Hans Mulder - Academia.edu (original) (raw)
Papers by Hans Mulder
BMJ open, 2014
Nursing home residents often have a high number of comorbidities resulting in polypharmacy. Inapp... more Nursing home residents often have a high number of comorbidities resulting in polypharmacy. Inappropriate prescribing is therefore likely to occur, which in turn is expected to worsen cognitive impairment, to increase the fall risk and to decrease residents' quality of life. The objective of the 'Discontinuing Inappropriate Medication in Nursing Home Residents' (DIM-NHR) study is to examine the efficacy and cost-effectiveness of the Multidisciplinary Multistep Medication Review (3MR) that is aimed at optimising prescribing and discontinuing inappropriate medication. A cluster randomised controlled trial will be conducted. Elderly care physicians and their wards (clusters) will be randomised. Data will be collected at baseline and 4 months after the 3MR has taken place. Six hundred nursing home residents will be recruited of whom more than half are expected to suffer from dementia. The 3MR will be based on consensus criteria and the relevant literature and will be perform...
Clinical Pharmacology & Therapeutics, 2011
reports nature publishing group Currently, there are very few guidelines linking the results of p... more reports nature publishing group Currently, there are very few guidelines linking the results of pharmacogenetic tests to specific therapeutic recommendations. Therefore, the Royal Dutch Association for the Advancement of Pharmacy established the Pharmacogenetics Working Group with the objective of developing pharmacogenetics-based therapeutic (dose) recommendations. After systematic review of the literature, recommendations were developed for 53 drugs associated with genes coding for CYP2D6, CYP2C19, CYP2C9, thiopurine-S-methyltransferase (TPMT), dihydropyrimidine dehydrogenase (DPD), vitamin K epoxide reductase (VKORC1), uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1), HLA-B44, HLA-B*5701, CYP3A5, and factor V Leiden (FVL).
Particle Accelerator, IEEE Conference, 1997
With the completion of the antiproton physics program, the Low Energy Antiproton Ring is now avai... more With the completion of the antiproton physics program, the Low Energy Antiproton Ring is now available to be used as an accumulator ring for heavy ions in the LBC injector chain. The proposed scheme for the injection of Pb ions is given, where an intensity gain of 125 is obtained by accumulating Pb ions with electron cooling in the LEAR
Clinical Pharmacology & Therapeutics, 2008
Despite initial enthusiasm, 1-3 the use of pharmacogenetics has remained limited to investigation... more Despite initial enthusiasm, 1-3 the use of pharmacogenetics has remained limited to investigation in only a few clinical fields such as oncology and psychiatry. 4-8 The main reason is the paucity of scientific evidence to show that pharmacogenetic testing leads to improved clinical outcomes. 9,10 Moreover, for most pharmacogenetic tests (such as tests for genetic variants of cytochrome P450 enzymes) a detailed knowledge of pharmacology is a prerequisite for application in clinical practice, and both physicians and pharmacists might find it difficult to interpret the clinical value of pharmacogenetic test results. Guidelines that link the result of a pharmacogenetic test to therapeutic recommendations might help to overcome these problems, but such guidelines are only sparsely available. In 2001, an early step was taken to develop such guidelines for the therapeutic use of antidepressants, and these included CYP2D6-related dose recommendations drawn from pharmacokinetic study data. 11 However, the use of such recommendations in routine clinical practice remains difficult, because they are currently outside the ambit of the clinical environment and are not accessible during the decision-making process by physicians and pharmacists, namely the prescription and dispensing of drugs.
Journal of Clinical Psychopharmacology, 2009
Weight gain is one of the most serious adverse effects of atypical antipsychotic agents. Genetic ... more Weight gain is one of the most serious adverse effects of atypical antipsychotic agents. Genetic factors influence the risk of an individual to gain weight. The objective of our study was to determine whether the LEPR Q223R polymorphism and the LEP promoter 2548G/A polymorphism are associated with obesity in a group of male and female patients using atypical antipsychotic drugs. A cross-sectional study design was used. The study population consisted of 200 patients aged between 18 and 65 years, diagnosed with a psychotic disorder, all of whom had been using an atypical antipsychotic for at least 3 months. The primary outcome measure was the presence of obesity. Determinants were the LEPR Q223R (rs1137101) polymorphism and the LEP promoter 2548G/A single nucleotide polymorphism ([SNP] rs7799039). Of the 200 included patients, 61 (31%) were obese. In females, the LEPR 223QR (adjusted odds ratio, 0.11; 95% confidence interval [CI], 0.02-0.54) and LEPR 223RR (adjusted odds ratio, 0.07; 95% CI, 0.01-0.63) genotypes were associated with a lower risk of obesity. In males, this association was not found. In females, the average body weight was 13.6 kg more (95% CI, 1.11-26.1) in the LEPR 223QQ group compared with the LEPR 223RR group. No significant association was found between the LEP promoter 2548G/A polymorphism and obesity. Taken together, the results of our study show that the LEPR Q223R polymorphism may be associated with obesity in women with a psychotic disorder treated with atypical antipsychotic drugs and stress the importance of stratification for gender when investigating the role of variations of the LEP- and LEPR genes on the metabolic side effects of antipsychotic medications.
