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A new technique, mini-FLOTAC, has recently been developed for the microscopic diagnosis of infections with gastro-intestinal nematodes in domestic animals. In this comparative study of diagnostic techniques, the mini-FLOTAC technique was compared to the commonly used McMaster technique for the detection and quantification of gastro-intestinal parasites in livestock as well as for the evaluation of the time needed to perform the assays. One hundred fecal samples (78 horses, 11 bovines, 6 sheep and 5 goats) were examined with both the mini-FLOTAC and McMaster technique. This revealed that more infections with gastro-intestinal parasites could be diagnosed with the mini-FLOTAC technique than with the McMaster technique, but the comparative study also showed a very high correlation (correlation coefficient = 0.90, p < 0.001) between both techniques regarding the number of eggs per gram feces (EPG) detected. The time needed to examine the samples with the mini-FLOTAC technique (13 minutes) was significantly higher (P < 0.05) than the time needed with the McMaster technique (6 minutes). This difference in time also depended on the observed EPG value, as with high EPG values, the difference in time between both techniques increased even more. In conclusion, the mini-FLOTAC technique can be preferred when an accurate diagnosis of a low infection level is necessary, e.g. to detect anthelmintic resistance. In other circumstances, the faster McMaster technique can be considered as the preferable technique.

Objective: The aim of this retrospective pilot study was to investigate whether other modern antidepressants than fluoxetine show low steady state plasma concentrations during pregnancy. The second aim of this study was to investigate the relationship between possibly lower blood levels and the score on the Montgomery-Asberg Depression Rating Scale (MADRS). Design and methods: In Bronovo hospital 12 mothers taking paroxetine were enrolled in the study. Trough plasma samples, collected 3 times during pregnancy and 1 time postpartum according to the standard Antidepressants and pregnancy in Bronovo hospital, were studied. The efficacy of the paroxetine treatment was evaluated with scores on the MADRS during pregnancy and postpartum. Results: Paroxetine concentrations were lower in the third trimester than in the first trimester (p = 0,011) and higher postpartum than in the third trimester (p = 0,012). MADRS scores were higher in the third trimester than in the first trimester (p = 0,041) and lower postpartum than in the third trimester (p = 0,017). There was no significant relationship between lower paroxetine concentrations and lower scores on the depression severity scale. Conclusion: Paroxetine concentrations decrease during pregnancy. No significant relationship was found between lower paroxetine concentrations and lower scores on the depression severity scale. Clinicians should be alert to the possibility that depression in pregnancy is under-treated. A multidisciplinary standard for hospital settings to deal with the use of antidepressants during pregnancy is important. Therapeutic drug monitoring can be useful in this respect.

Objective: The aim of this retrospective pilot study was to investigate whether other modern antidepressants than fluoxetine show low steady state plasma concentrations during pregnancy. The second aim of this study was to investigate the relationship between possibly lower blood levels and the score on the Montgomery-Asberg Depression Rating Scale (MADRS). Design and methods: In Bronovo hospital 12 mothers taking paroxetine were enrolled in the study. Trough plasma samples, collected 3 times during pregnancy and 1 time postpartum according to the standard Antidepressants and pregnancy in Bronovo hospital, were studied. The efficacy of the paroxetine treatment was evaluated with scores on the MADRS during pregnancy and postpartum. Results: Paroxetine concentrations were lower in the third trimester than in the first trimester (p = 0,011) and higher postpartum than in the third trimester (p = 0,012). MADRS scores were higher in the third trimester than in the first trimester (p = 0,041) and lower postpartum than in the third trimester (p = 0,017). There was no significant relationship between lower paroxetine concentrations and lower scores on the depression severity scale. Conclusion: Paroxetine concentrations decrease during pregnancy. No significant relationship was found between lower paroxetine concentrations and lower scores on the depression severity scale. Clinicians should be alert to the possibility that depression in pregnancy is under-treated. A multidisciplinary standard for hospital settings to deal with the use of antidepressants during pregnancy is important. Therapeutic drug monitoring can be useful in this respect.

