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AIMS: To investigate the nature and frequency of prescription modifications in Dutch community pharmacies. METHODS: In this cross-sectional study, Dutch community pharmacists documented prescription modifications in their pharmacy during 1 predetermined day. Pharmacists from all Dutch community pharmacies were invited to participate. A prescription modification was defined as any modification in a prescription for a medicine or other healthcare product because of an administrative problem, logistic issue or potential drug-related problem (DRP). All documented modifications were assessed to establish the nature and frequency of prescription modifications. RESULTS: Pharmacists in 275 pharmacies completed the study. A modification was performed in 5.5% of all prescriptions. 1.3% of the prescriptions contained an administrative problem, of which insufficient specification of the dosing regimen was most common (63.1%). A modification was performed due to a logistic issue in 2.4% of the prescriptions. The most frequently recorded issues were unavailability of medication (40.9%) and obligatory product substitutions due to reimbursement policies (33.2%). A modification was performed in 1.8% of the prescriptions to solve or prevent potential DRPs. Of these, 69.2% was potentially clinically relevant according to the pharmacist concerned. The most frequently prevented potential DRP was an incorrect strength or dose (31.9%). CONCLUSION: Dutch community pharmacists modified almost 1 in 20 prescriptions per pharmacy. The nature of the modifications reflects current community pharmacy practice, in which pharmacists frequently deal with logistic issues and intervene to solve or prevent for DRPs several times a day. The majority of the DRPs were considered to be potentially clinically relevant.

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WHAT IS KNOWN AND OBJECTIVE: It is often necessary to adjust drug therapy if renal function is impaired in elderly patients taking drugs for diabetes and/or cardiovascular disease that are cleared by the kidneys. Although clinical guidelines recommend regular monitoring of renal function in these patients, in practice adherence to these recommendations varies from 28% to 75%. To determine whether drug dosing is appropriate, pharmacists need have up-to-date information about patients' renal function. In this study, the feasibility of point-of-care creatinine testing (POCCT) in a community pharmacy was evaluated as part of monitoring the drug therapy of ambulatory elderly patients. METHODS: Elderly patients on maintenance therapy with renally excreted drugs for diabetes or cardiovascular disease were eligible for POCCT. After informed consent was obtained, POCCT was performed by trained personnel. A pharmacist assessed the clinical relevance of electronically generated drug alerts based on the patient's calculated renal function and the Dutch guidelines for adjusting drug dosage in patients with chronic kidney disease. If appropriate, the patient's general practitioner (GP) was consulted and adjustments to treatment were communicated to the patient. The feasibility of POCCT was evaluated by means of questionnaires completed by patients and healthcare professionals (GPs and pharmacists). RESULTS: Of 338 potentially eligible patients, 149 (44%) whose renal function was not known were asked, by letter, to participate in the study. Of these individuals, 46 (31%) gave their informed consent and underwent POCCT. Response rates for completing the patient and professional questionnaires were 87% and 100%, respectively. More than half of the patients who underwent POCCT had mild-to-moderate renal impairment. On the basis of information provided by patients and healthcare professionals, POCCT would appear to be feasible in community pharmacies. WHAT IS NEW AND CONCLUSION: POCCT improves the management of drug therapy by community pharmacists and is feasible in daily practice.

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The objective of this study was to investigate the influence of genotypes associated with reduced activity of vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) on anticoagulation with acenocoumarol during the first 6 weeks of treatment. In 1,525 patients from the Rotterdam Study who were started on anticoagulation therapy with acenocoumarol, the presence of VKORC1 1173C>T and CYP2C9*2 and *3 allele variants was determined. The first international normalized ratio (INR) after initial standard dose, risk of overanticoagulation, and mean dosage at the end of the initiation period were compared between genotypes. The initial standard dosage significantly increased the risk of severe overanticoagulation by 85% for each additional VKORC1 T-allele present. At the end of the initiation period, each VKORC1 T-allele present was shown to decrease the required acenocoumarol dosage by 5.1 mg/week, while each CYP2C9 variant allele present reduced the required dosage by 1.8 mg/week. Our conclusion was that an initial standard dosing regimen with acenocoumarol increases the risk of severe overanticoagulation in patients with variant alleles of the VKORC1 and CYP2C9 genes.

