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Biomedical subjects

A de Boer

Publications and source records attributed to A de Boer.

At least 19 recordsLinked to original sources
PubMed2007

Identification of responders and reactive domains to rivastigmine in Alzheimer's disease.

PURPOSE: Presently, it is unclear which patients suffering from Alzheimer's Disease (AD) respond to rivastigmine and if rivastigmine acts on specific cognitive domains. The aims of this study are thus to investigate treatment effects of rivastigmine on specific cognitive domains and to find possible responsive subpopulations to rivastigmine cognitive effects. METHODS: Mini Mental State Examination (MMSE) and Cambridge Cognitive Examination (CAMCOG) were administered at baseline and after 6 months in 83 rivastigmine users and 96 historical controls, representing natural decline. Treatment effects on different subsections of the CAMCOG and in different subpopulations were investigated by linear regression analyses. RESULTS: Rivastigmine showed effectiveness on total CAMCOG (p < 0.001), CAMCOG non-memory subsection (p < 0.001) and subscales of language (p = 0.002), attention/calculation (p = 0.043), abstract thinking (p < 0.001) and perception (p = 0.031). In patients with baseline MMSE < or =19 rivastigmine showed significant and favourable effects compared to historical controls on total CAMCOG (p < 0.001) and both non-memory (p < 0.001) and memory subsections (p = 0.002). CONCLUSION: Rivastigmine showed primarily effectiveness on the non-memory section of the CAMCOG and patients with a baseline MMSE < or = 19 appeared to show greater responses to rivastigmine compared to patients with baseline MMSE > or = 20.

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PubMed2006

VKORC1 and CYP2C9 genotypes and phenprocoumon anticoagulation status: interaction between both genotypes affects dose requirement.

In a prospective follow-up study of the effects of VKORC1 and CYP2C9 genotypes on the anticoagulation status of patients, we assessed the CYP2C9 and the VKORC1 C1173T genotypes of patients during the initial 6 months of phenprocoumon treatment. We used linear regression models and Cox proportional hazard models to determine the effects of the VKORC1 and CYP2C9 genotypes on phenprocoumon dose requirements, overanticoagulation, and time to achieve stability. Allele frequencies of interest within the cohort (N=281) were 40.8% VKORC1 T-1173, 12.8% CYP2C9*2, and 6.9% CYP2C9*3. In patients with the VKORC1 CC genotype, carriers of a CYP2C9 polymorphism needed dosages that were nearly 30% lower than those for CYP2C9*1/*1 patients (P<0.001). In patients with a VKORC1 polymorphism, differences between carriers of a CYP2C9 polymorphism and CYP2C9*1/*1 were far smaller and largely not statistically significant. A larger part of the variability in dose requirement was explained by the VKORC1 genotype than by the CYP2C9 genotype (28.7% and 7.2%, respectively). Carriers of a combination of a CYP2C9 polymorphism and a VKORC1 polymorphism had a strongly increased risk of severe overanticoagulation (hazard ratio (HR) 7.20, P=0.002). Only carriers of a CYP2C9*2 allele had a decreased chance to achieve stability compared to CYP2C9*1/*1 patients (HR 0.61, P=0.004). In conclusion, the VKORC1 genotype modifies the effect of the CYP2C9 genotype on phenprocoumon dose requirements. A combination of polymorphisms of both genotypes is associated with a strongly increased risk of overanticoagulation, whereas delayed stabilization is mainly associated with the CYP2C9 genotype.

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PubMed2006

Diuretic-gene interaction and the risk of myocardial infarction and stroke.

