Jens Bos

The population-based prescription database IADB.nl: its development, usefulness in outcomes research and challenges

Research databases with large numbers of prescriptions in observational settings can provide valuable information in addition to the initial randomized controlled trials. This paper reports on the development of prescription database IADB, formerly known as InterAction Database. IADB contains prescriptions from 54 community pharmacies in The Netherlands and covers a population of 500,000 people. Both the age distribution and the prevalence of drugs used are comparable to a large extent with the Dutch population. The representativeness of the population covered is examined by comparing population composition and drug use with data of the whole Dutch population. Enriching IADB with, among others, clinical parameters by linking to other databases is explored. A strong and unique aspect of IADB is the possibility to track patients over time, even when they receive their medication from different pharmacies. The authors conclude IADB is a useful tool for pharmacoepidemiological and pharmacoeconomic outcomes research.

Healthcare databases in Europe for studying medicine use and safety during pregnancy

The aim of this study was to describe a number of electronic healthcare databases in Europe in terms of the population covered, the source of the data captured and the availability of data on key variables required for evaluating medicine use and medicine safety during pregnancy.

Prenatal exposure to acid-suppressive drugs and the risk of allergic diseases in the offspring: a cohort study

Recent studies reported increased risks for the development of asthma in children after prenatal exposure to acid‐suppressive drugs. As a result of common pathogenesis, associations could also be present for other allergic diseases.

Using spatial analysis to predict health care use at the local level: a case study of type 2 diabetes medication use and its association with demographic change and socioeconomic status.

Local health status and health care use may be negatively influenced by low local socio-economic profile, population decline and population ageing. To support the need for targeted local health care, we explored spatial patterns of type 2 diabetes mellitus (T2DM) drug use at local level and determined its association with local demographic, socio-economic and access to care variables. We assessed spatial variability in these associations. We estimated the five-year prevalence of T2DM drug use (2005–2009) in persons aged 45 years and older at four-digit postal code level using the University of Groningen pharmacy database IADB.nl. Statistics Netherlands supplied data on potential predictor variables. We assessed spatial clustering, correlations and estimated a multiple linear regression model and a geographically weighted regression (GWR) model. Prevalence of T2DM medicine use ranged from 2.0% to 25.4%. The regression model included the extent of population ageing, proportion of social welfare/benefits, proportion of low incomes and proportion of pensioners, all significant positive predictors of local T2DM drug use. The GWR model demonstrated considerable spatial variability in the association between T2DM drug use and above predictors and was more accurate. The findings demonstrate the added value of spatial analysis in predicting health care use at local level.

Antiepileptic drug prescribing before, during and after pregnancy: a study in seven European regions

The aim of this study was to explore antiepileptic drug (AED) prescribing before, during and after pregnancy as recorded in seven population‐based electronic healthcare databases.

Co-prescription of antiepileptic drugs and contraceptives

BACKGROUND Enzyme-inducing antiepileptic drugs (AEDs) reduce the efficacy of oral contraceptives. Little is known of contraceptive practice among reproductive-age women who receive AEDs. STUDY DESIGN We explored the use of contraceptive methods among Dutch women aged 15 to 49 years with prescriptions of AEDs using pharmacy dispensing database. Drug dispensing data of AEDs and contraceptives in 2006 was retrieved from the InterAction Database (IADB.nl database). The prevalence of contraceptives use and distribution of different contraceptive methods were calculated. RESULTS Of women who used enzyme-inducing AEDs in combination with any highly effective contraceptive method, over 40% were on an oral contraceptive (OC) containing <50 mcg estrogen. IUDs and injectable contraception were used in 22.5% of women receiving AEDs in combination with any highly effective contraceptive method, and 33.2% in those receiving enzyme-inducing AEDs in combination with any highly effective contraceptive method. CONCLUSION Fertile-age women who received AEDs often relied on less effective contraceptive methods. Prescribers should be more aware of the interaction between AEDs and OCs.

