Paul B. van den Berg

Use of Antipsychotic Drugs Among Dutch Youths Between 1997 and 2005

OBJECTIVE The authors examined prevalence, incidence, and duration of antipsychotic drug use in the northern and eastern regions of the Netherlands between 1997 and 2005 among youths in regard to age, gender, and class of drug. METHODS Prescription drug dispensing data were collected from community pharmacies in the northern Netherlands (www.iadb.nl). Prevalence, incidence, and duration of use were studied among roughly 100,000 youths ranging in age from infancy to age 19 years, calculated by age group (zero to four years, five to nine years, ten to 14 years, and 15 to 19 years), for boys and girls, and for first- and second-generation antipsychotics. Duration of use was compared between youths who started antipsychotic treatment in 1998-1999 and those who started in 2001-2002. RESULTS From 1997 to 2005, prevalence increased from 3.0 to 6.8 per thousand. Prevalence was highest among ten-year-olds to 14-year-olds (11 per thousand), especially among boys (17 per thousand). The increased prevalence was mainly attributable to an increased use of second-generation antipsychotics and to a longer duration of use. Median duration of use doubled from .8 year in 1998-1999 to 1.6 years in 2001-2002. CONCLUSIONS Second-generation antipsychotic drugs were increasingly prescribed, and for longer periods of time, to younger children, probably because of new indications. This practice increases the exposure of a young population to (partly unknown) risks.

The InterAction Database: Synergy of Science and Practive in Pharmacy

In social pharmacy and pharmacoepidemiology the distribution, use and performance of medication after registration is studied. In both fields, the pharmacists are the main source of data on drug use. To increase the value of research, we think it important to exchange ideas and suggestions between scientific researchers and pharmacists who work in community pharmacies. Hence, the department of Social Pharmacy and Pharmacoepidemiology of the University of Groningen sought close collaboration with some community pharmacies in the region, resulting in the InterAction project. The pharmacists deliver data to the InterAction database and are explicitly invited to raise questions and issues from their practice, and to participate in research. Consequently, science and practice benefit from each others input and expertise. This paper describes the architecture and contents of the InterAction project. Additionally, the first experiences with the database as a laboratory for social pharmacy and pharmacoepidemiology are discussed.

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 <or=19 years between 1999 and 2005. 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 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 <or=19 years between 1999 and 2005. 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 usage, dosage and course length in children between 0 and 4 years.

Aim:  Antibiotic drugs are most frequently used by 0‐ to 4‐year‐old children. We performed a cross‐sectional study in the Netherlands using a pharmacy prescription database to investigate the use, dose and course length of antibiotic drugs in 0‐ to 4‐year‐olds.

Predictors for starting depot administration of risperidone in chronic users of antipsychotics.

Background: Risperidone long-acting injectable (RLAI), the first second-generation depot antipsychotic, has extensively been studied before introduction. Thereafter, questions about the type of patients actually treated with RLAI in daily practice remain to be answered for making valid antipsychotic treatment comparisons involving RLAI in observational studies. Objective: We aimed to determine in chronic antipsychotic users who switched treatment, predictors for the prescription of (1) depot versus oral antipsychotics and (2) RLAI versus first-generation antipsychotics (FGAs) depot. Methods: We used pharmacy dispensing data from 53 community pharmacies in the northeast of the Netherlands containing approximately 500,000 persons. Chronic antipsychotic users were defined and followed up for a switch in antipsychotic treatment within the first period that RLAI was on the market. Multivariable analysis was performed to relate patient, prescriber, and medication characteristics to prescription of a new antipsychotic drug. Results: Predictors for switching to depot versus oral antipsychotics were male sex, previous use of depot antipsychotics, recent anticholinergic drug use, and a gap in antipsychotic dispensation history. Predictors for switching to RLAI versus FGA depot were previous use of depot and consulting a specialist. Conclusions: The results suggest that, compared with oral antipsychotics, patients receiving a depot are less compliant users, with more extrapyramidal side effects. Compared with FGA depot, patients receiving RLAI tend to be more severely ill patients. We conclude that RLAI may be partly channeled to patients as a last resort, which may have important consequences for the interpretation of observational effectiveness comparisons between RLAI and other antipsychotics in daily practice.

Computer-assisted medication review for asthmatic patients as a basis for intervention Constructing and validating an algorithmic computer instrument in pharmacy practice

Objective: To construct and validate a computer instrument that identifies asthma patients receiving – theoretically – suboptimal drug therapy in community pharmacies, by the use of patient medication records. This selection enables the pharmacist to assist these patients in using medicines appropriately.Methods: According to Dutch asthma guidelines which describe a stepwise approach and in order to define correct profiles for the use at each level of these guidelines, the optimum use of drugs in the different levels in asthma treatment was expressed in defined daily doses (DDDs) per pharmacological drug-group during a period of one year. An algorithmic computer instrument was developed to select patients with medication use deviant from these profiles. By using nine different selection profiles, the computer instrument stratified patients according to the medication records filed in the pharmacy computer. Patient medication records in four community pharmacies were investigated to validate the selection profiles as indicators for theoretically suboptimal drug use by asthma patients. The validation was performed by comparing the professional judgement of participating pharmacists with the selections made by the computer.Main outcome measure: Positive predictive value and negative predictive value of the selection made by algorithmic computer instrument. Rate of false-positive results.Results: The computer instrument identified asthma patients using theoretically suboptimal drug therapy with approximately 95% predictive value compared with the professional judgement of the pharmacists. The rate of false-positive results was 5%.Conclusion: The results of the algorithmic computer instrument and the professional judgement of the pharmacists are in close agreement. The instrument will be utilised in further research in the IPMP study (Interventions on the principle of Pulmonary Medication Profiles) investigating the role of Dutch community pharmacists in counselling patients who are at risk of suboptimal drug use in the treatment of their asthma.