This study investigates whether the interaction between diuretics and alpha-adducin (ADD1) G460W or G-protein beta3-subunit (GNB3) rs2301339 polymorphism modifies the risk of myocardial infarction (MI) or stroke. Data were used from the Rotterdam Study. The drug-gene interaction was determined with a Cox proportional hazard model with adjustment for each drug class as time-dependent covariates. The risk of MI in current users of low-ceiling diuretics with one or two copies of the ADD1 W-allele (hazard ration (HR)=0.92) was similar compared to the expected joint effect of the W-allele and low-ceiling diuretics on a multiplicative scale (1.04 x 0.90=0.94) (synergy index (SI):0.99; 95% confidence interval (CI): 0.43-2.27). No drug-gene interaction was found on the risk of stroke (SI:0.66; 95% CI:0.43-1.27). In addition, a trend towards an interaction was found between current use and the GNB3 rs230119 G/A polymorphism on the risk of MI (SI: 0.51; 95% CI: 0.23-1.15), whereas no interaction on the risk of stroke was found (SI: 0.84; 95% CI: 0.46-1.56).

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PubMed2005

Antipsychotic-induced extrapyramidal syndromes in psychiatric practice: a case-control study.

BACKGROUND: While several clinical trials showed that atypical antipsychotics have a low risk of extrapyramidal side effects (EPS), this observation is not undisputed. This study compared the risk of EPS between specific subgroups of antipsychotics. METHODS: Using the automated dispensing records of a large psychiatric hospital in The Netherlands, we defined cases as first-time users of anticholinergic antiparkinson drugs. Controls were all patients with no recorded use of such medication. Cases and controls were compared with regard to previous use of antipsychotics and relevant co-factors. RESULTS: Out of 1403 patients, we identified 105 cases and 330 controls. Compared to non-users, antipsychotic-users were 10 times more likely to start with anticholinergic antiparkinson medication (adjusted odds ratio: 10.1; 95 CI 4.6-22.3). Depot and non-depot antipsychotics had similar adjusted odds ratios of 10.9 (95 CI 3.7-32.6) and 8.8 (95% CI 3.8-20.4) respectively. Low and high potency antipsychotics gave odds ratios of 3.0 (95% CI 0.9-10.3) versus 10.8 (95% CI 4.7-25.1). Classical and atypical antipsychotics showed comparable odds ratios: 10.0 (95% CI: 4.4-22.5) versus 8.0 (95% CI: 2.6-24.5). Applied doses of classical and atypical antipsychotic drugs were much lower and more equivalent than those used in previous clinical trials. CONCLUSIONS: Low potency antipsychotics had a much lower risk of EPS than other antipsychotics. However, we did not corroborate the reduced risk with atypical antipsychotics observed in several clinical trials. This discrepancy may result from the high and non-equivalent doses of classical antipsychotics used in many of these trials.

Adult↗
PubMed2005

Insertion/deletion polymorphism of the ACE gene and adherence to ACE inhibitors.

AIMS: We investigated whether the insertion/deletion (I/D) polymorphism of the ACE gene modified the adherence to ACE inhibitors as measured by the discontinuation of an ACE inhibitor, or addition of another antihypertensive drug. METHODS: This was a cohort study among 239 subjects who started ACE inhibitor therapy. A Cox proportional hazard model was used to calculate relative risk (RR). RESULTS: During follow-up there was no significant difference between subjects with the DD, ID or II genotype (DD vs II; RR = 1.17, 95%CI: 0.78, 1.77 and ID vs II; RR = 1.06, 95%CI: 0.73, 1.55) in adherence. CONCLUSIONS: The I/D polymorphism of the ACE gene does not influence the adherence to ACE inhibitors.

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PubMed2004

Methods to assess intended effects of drug treatment in observational studies are reviewed.

BACKGROUND AND OBJECTIVE: To review methods that seek to adjust for confounding in observational studies when assessing intended drug effects. METHODS: We reviewed the statistical, economical and medical literature on the development, comparison and use of methods adjusting for confounding. RESULTS: In addition to standard statistical techniques of (logistic) regression and Cox proportional hazards regression, alternative methods have been proposed to adjust for confounding in observational studies. A first group of methods focus on the main problem of nonrandomization by balancing treatment groups on observed covariates: selection, matching, stratification, multivariate confounder score, and propensity score methods, of which the latter can be combined with stratification or various matching methods. Another group of methods look for variables to be used like randomization in order to adjust also for unobserved covariates: instrumental variable methods, two-stage least squares, and grouped-treatment approach. Identifying these variables is difficult, however, and assumptions are strong. Sensitivity analyses are useful tools in assessing the robustness and plausibility of the estimated treatment effects to variations in assumptions about unmeasured confounders. CONCLUSION: In most studies regression-like techniques are routinely used for adjustment for confounding, although alternative methods are available. More complete empirical evaluations comparing these methods in different situations are needed.

