The limitations of some European healthcare databases for monitoring the effectiveness of pregnancy prevention programmes as risk minimisation measures.

PURPOSE: Pregnancy prevention programmes (PPPs) exist for some medicines known to be highly teratogenic. It is increasingly recognised that the impact of these risk minimisation measures requires periodic evaluation. This study aimed to assess the extent to which some of the data needed to monitor the effectiveness of PPPs may be present in European healthcare databases. METHODS: An inventory was completed for databases contributing to EUROmediCAT capturing pregnancy and prescription data in Denmark, Norway, the Netherlands, Italy (Tuscany/Emilia Romagna), Wales and the rest of the UK, to determine the extent of data collected that could be used to evaluate the impact of PPPs. RESULTS: Data availability varied between databases. All databases could be used to identify the frequency and duration of prescriptions to women of childbearing age from primary care, but there were specific issues with availability of data from secondary care and private care. To estimate the frequency of exposed pregnancies, all databases could be linked to pregnancy data, but the accuracy of timing of the start of pregnancy was variable, and data on pregnancies ending in induced abortions were often not available. Data availability on contraception to estimate compliance with contraception requirements was variable and no data were available on pregnancy tests. CONCLUSION: Current electronic healthcare databases do not contain all the data necessary to fully monitor the effectiveness of PPP implementation, and thus, special data collection measures need to be instituted.

Selective serotonin reuptake inhibitor prescribing before, during and after pregnancy: a population-based study in six European regions.

OBJECTIVE: To explore the prescribing patterns of selective serotonin reuptake inhibitors (SSRIs) before, during and after pregnancy in six European population-based databases. DESIGN: Descriptive drug utilisation study. SETTING: Six electronic healthcare databases in Denmark, the Netherlands, Italy (Emilia Romagna/Tuscany), Wales and the rest of the UK. POPULATION: All women with a pregnancy ending in a live or stillbirth starting and ending between 2004 and 2010. METHODS: A common protocol was implemented across databases to identify SSRI prescriptions issued (UK) or dispensed (non-UK) in the year before, during or in the year following pregnancy. MAIN OUTCOME MEASURES: The percentage of deliveries in which the woman received an SSRI prescription in the year before, during or in the year following pregnancy. We also compared the choice of SSRIs and changes in prescribing over the study period. RESULTS: In total, 721 632 women and 862,943 deliveries were identified. In the year preceding pregnancy, the prevalence of SSRI prescribing was highest in Wales [9.6%; 95% confidence interval (CI95 ), 9.4-9.8%] and lowest in Emilia Romagna (3.3%; CI95 , 3.2-3.4%). During pregnancy, SSRI prescribing had dropped to between 1.2% (CI95 , 1.1-1.3%) in Emilia Romagna and 4.5% (CI95 , 4.3-4.6%) in Wales. The higher UK pre-pregnancy prescribing rates resulted in higher first trimester exposures. After pregnancy, SSRI prescribing increased most rapidly in the UK. Paroxetine was more commonly prescribed in the Netherlands and Italian regions than in Denmark and the UK. CONCLUSIONS: The higher SSRI prescribing rates in the UK, compared with other European regions, raise questions about differences in the prevalence and severity of depression and its management in pregnancy across Europe.

Clomiphene citrate utilization in the Netherlands 1998-2007.

BACKGROUND: Infertility is a growing problem in western societies. Few studies have examined the drug utilization of common treatments for infertility. Clomiphene citrate (CC) is the first-line treatment for normogonadotropic women with absent or irregular ovulation. We examined CC use among women at reproductive age in the northern Netherlands. METHODS: Drug dispensing data of CC between 1998 and 2007 were retrieved from the IADB.nl database. Two-year prevalences of CC use per 1000 women covered by the database were calculated and stratified by 5-year age group. The duration of CC use was analyzed using Kaplan-Meier survival analysis. RESULTS: From the IADB.nl database, a total of 1854 women aged 20-44 years initiated ovulation induction treatment with CC only in the northern Netherlands during 1998 and 2007. The 2-year prevalence of CC use increased from 6.66 per 1000 women during 1998-1999 to 7.24 per 1000 during 2002-2003, followed by a decrease to 4.82 per 1000 in 2006-2007 (P < 0.05). Median duration of CC use was four cycles for women <30 years of age, three cycles for women aged 30-39 and two cycles for women aged above 40. CONCLUSIONS: There is no increase of CC use during 1998-2007, and indeed a decrease of CC use during recent years, among women at reproductive age in northern Netherlands.

