Nature and frequency of prescription modifications in community pharmacies: A nationwide study in the Netherlands.

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.

Feasibility of point-of-care creatinine testing in community pharmacy to monitor drug therapy in ambulatory elderly patients.

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.

Genotypes associated with reduced activity of VKORC1 and CYP2C9 and their modification of acenocoumarol anticoagulation during the initial treatment period.

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.

Prevalence and determinants of pharmacy shopping behaviour.

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.

Vitamin K epoxide reductase complex subunit 1 (VKORC1) polymorphism and aortic calcification: the Rotterdam Study.

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.

Antibiotic prescribing in primary care: first choice and restrictive prescribing are two different traits.

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.

[Thyrotoxicosis following the use of ashwagandha]. / Thyreotoxicose na gebruik van Ashwagandha.

A 32-year-old healthy woman developed thyrotoxicosis while taking capsules that contained ashwagandha herbal extract for symptoms of chronic fatigue. She was not taking any other remedies or medications. During the first few weeks, she took the capsules only occasionally without any symptoms, but after increasing the dose, she experienced clinical symptoms indicative of thyrotoxicosis. This was confirmed by laboratory assessment. The symptoms resolved spontaneously after discontinuation of the ashwagandha capsules and laboratory values normalised. To our knowledge, this relationship has not been reported previously in humans. Data from animal studies, however, have suggested that ashwagandha can increase serum concentrations of thyroid hormones. This case study suggests that thyrotoxicosis is a potentially serious side effect of ashwagandha.

Gender and regional differences in perceived job stress across Europe.

BACKGROUND: Over the last 20 years stress at work has been found to be predictive of several conditions such as coronary heart disease, high blood pressure and non-specific sick leave. The Karasek demand/control/strain concept has been the most widely used in prospective epidemiological studies. OBJECTIVES: To describe distribution in Karasek's demand/control (DC) dimensions as well as prevalence of strain in samples from different parts of Europe grouped into three regions (South, Middle, Sweden), adjusting for occupation. To describe gender differences in Karasek's DC dimensions along with strain prevalence and assess the regional stability of those differences in different occupational groups. DESIGN: The Job stress, Absenteeism and Coronary heart disease in Europe (JACE) study, a Concerted Action (Biomed I) of the European Union, is a multicentre prospective cohort epidemiological study: 38,019 subjects at work aged 35-59 years were surveyed at baseline. Standardised techniques were used for occupation coding (International Standardised Classification of Occupations) and for the DC model (Karasek scale): five items for the psychological demand and nine items for the control or decision latitude dimensions, respectively. RESULTS: A total of 34,972 subjects had a complete data set. There were important regional differences in the Karasek scales and in prevalence of strain even after adjustment for occupational class. Mean demand and control were higher in the Swedish centres when compared to two centres in Milano and Barcelona (Southern region) and values observed in four centres (Ghent, Brussels, Lille and Hoofddorp) in Middle Europe were closer to those observed in the Southern cities than to those obtained in the Swedish cities. Clerks (ISCO 4) and, more specifically, office clerks (ISCO 41) exhibited the smallest regional variation. In a multivariate model, the factor 'region' explained a small fraction of total variance. In the two Southern centres as well as in the four Middle European centres, men perceived marginally less job-demand as compared to women whereas the reverse was observed in the two Swedish centres. Differences were larger for control: men appeared to perceive more control at work than did women. In a multivariate model, gender explained a small fraction whereas occupational level explained a large fraction of the variance. CONCLUSIONS: In this standardised multicentre European study Karasek's DC model showed large gender and occupational differences whereas geographic region explained a small fraction of the total DC variance, notwithstanding large differences in labour market and working conditions as pointed out by the European Commission as recently as 2000.

User-related pharmaceutical care problems and factors affecting them: the importance of clinical relevance.

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.

Perceived job stress and incidence of coronary events: 3-year follow-up of the Belgian Job Stress Project cohort.