Confounding Factors, Epidemiologic↗
PubMed2004

Prevalence and determinants of undertreatment of hypertension in the Netherlands.

The objective of this study was to determine the prevalence, treatment, and control of hypertension, and the determinants of undertreatment in the Dutch population. The study design was cross-sectional. A population-based survey on cardiovascular disease risk factors in the Netherlands from 1996 to 2002 was the setting of the study. A total of 10 820 men and women, aged 30-59 years, were included in the study. The main outcome measures of the study were: Prevalence of hypertension, treatment, and control of hypertension and determinants of undertreatment of hypertension. Hypertension was defined as: systolic blood pressure (SBP) > or =140 mmHg and/or diastolic blood pressure (DBP) > or =90 mmHg, and/or the use of antihypertensive medication. Treated and controlled hypertension was defined as SBP <140 mmHg and DBP <90 mmHg. Multivariate logistic regression was used to assess the determinants of undertreatment. The prevalence of hypertension in men was 21.4% and in women 14.9%, and 17.9% of the hypertensive men and 38.5% of the hypertensive women were receiving antihypertensive medication. Of the untreated hypertensives, 21.9% of the men and 13.6% of the women were eligible for treatment with antihypertensive medication according to Dutch guidelines. Female gender and the use of cholesterol-lowering medication were associated with an increased chance of being treated. Subjects who were physically active, on a low salt diet, and current smokers had an increased chance of being untreated. Taking cholesterol-lowering medication and no asthma or allergy were factors associated with better control of blood pressure. In conclusion, a considerable proportion of hypertensives were untreated and uncontrolled. Therefore, the detection and control of hypertension in the Netherlands needs to improve. Several groups of hypertensives were identified that need additional care and attention.

Adult↗
PubMed2004

Evaluation of clinical pharmacist interventions on drug interactions in outpatient pharmaceutical HIV-care.

OBJECTIVE: To evaluate the usefulness of intervention in drug interactions of antiretroviral drugs with coadministered agents by a clinical pharmacist in outpatient HIV-treatment. METHODS: The study design included two intervention arms (A and B), which were both preceded by a control observation period. In arm A, a complete list of the currently used drugs, extracted from pharmacy records was provided to the treating physician. In arm B the same list was provided but with a notification when a drug interaction was present and an advice how to handle this. The infectious disease specialist obtained the information before the patient's visit to the outpatient clinic (time point 0). Three months prior (time point -3) and 3 months after (time point +3) the intervention, pharmacy records were also screened for drug interactions. The number of drug interactions (total and per patient) was determined at the three different time points (-3, 0, +3). In addition, drug interactions encountered at time points -3 and 0 were checked for their presence at time points 0 and +3, respectively, for both intervention arms. RESULTS: Arms A and B included 115 and 105 patients, respectively. Patient characteristics of both intervention arms were similar at time point 0. The number of interactions and the number of patients with interactions were similar in both intervention arms at time point 0. There were 42 and 40 potential drug interactions in 30 and 24 patients in arms A and B, respectively. The reduction in the number of interactions per patient over time and after intervention was small but significant, and was equal in both intervention arms. The advice of the clinical pharmacist had thus no additional value. CONCLUSION: Both interventions were effective in reducing the number of drug interactions per patient. The advice of a clinical pharmacist was, however, redundant in the studied setting.

Adult↗
PubMed2003

No benefit of intraoperative whole blood sequestration and autotransfusion during coronary artery bypass grafting: results of a randomized clinical trial.

