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)

Terrace Review, May, 28, 1986

Thrombosis and Hemostasi

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

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

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

Early life antibiotic exposure is associated with an increased risk of atopic eczema and hay fever

Background: Several studies suggested that early life exposure to antibiotics is associated with an increased risk of developing allergies later in life, but results are inconsistent. In this study we aimed to systematically review and quantify the relationship between early life exposure to antibiotics and the risk of atopic eczema (dermatitis) or hay fever (allergic rhinitis). Method: PubMed and Web of Science databases were searched for observational studies published from January 1966 through November 11, 2015. Studies were included that assessed the association between antibiotic consumption during the first 2 years of life and the risk of eczema or hay fever later in life. Separate metaanalyses were performed to assess the risk estimates for cohort studies, cross sectional studies and case control studies. Furthermore, in subgroup analyses the effect of child's age at the time of antibiotic use/diagnosis of allergies, and the number of courses of antibiotic treatments have been analyzed. Overall pooled estimates of the odds ratios (ORs) were obtained using fixed or random-effects models. Results: Twenty-two studies (including 394 517 patients) were selected to study the risk of eczema and 23 studies (including 256 609 patients) to study the risk of hay fever. In all separate meta-analyses of the distinct study designs, those who were exposed to antibiotics early in life were found to have a statistically significantly increased risk of eczema and hay fever. The summary OR for risk of eczema were 1.24 (95% CI, 1.09-1.41; I2: 60.0%) in the meta-analyses of the cohort studies (n = 50 824); 1.41 (95% CI, 1.33-1.49; I2: 0.0%) in the cross sectional studies (n = 217 752), and 1.15 (95% CI, 1.01- 1.42; I2: 79.5%) in the case control studies (n = 125 941). The summary OR for risk of hay fever were 1.18 (95% CI, 1.01-1.37; I2: 74.3%) in the cohort studies (n = 46 540); 1.56 (95% CI, 1.29-1.90; I2: 63.6%) in cross sectional studies (n = 27 608), and 1.14 (95% CI, 1.04-1.26; I2: 64.8%) in the case control studies (n = 182 461). In subgroup analyses, there was no statistically significant effect of the child's age at time of antibiotic use as well as the time of allergy diagnosis on these associations. The association was stronger if patients had been treated with ≥2 courses compared with one course of antibiotics both for eczema and for hay fever. Conclusion: Early life exposure to antibiotics is related to an increased risk of both atopic eczema and hay fever later in life

Phenotype standardization for statin-induced myotoxicity

Statins are widely used lipid-lowering drugs that are effective in reducing cardiovascular disease risk. Although they are generally well tolerated, they can cause muscle toxicity, which can lead to severe rhabdomyolysis. Research in this area has been hampered to some extent by the lack of standardized nomenclature and phenotypic definitions. We have used numerical and descriptive classifications and developed an algorithm to define statin-related myotoxicity phenotypes, including myalgia, myopathy, rhabdomyolysis, and necrotizing autoimmune myopathy.</p

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