P.B van den Berg

Drug prescription patterns before, during and after pregnancy for chronic, occasional and pregnancy-related drugs in the Netherlands.

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.

Antiepileptic drug utilization in children from 1997-2005--a study from the Netherlands.

ObjectiveTo investigate the utilization of antiepileptic drugs (AEDs) in Dutch children and compare this with guidelines on the treatment of epilepsy in children.MethodFrom 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.ResultsThe 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).ConclusionThe 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.

INVESTIGATING DRUG-USE IN PREGNANCY - METHODOLOGICAL PROBLEMS AND PERSPECTIVES

In this study the use of prescribed drugs before, during and after pregnancy is described. The study is based on data obtained from pharmacy records of 1,948 women who delivered a live-born infant. Different measures to evaluate drug exposure are used. During the nine months of pregnancy 86% of the women used on average 4.2 prescriptions. During the course of pregnancy the use of gastro-intestinal and blood-forming drugs increased, whereas the use of cardiovascular, antiphlogistic and central nervous system drugs decreased. Anti-emetics were predominantly used in the first trimester, and antacids in the last trimester, whereas laxatives were especially used after delivery. The percentage of women who used a treatment for vaginal infections increased from 2 to 7 during pregnancy. Most of the women (73%) received one or more iron prescriptions during the course of pregnancy, however, the prescribed daily dose was low (prescribed daily dose/defined daily dose=0.6). At least 1% of the women filled a new prescription for anticonceptives in the first trimester of pregnancy. Most likely, our data reflect the general prescribing pattern for Dutch pregnant women who delivered a live-born baby. Therefore, they form a good and detailed base for further studies, for instance, on the exposure to drugs with known or suspected risks or on the use of drugs in patients with chronic concomitant diseases. Such studies may lead to recommendations that may improve prescribing behaviour.

Prescribing of gastroprotective drugs among elderly NSAID users in the Netherlands

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; CI95 2.0-2.9), coumarins (ORadj 1.6; CI95 1.3-2.0), and low dose aspirin (ORadj 1.6; CI95 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.

Concomitant prescribing of benzodiazepines during antidepressant therapy in the elderly

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.

Vulvo-vaginal candidiasis associated with acitretin

The aim of this study was to estimate the risk of vulvo-vaginal candidiasis among the users of acitretin. The incidence rate ratio of vulvo-vaginal candidiasis was estimated in a cohort of acitretin users by using prescription sequence analysis. Study subjects were 196 women between 15 and 45 years of age, exposed to acitretin in 1990. Prescriptions of drugs for treatment of vulvo-vaginal candidiasis were used as proxy for the occurrence of vulvo-vaginal candidiasis. Validation of the proxy drug was performed by record linkage of pharmacy and medical records. In addition to the risk estimation by incidence rate ratios a case-crossover study with patient-stratified logistic regression analysis was performed to control for distortion due to individual differences in contribution of exposure time. The positive predictive value of the proxy drug for vulvo-vaginal candidiasis ranged between 57 and 100%, the sensitivity was 87% and the specificity estimated 99%. The crude incidence rate ratio for vulvo-vaginal candidiasis following acitretin exposure was 2.8 (CI95%: 1.1-7.1). The pooled Mantel-Haenszel incidence rate ratio was 3.3 (CI95%: 1.1-9.6) after stratification for accumulated level of exposure. Patient-stratified analysis on the subgroup of cases (n = 15) revealed an odds ratio of 6.5 (CI95%: 2.3-18.2). This study strongly suggests that the higher occurrence of vulvo-vaginal candidiasis during acitretin exposure is attributable to the drug.

Oral contraceptive use before and after the latest pill scare in the Netherlands - Changes in oral contraceptive use and how users change

Abstract In October 1995, a “pill scare” developed in Europe. In the Netherlands, the recommendations given were 1) to not alarm women without risk for deep vein thrombosis (DVT), and 2) to be reserved in prescribing third generation oral contraceptives (OC) for young women who were beginning OC use. To determine whether there is a change in the prescription of third generation OC after the latest pill scare, prescription data from 1/10/94 to 1/10/96, covering a population of ±120,000 persons, were studied with respect to OC use before and after the pill scare. Trend analyses revealed a significant decline in third generation compared with total OC prescribing only in the youngest age category (p = 0.0034). Further, switch behavior was studied. Switches from third to second generation OC were more prevalent after the pill scare than before (odds ratio = 2.63; 95% confidence interval 1.84–3.75) and switches from second to third generation OC were significantly less prevalent after the pill scare. This indicates that Dutch prescribers have reacted to the pill scare in the way that the government recommended.

Effect of a minimal pharmacy intervention on improvement of adherence to asthma guidelines

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 shortacting 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.

Excess drug prescriptions during influenza and RSV seasons in the Netherlands : Potential implications for extended influenza vaccination

Abstract 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.

Changes in laboratory values and their relationship with time after rupture of an abdominal aortic aneurysm

PurposeMany laboratory values are abnormal after surgery for a ruptured abdominal aortic aneurysm (RAAA). However, these changes have not been comprehensively evaluated. We analyzed the changes in routine laboratory values and how these changes related to outcome in a consecutive series of RAAA patients.MethodsAll patients who underwent surgery for an RAAA between January 1990 and June 2003 at our hospital were included in this study. We analyzed laboratory data acquired during the first week for all patients and at discharge for survivors. We categorized 29 different measurements into six categories based on the related pathological process, including hematology and coagulation, metabolism, systemic inflammation, renal function, liver function, and electrolytes.ResultsA total of 290 patients underwent RAAA surgery, with a hospital mortality of 34%. Hemorrhage was the most common cause of early death, whereas multiple-organ failure (MOF) was the most common cause of death several days after surgery. Most laboratory values deviated from normal at multiple time points and they differed significantly between survivors and nonsurvivors.ConclusionsBoth survivors and nonsurvivors of RAAA surgery displayed characteristic time-dependent laboratory abnormalities. Awareness of these responses may help us predict patients prone to complications.