OBJECTIVES: In a randomized clinical trial of patients undergoing elective coronary artery bypass grafting, we evaluated the effect of intraoperative whole blood sequestration and autotransfusion on postoperative blood loss and the use of allogeneic blood products. METHODS: Male patients were included if it was possible to obtain at least 500 mL of autologous blood. For patients in group H (heparin autotransfusion, 50 patients; mean age 59 +/- 8 years), an average of 670 +/- 160 mL heparinized blood was drawn before bypass and reinfused after the period of the extracorporeal circulation. For patients in group C (citrate autotransfusion, 48 patients; mean age 60 +/- 10 years), 450 +/- 109 mL of citrate blood, drawn before administration of heparin, was used. Controls (N-group) consisted of 46 patients aged 62 +/- 8 years. Strict transfusion criteria were used, and blood loss and use of allogeneic blood products during the hospital stays of all patients were recorded. Mean differences with their 95% confidence intervals adjusted for potential confounders were obtained by multiple linear regression. RESULTS: The mean difference (95% confidence interval) of blood loss of group H minus N was -93 mL (-307 to 139) and for C minus N was -66 mL (-186 to 179). The mean number of allogeneic blood transfusions for group H was 0.85 +/- 1.74. Group C and group N used 0.94 +/- 1.56 and 0.84 +/- 1.24. CONCLUSION: In coronary artery bypass grafting there is no effect of heparin or citrate intraoperative whole blood sequestration with regard to blood loss or use of allogeneic blood.

Blood Loss, Surgical↗
PubMed2003

Undertreatment of hypercholesterolaemia: a population-based study.

AIMS: To assess the level of undertreatment of hypercholesterolaemia in the general population, taking intra-person variability in serum cholesterol concentrations into account, and to identify determinants of undertreatment of hypercholesterolaemia. METHODS: In this cross-sectional study, data from two population-based surveys on cardiovascular disease risk factors conducted between 1987 and 1997 in the Netherlands were used. For all 64 757 respondents aged 20-59 years, treatment eligibility for lipid-lowering drug use was established according to the Dutch Cholesterol Consensus. Multivariate logistic models were used to identify determinants of undertreatment. RESULTS: During the study period, 56.8% of the study population had undesirable cholesterol concentrations (serum total cholesterol> 5 mmol l(-1)) and 5.5% of those were eligible for pharmacological treatment based on their absolute risk of coronary heart disease. Of those eligible for pharmacological treatment, 16.3% were treated, and 19.6% of those treated had their serum total cholesterol concentration controlled. Only 3.2% of those eligible for pharmacological treatment were both treated and controlled. We identified several determinants for undertreatment, e.g. male gender and younger age for primary prevention and female gender and older age for secondary prevention. Treatment has improved slightly in more recent years. CONCLUSIONS: Over 95% of the population eligible for the pharmacological treatment of hypercholesterolaemia was either untreated or was uncontrolled. To decrease undertreatment, identification of high-risk patients should be increased. Those who are treated with lipid-lowering medication could further benefit from more aggressive treatment, especially with statins.

Adult↗
PubMed2002

Antipsychotics and Parkinson's disease: association with disease and drug choice during the first 5 years of antiparkinsonian drug treatment.

OBJECTIVE: Psychosis is a common complication of the drug treatment of Parkinson's disease (PD). Treatment of this complication is difficult as most antipsychotic drugs worsen motor symptoms of PD. Only the atypical antipsychotic clozapine improves psychosis without worsening of parkinsonism. The aim of the present study was to assess the rate of initiation of antipsychotic treatment in patients with PD compared with controls. The quality of pharmacotherapy was determined by assessing which antipsychotic drugs were initiated. METHODS: Data came from the PHARMO database, which includes drug-dispensing information for all residents of six Dutch cities. Selected were all persons aged 55 years and older who used levodopa for at least 180 days and who started antiparkinsonian drugs at least 180 days after entry into PHARMO. These patients were matched to at most three controls for age, gender, pharmacy and time of use. The association between rate of initiation of antipsychotic drug treatment and PD was determined using the Cox proportional hazards model. RESULTS: The study included 271 patients with PD and 748 controls. During follow-up, 38 patients and 25 controls started taking an antipsychotic drug; relative risk was 3.9 (95% confidence interval 2.3, 6.4). Six patients with PD received an atypical agent (16%). Clozapine was given to five patients with PD. No control used clozapine. Haloperidol was most frequently prescribed to the patients (29%) and the controls (36%). CONCLUSION: Patients with PD began taking antipsychotic drugs almost four times more frequently than controls. The quality of pharmacotherapy can be improved by prescribing atypical antipsychotic drugs to patients with PD.