Psychosocial characteristics have been linked to coronary heart disease. In the Belgian Job Stress Project (1994-1999), the authors examined the independent role of perceived job stress on the short-term incidence of clinical manifest coronary events in a large occupational cohort. A total of 14,337 middle-aged men completed the Job Content Questionnaire to determine the dimensions of the extended job strain model, job demands, decision latitude, and social support. Jobs were categorized into high strain, low strain, active jobs, and passive jobs. During the 3-year follow-up, 87 coronary events were registered. At baseline, 17% of workers experienced high strain. Job demands and decision latitude were not significantly related to the development of coronary heart disease after adjustment for covariates. The 38% risk excess among subjects classified in the high-strain category did not reach statistical significance. However, coronary heart disease incidence was substantially associated with the social support scale independently of other risk factors, with an adjusted hazard ratio of 2.4 (95% confidence interval: 1.4, 4.0) between extreme tertiles. No convincing evidence for an association of job demands, decision latitude, or job strain with the short-term incidence of coronary heart disease was found. However, our study underscores the importance of a supportive social work environment in the prevention of coronary heart disease.

Occupational stress and incidence of sick leave in the Belgian workforce: the Belstress study.

CONTEXT: Sick leave is a major problem in public health. The Karasek demands/control/social support/strain (JDCS) model has been largely used to predict a wide range of health outcomes and to a lesser extent sickness absence. STUDY OBJECTIVE: The aim of the study was to test the predictive power of the JDCS model in relation with one year incidence of sick leave in a large cohort of workers. DESIGN AND SETTING: Cohort study conducted between 1994 and 1998 in 25 companies across Belgium. PARTICIPANTS: A total of 20 463 workers aged 35 to 59 years were followed up for sick leave during one year after the baseline survey. OUTCOMES: The outcomes were a high sick leave incidence, short spells (>/=7 days), long spells (>/=28 days), and repetitive spells of sickness absence (>/=3 spells/year). MAIN RESULTS: Independently from baseline confounding variables, a significant association between high strained jobs with low social support and repetitive spells of sickness absence was observed in both sexes with odds ratios of 1.32 (99% CI, 1.04 to 1.68) in men and 1.61 (99% CI, 1.13 to 2.33) in women. In men, high strained jobs with low social support was also significantly associated with high sick leave incidence, and short spells of sick leave with odds ratios of 1.38 (99% CI, 1.16 to 1.64) and 1.22 (99% CI, 1.05 to 1.44) respectively. CONCLUSIONS: Perceived high strain at work especially combined with low social support is predictive of sick leave in both sexes of a large cohort of the Belgian workforce.

Obesity, body fat distribution and incidence of sick leave in the Belgian workforce: the Belstress study.

OBJECTIVES: In many studies, obesity has been associated with morbidity or mortality, but only a few have studied the relation between obesity and sick leave. Our aim is to analyse the independent effects of both adiposity and body fat distribution in relation to the 1-y incidence of sick leave in a large cohort of male and female workers covering a variety of occupations, taking into account a wide range of socio-demographic, behavioural and bioclinical variables. DESIGN AND SETTING: The baseline survey of the Belstress study was conducted in 25 companies across Belgium between 1994 and 1998. A cohort of 20 463 workers (15 557 males and 4906 females) aged 35-59 y was followed for absenteeism during 1 y. The 75th percentile of the distribution of the total annual sickness days was used as a cutoff to classify the workers with a high 1-y incidence rate of sick leave. The relation between sick leave and both obesity and body fat distribution assessed by the body mass index (BMI) and the waist circumference, respectively, was analysed by multivariate logistic regression models. RESULTS: Using a backward procedure based on the likelihood ratio, we found central abdominal fatness to be an independent predictor of sick leave in both genders (high sick-leave incidence and long spells), but not BMI. In men, the odds ratios was 1.31 (99% CI 1.12-1.52, P<0.0001) and in women it ranged from 1.32 (99% CI 1.03-1.70, P=0.005) to 1.47 (99% CI 1.14-1.90, P<0.0001). Two baseline covariables, respiratory problems and perceived health, are confounders or mediators. CONCLUSIONS: In this study, body fat distribution was associated with a high annual sick-leave incidence and long spells of sickness absence. If this link is reversible, employers may benefit from programs aiming at the prevention and treatment of central obesity.