Journal of Clinical Psychopharmacology, 2009
Journal of Clinical Psychopharmacology, 2014
Journal of Clinical Psychopharmacology, 2007
The use of antipsychotics is associated with metabolic side effects, which put patients with schi... more The use of antipsychotics is associated with metabolic side effects, which put patients with schizophrenia or related disorders at risk for cardiovascular morbidity. The high interindividual variability in antipsychotic-induced metabolic abnormalities suggests that genetic makeup is a possible determinant. In this cross-sectional study, we investigated whether genotypes of the HTR2C receptor are associated with the metabolic syndrome in patients using antipsychotics. Patients were identified from a schizophrenia disease management program. In this program, patients' blood pressure, triglycerides, high-density lipoprotein-cholesterol, and waist circumference are measured regularly during follow-up. The primary end point of our study was the prevalence of the metabolic syndrome as classified by a modified version of the National Cholesterol Education Program's Adult Treatment Panel III. Primary determinants were polymorphisms in the HTR2C receptor gene (HTR2C:c.
Journal of Clinical Psychopharmacology, 2012
Journal of Child and Adolescent Psychopharmacology, 2010
Weight gain is an important adverse effect of risperidone, but predictors of significant weight g... more Weight gain is an important adverse effect of risperidone, but predictors of significant weight gain have yet to be identified in pediatric patients. Here, we investigated differences between age-and gender-normed body mass index-standardized z scores at baseline and after 8 weeks of open-label, flexible-dose risperidone treatment (mean dose: 1.70 mg/day) in 32 youths with pervasive developmental disorder (mean age ¼ 8.74, range ¼ 5-16 years) in relation to À759C/T 5-hydroxytryptamine 2C receptor (HTR2C) promoter and rs1414334 HTR2C intragenic C/G alleles, along with gender, age, and risperidone dose, using repeated measures analyses of variance. Carriers of the HTR2C promoter T allele gained an average of 0.043 AE 0.017 body mass index-standardized z scores (1.84 AE 1.51 kg) versus 0.64 AE 0.35 z (3.23 AE 1.47 kg) for non-T-allele carriers ( p < 0.001). Presence of the rs1414334 C allele played no significant role. Further, weight gain appeared to be associated with younger age and higher doses of risperidone. The current preliminary findings suggest that the variant T allele of the À759C/T HTR2C promoter polymorphism is protective against risperidone-induced weight gain. Younger children and those treated with higher doses of risperidone may be at higher risk for weight gain.
Annals of Pharmacotherapy, 2007
Despite a large number of studies investigating the potential clinical relevance of CYP2D6 genoty... more Despite a large number of studies investigating the potential clinical relevance of CYP2D6 genotyping in preventing treatment failure (eg, insufficient efficacy and/or unacceptable adverse effects), the prevalence of patients using drugs metabolized by that isoenzyme is relatively unknown. To investigate the prevalence of patients in different populations using drugs metabolized by CYP2D6. In this cross-sectional study, 6 different patient populations were investigated: general, general hospital, geriatric, psychogeriatric, psychiatric, and mentally retarded. From every population, 150 adults using at least one drug were randomly selected. Primary outcome was the prevalence of patients using at least one drug metabolized by CYP2D6. The prevalence of patients using at least one CYP2D6 substrate in different populations was compared with the general population using chi(2) statistics. Data were expressed as a relative risk with a 95% confidence interval. Patients from the general hospital (RR 1.81; 95% CI 1.26 to 2.62), geriatric patients (RR 2.16; 95% CI 1.26 to 2.62), psychogeriatric patients (RR 2.31; 95% CI 1.63 to 3.27), and psychiatric patients (RR 2.44; 95% CI 1.73 to 3.44) were treated more frequently with at least one drug metabolized by CYP2D6 compared with patients in the general population. Approximately 50% of psychiatric (52%), psychogeriatric (49%), and geriatric (46%) patients used at least one drug metabolized by CYP2D6. In total, 416 drugs metabolized by CYP2D6 were prescribed, with 257 (62%) of these classified as an antidepressant (Anatomical and Therapeutic Chemical [ATC] category N06A) or antipsychotic (ATC N05A). Several patient populations (eg, psychiatric, psychogeriatric, geriatric) have a high prevalence of patients treated with at least one drug metabolized by CYP2D6. This study does not provide evidence regarding the clinical evidence of CYP2D6 genotyping, but shows that, if CYP2D6 genotyping is relevant for patient care, the highest probability of cost-effectiveness will, most likely, be in specific populations.
