AdDIT Editorial comment—challenges in medication treatment of renal and cardiovascular diseases and risk factors in adolescents with type 1 diabetes

A large body of evidence revealed that compared with children and adolescents in the general population, those with type 1 diabetes mellitus (T1DM) are at excessive risk of diabetes related complications (1,2). Presence and long-term diabetes complications are known to increase cardiovascular (CV) morbidity and mortality in population with T1DM in which 26.1% of all deaths are associated with diabetes complications (3)

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

The children anticoagulation and pharmacogenetics study (CAPS): Developing a dosing algorithm for acencocoumarol in paediatric patients

Background: Dosing of vitamin K antagonists (VKA) in paediatric patients is complex. The large variability in VKA dose requirement asks for elucidating the factors associated with this variability and taking these into account when defining the dose for a patient. For warfarin, paediatric dosing algorithms have been developed, but not for acenocoumarol. Objectives: To develop a dosing algorithm for acenocoumarol in pediatric patients with and without genetic information. Methods: This multicentre retrospective follow-up study was carried out in Dutch anticoagulation clinics and children's hospitals. Patients were selected when they used acenocoumarol for >1 month between January 1995 and December 2014 and were ≤18 years of age. The primary outcome was the mean daily dose during a stable period. A stable period was defined as ≥3 consecutive international normalized ratio measurements within therapeutic range over a period of ≥3 weeks. Clinical information (including height, weight and indication) and saliva samples for genotyping of CYP2C9 (∗2 and ∗3), VKORC1, CYP4F2, CYP2C18 and CYP3A4 (∗1B and ∗22) were collected. Linear regression was used to analyse their association with the log mean stable dose. Results: In total, 175 patients were included of whom 86 patients had a stable period and no missing clinical information (clinical algorithm cohort) and of 80 also genetic information was available (genetic algorithm cohort). The mean age at the stable period was 9 years. The most common indications were Fontan circulation, prosthetic heart valve, deep venous thrombosis and dilated cardiomyopathy. The clinical algorithm, containing body surface area and indication, explained 45.0% of the variability in dose requirement of acenocoumarol. By adding the genotypes of VKORC1, CYP2C18, and CYP2C9∗2/∗3, 61.8% of the variability was explained (genetic algorithm). Conclusions: Clinical factors had the largest impact on the required dose of acenocoumarol in pediatric patients. Including genetic factors in the algorithm, and especially VKORC1, increased this with 16.8%

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

Clinical and economic consequences of pharmacogenetic-guided dosing of warfarin

Patients using warfarin for oral anticoagulant therapy need to be frequently monitored because of warfarins narrow therapeutic range and the large variation in dose requirements among patients. Patients receiving the wrong dose have an increased risk of bleeding or thromboembolic events. The required dose is influenced by environmental factors, such as gender, age, diet and concomitant medication, as well as genetic factors. Pharmacogenetic testing prior to warfarin initiation might improve dosing accuracy and, therefore, safety and efficacy of warfarin treatment. Meckley et al. studied the clinical consequences and costs of genotyping before warfarin treatment. The results of their study suggest that pharmacogenetic-guided dosing of patients initiating warfarin could improve health (quality-adjusted life-years) but at a high cost per quality-adjusted life-year gained. Owing to the inevitable assumptions that have to be made in all cost-effectiveness models, great uncertainty remains regarding the cost-effectiveness of pharmacogenetic-guided warfarin dosing

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

Incidence of bleeding and thrombotic events in non-institutionalized paediatric patients using warfarin in the united kingdom

Background: Dosing of vitamin K antagonists (VKA) is complex with large inter- and intra-individual variability in patients' required VKA dose. Over- and underdosing can result in bleeding and thrombotic events. The incidence of these events in paediatric patients on warfarin therapy in a European population is unknown. Objectives: To estimate the incidence of bleeding and thrombotic events in warfarin using paediatric patients in the UK and to characterise patients who do or do not experience a bleeding or thrombotic event. Methods: Data were obtained from the UK CPRD in the period between January 1998 and November 2016. Using a cohort design, we identified all patients with ≥1 prescription for warfarin and who were ≤18 years. The date of the first prescription marked the start of the follow-up. Follow-up was classified into periods of warfarin use and non-use. Patients were followed until 19 years of age, death or departure from the practice. The incidence of non-fatal bleeding and thrombotic events was assessed using both information from CPRD and the linked Hospital Episode Statistics (HES). Fatal events were identified usings the linked mortality data from the Office for National Statistics (ONS). For calculating the incidence of thrombotic events only patients without a history of thrombosis were included. Results: In total, 685 patients were identified (median age 15 years, 45.4% female) of whom 372 could be linked to the HES and ONS databases. The incidence of bleeding and thrombotic events during warfarin use was 4.08 and 1.27/100 patient years, respectively. The incidence of bleeding events during non-use was 2.65/100 patient years (relative risk 1.58, 95% confidence interval [0.89-2.80]). Only 2 fatal events occurred, one bleeding and one thrombotic event. Patients with a bleeding event tended to have a higher percentage of INR measurements with a value above 4 (9.4 vs 3.9%) and a lower fraction below 2 (18.4 vs 39.1%) compared to patients without a bleeding event during the whole follow-up. Patients with a thrombotic event showed the opposite trend, a higher percentage of INRs below 2 (45.8 vs 29.5%) and a lower percentage of INRs above 4 (2.7 vs 5.3%). All differences were not statistically significant which maybe due to the small sample size. Conclusions: The incidence of bleeding events was higher than of thrombotic events. The trends in percentages of INRs under and above therapeutic range suggest that keeping the INR within range could decrease the occurence of these events

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