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Objective: To study the effectiveness of a minimal intervention strategy to improve adherence to paediatric asthma guidelines., Design and Setting: A group of pharmacists was encouraged to discuss essential elements of asthma care with the general practitioners they normally worked with. Adherence to guidelines was evaluated by studying prescriptions for children with asthma. We compared the treatment of children registered at pharmacies which participated in the study (intervention group) with a control group of children registered at other, non-participating pharmacies (reference group) and with the results of an earlier study., Main Outcome Measures: The numbers of children who had no short-acting betamimetics, no inhaled corticosteroids while on long-acting betamimetics, and more than one type of inhaler., Results: The number of children who had no short-acting betamimetics was significantly lower in the intervention group (176/1447 vs 534/3527; p<0.01) and fewer children had no inhaled corticosteroid although on long-acting betamimetics (6/219 vs 41/477; p=0.03). The number of children who had more than one type of inhaler was equal in both groups (5.1%), but this was significantly lower compared with the earlier study (119/2311 vs 239/3217; p<0.01)., Conclusions: The assistance of pharmacists with adherence to paediatric asthma guidelines is beneficial. Pharmacists should be involved actively in the care of children with asthma.

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., Methods: We used a database with pharmacy drug-dispensing data. We investigated all prescriptions of systemic antibiotics prescribed in the years 2002-2006 for children of 0-4 years of age. Prescriptions for children under the age of 3 months were excluded., Results: Children of 9-12 months of age received more antibiotics than children in other age groups. In the 3- to 6-month-olds, amoxicillin was prescribed in 75.2% of the cases. This percentage was 50.4% in the 4-year-olds. The contribution of other broad-spectrum antibiotics increased with age (clarithromycin and amoxicillin/clavulanic acid). Small-spectrum penicillins were prescribed less often than the broad-spectrum antibiotics. From the prescriptions of the five most used drugs, 97.6% were within the recommended dose range. Most course lengths corresponded with the guidelines. Of the prescriptions, 3.9% were unlicensed or off-label., Conclusion: Within the group of 0- to 4-year-old children, most antibiotics were used by 9- to 12-month-olds. The doses and course lengths were mostly correct, but the choice of antibiotics was not according to the guidelines. Young children received unlicensed and off-label prescribed antibiotics.

Influenza and respiratory syncytial virus (RSV) infections are responsible for considerable morbidity, mortality and health-care resource use. For the Netherlands, we estimated age and risk-group specific numbers of antibiotics, otologicals and cardiovascular prescriptions per 10,000 person-years during periods with elevated activity of influenza or RSV, and compared these with peri-season rates. Data were taken from the University of Groningen in-house prescription database (www.iadb.nl) and virological surveillance for the period 1998-2006. During influenza and RSV periods excess antibiotic prescriptions were estimated for all age groups. In the age groups 0-1 and 2-4 years, excess antibiotic prescriptions during periods with elevated RSV activity (65% and 59% of peri-seasonal rates) exceeded the surpluses estimated during the influenza-activity periods (24% and 34% of peri-seasonal rates) while for otologicals excess prescriptions were higher for influenza (22% and 27%) than for RSV (14% and 17%). Among persons of 50 years and older, notably those without medical high-risk conditions, excess prescriptions for cardiovascular medications were estimated during the influenza periods at approximately 10% (this was also already seen in persons aged 45-49). Our results may have implications for influenza vaccination policies. In particular, extension of influenza vaccination to groups of non-elderly adults and young children may lower excess prescriptions during these influenza periods for all three types of drug prescriptions investigated.

Background: Persons with profound intellectual and multiple disabilities (PIMD) suffer from a wide range of health problems and use a wide range of different drugs. This study investigated for frequently used medication whether there was a health problem documented in the medical notes for the drug prescribed., Method: Persons with PIMD with an estimated intelligence quotient of 25 and profound or severe motor disorders were studied. Data on health problems were taken from medical notes and prescribing data were obtained from pharmacies. Data covering 1 year were analysed. For four therapeutic areas (anticonvulsants, laxatives, drugs for peptic ulcer and gastro-oesophageal reflux disease and psycholeptics), we determined whether we could find an indication for prescribed medication., Results: Some 254 persons with PIMD (46% male, 54% female; median age 49 years, range 6-82) from eight residential facilities participated. Some 226 participants (89%) were prescribed medication over the course of 1 year. An indication for the prescribed medication was documented for 92% (n = 130) (95% confidence interval 88-96%) of 141 participants on anticonvulsants, for 68% (n = 112) (61-75%) of 165 participants on laxatives, for 44% (n = 58) (36-52%) of 132 participants on drugs for peptic ulcer and gastro-oesophageal reflux disease, and for 89% (n = 102) (83-95%) of 115 participants on psycholeptic drugs., Conclusions: The best level of documentation was found for anticonvulsants the worst for drugs for peptic ulcer and gastro-oesophageal reflux disease. Lack of documenting an indication may be due to off-label use, inadvertent continuation of no longer indicated medication, inadequate documentation and underdiagnosis. Adequate documentation practices are essential because of the communication problems that are characteristic for persons with PIMD.