Compliance with pregnancy prevention programmes of isotretinoin in Europe: a systematic review.

Most of the publications on isotretinoin, pregnancy and compliance with the pregnancy prevention programme (PPP) originate from North America. Information specific for the European situation is very limited. The aim of this study was to identify publications describing the use of isotretinoin in humans and the compliance with the PPP in Europe, a systematic search in Medline and Embase was conducted using the terms 'isotretinoin, pregnancy (and Europe)'. Furthermore, a manual search in publications was performed. A total of 17 publications were identified. Publications consisted of case reports of exposed pregnancies, surveys among dermatologists or pharmacists and database studies evaluating compliance with the PPP. The studies and surveys dealt with groups of patients exposed to isotretinoin before or during pregnancy and/or compliance with the isotretinoin PPP. Where the information was provided, in 6-26% of cases isotretinoin was prescribed in full accordance with the PPP. Pregnancy incidence was seen in 0·2-1·0 per 1000 women of childbearing age using isotretinoin. Between 65% and 87% of these pregnancies were terminated. This review of studies in Europe performed to date shows failures in the implementation of the PPP. Therefore, the isotretinoin PPP must be scrutinized to identify whether new measures should be taken or whether the failures in the implementation need to be corrected. New measures should take into account the definition of the ultimate goal of a PPP and the acceptable burden. In the meantime, stakeholders could make a start with adjustments in the implementation of the PPP by taking responsibility and enhancing the performance by explicit instructions, monitoring the performance and adjusting, if necessary.

Association between antidepressant drug use during pregnancy and child healthcare utilisation.

OBJECTIVE: To evaluate healthcare utilisation by children who were exposed to antidepressant drug use during pregnancy and those whose mothers stopped using antidepressants before pregnancy compared with a control group. DESIGN: Cohort study. Setting Health insurance records in the Netherlands. POPULATION: A total of 38 602 children born between 2000 and 2005. METHODS: Survey of child healthcare utilisation in relation to gestational antidepressant use. MAIN OUTCOME MEASURE: Healthcare utilisation rates during the first year of life, with special emphasis to medical care related to cardiac disease. RESULTS: Children of mothers who used antidepressants during pregnancy showed increased healthcare use during the first year of life, independent of the mother's healthcare use. The relative risk of more than two visits to general practitioners was 1.5 (95% confidence interval, CI: 1.3-1.8) in the continuous antidepressant users group and 1.3 (95% CI: 1.2-1.5) in the group of children whose mothers stopped taking medication. In both study groups there was a trend towards more drug use for infections and inflammation compared with the control group. Children continuously exposed to antidepressants had an increased risk of cardiac interventions such as cardiovascular surgery or heart catheterisation, relative risk of 5.6 (95% CI: 1.8-17.4). The risk of physiotherapy was twice as high in the antidepressant group compared with the control group (relative risk 2.0; 95% CI: 1.5-2.6). CONCLUSION: Antidepressant use during pregnancy is associated with increased child healthcare utilisation and increased risk of major cardiac interventions in early childhood.

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

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.

Treatment of pregnant and non-pregnant rheumatic patients: a survey among Dutch rheumatologists.

BACKGROUND: The aim of this study was to explore, among Dutch rheumatologists, aspects such as attitude towards guidelines, pharmacotherapy and information needs in the treatment of pregnant as well as non-pregnant rheumatoid arthritis (RA) patients. METHODS: Fifteen rheumatologists from nine different hospitals were interviewed by means of a semi-structured interview. Questions addressing attitude towards guidelines, pharmacotherapy preferences and information needs with respect to the pregnant and non-pregnant patient were asked. The analysis will be based on descriptive statistics. RESULTS: Guidelines are used by almost half of the hospitals with respect to pregnant RA patients and by all hospitals for RA patients in general. With respect to pregnant women, nine respondents preferred stopping the medication as soon pregnancy is known. When treating RA patients, in general sulfasalazine and methotrexate would be drugs of first choice. Information is found in international and national books and guidelines. CONCLUSION: Dutch rheumatologists are of the view that there is sufficient information on the treatment of RA in pregnant women or women wishing to become pregnant, except for safe use of medication during pregnancy. In the future, pregnancy risk categorization should be updated and discussed regularly. This should be based on more recent literature and experience. A good monitoring system for following all young patients with a rheumatic disease should be set up as a first step to collect more information on the safe use of medication during pregnancy.

