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

Antibiotic use in children and the use of medicines by parents

Objective Antibiotic drugs are frequently used for viral infections in children. It is probable that health beliefs and parental concern have great influence on the use of drugs in children. This study, performed in The Netherlands, investigates whether the use of antibiotics in children is associated with the use of medicines by parents. Patients and methods In this observational cohort study, the authors selected 6731 children from the prescription database IADB.nl who did not receive antibiotics until their fifth birthday and 1479 children who received at least one antibiotic prescription every year. The authors then selected parents for each group of children (5790 mothers and 4250 fathers for the children who did not receive antibiotics and 1234 mothers and 1032 fathers for the children who regularly received antibiotics). The authors compared the use of antibiotics and other medicines between the two groups of parents. Results Parents of children who received antibiotics recurrently were found to use more antibiotics themselves compared with parents of children who did not receive antibiotics. Moreover, this group also showed a higher percentage of chronic medication use: (11.3 vs 6.2% (mothers) and 13.1% vs 9.5% (fathers)). Mothers more often use antacids, non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, anxiolytics, hypnotics, antidepressants, drugs for treatment of asthma and antihistamines. Fathers use more antacids, cardiovascular drugs, NSAIDs and asthma drugs. Conclusions The parents of children who receive antibiotic drugs regularly use more medicines compared with the parents of children who use no antibiotic drugs. Parents' medicine use may influence that of children and is a factor physicians and pharmacists should take into account

Use of antibiotics in rural and urban regions in the Netherlands:an observational drug utilization study

Background: Large livestock farms might increase the infection risk for the nearby human population because of an increased risk for disease outbreaks and because antibiotic-resistant bacteria are more likely to be present. We hypothesized that populations residing in rural areas have more contact with cattle compared with populations in urban areas, and will use more antibiotics or more frequently require a new course of antibiotics. Methods: Using data from the prescription database IADB.nl, we compared antibiotic use by patients living in rural areas to the use by patients living in urban areas. We also followed cohorts of antibiotic users and determined the patients who required a second antibiotic within 14 days after beginning the first antibiotic. Results: The yearly prevalence of antibiotic use was greater in rural areas compared with urban areas (2009: 23.6% versus 20.2% (p <0.001), especially in the younger age groups. More adult patients residing in rural areas required a second course of antibiotic treatment within 14 days after starting the first treatment. Conclusion: Individuals use more antibiotics, and adults more frequently require a second antibiotic prescription within 14 days, in rural areas compared with urban areas. Although the differences were small and the risks for the general rural population were not high, this difference should be investigated further

Insulin analogues in pregnancy and specific congenital anomalies:a literature review

BACKGROUND: Insulin analogues are commonly used in pregnant women with diabetes. It is not known if the use of insulin analogues in pregnancy is associated with any higher risk of congenital anomalies in the offspring compared with use of human insulin.METHODS: We performed a literature search for studies of pregnant women with pregestational diabetes using insulin analogues in the first trimester and information on congenital anomalies. The studies were analyzed to compare the congenital anomaly rate among fetuses of mothers using insulin analogues with fetuses of mothers using human insulin.RESULTS: Of 29 studies we included 1286 fetuses of mothers using short-acting insulin analogues with 1089 references of mothers using human insulin and 768 fetuses of mothers using long-acting insulin analogues with 685 references of mothers using long-acting human insulin (Neutral Protamine Hagedorn; NPH). The congenital anomaly rate was 4.84% and 4.29% among the fetuses of mothers using lispro and aspart. For glargine and detemir the congenital anomaly rate was 2.86% and 3.47% respectively. No studies on the use of insulin glulisine and degludec in pregnancy were found. There was no statistically significant difference in the congenital anomaly rate among fetuses exposed to insulin analogues (lispro, aspart, glargine or detemir) compared to those exposed to human insulin or NPH insulin.CONCLUSION: The total prevalence of congenital anomalies was not increased for fetuses exposed to insulin analogues. The small samples in the included studies provided insufficient statistical power to identify a moderate increased risk of specific congenital anomalies. This article is protected by copyright. All rights reserved.</p