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.

Objective: To investigate the utilization of antiepileptic drugs (AEDs) in Dutch children and compare this with guidelines on the treatment of epilepsy in children., Method: From the Dutch Interaction Database (IADB.nl) we selected children aged 0-19 years who received at least one prescription for an AED (ATC-code beginning with N03A) between 1997 and 2005. We calculated cumulative incidences and prevalences per 1000 children per year, stratified by age-category, sex and type of AED, and the total number of months each patient received at least one prescription of AEDs, and we counted the number of person-months and AEDs prescribed. For each AED, proportions of person-months were calculated for mono- and combination therapy. Kaplan-Meier survival analysis was used to analyse the duration of AED use, stratified by sex., Results: The overall prevalence of the prescription of AEDs to children was constant at approximately 4.0 per 1000 children during the years of the study. The overall cumulative incidence from 1997-2005 was 0.67 per 1000 children. When stratified by age category or sex, there were no relevant differences in incidence or prevalence. Valproic acid was the most frequently prescribed drug, followed by carbamazepine and lamotrigine. In 20.3% of all person-months, patients received combination therapy; of these, 34.2% received combination therapy for 3 person-months or less. The older AEDs were prescribed more often as monotherapy than combination therapy, in contrast with the newer AEDs, for which the opposite was true. The 50% survival probability (= time period when 50% of children had stopped using AEDs) was around 2 years, with a significantly lower discontinuation of treatment for girls than boys (P = 0.04)., Conclusion: The overall cumulative incidence of AEDs was determined to be 0.67 per 1000 children, and the prevalence 4.0 per 1000 children. The most frequently prescribed drug is valproic acid, followed by carbamazepine and lamotrigine. The prescribing of AEDs seems to be in conformity with the overall recommendations of the guidelines on the treatment of epilepsy in children.

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

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.

What Is Already Known About This Subject: * Recently, the use of selective serotonin reuptake inhibitors (SSRIs), particularly paroxetine, in pregnancy has been associated with an increased risk on specific birth defects or other adverse pregnancy outcomes. * However, the extent of SSRI use in pregnancy is largely unknown., What This Study Adds: * In the last decade the use of SSRIs in the year preceding delivery has increased twofold. * This increase runs parallel with the increase in use of SSRIs among women of fertile age. * Paroxetine is one of the most commonly used SSRIs. * Only recently have sufficient data become available on the use of paroxetine to detect moderate increased risks for specific malformations. * The safety of SSRIs which are less frequently used is not yet established. * Case-control birth defect-monitoring systems may be helpful in providing safety and risk estimates that become more precise as data accumulate for these drugs., Aims: Recent case-control studies suggest a relationship between the use of selective serotonin reuptake inhibitors (SSRIs) and the occurrence of birth defects and other adverse pregnancy outcomes. The aim was to determine the extent of the use of SSRIs before and during pregnancy and its trend over the years 1995-2004 in the Netherlands., Methods: The study was performed with data from a population-based prescription database. Within this database, women giving birth to a child between 1995 and 2004 were identified. The exposure rate and 95% confidence interval (CI) were calculated as the number of pregnancies per 1000 that were exposed to an SSRI in a defined period (per trimester or in the year preceding delivery). Exposure rates were calculated for 2-year periods: 1995/1996, 1997/1998, 1999/2000, 2001/2002 and 2003/2004. Trends in exposure rates were analysed using the chi(2) test for trend., Results: Included were 14,902 pregnancies for which complete pharmacy records were available from 3 months before pregnancy until delivery. A total of 310 pregnancies were exposed to an SSRI in the year preceding delivery. The exposure rate increased from 12.2 (95% CI 7.0, 19.8) in 1995/1996 to 28.5 (95% CI 23.0, 34.9) in 2003/2004., Conclusion: There has been a significant increase in the use of SSRIs among pregnant women in the Netherlands over the last 10 years, parallel with the increase in exposure in women of fertile age. In light of the recent warnings about the use of SSRIs in pregnancy, healthcare professionals should be careful in prescribing SSRIs to women planning a pregnancy.

