plays an important role in the regulation of IgE responses. A genetic variant of the FCER2 gene (T2206C) was previously shown to be associated with IgE levels in asthmatic children. IgE sen‐ sitization has also been linked to increased levels of fractional exhaled nitric oxide (FENO). Objective: To investigate whether the FCER2 T2206C variant influences FENO levels in asthmatic children with a reported use of inhaled corticosteroids (ICS). Methods: This cross‐sectional study involved 593 asthmatic children with a reported use of ICS, availability of FENO measurements and genotyping data on the FCER2 T2206C variant (rs28364072). An additive genetic model was assumed, and the asso‐ ciation between the FCER2 T2206C variant and the log‐transformed (ln) FENO levels was evaluated using linear regression analysis, adjusted for age, sex, adapted British Thoracic Society (BTS) treatment steps and atopy. Results: The mean age of the population was 9.1 ± 2.2 years, and the median of FENO levels was 13.0 ppb with an interquartile range (IQR) of (8.0‐27.5 ppb). The minor al‐ lele (G) frequency of rs28364072 was 29.6%, and each extra copy of the G allele was significantly associated with a lower level of the geometric mean of FENO (log scale, β = −0.12, 95% CI: −0.23, −0.02). Conclusion and Clinical Relevance: Our results showed that the FCER2 T2206C vari‐ ant was significantly associated with lower FENO levels in carriers of the G allele. Nevertheless, this SNP contributed little to the variability in FENO levels in this pa‐ tient population. Our findings contribute to the present knowledge on FENO in asth‐ matic children; however, future replication studies are required to establish the role of this gene in relation to FENO

Pharmacogenomic testing in paediatrics: Clinical implementation strategies

Pharmacogenomics (PGx) relates to the study of genetic factors determining variability in drug response. Implementing PGx testing in paediatric patients can enhance drug safety, helping to improve drug efficacy or reduce the risk of toxicity. Despite its clinical relevance, the implementation of PGx testing in paediatric practice to date has been variable and limited. As with most paediatric pharmacological studies, there are well-recognised barriers to obtaining high-quality PGx evidence, particularly when patient numbers may be small, and off-label or unlicensed prescribing remains widespread. Furthermore, trials enrolling small numbers of children can rarely, in isolation, provide sufficient PGx evidence to change clinical practice, so extrapolation from larger PGx studies in adult patients, where scientifically sound, is essential. This review paper discusses the relevance of PGx to paediatrics and considers implementation strategies from a child health perspective. Examples are provided from Canada, the Netherlands and the UK, with consideration of the different healthcare systems and their distinct approaches to implementation, followed by future recommendations based on these cumulative experiences. Improving the evidence base demonstrating the clinical utility and cost-effectiveness of paediatric PGx testing will be critical to drive implementation forwards. International, interdisciplinary collaborations will enhance paediatric data collation, interpretation and evidence curation, while also supporting dedicated paediatric PGx educational initiatives. PGx consortia and paediatric clinical research networks will continue to play a central role in the streamlined development of effective PGx implementation strategies to help optimise paediatric pharmacotherapy