Antibiotics and oral contraceptive failure - a case-crossover study

Background: Evidence on the association between antibiotic use and combined oral contraceptive (COC) failure is controversial. We examined the effect of concomitant antibiotic treatment on the risk of breakthrough pregnancy among COC users. Study Designs: We performed a case-crossover study of 1330 COC failure cases among 17,721 women from the Slone Epidemiology Center Birth Defects Study (1997-2008) and among 25,941 women from the National Birth Defects Prevention Study (NBDPS, 1997-2005). Self-matched odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by comparing antibiotic use between the 4 weeks before conception ("case period") and the 4-8 weeks before conception ("control period") using conditional logistic regression. A case time-control analysis was conducted using nonusers of COCs with unplanned pregnancies as controls. Results: For the combined data, the self-matched OR was 1.08 (95% CI: 0.63-1.84) and the case time-control OR was 1.12 (0.63-1.98) for antibiotics overall. The results did not appreciably differ when adjusted for characteristics that might vary between the case and control period. However, among COC failure cases from the NBDPS, allowing a 1-month gap between the case and control period resulted in a self-matched OR of 1.45 (0.85-2.50) and a case time-control OR of 1.55 (0.86-2.79) for antibiotics overall. Conclusions: We did not find an association between concomitant antibiotic use and the risk of breakthrough pregnancy among COC users. However, due to limited power and potential carryover effects, findings from this study cannot rule out an elevated risk of COC failure among antibiotic users. (C) 2011 Elsevier Inc. All rights reserved

Inclusion of the birth cohort dimension improved description and explanation of trends in statin use

Objective: Including the birth cohort dimension improves trend studies of mortality and health. We investigated the effect of including the birth cohort dimension in trend studies of prescription drug use by studying prevalence of statin use among adults. Study Design and Setting: Data from a drug prescription database in the Netherlands (IADB.nl) were used to obtain the number of users of statin per 1,000 population (prevalence) in the age range 18-85 years from 1994 to 2008. We applied descriptive graphs and standard age-period-cohort (APC) models. Results: From 1994 to 2008, the prevalence increased from similar to 10 to similar to 90 users per 1,000 population, with the peak in prevalence shifting from age 63 to 78 years. The APC model shows patterns that were masked in the age-period (AP) model. The prevalence rate ratio increased from the 1911 birth cohort to the 1930 birth cohort and then declined. Similar for both sexes, adding nonlinear period effects contributed similar to 4.4% to reductions in deviance, whereas adding nonlinear birth cohort effects contributed similar to 12.9%. Conclusion: Adding the birth cohort dimension to AP analysis is valuable for academic and professional practice as trends can be more accurately described and explained and it can help improve projections of future trends. (c) 2012 Elsevier Inc. All rights reserved

Ten years after the Dutch public health campaign on folic acid: the continuing challenge

BACKGROUND: Folic acid use in the periconceptional period reduces the risk of neural tube defects (NTDs). However, applying this knowledge in daily practice is not an easy task. We report here the current level of folic acid use in the Netherlands and discuss the figures within the framework of a national governmental campaign held in 1995 promoting the use of folic acid and the professional interventions undertaken since then. METHODS: We carried out six studies in the northern Netherlands during 1995, 1996, 1998, 2000, 2003 and 2005, respectively. The same methodology in the same health professionals' practices was followed in all studies. Pregnant women attending their first or second antenatal visit were asked to fill in a questionnaire aimed at assessing their awareness and use of folic acid. RESULTS: In 2005, most of the pregnant women used folic acid "at some time in their pregnancy", and 51% used it for the entire advised period. Prior knowledge on the protective affect of folic acid and on the period of use was strongly related to the level of education. The use of folic acid in a previous pregnancy [odds ratio (OR) 3.9, 95% confidence interval (95% CI) 1.6-9.9], the use of an oral contraceptive (OR 2.1, 95% CI 1.1-4.1) and parity (OR 0.08, 95% CI 0.01-0.5) significantly predicted the current correct use. The most recent figures revealed that there is still a large gap between more highly and less educated women in terms of taking folic acid in the advised period: 63 versus 31%, respectively. DISCUSSION: The aim of the Dutch Ministry of Health is to have 70% of Dutch women wanting to become pregnant use folic acid supplements in the advised period by 2010. While this level has almost been reached among more highly educated women (63%), it will take a great deal more effort, money and creativity to achieve the necessary increase from the current level of 31% among women with a lower educational background