[Folic acid fortification of bread recommendable]. / Toevoeging van foliumzuur aan brood aan te bevelen.

Folic acid supplementation was recommended in the Netherlands after it had been demonstrated that periconceptional use of folic acid protected against foetal neural tube defects; this recommendation led to a slight decrease in prevalence only. According to the Dutch Health Council, fortification of bread should now be considered. Policy-making is complicated by uncertainties regarding potential side effects, such as adverse effects in children, for which scientific evidence is lacking however.

Growing gap in folic acid intake with respect to level of education in the Netherlands.

OBJECTIVE: To evaluate the prevalence of the awareness of and the behaviour towards folic acid in 2003 and the trend of folic acid use among pregnant Dutch women between 1995 and 2003 with regard to socio-economic status (SES). METHOD: We conducted 2-yearly cross-sectional studies among pregnant women who filled in a questionnaire during the first or second antenatal visit. The highest achieved level of education was taken as a proxy for SES. RESULTS: In 2003 the general level of folic acid awareness was high but with significant differences relating to SES; a quarter of the lower educated women did not know about folic acid before pregnancy. Of the subjects with a lower SES 20% knew the correct period of use compared with nearly 50% in the higher SES group. The reported correct use of folic acid among the lower educated women has decreased over the past 3 years (22% in 2003), while it has increased for the higher SES groups (59% in 2003), implying larger differences in health. CONCLUSION: In 2003, 8 years after a mass media campaign, awareness and use of folic acid were increased considerably in comparison with the start of the campaign. However, differences in knowledge and use of folic acid with respect to the level of education had never been so impressive in the Netherlands as in 2003. A once-only campaign has a short-term effect especially for lower educated women. Implementing strategies to promote folic acid use in daily structural health care systems are needed.

Hypertrichosis as a side effect of inhaled steroids in children.

Three spontaneous reports of patients in whom a relationship between hypertrichosis and inhaled corticosteroids (ICS) was suspected, were reported to Lareb, The Netherlands Pharmacovigilance Center. We sought evidence for and against a causal relationship between hypertrichosis and ICS in children. The relationship between hypertrichosis and ICS was studied mathematically by assessing the Reporting Odds Ratio (ROR) and by determining the Naranjo Score (NS). We also studied the reports sent to the Pharmacovigilance Database of the Uppsala Monitoring Centre (UMC) of the WHO and reviewed the literature. In the Dutch children, the ROR between hypertrichosis and ICS was 14.6 (95%CI 3.6-59.5), the NS was 4. In the database of the UMC 20 more reports on hypertrichosis and ICS were found, contributing to the results of the Dutch database. Taken together, 11 boys and 12 girls were involved with a mean age of 7 years (range 1-17). The time between the start of ICS and the occurrence of hypertrichosis varied between 1 month and 3 years. Besides the hypertrichosis, growth retardation was found in 5 children and adrenal suppression in 12. In 12 children the outcome after cessation was reported: in 6 children the hypertrichosis improved, whilst in 6 it did not. We found sufficient evidence to support the suspicion that hypertrichosis might be a true adverse effect of ICS. We found no simple dose-effect relationship but obviously there is an individual susceptibility. After cessation of ICS the exaggerated hair growth will not disappear in all children. Hypertrichosis may be a useful clinical pointer to exogenous steroid excess.

Switch patterns before and after patent expiry of omeprazole: a case study in The Netherlands.

BACKGROUND: An increase of therapeutic substitution after patent expiry might have a negative effect on cost-savings generated with newly introduced generic drugs. To evaluate influences of patent expiry on therapeutic substitution, switch behaviour before and after patent expiry was investigated. AIM: To describe proton pump inhibitor use and investigate substitution patterns from omeprazole before and after patent expiry. METHODS: Data were obtained from the InterAction DataBase. Proportional proton-pump inhibitor use was identified per quarter during the study period 2000-2003. For the second part two cohorts--one before and one after patent expiry--were defined. The number of switchers was quarterly identified during 2-year follow-up period. For statistical analyses the chi-square test and hazard ratio were used. RESULTS: In proportional use, a downward trend for omeprazole was found. After patent expiry, significantly more patients switched to other proton pump inhibitors (P < 0.001). The hazard ratio of 0.62 (95% CI: 0.57-0.69), indicates that for every six patients switching before patent expiry, 10 patients switch after patent expiry. CONCLUSION: After patent expiry more patients switch to another proton pump inhibitor. In light of the total savings achieved with generic omeprazole, the importance of this negative impact on total cost-savings on proton pump inhibitors is unclear.