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BACKGROUND AND OBJECTIVE: Discontinuity of care bears the risk of medication errors and poor clinical outcomes. Little is known about the continuity of care related to pharmacies. Therefore, we studied the prevalence and determinants of pharmacy shopping behaviour in the Netherlands. METHODS: Beneficiaries from a Dutch pharmacy claims database who had visited two or more pharmacies in 2001 were indicated as 'shoppers' (n = 45 805). A random sample was taken from all the other beneficiaries who had received at least one prescription: 'non-shoppers' (n = 45 805). Shoppers were classified as light (all patients who visited more than one pharmacy at least once in 2001, except for patients defined as heavy or moderate shoppers), moderate (visited 3 or 4 pharmacies and had proportion of prescriptions elsewhere >10% and number of prescriptions elsewhere >10) or heavy (visited 5 or more pharmacies and had proportion of prescriptions elsewhere >10% and number of prescriptions elsewhere >10). Determinants of shopping behaviour were investigated as well as the association between any dispensing of Anatomical Therapeutic Chemical (ATC) classes of drugs and this behaviour. RESULTS: 10.8% beneficiaries were identified as shoppers: 98.8%'light shoppers', 1.0%'moderate shoppers' and 0.2%'heavy shoppers'. Female gender [odds ratio (OR)(adj) 1.2; 95% confidence interval (CI) 1.1-1.2], younger age (OR(adj) 1.7; 95%CI 1.7-1.8), the use of > or =3 drugs (OR(adj) 2.9; 95%CI 2.8-3.0) and visiting different kind of prescribers (OR(adj) 2.4; 95%CI 2.4-2.5) were associated with shopping behaviour. Shoppers more frequently received at least one prescription for systemic anti-infectives (51.7% vs. 30.8%; OR 2.4; 95%Cl 2.3-2.5) and for nervous system drugs (46.2% vs. 29.3%; OR 2.1; 95%Cl 2.0-2.1). CONCLUSIONS: Pharmacy shopping behaviour is limited in the Netherlands. However, it may put the patient at risk for unintentional problems, such as drug-drug interactions with anti-infectives. A small proportion of patients exhibit possibly intentional shopping behaviour with psychotropic drugs.

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OBJECTIVE: Besides effects on hemostasis, vitamin K-dependent proteins play a role in bone mineralization and arterial calcification. We investigated the association between the VKORC1 1173C>T polymorphism and calcification of the aortic far wall in a large population-based cohort. METHODS AND RESULTS: Aortic calcification was diagnosed by radiographic detection of calcified deposits in the abdominal aorta. In all cohort members for whom DNA was available, the C1173T SNP of VKORC1 (rs9934438) was determined. With multivariable logistic regression analysis the association between this polymorphism and the risk of aortic calcification was calculated, adjusted for potential confounders. The T allele frequency of the VKORC1 1173C>T polymorphism was 38.8%. 1185 (37.2%) persons were homozygous CC, 1529 (48,0%) were heterozygous CT and 473 (14.8%) were homozygous TT. Persons with at least one T-allele had a statistically significant 19% (95% CI 2 to 40%) risk increase of calcification of the aortic far wall compared to CC homozygous persons, adjusted for age and gender. CONCLUSIONS: The T-allele of the VKORC1 1173C>T polymorphism was associated with a significantly higher risk of aortic calcification in Whites.

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OBJECTIVE: To investigate the quality of antibiotic prescribing in primary care using quality indicators and the relatedness of these indicators. To determine the influence of general practice and practice population characteristics on the indicator scores. METHODS: Data on performance were collected during the Second National Survey of General Practice over 1 year between May 2000 and April 2002 in The Netherlands. The study was carried out in 104 computerised general practices, comprising 195 general practitioners and about 400,000 patients. From a preliminary set of quality indicators on antibiotic prescribing (n = 15), eight were selected covering various medical conditions. Indicator scores were derived. A factor analysis was performed to examine the relatedness of these indicators. Composite scores were calculated for the indicators loading on the same factor. The influence of general practice and practice population characteristics on the quality of antibiotic prescribing was investigated. RESULTS: Considerable variation was found between indicator scores (32.8-94.2%) and between practices. The factor analysis discovered two interpretable factors-namely, "first choice prescribing" and "restrictive prescribing". The composite scores were 64% and 68%, respectively. No significant correlation was found between the two composite scores. Practice and population characteristics explained only a small proportion of the variance between practices. CONCLUSIONS: Although different quality indicators on antibiotic prescribing are grouped together over several medical conditions, there is large variation between those indicators. General practices performing well on first choice prescribing do not automatically perform well on restrictive prescribing. There is room for improvement on both aspects of prescribing. The variation between practices is clearly present and should be further investigated.