Purpose: Continuation or discontinuation of drugs during pregnancy in chronic diseases is an issue of concern. Information on prescribing of disease modifying anti-rheumatic drugs (DMARDs) during pregnancy is scarce. In this study, we report prescribing patterns round pregnancy of sulfasalazine (SSZ), azathioprine (AZA), methotrexate (MTX) and co-medications among women to whom one of these DMARDs were prescribed before pregnancy., Methods: The pregnancy-interaction database (IADB.nl, 1994-2004), containing pharmacy dispensing data from Northern- Netherlands, was used. Women to whom SSZ (N = 13), AZA (N = 10) or MTX (N = 6) was prescribed before their first pregnancy were identified and described in detail., Results: AZA and SSZ are continued during pregnancy by 60% and 38% of the women, respectively, MTX was stopped before pregnancy. Among women receiving SSZ (N = 13) as their initial DMARD, anti-inflammatory and anti-rheumatic drugs (69%) and analgesics (45%) were the most commonly prescribed co-medications. Among women receiving AZA (N = 8) as their initial DMARD, corticosteroids for systemic use (100%) and intestinal anti-inflammatory agents (88%) were the most commonly prescribed co-medications. All women receiving intestinal anti-inflammatory drugs before pregnancy continued this during pregnancy, in contrast to other co-medications which were mainly discontinued., Conclusions: Our study showed that DMARDs and co-medication are received before, during and after pregnancy, although no specific prescription patterns were found. Administrative databases, such as the pregnancy-IADB.nl, are useful in describing drug-prescribing patterns for better understanding of drug prescribing around pregnancy in daily practice. Based on these data, we conclude that prescribing of DMARDs and related co-medication is based on the individual patient.

Unlabelled: We investigated prevention trends and predictors for osteoporosis prevention in long term corticosteroid users. The use of bisphosphonates increased from 2001 to 2005. Longer duration of corticosteroid use and DMARD use were predictors for receiving prevention. Females appear reasonably well treated; however, men require more attention., Introduction: Previous studies have shown that long-term corticosteroid users are undertreated for osteoporosis prevention. Our aim was to identify prevention trends in long-term corticosteroid users from 2001-2005 in The Netherlands and to identify predictors for bisphosphonate prophylaxis., Methods: Pharmacy dispensing data were used from 9 community pharmacies. All oral corticosteroid doses were converted to "prednisolone equivalents". We then identified long-term (> or =90 days) corticosteroid episodes, which required bisphosphonate prophylaxis as per 2002 Dutch guidelines; Multivariate logistic regression was used to identify predictors for receiving prevention., Results: We identified 615 different corticosteroid patients requiring prophylaxis. From 2001-2005 the use of bisphosphonates increased from 38% to 54% (p = 0.001). In 2005 females were prescribed more bisphosphonates than males (61% vs. 39%; p = 0.002), or any treatment (72% vs. 45%; p < 0.001). Multivariate analysis showed that longer duration of corticosteroid use and disease-modifying anti-rheumatic drug (DMARD) use were independent predictors of bisphosphonate use. Use of respiratory medication was a negative predictor of bisphosphonate use., Conclusion: There has been a significant increase in osteoporosis prophylaxis in a population at high risk for osteoporosis/fractures. In particular, females appear reasonably well treated; however, men are still not receiving prevention to the same degree as women.

Background: In case-control studies on teratogenic risks of maternal drug use during pregnancy, the use of normal or malformed controls may lead to recall-bias or selection bias. This can be avoided by using controls with a genetic disorder. However, researchers are hesitant to use these as controls because it is unknown whether their selection is independent of exposure status. The aim of this study is to investigate whether first trimester drug use among mothers of children with genetic disorders is representative for the "general pregnant population"., Methods: From a birth defects registry 565 mothers of infants with a genetic disorder born between 1998-2004 were selected (the "genetic population"). The first trimester exposure rate was calculated for prescription-only drugs as the number of exposed women per 100. By calculating the rate ratio (RR) and 95% CI, the exposure rates in the genetic population were compared with those in the "source population" obtained from a population-based prescription database and consisting of 10,870 mothers who gave birth to a child between 1998-2004., Results: The mean age at birth was 32.1 for the genetic population and 29.6 for the source population (p = .000). In the genetic population, a higher use was found for antimigraine medication (RR = 2.7, 95% CI = 1.0-7.8) and for ovulation stimulants (RR = 1.6, 95% CI = 1.0-2.6). After adjustment for maternal age, the difference in use of ovulation stimulants disappeared., Conclusions: Except for antimigraine medication, first trimester drug use among mothers of infants with genetic disorders is representative for the general pregnant population.