Folic acid--the scientific debate as a base for public health policy.

Randomized controlled trials have proven that periconceptional folic acid intake reduces the risk of neural tube defects (NTDs). This lead to different public health policies: fortification of foods in many countries and supplementation in some others. We concentrate here on pro's and con's of fortification policies. Meanwhile, new beneficial but also potential adverse effects are being hypothesized. Highest level evidence is available for the protective effect of folic acid on NTDs. Lower level evidence suggests other protective effects, but also some potential adverse effects, such as masking Vitamin B-12 deficiency, increasing twinning rates and an 'acceleration phenomenon' in pre-existing malignant neoplasms. While observational studies show lower cancer rates associated with increased folate intake, some case reports and animal experiments suggest opposite effects. Thus, public health policy makers are facing the question of balancing beneficial and potential adverse effects repeatedly. We propose that the scientific debate no longer focuses on NTDs alone, but that a comprehensive evaluation be undertaken by a public health authority with experience in complex meta-analyses and technology assessment.

Oral contraceptive use and hormone replacement therapy are associated with microalbuminuria.

BACKGROUND: Controversy exists regarding the adverse and beneficial effects of oral contraceptive use and hormone replacement therapy. Microalbuminuria is associated with increased risk of renal and cardiovascular disease. OBJECTIVE: To examine the association between oral contraceptive use or hormone replacement therapy and microalbuminuria. METHODS: We performed a case-control study of the baseline data and historical pharmacy data of 4301 female subjects of the Prevention of Renal and Vascular End Stage Disease study cohort, aged 28 to 75 years, excluding women who were pregnant or had type 1 diabetes mellitus. The main outcome measure was microalbuminuria, defined as a urinary albumin excretion of 30 to 300 mg per 24 hours (recorded as the mean of two 24-hour urine collections). RESULTS: After adjusting for age, hypertension, diabetes, obesity, hyperlipidemia, and smoking, the odds ratio (OR) for having microalbuminuria was 1.90 (95% confidence interval [CI], 1.23-2.93) for premenopausal oral contraceptive users and 2.05 (95% CI, 1.12-3.77) for postmenopausal hormone replacement therapy users. The point estimate increased in a dose-dependent fashion, albeit insignificantly, according to the estrogen content of the oral contraceptives (<30 microg ethinyl estradiol: OR, 1.11; 95% CI, 0.14-8.56; 30 to <50 microg: OR, 1.83; 95% CI, 1.17-2.87; and 50 microg: OR, 2.72; 95% CI, 0.81-9.08). The OR was greater in oral contraceptives with a second-generation (OR, 2.04; 95% CI, 1.28-3.25) vs a third-generation progestin (OR, 1.39; 95% CI, 0.63-3.06). The OR increased with the duration of hormone replacement therapy (< or =5 years, OR, 1.28; 95% CI, 0.37-4.50; >5 years, OR, 2.56; 95% CI, 1.32-4.97). CONCLUSION: Regular and long-term oral contraceptive use and hormone replacement therapy are associated with an increased risk for microalbuminuria and cardiovascular disease.

The role of hospital and community pharmacists in pharmacovigilance.

In this paper, we give an overview of the role pharmacists actually have and could have in collecting reports of adverse drug reactions (ADRs) and more widely in pharmacovigilance. In the literature, several ways are mentioned in which the pharmacist, both the community pharmacist and the hospital pharmacist, can contribute to the safe use of drugs. In addition to their responsibilities regarding drug dispensing and compliance, they can have a substantial role in ADR reporting. Especially, hospital pharmacists can play a significant role in ADR reporting because the most serious adverse drug events occur in hospitals, and ADRs account for a substantial proportion of hospital admissions. Community pharmacists, however, can also play an important role in ADR reporting. This is, for example, the case in the Netherlands where community pharmacists contribute substantially, both in numbers and in quality of ADR reports. The contribution of the pharmacist to pharmacovigilance should, however, not be limited to ADR reporting. The various pharmaceutical disciplines could also greatly enhance our understanding of the nature of ADRs. If those involved in pharmaceutical disciplines can rise to this challenge, they will significantly help deepen our insights into ADRs.