There are a number of effective but highly toxic drugs that exhibit a narrow therapeutic index and marked intersubject pharmacokinetic variability. Optimal therapy with such drugs requires therapeutic drug monitoring (TDM) in order to safely obtain the desired clinical effects. A systematic review was carried out to document the cost-effectiveness of TDM. The Cochrane database and Medline were searched. Reference lists of articles found were searched manually for relevant articles. Very few studies are performed that document the cost-effectiveness of TDM. Only for aminoglycosides it has been demonstrated that TDM is cost-effective. For the other classes of TDM drugs, its rationale has been made plausible, but cost-effectiveness has not been investigated. Since the use of many of these drugs would contain risks of underdosing or overdosing without TDM, emphasis should not be placed on its cost-effectiveness, but rather on how to use it in the most cost-effective and clinically effective manner possible.

BACKGROUND: There is an increasing interest in the treatment of psychiatric symptoms with anticonvulsants, especially in the treatment of refractory patients. It is questionable whether or not the efficacy of anticonvulsants as psychotropic drugs is sufficiently verified. AIM: To examine the efficacy ofanticonvulsants based on the available studies. Possible indications considered are aggression, anxiety, psychosis and alcohol and cocaine withdrawal symptoms. METHOD: Relevant literature is derivedfor the period between 1966 till now from Medline, Embase, the Cochrane Library and PsycInfo, using as key words anticonvulsants, antiepileptics, carbamazepine, (sodium)valproate, valproic acid, divalproex, clonazepam, oxcarbazepine, lamotrigine, vigabatrin, topiramate, gabapentin, phenytoin, diphenylhydantoin, mental disorders, epilepsy, affective disorders and trials. RESULs: Forty-six studies were included, which explored the efficacy of carbamazepine, clonazepam, phenytoin, gabapentin and valproic acid. The efficacy of carbamazepine in the treatment of aggression and of clonazepam in the treatment of the panic disorder are sufficientty verified. The additional value of carbamazepine and valproic acidfor alcohol withdrawal is the increased rate of improvement. In the treatment of psychosis there is some evidence for the efficacy of anticonvulsants, especially as suppleraentary treatraent. CONCLUSIONS: Carbamazepine is effective in the treatment of aggression and alcohol withdrawal. Clonazepam is effective in the treatment of the panic disorder. Concerning the other applications, there are indicationsfor the efficacy of anticonvulsants. Additional research is needed to obtain more evidence for the support of these applications.

In this paper we consider the Dutch guidelines for pharmacoeconomic research in relation to recently published pharmacoeconomic analyses. The Dutch guidelines specify 19 aspects. We investigated whether analyses already adhered to five methodological guidelines: the societal perspective should be taken; an adequate time horizon for analysis should be deployed; explicit distinction should be made between efficacy and effectiveness; an incremental approach should be taken; and costs, benefits and health effects should be discounted. Studies were selected if published in Dutch in the period 1991-2002, resulting in a total of 20 studies selected. The majority of studies already adhered to 4 of the 5 the guidelines, suggesting that no major changes in conducting studies is required. However, less than 50% of the studies already adhered to the guideline on the societal perspective. In particular, indirect costs of production losses were often not included. We conclude that with respect to adherence to the Dutch guidelines for pharmacoeconomic research, inclusion of indirect costs into pharmacoeconomic analyses presents an important challenge for Dutch pharmacoeconomist in the upcoming years.

In this paper we consider the Dutch guidelines for pharmacoeconomic research in relation to recently published pharmacoeconomic analyses. The Dutch guidelines specify 19 aspects. We investigated whether analyses already adhered to five methodological guidelines: the societal perspective should be taken; an adequate time horizon for analysis should be deployed; explicit distinction should be made between efficacy and effectiveness; an incremental approach should be taken; and costs, benefits and health effects should be discounted. Studies were selected if published in Dutch in the period 1991-2002, resulting in a total of 20 studies selected. The majority of studies already adhered to 4 of the 5 the guidelines, suggesting that no major changes in conducting studies is required. However, less than 50% of the studies already adhered to the guideline on the societal perspective. In particular, indirect costs of production losses were often not included. We conclude that with respect to adherence to the Dutch guidelines for pharmacoeconomic research, inclusion of indirect costs into pharmacoeconomic analyses presents an important challenge for Dutch pharmacoeconomist in the upcoming years.

