Antibiotic drug use of children in the Netherlands from 1999 till 2005

Objective Antibiotics are the most commonly prescribed drugs used by children. Excessive and irrational use of antibiotic drugs is a world-wide concern. We performed a drug utilization study describing the patterns of antibiotic use in children aged 0-19 years between 1999 and 2005 in the Netherlands. Methods We used IADB.nl, a database with pharmacy drug dispensing data covering a population of 500,000 people and investigated all prescriptions of oral antibiotic drugs (ATC J01) for children Results The total number of antibiotic prescriptions per 1000 children per year ranged from 282 in 2004 to 307 in 2001 and did not change between years during the study period in a clinically relevant way. The prevalence of receiving at least one prescription varied between 17.8% in 2004 and 19.3% in 2001. Amoxicillin was the most frequently prescribed drug (46.4% of all antibiotic prescriptions in 1999 and 43.2% in 2005). Between 1999 and 2005 there was a shift from the small-spectrum phenethicillin, a penicillin preparation [ratio 2005/1999 0.76; 95% confidence interval (CI) 0.72-0.81], to amoxicillin/clavulanic acid (ratio 2005/1999 1.70; 95% CI 1.61-1.79) and from the old macrolide erythromycin (ratio 2005/1999 0.35; 95% CI 0.32-0.39) to the new macrolide antibiotic azithromycin (ratio 2005/1999 1.78; 95% CI 1.65-1.92). Conclusion The use of antibiotic drugs in treating children in the Netherlands is comparable to that in other northern European countries. Broad-spectrum antibiotics were prescribed more frequently than recommended by the guidelines and increased during our study period. Initiatives to improve guideline-directed antibiotic prescribing are strongly recommended

Willingness to participate in a lifestyle intervention program of patients with type 2 diabetes mellitus: a conjoint analysis

Background: Several studies suggest that lifestyle interventions can be effective for people with, or at risk for, diabetes. The participation in lifestyle interventions is generally low. Financial incentives may encourage participation in lifestyle intervention programs. Objetive: The main aim of this exploratory analysis is to study empirically potential effects of financial incentives on diabetes patients' willingness to participate in lifestyle interventions. One financial incentive is negative ("copayment") and the other incentive is positive ("bonus"). The key part of this research is to contrast both incentives. The second aim is to investigate the factors that influence participation in a lifestyle intervention program. Methods: Conjoint analysis techniques were used to empirically identify factors that influence willingness to participate in a lifestyle intervention. For this purpose diabetic patients received a questionnaire with descriptions of various forms of hypothetical lifestyle interventions. They were asked if they would be willing to participate in these hypothetical programs. Results: In total, 174 observations were rated by 46 respondents. Analysis showed that money was an important factor independently associated with respondents' willingness to participate. Receiving a bonus seemed to be associated with a higher willingness to participate, but having to pay was negatively associated with participation in the lifestyle intervention. Conclusion: Conjoint analysis results suggest that financial considerations may influence willingness to participate in lifestyle intervention programs. Financial disincentives in the form of copayments might discourage participation. Although the positive impact of bonuses is smaller than the negative impact of copayments, bonuses could still be used to encourage willingness to participate

The polypill in the primary prevention of cardiovascular disease: cost-effectiveness in the Dutch population

OBJECTIVES: The aim of the present study was to estimate the cost-effectiveness of the polypill in the primary prevention of cardiovascular disease. DESIGN: A health economic modeling study. SETTING: Primary health care in the Netherlands. PARTICIPANTS: Simulated individuals from the general Dutch population, aged 45-75 years of age. INTERVENTIONS: Opportunistic screening followed by prescription of the polypill to eligible individuals. Eligibility was defined as having a minimum 10-year risk of cardiovascular death as assessed with the SCORE function of alternatively 5%, 7.5%, or 10%. Different versions of the polypill were considered, depending on composition: 1) the Indian polycap, with three different types of blood pressure lowering drugs, a statin, and aspirin; 2) as 1) but without aspirin; 3) as 2) but with a double statin dose. In addition, a scenario of (targeted) separate antihypertensive and/or statin medication was simulated. PRIMARY OUTCOME MEASURES: Cases of acute myocardial infarction or stroke prevented, QALYs gained, and the costs per QALY gained. All interventions were compared with usual care. RESULTS: All scenarios were cost-effective with an incremental cost-effectiveness ratio between €7,900-12,300 per QALY compared with usual care. Most health gains were achieved with the polypill without aspirin and containing a double dose of statins. With a 10-year risk of 7.5% as threshold, this pill would prevent approximately 3.5% of all cardiovascular events. CONCLUSIONS: Opportunistic screening based on global cardiovascular risk assessment followed by polypill prescription to those with increased risk offers a cost-effective strategy. Most health gain is achieved by the polypill without aspirin and a double statin dose