Research in Developmental Disabilities, 2013
Individuals with intellectual disability frequently use antipsychotics for many years. This may h... more Individuals with intellectual disability frequently use antipsychotics for many years. This may have detrimental health effects, including neurological symptoms and metabolic and hormonal dysregulation, the latter possibly affecting bone metabolism. There is large variability in the degree in which antipsychotic agents lead to these health problems. In the current study we investigated potential determinants of physical symptoms and biological parameters known to be associated with use of antipsychotics in a convenience sample of 99 individuals with intellectual disability who had used antipsychotics for more than one year for behavioural symptoms. We focused on extrapyramidal symptoms; on overweight and presence of components of the metabolic syndrome; and on elevated plasma prolactin and bone turnover parameters. As predictor variables, we used patient (sex, age, genetic polymorphisms, and severity of intellectual disability) and medication use (type and dosage) characteristics. We found extrapyramidal symptoms to be present in 53%, overweight or obesity in 46%, and the metabolic syndrome in 11% of participants. Hyperprolactineaemia and one or more elevated bone turnover markers were present in 17% and 25%, respectively. Higher age and more severe intellectual disability were associated with dyskinesia and a higher dosage of the antipsychotic drug was associated with parkinsonism. Less severe intellectual disability was related to higher Body Mass Index. Use of atypical antipsychotics was associated with higher diastolic blood pressure and elevated fasting glucose. Clinicians who prescribe antipsychotics in individuals with intellectual disability should carefully balance the potential benefits of prolonged treatment against the risk of health hazards associated with the use of antipsychotics.
BMJ open, 2014
Nursing home residents often have a high number of comorbidities resulting in polypharmacy. Inapp... more Nursing home residents often have a high number of comorbidities resulting in polypharmacy. Inappropriate prescribing is therefore likely to occur, which in turn is expected to worsen cognitive impairment, to increase the fall risk and to decrease residents' quality of life. The objective of the 'Discontinuing Inappropriate Medication in Nursing Home Residents' (DIM-NHR) study is to examine the efficacy and cost-effectiveness of the Multidisciplinary Multistep Medication Review (3MR) that is aimed at optimising prescribing and discontinuing inappropriate medication. A cluster randomised controlled trial will be conducted. Elderly care physicians and their wards (clusters) will be randomised. Data will be collected at baseline and 4 months after the 3MR has taken place. Six hundred nursing home residents will be recruited of whom more than half are expected to suffer from dementia. The 3MR will be based on consensus criteria and the relevant literature and will be perform...
Clinical Pharmacology & Therapeutics, 2011
reports nature publishing group Currently, there are very few guidelines linking the results of p... more reports nature publishing group Currently, there are very few guidelines linking the results of pharmacogenetic tests to specific therapeutic recommendations. Therefore, the Royal Dutch Association for the Advancement of Pharmacy established the Pharmacogenetics Working Group with the objective of developing pharmacogenetics-based therapeutic (dose) recommendations. After systematic review of the literature, recommendations were developed for 53 drugs associated with genes coding for CYP2D6, CYP2C19, CYP2C9, thiopurine-S-methyltransferase (TPMT), dihydropyrimidine dehydrogenase (DPD), vitamin K epoxide reductase (VKORC1), uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1), HLA-B44, HLA-B*5701, CYP3A5, and factor V Leiden (FVL).