Purpose: To show the necessity of distinguishing several patterns of drug prescribing that may lead to co-medication. It is demonstrated how these different patterns can be investigated using large databases containing pharmacy data or reimbursement data., Methods: Two examples illustrate how the particular pattern of co-medication studied will influence the reported proportion of patients having co-medication, the use of antidepressants among people using anticonvulsants, and the use of antihistamines among people receiving penicillines., Results: Depending on definition and period considered, the percentage of anticonvulsant users co-medicated with antidepressants ranged from 5.8% (95%CI 5.0%, 6.8%) to 14.5% (95%CI 13.2%, 15.9%) in 2000. Comparing 2002 with 2000, the ratio of proportions ranged from 1.3 to 2.1. The percentage of people who received penicillines and were co-medicated with antihistamines ranged from 0.5% (95%CI 0.4%, 0.6%) to 9.7% (95%CI 9.3%, 10.2%) in 2000. Comparing 2002 with 2000, the ratio of proportions ranged from 1.2 to 1.6., Conclusion: The co-medication patterns investigated yielded clinical as well as statistically significant different estimates. The estimates differed up to a factor 2.5 for the drugs usually prescribed for long periods, and a factor 12 for drugs prescribed for short periods. Hence, we propose to distinguish the patterns 'co-prescribing', 'concomitant medication,' and 'possibly concurrent medication.' The research question determines the co-medication pattern of interest, and the drug and disease under study determine the time window.

Objectives: An N-of-1 trial is a double-blind placebo-controlled randomized trial to objectively and systematically evaluate the individual's response. This approach seems extraordinarily suitable for assessing the efficacy of stimulants in the treatment of attention deficit hyperactivity disorder (ADHD). The aim is to examine the use of N-of-1 trials among youths in the Netherlands, the protocols used, and the continuation of stimulant treatment thereafter., Methods: Physicians requesting N-of-1 trials with stimulants were interviewed about their rationale and protocol. Prevalence and continuation were investigated by extracting N-of-1 trials among youths <20 years of age from a large pharmacy dispensing database for 2000-2004., Results: The main purpose of N-of-1 trials mentioned by physicians was the assessing of individuals' response and dose-finding. Trial length, dosing schedule and efficacy assessment differed per physician. Trials consisted of a maximum of two treatment periods per dose. The annual percentage of youths starting stimulant treatment with an N-of-1 trial fluctuated between 0.6% (3/462) and 3.3% (10/301). No statistical significant difference could be detected between the continuation of stimulant treatment with or without an N-of-1 trial (p = 0.71)., Conclusions: N-of-1 trials with stimulants are infrequently and not optimally used in the Netherlands. The results of N-of-1 protocols described by physicians are of questionable value, due to the small number of treatment periods per dose. More uniformity in the protocols would make it easier to encompass the N-of-1 methodology in physicians' daily practice.

Aims: The aim of this study was to investigate the impact of new insights and revised guidelines on initial and follow-up treatment with antihyperglycaemic drugs over the period 1998-2003., Methods: The InterAction Database (IADB), which contains pharmacy dispensing data from 53 community pharmacies in the Northern and Eastern part of the Netherlands, was used in this study. Prevalence and incidence rates of oral antihyperglycaemic drug use were calculated for each year. Follow-up treatment was compared for two cohorts of initial users of oral antihyperglycaemic drugs, starting treatment either 1 year before or 1 year after guideline revision., Results: The prevalence and incidence rate of oral antihyperglycaemic drug use increased over the study period from 1.8% to 2.4% (P < 0.001) and 0.3% to 0.4% (P = 0.04). The proportion of metformin as initial treatment increased rapidly in the observation period from 14% to 50% (P < 0.001). Initial users of metformin in 2000 received additional treatment with a sulphonylurea in the follow-up period less often compared with those who started metformin in 1998 (46%vs. 60%, P < 0.004). In contrast, initial users of sulphonylurea in 2000 received additional treatment with metformin more often compared with those who started a sulphonylurea in 1998 (42%vs. 36%, P < 0.008). The new drugs, thiazolidinediones and meglitinides, were seldom used as initial treatment., Conclusions: New insights and the revision of the practice guideline were followed by a significant increase in both initial and follow-up treatment with metformin among patients with Type 2 diabetes mellitus.