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PubMed2002

Evaluation of patient outcomes in an area where prescribing of anticholinergic antidepressants was influenced by academic detailing.

OBJECTIVE: To evaluate, on a patient level, the effect of a "physician-level intervention" that successfully reduced the incidence of anticholinergic antidepressant prescribing. DESIGN: Cross-sectional surveys with questionnaires sent before and after intervention. SETTING: Additional study in an RCT to reduce the prescribing of highly anticholinergic antidepressants in the elderly in the South Holland Islands. PARTICIPANTS: Elderly patients (age 60-95 years) who used antidepressants in 1995 and 1996 in our research area according to a health insurance prescription database. MAIN OUTCOME MEASURES: Prevalence of adverse events related to antidepressant use, severity of depression and quality of life were compared in users living in the intervention and control areas. RESULTS: Prior to our intervention we sent 2,359 questionnaires of which we could use 827 (35%) for analysis. At baseline, there were no statistically significant differences between the intervention and control areas. After the intervention 3,375 questionnaires were sent, of which 939 (28%) could be used. The occurrence of "dry mouth" and "coughing" and the "amount of pain" were lower in the intervention area compared to the control area (p < 0.05). CONCLUSION: We found no indications that adverse events, severity of depression or quality of life were changed in an unfavourable direction, when comparing patients inside and outside the intervention area.

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PubMed2002

Influence of benzodiazepines on antiparkinsonian drug treatment in levodopa users.

OBJECTIVES: Animal studies showed that benzodiazepines decrease the concentration of dopamine in the striatum. Benzodiazepines may therefore affect the treatment of Parkinson's disease. This study determined whether start of a benzodiazepine in patients on levodopa was followed by a faster increase of antiparkinsonian drug treatment. METHODS: Data came from the PHARMO database, which includes information on drug dispensing for all residents of six Dutch cities. Selected were all patients aged 55 years and older who used levodopa for at least 360 days. The rate of increase of antiparkinsonian drug treatment was compared between starters of a benzodiazepine and controls who did not start a benzodiazepine with the use of Cox's proportional hazard model. RESULTS: Identified were 45 benzodiazepine starters (27 women, mean age 76.4 years) and 169 controls (83 women, 74.3 years). Antiparkinsonian drug treatment increased faster in the benzodiazepine group; relative risk was 1.44 (95% confidence interval 0.80-2.59). CONCLUSION: This study has not found any statistically significant increase in antiparkinsonian drug treatment when a benzodiazepine was started in a small population of chronic levodopa users.

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PubMed2002

Start of a selective serotonin reuptake inhibitor (SSRI) and increase of antiparkinsonian drug treatment in patients on levodopa.

AIMS: We determined whether the start of selective serotonin reuptake inhibitors (SSRI) in levodopa users was followed by a faster increase of antiparkinsonian drug treatment. METHODS: Selected were all levodopa users of 55 years and older from the PHARMO prescription database. The rate of increase of antiparkinsonian drug treatment was compared using Cox's proportional hazard model for starters of SSRI (n = 15) with starters of tricyclic antidepressants (TCA) (n = 31) and with patients not using antidepressants (n = 304), and was adjusted for age, gender, and duration of levodopa use. RESULTS: The hazard ratio for the SSRI group compared with the TCA group was 4.2 (95% confidence interval 1.4, 12.6) and compared with the second control group was 2.7 (1.2, 5.2). CONCLUSIONS: The start of SSRI therapy in levodopa users is followed by a faster increase of antiparkinsonian drug treatment.

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PubMed2002

Extrapyramidal syndromes associated with selective serotonin reuptake inhibitors: a case-control study using spontaneous reports.