Female Sex and IL28B, a Synergism for Spontaneous Viral Clearance in Hepatitis C Virus (HCV) Seroconverters from a Community-Based Cohort

BACKGROUND & AIMS: Since acute hepatitis C virus (HCV) infection is often asymptomatic, it is difficult to examine the rate and determinants of spontaneous clearance. Consequently, these studies are subject to bias, which can potentially lead to biased rates of viral clearance and risk estimates. We evaluated determinants of spontaneous HCV clearance among HCV seroconverters identified in a unique community-based cohort. METHODS: Subjects were 106 drug users with documented dates of HCV seroconversion from the Amsterdam Cohort Study. Logistic regression was used to examine sociodemographic, behavioral, clinical, viral and host determinants, measured around acute infection, of HCV clearance. RESULTS: The spontaneous viral clearance rate was 33.0% (95% confidence interval (CI) 24.2-42.8). In univariate analyses female sex and fever were significantly associated with spontaneous clearance. The favorable genotypes for rs12979860 (CC) and rs8099917 (TT) were associated with spontaneous clearance, although borderline significant. In multivariate analysis, females with the favorable genotype for rs12979860 (CC) had an increased odds to spontaneously clear HCV infection (adjusted OR 6.62, 95% 2.69-26.13), whereas females with the unfavorable genotype were as likely as men with the favorable and unfavorable genotype to clear HCV. Chronic Hepatitis B infection and absence of HIV coinfection around HCV seroconversion also favor HCV clearance. CONCLUSIONS: This study shows that co-infection with HIV and HBV and genetic variation in the IL28B region play an important role in spontaneous clearance of HCV. Our findings suggest a possible synergistic interaction between female sex and IL28B in spontaneous clearance of HCV

Characterization of the neural stem cell gene regulatory network identifies OLIG2 as a multifunctional regulator of self-renewal

The gene regulatory network (GRN) that supports neural stem cell (NS cell) self-renewal has so far been poorly characterized. Knowledge of the central transcription factors (TFs), the noncoding gene regulatory regions that they bind to, and the genes whose expression they modulate will be crucial in unlocking the full therapeutic potential of these cells. Here, we use DNase-seq in combination with analysis of histone modifications to identify multiple classes of epigenetically and functionally distinct cis-regulatory elements (CREs). Through motif analysis and ChIP-seq, we identify several of the crucial TF regulators of NS cells. At the core of the network are TFs of the basic helix-loop-helix (bHLH), nuclear factor I (NFI), SOX, and FOX families, with CREs often densely bound by several of these different TFs. We use machine learning to highlight several crucial regulatory features of the network that underpin NS cell self-renewal and multipotency. We validate our predictions by functional analysis of the bHLH TF OLIG2. This TF makes an important contribution to NS cell self-renewal by concurrently activating pro-proliferation genes and preventing the untimely activation of genes promoting neuronal differentiation and stem cell quiescence.Welcome Trust grants: (WT095908, WT098051), FEBS Long-Term Fellowship, Medical Research Council Grant-in-Aid (U117570528)

Observer variability of absolute and relative thrombus density measurements in patients with acute ischemic stroke

Introduction: Thrombus density may be a predictor for acute ischemic stroke treatment success. However, only limited data on observer variability for thrombus density measurements exist. This study assesses the variability and bias of four common thrombus density measurement methods by expert and non-expert observers. Methods: For 132 consecutive patients with acute ischemic stroke, three experts and two trained observers determined thrombus density by placing three standardized regions of interest (ROIs) in the thrombus and corresponding contralateral arterial segment. Subsequently, absolute and relative thrombus densities were determined using either one or three ROIs. Intraclass correlation coefficient (ICC) was determined, and Bland–Altman analysis was performed to evaluate interobserver and intermethod agreement. Accuracy of the trained observer was evaluated with a reference expert observer using the same statistical analysis. Results: The highest interobserver agreement was obtained for absolute thrombus measurements using three ROIs (ICCs ranging from 0.54 to 0.91). In general, interobserver agreement was lower for relative measurements, and for using one instead of three ROIs. Interobserver agreement of trained non-experts and experts was similar. Accuracy of the trained observer measurements was comparable to the expert interobserver agreement and was better for absolute measurements and with three ROIs. The agreement between the one ROI and three ROI methods was good. Conclusion: Absolute thrombus density measurement has superior interobserver agreement compared to relative density measurement. Interobserver variation is smaller when multiple ROIs are used. Trained non-expert observers can accurately and reproducibly assess absolute thrombus densities using three ROIs