Screen-and-Treat Strategies for Albuminuria to Prevent Cardiovascular and Renal Disease:Cost-Effectiveness of Nationwide and Targeted Interventions Based on Analysis of Cohort Data From the Netherlands

Background: Albuminuria is a marker for renal and cardiovascular (CV) risk, allowing early diagnosis of subjects with elevated renal and CV risk. Objective: This study aimed to estimate the cost-effectiveness and budget impact of various population-based screen-and-treat scenarios for elevated albuminuria levels (ie, microalbuminuria) in the Netherlands. Methods: A multistate transition Markov model was developed to simulate the natural course of albuminuria-based disease progression to dialysis and occurrence of CV events. Several population-based strategies directed at screening for elevated albuminuria were evaluated. These strategies depended on urinary albumin concentration (UAC), urinary albumin excretion (UAE), and age. Transition probabilities were derived from the observational community-based Prevention of Renal and Vascular End Stage Disease (PREVEND) cohort study. Health care costs (in year-2008 euros) and life-years gained were calculated over an 8-year period. In the base-case analysis, we analyzed screening for and treatment of microalbuminuria. Screening for microalbuminuria involved prescreening for UAC >= 20 mg/L, followed by a confirmation test for UAE >= 30 mg/d. Other options based on combinations of albuminuria for UAC prescreening (no prescreening, and >= 10, >= 20, >= 100, and >= 200 mg/L) and UAE confirmation test (>= 15, >= 30, and 300 mg/d) for treatment were investigated in scenario analyses. Furthermore, these various strategies based on UAC and UAE values were analyzed in different subgroups based on age (all ages, aged >= 50 years, and aged >= 60 years). Results: The PREVEND study included 8592 Dutch residents aged 28 to 75 years at the time of initial screening. Among a hypothetical cohort of 1000 subjects identified and treated in the base-case analysis, it was estimated (based on PREVEND follow-up data) that, in the screening/treatment and no-screening scenarios, 76 versus 124 CV events occurred, 16 versus 27 CV deaths, and 3 versus 5 dialysis cases, respectively. The per-person difference in net costs for screening was calculated at (sic)926 ((sic)2003 vs (sic)1077), and prevention of CV deaths was estimated to gain 0.0421 discounted life-year per person. Correspondingly, the cost-effectiveness was estimated at (sic)22,000 per life-year gained. In the base-case analysis, probabilistic sensitivity analysis indicated that the likelihood of cost-effectiveness of a screen-and-treat strategy was 54%, 90%, and 95% for a maximum acceptable cost-effectiveness threshold of (sic)20,000, (sic)50,000, and (sic)80,000 per life-year gained, respectively. Higher albuminuria thresholds for screening and start of treatment further improved the cost-effectiveness but reduced the overall health gains achieved. Limiting screening to those subjects aged >= 50 and >= 60 years resulted in more favorable cost-effectiveness compared with population-based screening without age restriction. Conclusions: Our analyses suggest the potentially favorable cost-effectiveness of population-based screen

Pharmacological aspects of neonatal antidepressant withdrawal

Depression is common in reproductive age women, and continued pharmacologic treatment of depression during pregnancy may be necessary to prevent relapse, which could be harmful for both the fetus and the mother. Although data on drug safety are imperfect and incomplete, the benefits of antidepressant therapy during pregnancy generally outweigh the risks. Neonates who are exposed to antidepressant medications during gestation are at increased risk to have neonatal withdrawal syndrome, although the exact incidence of this complication is unknown because the definition of the syndrome is not clear and withdrawal reactions are probably underreported. Tricyclic antidepressant withdrawal syndrome is most likely related to muscarinergic activity and individual drug half-lives, and selective serotonin reuptake inhibitor withdrawal may be due to a decrease in available synaptic serotonin in the face of down-regulated serotonin receptors, the secondary effects of other neurotransmitters, and biological or cognitive sensitivity. Other factors that influence neonatal toxicity or withdrawal include the normal physiologic changes of pregnancy, the altered activity of CYP450 enzymes during pregnancy, drug-drug transporter (PgP and OCT3) interaction, and the presence of genetic polymorphisms in genes influencing drug metabolism. Further research is necessary