The aim of this study was to assess whether use of selective serotonin reuptake inhibitors (SSRIs) is associated with extrapyramidal syndromes (EPS). We analysed the spontaneous reports of adverse drug reactions (ADRs) collected by The Netherlands Pharmacovigilance Foundation Lareb in the period 1985-99 (n = 24,263). The study population comprised all patients using an antidepressant drug at the time the ADR occurred. We calculated ADR-reporting odds ratios (ADR-OR) to estimate the association between SSRI-use and EPS, relative to other antidepressants. We identified 61 patients with EPS. SSRI-use was associated with spontaneous reporting of EPS compared to other antidepressants (adjusted ADR-OR 2.2; 95% confidence interval 1.2-3.9). This risk estimate appeared to be higher in patients concurrently using antipsychotic medication (6.9, 0.7-68.0), although the confidence interval was very wide. In conclusion, SSRI-use seems only to be moderately associated with EPS compared to other antidepressants. However, those concurrently using antipsychotic drugs or presenting with other risk factors may be more susceptible and should be closely monitored.

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PubMed2002

Population pharmacokinetics and relationship between demographic and clinical variables and pharmacokinetics of gentamicin in neonates.

Population pharmacokinetic parameter estimates were calculated from 725 routine plasma gentamicin concentrations obtained in 177 neonates of 24 to 42 weeks' gestational age in their first week of life. Kel increases and V/W decreases with increasing gestational age. Almost identical results were obtained with iterative two-stage Bayesian fitting (MW\PHARM 3.30) as with a non-parametric maximization algorithm (NPEM2). The effect of various covariates on drug disposition was investigated retrospectively using multiple regression analysis. Predictive power for Kel increases with rising gestational age. For neonates </=28.5 weeks and neonates >28.5 weeks and </=30.9 weeks, the predictive power of the regression equation for Kel was relatively low (r2 respectively 0.270 and 0.364). Better predictivity was found for Kel at gestational ages >30.9 weeks (r2 = 0.482), with gestational age, postnatal age, and Apgar score at 5 minutes being predictors. A very strong correlation existed between volume of distribution and weight (r2 = 0.83). Volume as a function of weight could be described with low predictivity by gestational age and to a lesser degree by Apgar score at 5 minutes (r2 = 0.298). The developed models need appropriate prospective clinical validation.

Anti-Bacterial Agents↗
PubMed2001

Reducing prescribing of highly anticholinergic antidepressants for elderly people: randomised trial of group versus individual academic detailing.

OBJECTIVE: To compare the effect of individual educational visits versus group visits using academic detailing to discuss prescribing of highly anticholinergic antidepressants in elderly people. DESIGN: Randomised controlled trial with three arms (individual visits, group visits, and a control arm). SETTING: Southwest Netherlands. PARTICIPANTS: 190 general practitioners and 37 pharmacists organised in 21 peer review groups were studied using a database covering all prescriptions to people covered by national health insurance in the area (about 240 000). INTERVENTION: All general practitioners and pharmacists in both intervention arms were offered two educational visits. For physicians in groups randomised to the individual visit arm, 43 of 70 general practitioners participated; in the group visit intervention arm, five of seven groups (41 of 52 general practitioners) participated. MAIN OUTCOME MEASURES: Numbers of elderly people (>/=60 years) with new prescriptions of highly anticholinergic antidepressants and less anticholinergic antidepressants. RESULTS: An intention to treat analysis found a 26% reduction in the rate of starting highly anticholinergic antidepressants in elderly people (95% confidence interval -4% to 48%) in the individual intervention arm and 45% (8% to 67%) in the group intervention arm. The use of less anticholinergic antidepressants increased by 40% (6% to 83%) in the individual intervention arm and 29% (-7% to 79%) in the group intervention arm. CONCLUSIONS: Both the individual and the group visits decreased the use of highly anticholinergic antidepressants and increased the use of less anticholinergic antidepressant in elderly people. These approaches are practical means to improve prescribing by continuing medical education.

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