Aims: To investigate the dosage and duration of inhaled steroids prescribed to children and to compare the prescribed doses with recommended doses for the treatment of asthma in children., Methods: For 2514 Dutch children aged 0-12 years who had used inhaled steroids in 2002, pharmacy dispensing data were obtained from the InterAction database, type of steroid (beclomethason, budesonide, fluticasone) and type of user (first time or existing) and the average prescribed doses according to age were determined and compared with the doses as recommended in the national Dutch Nederlands Huisartsen Genootschap (NHG) guideline. Furthermore, for all first-time users the duration of therapy with inhaled steroids was determined using a Kaplan-Meier analysis., Results: The major findings were that: (i) overall 43% of children starting inhaled steroids were prescribed doses that are half the recommended dose or less; (ii) overall 8% of the children starting inhaled steroids were prescribed doses that were twice the recommended dose or more, up to 50% in the 12-year-olds fluticasone group; and (iii) only 8% of the children who started with inhaled steroids used them continuously for a full year., Conclusions: Doses of inhaled steroids for many children deviate from those recommended, with lower doses more frequently occurring than higher doses. Less than 10% of the children receive prescriptions for a prolonged period of time.

Objective: Did the publication of the Women Health Initiative (WHI) trial in 2002 and the Million Women Study (MWS) in 2003 lead to changes in prescription rates of hormone replacement therapy (HRT). Therefore, we compare the prescribing of HRT in 2004 (after) with that of 2001 (before the publications) in The Netherlands., Method: Community pharmacy dispensing data from a population of approximately 500,000 patients in The Netherlands. Women aged 40-74 years to whom at least one HRT prescription was dispensed in 2001 or 2004 were included. Annual prevalences of HRT in 2001 and 2004 and the percentage change (2004 versus 2001) were calculated for overall HRT (excluding vaginal products) and per HRT category (combined estrogens and progestagens, estrogens only, tibolon and vaginal preparations) and age category., Results: In 2001, 5.64% of the women aged 40-74 used HRT and this percentage declined to 2.39 in 2004. The use of vaginal products among these women did not change, 1.76% in 2001 and 1.65% in 2004. The percentage change was highest in the opposed HRT group (66% decrease) and in women aged 50-54 (64.4% decrease). In 2004, compared with 2001, the proportion of long-term users (>3 year) increased with 12.7%., Conclusions: In The Netherlands, after publication of the WHI study and the MWS the prescribing of HRT fell dramatically whereas the prescribing of vaginal products did not change. Future patterns of HRT use should be monitored to know whether this decrease will be sustained.

Objective: To compare the prescription of drugs in women over a period from 2 years before until 3 months after pregnancy, regarding the type of drugs used and the fetal risk., Design: A cohort study based on pharmacy records of women giving birth to a child between 1994 and 2003., Setting: The study was performed with data from the InterAction database, containing prescription-drug-dispensing data from community pharmacies., Population: The study population included 5412 women for whom complete pharmacy records were available., Methods: Drugs were classified into three categories: (1) drugs for chronic conditions, (2) drugs for occasional use and (3) drugs for pregnancy-related symptoms and also classified according to the Australian classification system., Main Outcome Measures: The prescription rate was calculated as the number of women per 100 women who received one or more prescriptions for a given drug within a specified time period., Results: About 79.1% of the women received at least one prescription during pregnancy. The prescription rate for most drugs for chronic diseases and for occasional use decreased during pregnancy, whereas, as expected, the prescription rate for pregnancy-related drugs increased. During the first trimester of pregnancy, 1.7% of all drugs prescribed for chronic conditions and 2.3% of the occasional drugs were classified as harmful., Conclusions: The increase in prescription rate during pregnancy is caused by an increase in prescription rate of drugs for pregnancy-related symptoms. The prescription of harmful drugs is more commonly associated with drugs for occasional use rather than with drugs for chronic conditions. Therefore, a more cautious prescribing of drugs to healthy women in the fertile age is necessary.

Purpose: It is generally agreed that a confidence interval (CI) is usually more informative than a point estimate or p-value, but we rarely encounter small proportions with CI in the pharmaco-epidemiological literature. When a CI is given it is sporadically reported, how it was calculated. This incorrectly suggests one single method to calculate CIs. To identify the method best suited for small proportions, seven approximate methods and the Clopper-Pearson Exact method to calculate CIs were compared., Methods: In a simulation study for 90-, 95- and 99%CIs, with sample size 1000 and proportions ranging from 0.001 to 0.01, were evaluated systematically. Main quality criteria were coverage and interval width. The methods are illustrated using data from pharmaco-epidemiology studies., Results: Simulations showed that standard Wald methods have insufficient coverage probability regardless of how the desired coverage is perceived. Overall, the Exact method and the Score method with continuity correction (CC) performed best. Real life examples showed the methods to yield different results too., Conclusions: For CIs for small proportions (pi < or = 0.01), the use of the Exact method and the Score method with CC are advocated based on this study.