Prescribing of NSAIDs and ASA during pregnancy; do we need to be more careful?

In 2005, a warning based on epidemiological studies describing associations between nonsteroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid (ASA) use in early pregnancy and risks of miscarriages, cardiac malformations and gastroschisis [1], was given by European registration authorities (e.g. the Dutch). NSAIDs and ASA should not be used during the first trimesters of pregnancy except when this is strictly indicated. We describe to what extent NSAIDs and ASA were prescribed during pregnancy in the Netherlands before this warning. We performed our study by using pharmacy dispensing data from IADB.nl (population-based database) in Northern and Eastern Netherlands. This database comprises all prescription drugs, excluding drugs dispensed during hospitalizations and over the counter (OTC)-drugs. Date of birth and gender of each patient are available and all patients have an unique anonymous identifier. The pregnancy-IADB.nl (1995–2004) was extracted from the main IADB.nl-database. Children were selected by date of birth and by using an address code the mother of this child was identified. With this method, which is described in detail by Schirm et al.[2], approximately 65% of the children could be linked to their mother and validation showed 99% correctness. Only live-born children are registered in this database. Gestational age is calculated for every mother by subtracting 273 days (three trimesters of 91 days, approximately 9 months) from day of birth of the child. This period will be considered as gestation and is per definition 273 days. Prevalence, calculated before, during and after pregnancy, is based on exposure rate. Exposure rate is defined as the number of pregnancies in which, in theory, a women has availability to a drug or class of drugs, i.e. those who received a prescription in one trimester which was extended into the next, are counted for both trimesters in which they had access to the drug. We identified 14 666 pregnancies from which we had information of a defined time window of 3 months before gestation till 3 months after delivery. NSAIDs (ATC-code: M01A) and/or ASA (ATC-code: N02BA) were prescribed during this defined time window to 2020 women (13.8%). In 7.6% (1113/14 666) of the pregnancies these drugs were prescribed before conception, in 3.8% (557/14 666) during gestation and in 5.3% (781/14 666) after pregnancy (Figure 1). Ninety-six % of the women received NSAIDs (mainly diclofenac, ibuprofen and naproxen), less than 5.5% received ASA and approximately 1.5% received both drugs. Average age at time of delivery of women receiving NSAIDs and/or ASA (29.74 years, range 16–49) did not differ from those not receiving these drugs (29.91 years, P = 0.077 (Students t-test). Figure 1 Number of pregnancies in which a NSAID and/or ASA was prescribed before, during and after pregnancy In the majority of the pregnancies (75.6%, 421/557) NSAIDs and/or ASA were prescribed during the first trimester, resulting in an overall first trimester exposure of 2.9%. International studies from Canada [3], Denmark [4] and Sweden [5], reporting on first trimester NSAID use/prescribing showed comparable results: 2.9%, 3% and 3.4%, respectively. Third trimester prescribing of NSAIDs and/or ASA was low (0.6%, n = 94) which was to be expected due to guidelines stating not to prescribe these drugs during the third trimester. Part of the first trimester exposure will be due to unawareness of pregnancy by the women. By using a standardized gestational age to determine drug prescribing, misclassification especially in the first trimester of pregnancy will be introduced, leading to overestimation of actual use. On the other hand, our data lack information about OTC-use which will lead to underestimate of actual use. Unpublished data of EUROCAT-registration Northern-Netherlands showed that NSAID exposure in pregnancy was due to 60% on prescription and 35% OTC. We do realize these data represent prescribing of NSAIDs and/or ASA before the warning from European authorities. However, we strongly recommend that prescribing physicians need to be careful in prescribingthese drugs to women of fertile age, especially when use of these drugs during pregnancy increases risks of miscarriages and birth defects. Whether this warning will result in less prescribing of NSAIDs and/or ASA, especially during the first trimester, has to be examined in future research, national as well as international.

Occurrence of potential drug-drug interactions in nursing home residents

Objective — It has been suggested that elderly people are at increased risk of drug‐related problems such as drug‐induced adverse effects, drug‐drug interactions and drug‐disease interactions. This is particularly the case for nursing home residents because of the often complicated and multiple co‐morbidity that occurs in these people. The aim of this study was to develop prescribing indicators to assess systematically the occurrence and nature of potential drug‐drug interactions (DDIs) in a cohort of Dutch nursing home residents.

Pharmacoeconomics of gastrointestinal drug utilisation prior and post Helicobacter pylori eradication

Background.  Eradication of Helicobacter pylori prevents recurrence of peptic ulcer. In pharmacoeconomic analyses it is often presumed that after successful eradication no more gastrointestinal drugs are used. We investigated this presumed positive monetary effect using General Practitioners prescribing data, including information in diagnosis.