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BACKGROUND AND OBJECTIVES: Many studies determined the number and nature of user-related Pharmaceutical Care Problems (PCP) and factors affecting them, but none considered the inclusion of clinical relevance. The aims of this study are (i) to investigate the type, number and clinical relevance of user-related PCP self-reported by home dwelling elderly on polypharmacy and (ii) to develop a risk-model for detecting elderly drug-users at risk of user-related PCP. METHODS: The study was a cross-sectional study conducted among 286 home dwelling elderly on polypharmacy (> or =75 years, > or =4 medicines) in the Netherlands. The user-related PCP found were divided into problem categories and subsequently a pharmacist and a general practitioner classified the problems into those with low and those with (potential) clinical relevance. Factors possibly associated with PCP (both for all and relevant problems) were identified, and subsequently tested in multivariate models using logistic regression. RESULTS: Three hundred and ninety-eight user-related PCP were observed in 189 patients (66% of all participants). After classification of user-related PCP only 26% appeared to be of clinical relevance (26% of all participants). When including clinical relevance a shift in predominantly present problem categories is observed. Furthermore, the risk model for problems with clinical relevance contains more factors than the model which considered all problems. Factors associated with clinically relevant PCP are emotional or physical problems interfering with social life, communication skills (vision and hearing), using tablets that have to be divided, using inhaled medicines, and the number of medicines used. This risk-model has a specificity of 92% and a sensitivity of 32%. CONCLUSIONS: Although user-related PCP were seen in about two-thirds of the participants, in only one out of four participants was the PCP considered to be of clinical relevance. With inclusion of clinical relevance, other problem categories become more dominant. A specific risk model is designed to select elderly patients that are most likely to have PCP in need of more urgent intervention. Unfortunately higher specificity is accompanied by low sensitivity in the present model.

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Regional differences of antibiotic use and antibiotic resistance in the fecal indicator bacteria Escherichia coli and enterococci were determined in different cities in the south, west, and north of The Netherlands. In 1999, differences in antibiotic consumption were observed between the different regions: 11.19, 10.84, and 7.16 DDD (defined daily dosage) per 1,000 inhabitants per day, respectively. No significant regional differences were found in the prevalence of antibiotic resistance for both E. coli and enterococci. However, the differences in antibiotic consumption observed might lead to changes in antibiotic resistance in the near future. Surveillance of antibiotic use and antibiotic resistance is strongly recommended to control the development of antibiotic resistance because it provides epidemiological data to set up and control antibiotic guidelines.

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Class substitution is the substitution of a drug by another cheaper drug from the same pharmacological drug class to save costs. This principle is applied in drug formularies and reference-based drug-pricing systems. Class substitution should not only consider similarities in pharmacological mechanisms of action but should also assess whether the different drugs within the class are equivalent at a population level with respect to efficacy, effectiveness, applicability, and safety. The implementation of class substitution requires protocols as well as a monitoring system to evaluate compliance with the protocols and their effects on drug costs. In addition, specific studies are needed to establish whether undesirable effects occur at the patient level.

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A 42-year-old woman developed jaundice due to acute hepatitis several weeks after ingestion of a herbal preparation containing greater celandine (Chelidonium majus) and curcuma root, which had been prescribed by an alternative therapist due to a skin complaint. After the medication had been withdrawn, clinical recovery was rapid and the hepatic functions returned to normal within 2 months. The hepatitis was ascribed to the known hepatotoxic effects of C. majus. In view of the increasing popularity of herbal remedies, greater awareness of side effects, such as hepatotoxicity, is needed. Quite a number of herbal preparations carry the risk of liver damage. The supposed clinical effectiveness of herbal remedies does not seem to always outweigh the potential risks. In the event of non-clarified liver function disturbances the ingestion of supposedly harmless, but potentially hepatotoxic, herbal products should be considered.

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