Objectives: The aim of this study was to examine stimulant use from 1998 to 2002 among children in the Dutch pediatric population with emphasis on psychotropic co-medication., Methods: A drug utilization study was based on community pharmacy-dispensing data from 1998 to 2002 for children aged 0-19 years in the northern and eastern part of The Netherlands., Results: The prevalence of stimulant use increased from 0.6% in 1998 to 1.2% in 2002. Duration of stimulant treatment was longest in children aged 5-14 years. The use of any psychotropic co-medication in stimulant users increased from 12% in 1998 to nearly 15% in 2002. Of those youths who were prescribed stimulant medication in 2002, the most co-prescribed class was the antipsychotics (7.9%). In 1998, none of the stimulant-treated children received antidepressants for co-medication; in 2002, this was 1.8%., Conclusion: The prevalence of stimulant use among children in The Netherlands has increased in recent years, mainly as a result of the duration of stimulant treatment. Psychotropic co-medication among stimulant-treated children increased moderately.

Background: In order to increase price competition, government regulations focus on controlling drug costs. Drug costs after patent expiry are an area of particular interest because the substitution of branded medication with generics represents an opportunity for lowering drug costs. However, drug costs may not decrease after patent expiry, because of a lack of price competition and different national pricing systems., Aim: The aim of this study was to investigate the trends in the use of generics after patent expiry for enalapril, fluoxetine and ranitidine and the subsequent changes, if any, in the costs of these medications., Methods: A drug-utilisation study was performed using data from a large sample of Dutch pharmacies. Both volumes (measured as defined daily doses [DDD] per 1000 population) as well as drug costs (calculated per DDD) prior to and after patent expiry were calculated. Costs per DDD were compared using trend-line analysis. In addition, the relative market shares of the different trade channels (branded, parallel imported and generic) were compared before and after patent expiry., Results: The costs per DDD decreased for all three drugs and, as expected, these costs decrease more rapidly after patent expiry. Significant differences in the trend lines were found for enalapril and fluoxetine., Conclusions: Despite relatively high reimbursement prices for generics in the Netherlands, this example from the Dutch pharmaceutical market demonstrates the benefit of generic substitution for containing pharmaceutical costs, which contrasts with concerns raised by the Dutch government.

Objective: To describe the use of contraceptives among women aged 10-59, particularly in relation to the type of oral contraceptives (OCs) among starting users and women already using OCs., Design: Descriptive., Method: Data on the use of medication in the period 1994-2002 by women in the age range 10-59 years were selected from the Interaction Database of North and East Netherlands. The study population was 33,795 women in 1994 and 102,894 in 2002. Cross-sectional studies were performed of prevalent and incident OC users per year and the contribution of the various types of OC was measured., Results: The use of contraceptives among women aged 10-59 years has remained fairly constant since 1994, being about 33%. However, Dutch women started using OCs at an increasingly younger age: 47% of the 15-19-year-olds in 2002 compared with 35% in 1994. The use of third-generation OCs among young starting OC-users (10-19 years of age) in 2002 was very low (3.5% of all OCs). Among women who already used OCs, the switch from third- to second-generation OCs was less pronounced. In 2002, 23% of all OC-users used third-generation preparations compared with 46.5% in 1994. The proportion using cyproteron-ethinylestradiol increased slightly over the years., Conclusion: After 1994, mainly second-generation OCs have been prescribed. The switch from third- to second-generation OCs was especially marked among the young starting users. The use of cyproteron-ethinylestradiol increased slightly during the years.

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.

Purpose: Pharmacy-dispensing data are valuable sources of drug information, but the population that is covered by the pharmacies is often difficult to determine. We evaluated two methods using drug utilisation information to estimate the population size: a drug-use-based extrapolation of a known part of the population and a capture-recapture estimation without any prior knowledge of the population., Methods: Using pharmacy-dispensing data of three towns with known populations in the Netherlands, we estimated age-and-sex specific population sizes by extrapolating the proportion of drug-using inhabitants. In addition, we applied two-source and three-source capture-recapture models with all combinations of the following drug groups as different sources: anti-asthmatics, analgesics, antibiotics and anti-histamines., Results: Drug-use-based extrapolation resulted in the best estimates with the least variability. All capture-recapture models provided underestimations of the true population. Three-source capture-recapture resulted in better average estimates than two-source capture-recapture, but also had more variability., Conclusions: If a part of the population is known, and if there is reason to assume that drug utilisation patterns do not vary within the region, it is best to use drug-use-based extrapolation. In all other situations capture-recapture may be considered, with as main limitation that we found all models to underestimate the population considerably.