This article evaluates the efficacy, safety, incidence and reason of withdrawal of leflunomide in an outpatient population in Friesland (the Netherlands) with rheumatoid arthritis in a setting of care-as-usual. A large part of the population showed a good or moderate response on leflunomide. Adverse events were generally mild. Most frequently reported were gastrointestinal and dermal events. No potential risk factors for leflunomide withdrawal were found.

This article evaluates the efficacy, safety, incidence and reason of withdrawal of leflunomide in an outpatient population in Friesland (the Netherlands) with rheumatoid arthritis in a setting of care-as-usual. A large part of the population showed a good or moderate response on leflunomide. Adverse events were generally mild. Most frequently reported were gastrointestinal and dermal events. No potential risk factors for leflunomide withdrawal were found.

In The Netherlands anti-TNF-therapy, etanercept and infliximab, has become available for treatment of rheumatoid arthritis in patients with inadequate response to conventional therapy. The first randomized, clinical trials show good efficacy and (short term) safety, in monotherapy as well as in combination with methotrexate. Safety and efficacy on the long term are currently the most important questions concerning the use of etanercept and infliximab. This article provides an overview of the results of randomized, clinical trials and considerations for the use of anti-TNF-therapy.

In The Netherlands anti-TNF-therapy, etanercept and infliximab, has become available for treatment of rheumatoid arthritis in patients with inadequate response to conventional therapy. The first randomized, clinical trials show good efficacy and (short term) safety, in monotherapy as well as in combination with methotrexate. Safety and efficacy on the long term are currently the most important questions concerning the use of etanercept and infliximab. This article provides an overview of the results of randomized, clinical trials and considerations for the use of anti-TNF-therapy.

The goal of therapeutic drug monitoring (TDM) is to maximise the effect of drug therapy and to minimise toxicity. TDM is meaningful if on the one hand there is a relationship between the serum concentration of the drug and its effect and on the other hand there is no obvious relationship between dose and efficacy due to wide interindividual variability in pharmacokinetics. In case of digoxin, phenytoin, carbamazepine and valproic acid interindividual pharmacokinetics can vary to such an extent, that drug therapy should be guided by determination of serum drug levels.

The goal of therapeutic drug monitoring (TDM) is to maximise the effect of drug therapy and to minimise toxicity. TDM is meaningful if on the one hand there is a relationship between the serum concentration of the drug and its effect and on the other hand there is no obvious relationship between dose and efficacy due to wide interindividual variability in pharmacokinetics. In case of digoxin, phenytoin, carbamazepine and valproic acid interindividual pharmacokinetics can vary to such an extent, that drug therapy should be guided by determination of serum drug levels.

Recently, two importance articles about St. John's wort (Hypericum perforatum) appeared in the medical literature: a randomised clinical trial comparing St. John's wort with placebo and imipramine and a commentary about interactions between St. John's wort and registered medicines. These publications are discussed in the broader perspective of a benefit-risk assessment.

Recently, two importance articles about St. John's wort (Hypericum perforatum) appeared in the medical literature: a randomised clinical trial comparing St. John's wort with placebo and imipramine and a commentary about interactions between St. John's wort and registered medicines. These publications are discussed in the broader perspective of a benefit-risk assessment.

On the Dutch market soon the first COX-2-selective NSAID's will become available. Because these agents selective inhibit the isoenzyme that is involved in inflammation, these drugs will show a better effectiveness/safety ratio, compared to classic NSAID's. In this article we present the current insights on COX-2-NSAID's.

On the Dutch market soon the first COX-2-selective NSAID's will become available. Because these agents selective inhibit the isoenzyme that is involved in inflammation, these drugs will show a better effectiveness/safety ratio, compared to classic NSAID's. In this article we present the current insights on COX-2-NSAID's.