Calcineurin and intracellular Ca2+-release channels: regulation or association?

The Ca(2+)- and calmodulin-dependent phosphatase calcineurin was reported to interact with the inositol 1,4,5-trisphosphate receptor (IP(3)R) and the ryanodine receptor (RyR) and to modulate their phosphorylation status and activity. However, controversial data on the molecular mechanisms involved and on the functional relevance of calcineurin for these channel-complexes have been described. Hence, we will focus on the functional importance of calcineurin for IP(3)R and RyR function and on the different mechanisms by which Ca(2+)-dependent dephosphorylation can affect the gating of those intracellular Ca(2+)-release channels. Since many studies made use of immunosuppressive drugs that are inhibiting calcineurin activity, we will also have to take the different side effects of these drugs into account for the proper interpretation of the effects of calcineurin on intracellular Ca(2+)-release channels. In addition, it became recently known that various other phosphatases and kinases can associate with these channels, thereby forming macromolecular complexes. The relevance of these enzymes for IP(3)R and RyR functioning will be reviewed since in some cases they could interfere with the effects ascribed to calcineurin. Finally, we will discuss the downstream effects of calcineurin on the regulation of the expression levels of intracellular Ca(2+)-release channels as well as the relation between IP(3)R- and RyR-mediated Ca(2+) release and calcineurin-dependent gene expression.

Antibiotic use and the prevalence of antibiotic resistance in bacteria from healthy volunteers in the dutch community.

BACKGROUND: Although most antibiotics are consumed in the community (80%), the relation of antibiotic consumption and resistance in the community has not been thoroughly studied. MATERIALS AND METHODS: In the present study, antibiotic use was related to the prevalence of antibiotic resistance of Escherichia coli and enterococci isolated from healthy volunteers living in the southern part of the Netherlands in 1996 and 1999. RESULTS: No change in the total antibiotic use in the Dutch community was observed between 1996 and 1999 (3542 and 3598 defined daily doses [DDD] per 1000 inhabitants/year). However, the increased fluoroquinolone use (+ 18%) and the increased prevalence of ciprofloxacin resistance from 0 to 2% is a point of concern, especially since this was accompanied by a significant shift towards higher minimum inhibitory concentration (MIC) values (p < 0.05). A significant decrease in the prevalence of vancomycin-resistant enterococci (p < 0.05) was found in addition to a significant shift towards lower MIC valued for avoparcin, a glycopeptide previously used as growth promoter in animal husbandry (p < 0.05). This was very likely due to the banning of avoparcin for this purpose from April 1997 onwards. CONCLUSION: In order to maintain the low level of antibiotic use and resistance in The Netherlands, surveillance of antibiotic resistance in nonclinical isolates in relation to antibiotic use is very important.

Job conditions and fibrinogen in 14226 Belgian workers: the Belstress study.