Particle Accelerator, IEEE Conference, 1997
With the completion of the antiproton physics program, the Low Energy Antiproton Ring is now avai... more With the completion of the antiproton physics program, the Low Energy Antiproton Ring is now available to be used as an accumulator ring for heavy ions in the LBC injector chain. The proposed scheme for the injection of Pb ions is given, where an intensity gain of 125 is obtained by accumulating Pb ions with electron cooling in the LEAR
Clinical Pharmacology & Therapeutics, 2008
Despite initial enthusiasm, 1-3 the use of pharmacogenetics has remained limited to investigation... more Despite initial enthusiasm, 1-3 the use of pharmacogenetics has remained limited to investigation in only a few clinical fields such as oncology and psychiatry. 4-8 The main reason is the paucity of scientific evidence to show that pharmacogenetic testing leads to improved clinical outcomes. 9,10 Moreover, for most pharmacogenetic tests (such as tests for genetic variants of cytochrome P450 enzymes) a detailed knowledge of pharmacology is a prerequisite for application in clinical practice, and both physicians and pharmacists might find it difficult to interpret the clinical value of pharmacogenetic test results. Guidelines that link the result of a pharmacogenetic test to therapeutic recommendations might help to overcome these problems, but such guidelines are only sparsely available. In 2001, an early step was taken to develop such guidelines for the therapeutic use of antidepressants, and these included CYP2D6-related dose recommendations drawn from pharmacokinetic study data. 11 However, the use of such recommendations in routine clinical practice remains difficult, because they are currently outside the ambit of the clinical environment and are not accessible during the decision-making process by physicians and pharmacists, namely the prescription and dispensing of drugs.
Journal of Clinical Psychopharmacology, 2009
Weight gain is one of the most serious adverse effects of atypical antipsychotic agents. Genetic ... more Weight gain is one of the most serious adverse effects of atypical antipsychotic agents. Genetic factors influence the risk of an individual to gain weight. The objective of our study was to determine whether the LEPR Q223R polymorphism and the LEP promoter 2548G/A polymorphism are associated with obesity in a group of male and female patients using atypical antipsychotic drugs. A cross-sectional study design was used. The study population consisted of 200 patients aged between 18 and 65 years, diagnosed with a psychotic disorder, all of whom had been using an atypical antipsychotic for at least 3 months. The primary outcome measure was the presence of obesity. Determinants were the LEPR Q223R (rs1137101) polymorphism and the LEP promoter 2548G/A single nucleotide polymorphism ([SNP] rs7799039). Of the 200 included patients, 61 (31%) were obese. In females, the LEPR 223QR (adjusted odds ratio, 0.11; 95% confidence interval [CI], 0.02-0.54) and LEPR 223RR (adjusted odds ratio, 0.07; 95% CI, 0.01-0.63) genotypes were associated with a lower risk of obesity. In males, this association was not found. In females, the average body weight was 13.6 kg more (95% CI, 1.11-26.1) in the LEPR 223QQ group compared with the LEPR 223RR group. No significant association was found between the LEP promoter 2548G/A polymorphism and obesity. Taken together, the results of our study show that the LEPR Q223R polymorphism may be associated with obesity in women with a psychotic disorder treated with atypical antipsychotic drugs and stress the importance of stratification for gender when investigating the role of variations of the LEP- and LEPR genes on the metabolic side effects of antipsychotic medications.
Journal of Clinical Psychopharmacology, 2009
Journal of Clinical Psychopharmacology, 2014
Journal of Clinical Psychopharmacology, 2007
The use of antipsychotics is associated with metabolic side effects, which put patients with schi... more The use of antipsychotics is associated with metabolic side effects, which put patients with schizophrenia or related disorders at risk for cardiovascular morbidity. The high interindividual variability in antipsychotic-induced metabolic abnormalities suggests that genetic makeup is a possible determinant. In this cross-sectional study, we investigated whether genotypes of the HTR2C receptor are associated with the metabolic syndrome in patients using antipsychotics. Patients were identified from a schizophrenia disease management program. In this program, patients' blood pressure, triglycerides, high-density lipoprotein-cholesterol, and waist circumference are measured regularly during follow-up. The primary end point of our study was the prevalence of the metabolic syndrome as classified by a modified version of the National Cholesterol Education Program's Adult Treatment Panel III. Primary determinants were polymorphisms in the HTR2C receptor gene (HTR2C:c.