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., Methods: From the RNG-database we identified patients with a H. pylori eradication in the years 1997-2000. H. pylori eradication was defined as a prescription of two antibiotics and one gastrointestinal drug on the same day. Patients were divided into a group with diagnosed ulcers and a group without diagnosed ulcers. Gastrointestinal drug costs were calculated for 4 months prior to eradication and 9-12 months post eradication. For comparison costs in all periods were expressed per patient per period. For statistical analysis the paired t-test was used., Results: One hundred and two patients were eligible for evaluation. Of these patients 35 had a diagnosed ulcer and 67 had not. Generally the number of patients on gastrointestinal drugs decreased (61% prior vs. 33% post), however, the drug costs did not change (Euro 33 prior vs. Euro 34 post). Costs for proton pump inhibitors increased post eradication (Euro 14 prior vs. Euro 28 post). The ulcer and nonulcer group showed similar results., Conclusion: Helicobacter pylori eradication is thought to be cost effective, however, we did not find a decrease in costs for all gastrointestinal drugs. There may be a great pharmacoeconomical advantage when it is possible to predict which patients are more likely to 'fail' eradication therapy.

Objective: To describe the use of hormone replacement therapy (HRT) and oral contraceptives (OC) among women in the Netherlands in the 45 to 69 years age group during the year 2002., Design: Descriptive., Method: Pharmaceutical data on 42,032 women who were in the 45-69 years age group on 31 December 2002 was selected from the InterAction database, a collection of community pharmacy data from the north of the Netherlands. The duration of the therapy was investigated for women who had received at least one HRT or OC prescription in 2002., Results: Oral contraceptives were used by 11.3% of women aged 50-54 years and 1.8% of women aged 55-59 years. The prevalence of HRT ranged from 6.0% to 11.7% depending on age. Of these users (n = 3885) 28.6% used an oestrogen-progestagen preparation. A treatment period of more than one year was found in 62.3% of women aged 45-49 years and 82.6% of women aged 55-59 years. In particular, preparations containing just oestrogen had been used for a longer period; 43.4% had used these for more than 5 years., Conclusion: More than half of the women who used HRT had done so for more than one year.

Aims: To investigate the relationship between the use of antidepressants with or without NSAIDs and the risk of gastrointestinal side-effects., Methods: This was a population-based cohort study. Medication data of 180,000 patients from 16 pharmacies in The Netherlands were studied. The subjects were a group of 15 445 new users of antidepressants with or without NSAIDs. A review of patient profiles for cases of gastrointestinal adverse effects caused by first time use of antidepressants with or without NSAIDs was carried out. The number of first prescriptions for peptic ulcer drugs (Anatomical Therapeutic Chemical classification A02B) in the period from day 2 after starting antidepressants with or without NSAIDs until 10 days after the last dose was the main outcome measure., Results: In the reference group of 619 new users of nonselective antidepressants (TCAs), the incidence of first prescriptions for peptic ulcer drugs was 0.051 (95% confidence interval 0.021, 0.105). The use of SSRIs (n = 1181) caused a slightly higher incidence rate ratio (IRR) of 1.2 (0.5, 2.8). The combined use of SSRIs and NSAIDs (n = 86) increased the IRR to 12.4 (3.2, 48.0). In contrast, the combination of nonselective antidepressants and NSAIDs (n = 74) increased the IRR to 2.5 (0.3, 20.3)., Conclusions: SSRIs increase the risk of gastrointestinal adverse effects in first time users as compared with nonselective antidepressants. The combined use of SSRIs and NSAIDs strongly increases the risk of gastrointestinal adverse effects and should be avoided. The combination of nonselective antidepressants and NSAIDs does not have this effect.

A follow-up study was performed in two ambulatory cohorts aged > or =65 to investigate whether the prevalence and incidence of anxiolytic/hypnotic benzodiazepine drug prescribing is comparable between users of serotonin reuptake inhibitors (SSRIs) and users of tricyclic antidepressants (TCAs). The prevalence and incidence of benzodiazepines during antidepressant therapy was estimated among users of TCAs and SSRIs. Coprescribing of benzodiazepines occurred in 53% of the TCA users and 57% of the SSRI users (prevalence RR 1.1; CI(95) 0.9-1.2). The average duration of benzodiazepine drug use was >65 days per 100 days of antidepressant use. During SSRI therapy, significantly more people started benzodiazepine drug therapy than during TCA therapy (incidence rate ratio (RR) 1.7; CI(95) 1.2-2.4). Analyses repeated 5 years later yielded similar results (overall incidence RR(MH) 1.6; CI(95) 1.3-2.0). These data indicate that SSRI use is associated with a significantly higher chance of starting benzodiazepines compared with TCA use.