Drugs associated with teratogenic mechanisms. Part I: dispensing rates among pregnant women in the Netherlands, 1998–2009

STUDY QUESTION What are the dispensing rates of drugs suspected to be associated with teratogenic mechanisms among pregnant Dutch women? SUMMARY ANSWER In a substantial proportion of pregnancies in our study population at least one drug associated with a teratogenic mechanism was dispensed in the first trimester of pregnancy. WHAT IS KNOWN ALREADY The main teratogenic mechanisms of medical drugs that may affect fetal development in the first trimester of pregnancy have been described previously. However, information on the dispensing rate of such drugs among women at all stages of pregnancy is lacking. STUDY DESIGN, SIZE, DURATION To determine how often medications suspected to be associated with a teratogenic mechanism are used by pregnant women, we studied 32 016 pregnancies included in the IADB.nl database between 1998 and 2009. PARTICIPANTS/MATERIALS, SETTING, METHODS We estimated dispensing rates of medical drugs suspected to be associated with teratogenic mechanisms in our study population. The IADB.nl database includes all pharmacy dispensings for an estimated population of 220 000 in 1994-1998 and c.500 000 since 1999. In addition, trends in first trimester dispensing rates over time and patterns of receiving multiple drugs associated with teratogenic mechanisms were evaluated. In addition, we determined the number of pregnancies in which multiple prescription drugs from one or more teratogenic categories were dispensed in the first trimester, and we evaluated the numbers of different medications dispensed that could be grouped within a specific teratogenic mechanism. MAIN RESULTS AND THE ROLE OF CHANCE In 175 per 1000 pregnancies [95% confidence interval (CI), 171-179] at least one drug associated with a teratogenic mechanism was dispensed in the first trimester. The total dispensing rate was 236 per 1000 pregnancies (95% CI 232-241) in the 3 months before pregnancy and an increasing trend was seen in the second [214 per 1000 (95% CI 209-218)] and third [327 per 1000 (95% CI 322-332)] trimesters. The first trimester dispensing rates increased between 1998 and 2009 for selective serotonin-reuptake inhibitors (P < 0.001) and serotonin receptor agonists/antagonists (P < 0.001). In 71.8% of pregnancies in which drugs associated with teratogenic mechanisms were dispensed in the first trimester, women received drugs related to only one mechanism. Of the pregnancies in which drugs from multiple teratogenic categories were dispensed in the first trimester, 1148 (72.6%) women received drugs from 2 categories, 317 (20.0%) from three categories, 88 (5.6%) from 4 categories, 28 (1.8%) from 5 categories and 1 from 6 categories. Several women received multiple prescription medications grouped within a single teratogenic mechanism in the first trimester, ranging between 13.3% for cyclo-oxygenase inhibitors and 41.8% for serotonin receptor agonists/antagonists. LIMITATIONS, REASONS FOR CAUTION We used a dispensing database, therefore actual use of the medication prescribed is unknown and non-compliance could have led to overestimation of exposure prevalences. WIDER IMPLICATIONS OF THE FINDINGS Owing to the uncertainties concerning the safety of medication use during pregnancy, the results of this study stress the need for cautious prescription of medication associated with teratogenic mechanisms to women of reproductive age. This is further supported by our finding that women received multiple prescription medications grouped within a single teratogenic mechanism in the first trimester, which would theoretically increase strongly the risk of birth defects. STUDY FUNDING/COMPETING INTEREST(S) Marleen van Gelder was supported by the Netherlands Organisation for Scientific Research/NWO (grant no. 021.001.008). No competing interests are declared. TRIAL REGISTRATION NUMBER N/A.

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 ∼10 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 ∼4.4% to reductions in deviance, whereas adding nonlinear birth cohort effects contributed ∼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.

Assessing the effect of a guideline change on drug use prevalence by including the birth cohort dimension: the case of benzodiazepines.

The aim of this study was to investigate whether including the birth cohort dimension in time series analysis leads to a more accurate estimation of the (long‐term) effect of a guideline change on the trend of benzodiazepine use.

Are antibiotics related to oral combination contraceptive failures in the Netherlands? A case-crossover study

To investigate whether there is an association between use of antibiotics and breakthrough pregnancy.