Journal of Clinical Psychopharmacology, 2012
Journal of Child and Adolescent Psychopharmacology, 2010
Weight gain is an important adverse effect of risperidone, but predictors of significant weight g... more Weight gain is an important adverse effect of risperidone, but predictors of significant weight gain have yet to be identified in pediatric patients. Here, we investigated differences between age-and gender-normed body mass index-standardized z scores at baseline and after 8 weeks of open-label, flexible-dose risperidone treatment (mean dose: 1.70 mg/day) in 32 youths with pervasive developmental disorder (mean age ¼ 8.74, range ¼ 5-16 years) in relation to À759C/T 5-hydroxytryptamine 2C receptor (HTR2C) promoter and rs1414334 HTR2C intragenic C/G alleles, along with gender, age, and risperidone dose, using repeated measures analyses of variance. Carriers of the HTR2C promoter T allele gained an average of 0.043 AE 0.017 body mass index-standardized z scores (1.84 AE 1.51 kg) versus 0.64 AE 0.35 z (3.23 AE 1.47 kg) for non-T-allele carriers ( p < 0.001). Presence of the rs1414334 C allele played no significant role. Further, weight gain appeared to be associated with younger age and higher doses of risperidone. The current preliminary findings suggest that the variant T allele of the À759C/T HTR2C promoter polymorphism is protective against risperidone-induced weight gain. Younger children and those treated with higher doses of risperidone may be at higher risk for weight gain.
Annals of Pharmacotherapy, 2007
Despite a large number of studies investigating the potential clinical relevance of CYP2D6 genoty... more Despite a large number of studies investigating the potential clinical relevance of CYP2D6 genotyping in preventing treatment failure (eg, insufficient efficacy and/or unacceptable adverse effects), the prevalence of patients using drugs metabolized by that isoenzyme is relatively unknown. To investigate the prevalence of patients in different populations using drugs metabolized by CYP2D6. In this cross-sectional study, 6 different patient populations were investigated: general, general hospital, geriatric, psychogeriatric, psychiatric, and mentally retarded. From every population, 150 adults using at least one drug were randomly selected. Primary outcome was the prevalence of patients using at least one drug metabolized by CYP2D6. The prevalence of patients using at least one CYP2D6 substrate in different populations was compared with the general population using chi(2) statistics. Data were expressed as a relative risk with a 95% confidence interval. Patients from the general hospital (RR 1.81; 95% CI 1.26 to 2.62), geriatric patients (RR 2.16; 95% CI 1.26 to 2.62), psychogeriatric patients (RR 2.31; 95% CI 1.63 to 3.27), and psychiatric patients (RR 2.44; 95% CI 1.73 to 3.44) were treated more frequently with at least one drug metabolized by CYP2D6 compared with patients in the general population. Approximately 50% of psychiatric (52%), psychogeriatric (49%), and geriatric (46%) patients used at least one drug metabolized by CYP2D6. In total, 416 drugs metabolized by CYP2D6 were prescribed, with 257 (62%) of these classified as an antidepressant (Anatomical and Therapeutic Chemical [ATC] category N06A) or antipsychotic (ATC N05A). Several patient populations (eg, psychiatric, psychogeriatric, geriatric) have a high prevalence of patients treated with at least one drug metabolized by CYP2D6. This study does not provide evidence regarding the clinical evidence of CYP2D6 genotyping, but shows that, if CYP2D6 genotyping is relevant for patient care, the highest probability of cost-effectiveness will, most likely, be in specific populations.
Research in Developmental Disabilities, 2013
Individuals with intellectual disability frequently use antipsychotics for many years. This may h... more Individuals with intellectual disability frequently use antipsychotics for many years. This may have detrimental health effects, including neurological symptoms and metabolic and hormonal dysregulation, the latter possibly affecting bone metabolism. There is large variability in the degree in which antipsychotic agents lead to these health problems. In the current study we investigated potential determinants of physical symptoms and biological parameters known to be associated with use of antipsychotics in a convenience sample of 99 individuals with intellectual disability who had used antipsychotics for more than one year for behavioural symptoms. We focused on extrapyramidal symptoms; on overweight and presence of components of the metabolic syndrome; and on elevated plasma prolactin and bone turnover parameters. As predictor variables, we used patient (sex, age, genetic polymorphisms, and severity of intellectual disability) and medication use (type and dosage) characteristics. We found extrapyramidal symptoms to be present in 53%, overweight or obesity in 46%, and the metabolic syndrome in 11% of participants. Hyperprolactineaemia and one or more elevated bone turnover markers were present in 17% and 25%, respectively. Higher age and more severe intellectual disability were associated with dyskinesia and a higher dosage of the antipsychotic drug was associated with parkinsonism. Less severe intellectual disability was related to higher Body Mass Index. Use of atypical antipsychotics was associated with higher diastolic blood pressure and elevated fasting glucose. Clinicians who prescribe antipsychotics in individuals with intellectual disability should carefully balance the potential benefits of prolonged treatment against the risk of health hazards associated with the use of antipsychotics.