Aim: We tried to get insight into the usefulness of a large-scale pneumococcal immunization program among elderly in Dutch general practice. Design: Systematic review of the literature. Methods: We searched for relevant publications on six different aspects of usefulness in Online Contents (1992-1997), Science Citation Index (1992-1997) and Medline (1996- 1997). Effectiveness studies were ranked according to level of validity and precision. Cited cost-effectiveness analyses determined prevalent direct costs from a societal perspective. Results: Among all pneumococcal infections, pneumonia has most impact on public health but valid and precise data on incidence rates in general practice are lacking. Pneumococcal polysaccharide vaccines induce a protective antibody response in patients at risk. Until now, data on clinical vaccine effectiveness are controversial. Immunization of elderly patients can efficiently be carried out in the GP's office, but annual costs will exceed 16 million guilders. Cost-effectiveness estimates calculated for the situation in the Netherlands, Belgium and United States range from savings to more than NLG 65.000,- per live-year saved. Data on the incremental effectiveness as opposed to influenza vaccination alone are not available yet. Conclusion: Evidence for usefulness of large-scale immunization of elderly against pneumococci is conflicting and its introduction in Dutch general practice seems therefore premature.

Aim: We tried to get insight into the usefulness of a large-scale pneumococcal immunization program among elderly in Dutch general practice. Design: Systematic review of the literature. Methods: We searched for relevant publications on six different aspects of usefulness in Online Contents (1992-1997), Science Citation Index (1992-1997) and Medline (1996- 1997). Effectiveness studies were ranked according to level of validity and precision. Cited cost-effectiveness analyses determined prevalent direct costs from a societal perspective. Results: Among all pneumococcal infections, pneumonia has most impact on public health but valid and precise data on incidence rates in general practice are lacking. Pneumococcal polysaccharide vaccines induce a protective antibody response in patients at risk. Until now, data on clinical vaccine effectiveness are controversial. Immunization of elderly patients can efficiently be carried out in the GP's office, but annual costs will exceed 16 million guilders. Cost-effectiveness estimates calculated for the situation in the Netherlands, Belgium and United States range from savings to more than NLG 65.000,- per live-year saved. Data on the incremental effectiveness as opposed to influenza vaccination alone are not available yet. Conclusion: Evidence for usefulness of large-scale immunization of elderly against pneumococci is conflicting and its introduction in Dutch general practice seems therefore premature.

There are a number of effective but highly toxic drugs that exhibit a narrow therapeutic index and marked intersubject pharmacokinetic variability. Optimal therapy with such drugs requires therapeutic drug monitoring (TDM) in order to safely obtain the desired clinical effects. A systematic review was carried out to document the cost-effectiveness of TDM. The Cochrane database and Medline were searched. Reference lists of articles found were searched manually for relevant articles. Very few studies are performed that document the cost-effectiveness of TDM. Only for aminoglycosides it has been demonstrated that TDM is cost-effective. For the other classes of TDM drugs, its rationale has been made plausible, but cost-effectiveness has not been investigated. Since the use of many of these drugs would contain risks of underdosing or overdosing without TDM, emphasis should not be placed on its cost-effectiveness, but rather on how to use it in the most cost-effective and clinically effective manner possible.

BACKGROUND: There is an increasing interest in the treatment of psychiatric symptoms with anticonvulsants, especially in the treatment of refractory patients. It is questionable whether or not the efficacy of anticonvulsants as psychotropic drugs is sufficiently verified. AIM: To examine the efficacy ofanticonvulsants based on the available studies. Possible indications considered are aggression, anxiety, psychosis and alcohol and cocaine withdrawal symptoms. METHOD: Relevant literature is derivedfor the period between 1966 till now from Medline, Embase, the Cochrane Library and PsycInfo, using as key words anticonvulsants, antiepileptics, carbamazepine, (sodium)valproate, valproic acid, divalproex, clonazepam, oxcarbazepine, lamotrigine, vigabatrin, topiramate, gabapentin, phenytoin, diphenylhydantoin, mental disorders, epilepsy, affective disorders and trials. RESULs: Forty-six studies were included, which explored the efficacy of carbamazepine, clonazepam, phenytoin, gabapentin and valproic acid. The efficacy of carbamazepine in the treatment of aggression and of clonazepam in the treatment of the panic disorder are sufficientty verified. The additional value of carbamazepine and valproic acidfor alcohol withdrawal is the increased rate of improvement. In the treatment of psychosis there is some evidence for the efficacy of anticonvulsants, especially as suppleraentary treatraent. CONCLUSIONS: Carbamazepine is effective in the treatment of aggression and alcohol withdrawal. Clonazepam is effective in the treatment of the panic disorder. Concerning the other applications, there are indicationsfor the efficacy of anticonvulsants. Additional research is needed to obtain more evidence for the support of these applications.