Background: Use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with an increased risk of gastrointestinal toxicity, in particular when risk factors are present., Methods: A study was performed to investigate concomitant prescribing of gastroprotective agents (H2-receptor antagonists, proton pump inhibitors, or misoprostol) in an ambulatory cohort of NSAID users aged 65 years and over. The prevalence of concomitant prescribing was studied, as well as the prophylactic prescribing of gastroprotective drugs. A stepwise logistic regression was performed to determine predictive variables of prophylactic and concomitant gastroprotective drug prescribing., Results: Co-prescribing of gastroprotective drugs occurred in 1522 (23%) (of which 944 concerned prophylactic prescribing) of the NSAID users (n = 6557), with an average duration of 67 days per 100 days of NSAID use. Co-prescribing of gastroprotective drugs varied among individual NSAIDs. Concomitant use of oral corticosteroids (ORadj 2.4; Cl95 2.0-2.9), coumarins (ORadj 1.6; Cl95 1.3-2.0), and low dose aspirin (ORadj 1.6; Cl95 1.4-1.9) were significantly associated with both prophylactic and concomitant prescribing of gastroprotective agents during NSAID therapy., Discussion: Despite current guidelines recommending gastroprotective drug prescribing among high risk groups, the rate of concomitant prescribing of gastroprotective agents in NSAID users aged 65 years and over is low. Feedback to prescribers should be given to improve prescribing practices in this high risk group.

Objectives: Assessment of predictors for initiating prophylactic antithrombotic prescribing for patients newly diagnosed with ischaemic heart disease (IHD) and the impact of the introduction of national guidelines., Design and Setting: A retrospective case-control study was performed using pharmacy prescription data from 120,000 Dutch patients over a 5-year period. IHD patients were identified using as a marker multiple nitrate prescriptions [anatomical-chemical-therapeutic (ATC) code CO1D] indicating chronic use. Initiation of antithrombotic therapy was likewise identified using ATC codes B01AA and B01AC (oral anticoagulants and thrombocyte aggregation inhibitors), prescribed within 6 months following the first nitrate prescription. Statistically significant (P<0.05) predictors were assessed using multivariable analysis considering patient, prescriber and medication characteristics., Results: Of the 2598 patients who met specified inclusion criteria for newly diagnosed IHD, approximately 35% was not prescribed any type of antithrombotic therapy. Male patients [odds ratio (OR) 2.4, 95% confidence interval (CI) 2.0-2.9], patients with cardiovascular (other than IHD) and diabetic co-morbidity (OR 6.4, 95% CI 4.8-7.9 and OR 1.6, 95% CI 1.1-2.1, respectively) and patients using isosorbide mononitrate rather than isosorbide dinitrate as anti-ischaemic main therapy (OR 2.1, 95% CI 1.3-2.5) were most likely to be prescribed antithrombotic therapy. Furthermore, initiating antithrombotic prescribing was more likely after the introduction of national guidelines (OR 1.4, 95% CI 1.1-1.7)., Conclusions: Initiating antithrombotic prescribing in newly diagnosed IHD patients can be predicted by patient gender, certain co-morbidity and main type of nitrate therapy. The introduction of national guidelines has resulted in an increase of prophylactic antithrombotic prescribing in accordance with their contents.

Objective: To quantify and evaluate drug utilisation in a sample of Dutch nursing homes., Methods: A retrospective analysis of computerised medication data of 2355 residents aged 65 years and over from six nursing homes in the Netherlands was performed. For each therapeutic drug group, the number of users was determined. The ten therapeutic groups used most frequently were investigated further. For these, patient characteristics, use of therapeutic subgroups, the average daily dosages and the chronicity of drug use were determined. Chronicity was expressed as the percentage of treatment days divided by the number of residents' days in the nursing home., Results: During the study period, 89%, 77% and 56% of the study population used a drug from the anatomical therapeutic chemical (ATC) main group N (nervous system), A (alimentary tract and metabolism) and C (cardiovascular system), respectively. Eight of the ten therapeutic drug groups prescribed most frequently were used for more than 50% of the time. In particular, psycholeptic drugs, diuretics and laxatives were used chronically (83%, 81%, and 80% of the nursing home stay, respectively). Except for a few drug groups, such as laxatives and diuretics, the prescribed daily dosages were relatively low. Twenty-eight percent of the residents received loop diuretics; these were prescribed in relatively high dosages., Conclusion: Drug utilisation in the nursing homes was high and many drugs were used chronically. In view of the risk of possible adverse effects and drug-drug interactions, the prescribing and dosage of psycholeptic drugs, laxatives, loop diuretics and ulcer-healing drugs should be re-evaluated, carefully.