AIMS: To investigate the relationship between fibrinogen and stressful work conditions, where perceived strain is defined by the simultaneous presence of high psychological demands and low control, according to Karasek's Demand/Control/(Social Support) model. METHODS AND RESULTS: A cross-sectional study was realized between 1994 and 1998 in 24 Belgian enterprises, on 16335 male and 5084 female middle-aged workers of different Belgian companies participating in the Belstress study. This study confirmed the well-documented bivariate relationship between plasma fibrinogen levels and gender, age, educational level, smoking, obesity, physical activity, alcohol consumption, total cholesterol, HDL-cholesterol, arterial hypertension and diabetes. No independent multivariate relationship was observed between job control, psychological job demands or social support at work and plasma fibrinogen, but after stratification a positive association (P< or =0.05) was observed between psychological job demands and plasma fibrinogen for males in the lowest educational level. Moreover a positive statistically significant association between job strain and plasma fibrinogen was observed in males but not in females. After stratification for educational level this association remained significant for males especially in the lowest educational level (P< or =0.001) and became significant for females in the middle educational level. CONCLUSIONS; As suggested in our study and others, plasma fibrinogen could be one of the potential mediators explaining the relationship between job stress and coronary heart disease.

Antibiotic usage and resistance in different regions of the Dutch community.

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.

IP(3)-mediated Ca(2+) signals in human neuroblastoma SH-SY5Y cells with exogenous overexpression of type 3 IP(3) receptor.

Human neuroblastoma SH-SY5Y cells, predominantly expressing type 1 inositol 1,4,5-trisphosphate (IP(3)) receptor (IP(3)R), were stably transfected with IP(3)R type 3 (IP(3)R3) cDNA. Immunocytochemistry experiments showed a homogeneous cytoplasmic distribution of type 3 IP(3)Rs in transfected and selected high expression cloned cells. Using confocal Ca(2+) imaging, carbachol (CCh)-induced Ca(2+) release signals were studied. Low CCh concentrations (< or = 750 nM) evoked baseline Ca(2+) oscillations. Transfected cells displayed a higher CCh responsiveness than control or cloned cells. Ca(2+) responses varied between fast, large Ca(2+) spikes and slow, small Ca(2+) humps, while in the clone only Ca(2+) humps were observed. Ca(2+) humps in the transfected cells were associated with a high expression level of IP(3)R3. At high CCh concentrations (10 microM) Ca(2+) transients in transfected and cloned cells were similar to those in control cells. In the clone exogenous IP(3)R3 lacked the C-terminal channel domain but IP(3)-binding capacity was preserved. Transfected cells mainly expressed intact type 3 IP(3)Rs but some protein degradation was also observed. We conclude that in transfected cells expression of functional type 3 IP(3)Rs causes an apparent higher affinity for IP(3). In the clone, the presence of degraded receptors leads to an efficient cellular IP(3) buffer and attenuated IP(3)-evoked Ca(2+) release.

[Health inequalities: self-reported complaints and their predictors in pupils from Belgium].

BACKGROUND: This paper identifies socioeconomic and sociodemographic predictors of respiratory/allergic health problems and subjective complaints in adolescents in Belgium. METHODS: A cross-sectional analysis of the 1998 cross-national study "Health Behaviour of School aged Children" (HBSC) in French-speaking Belgium was undertaken. The survey was based on a self-completed questionnaire concerning various aspects of physical, emotional and social health. The five health problems (asthma, any other respiratory difficulty, allergy, poor subjective health, overweight and depressed feeling) were considered present when a positive reply was given to close-end questions stating if the pupils suffered, or have suffered from these problems during the last six months. We analysed a representative sample of 12,012 pupils aged 11 to 19 years in fifth and sixth grades of primary school, and in all six grades of secondary school. RESULTS: socioeconomics gradients were found for subjective ill health, depressed state and overweight (p<0.01). Depressed state and overweight were linearly associated with a family economic score. Respiratory difficulties and allergies were observed mainly in pupils in technical training. CONCLUSION: Pupils with a lower economic score have a higher prevalence of subjective complaints. It remains important to define determinants of subjective ill health and moreover, to act upon these results by increasing accessibility to health services when necessary, by adapting some others to young people and by tailoring interventions to objective and self-perceived needs.

[Class substitution as an instrument of efficiency in the supply of medicines: possibilities and limitations]. / Klassensubstitutie als doelmatigheidsinstrument in de geneesmiddelenvoorziening: mogelijkheden en beperkingen.

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.