[Use of oral contraceptives in the years 1994-2002: different but not less]. / Gebruik van orale anticonceptiva in de jaren 1994-2002: wel anders, niet minder.

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.

Cost effectiveness of expanded antenatal HIV testing in London.

BACKGROUND: Recently the Department of Health announced the introduction in England of voluntary universal HIV screening in early pregnancy to prevent vertical transmission. New data have shown the importance of HIV infection in infants born to mothers who were HIV-negative in early pregnancy and who acquired HIV later in pregnancy or during lactation. This requires consideration of repeat testing in late pregnancy and testing of partners of pregnant women (expanded antenatal HIV testing). OBJECTIVE: To estimate cost effectiveness of expanded antenatal HIV testing in London (England) within the framework of universal voluntary HIV screening in early pregnancy. DESIGN: Incremental cost-effectiveness analysis. METHODS: Cost estimates of service provision for HIV-positive children and adults by stage of HIV infection were combined with estimates of health benefits for infants and parents and with costs of counselling and testing (testing costs). In a pharmacoeconomic model cost effectiveness was estimated for expanded antenatal HIV testing in London for universal and selective strategies. RESULTS: Testing costs in the plausible range of pounds sterling 4 to pounds sterling 40 translate into favourable incremental cost-effectiveness estimates for expanded antenatal HIV testing in London which is already at low numbers of vertical transmissions averted per 100000 pregnant women who test HIV-negative in early pregnancy. Favourable cost effectiveness for universal expanded testing would require testing costs in the lower range, whereas selective expanded testing may produce favourable cost effectiveness at testing costs close to pounds sterling 40. CONCLUSION: Based on pharmaco-economic considerations, the authors believe that implementation of expanded HIV testing in London should be considered.

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.

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.

Drug-related problems in hospitalised patients.

Drug-related problems include medication errors (involving an error in the process of prescribing, dispensing, or administering a drug, whether there are adverse consequences or not) and adverse drug reactions (any response to a drug which is noxious and unintended, and which occurs at doses normally used in humans for prophylaxis, diagnosis or therapy of disease, or for the modification of physiological function). Furthermore, adverse drug events can be defined as an injury--whether or not causally-related to the use of a drug. Drug-related problems are relatively common in hospitalised patients and can result in patient morbidity and mortality, and increased costs. In order to get an overview of studies on drug-related problems in hospitalised patients, with specific attention to the incidence of drug-related problems and their costs, to the possibilities of prevention and to the effect of these interventions, we performed a literature search. Incidences of medication errors reported in studies vary widely. The range of reported incidences of adverse drug reactions is even wider. These wide ranges can be largely explained by the different study methods and definitions used. Problems related to drug therapy may be averted by preventive interventions. Several possibilities for prevention exist, especially for the prevention of medication errors. Prescribing, transcription and interpretation errors can be reduced by using computerised physician order entry. Together with the use of automated dispensing systems and bar-code technology, this will aid in the reduction of both dispensing and administration errors. Education of nursing staff involved in the process of drug distribution is another important measure for preventing medication errors. Finally, the introduction of systems for the early detection of adverse drug reactions may help to reduce problems related to drug therapy. Identifying risk factors that contribute to the development of adverse drug reactions, may aid in the prevention of these reactions.

Changing prescribing in the light of tolerability concerns: how is this best achieved?

Despite our knowledge regarding the efficacy, tolerability and optimal use of drugs, suboptimal prescribing still occurs. In view of all the factors that influence prescribing, this is not surprising. The focus of drug tolerability has changed from 'choosing the best alternative' when a drug is prescribed, to a balanced decision incorporating various different treatments from separate healthcare providers. This article reviews strategies that may influence prescribing behaviour and discusses practical considerations for achieving optimal prescribing in view of tolerability concerns. The patient has a major influence on prescribing and, with the current diversification of healthcare, the patient now controls prescribing behaviour more than ever before. Communication between healthcare providers consequently assumes a vital role. If messages are to be coherent and transferable, it is increasingly important that healthcare workers communicate effectively with one another regarding patients, prescribing patterns, and drug tolerability issues.