Harald Vonkeman - Academia.edu (original) (raw)

Papers by Harald Vonkeman

Arthritis Care & Research, 2014

To evaluate the reliability of a crosswalk, developed in The Netherlands, between the Health Asse... more To evaluate the reliability of a crosswalk, developed in The Netherlands, between the Health Assessment Questionnaire (HAQ) disability index (DI) and the Short Form 36 physical functioning scale (PF-10) in a sample of patients with various rheumatic diseases in the US. Baseline data from patients with rheumatoid arthritis (RA; n = 29,020), fibromyalgia (FM; n = 3,776), and systemic lupus erythematosus (SLE; n = 1,609) participating in the National Data Bank for Rheumatic Diseases were analyzed. Reliability of the crosswalk was evaluated by calculating intraclass correlation coefficients (ICCs), and agreement between observed and predicted scores was evaluated using the Bland-Altman approach. RESULTS. The crosswalk produced reliable conversions for both the HAQ DI (ICC range 0.70-0.77) and PF-10 (ICC range 0.73-0.78) in all 3 disease groups. The mean difference between observed and expected scores was close to zero in US patients with RA. For all 3 disease groups, the limits of agreement were fairly wide and conversion at the level of individual patients is not recommended. The crosswalk produced reliable conversions at the group level in a crosscultural setting and can be used to convert HAQ DI to PF-10 scores and vice versa in US patients with RA, FM, or SLE.

Health and Quality of Life Outcomes, 2015

This paper demonstrates the mechanism of a multidimensional computerized adaptive test (CAT) to m... more This paper demonstrates the mechanism of a multidimensional computerized adaptive test (CAT) to measure fatigue in patients with rheumatoid arthritis (RA). A CAT can be used to precisely measure patient-reported outcomes at an individual level as items are consequentially selected based on the patient's previous answers. The item bank of the CAT Fatigue RA has been developed from the patients' perspective and consists of 196 items pertaining to three fatigue dimensions: severity, impact and variability of fatigue. The CAT Fatigue RA was completed by fifteen patients. To test the CAT's working mechanism, we applied the flowchart-check-method. The adaptive item selection procedure for each patient was checked by the researchers. The estimated fatigue levels and the measurement precision per dimension were illustrated with the selected items, answers and flowcharts. The CAT Fatigue RA selected all items in a logical sequence and those items were selected which provided the most information about the patient's individual fatigue. Flowcharts further illustrated that the CAT reached a satisfactory measurement precision, with less than 20 items, on the dimensions severity and impact and to somewhat lesser extent also for the dimension variability. Patients' fatigue scores varied across the three dimensions; sometimes severity scored highest, other times impact or variability. The CAT's ability to display different fatigue experiences can improve communication in daily clinical practice, guide interventions, and facilitate research into possible predictors of fatigue. The results indicate that the CAT Fatigue RA measures precise and comprehensive. Once it is examined in more detail in a consecutive, elaborate validation study, the CAT will be available for implementation in daily clinical practice and for research purposes.

Helicobacter, 2007

Background: Helicobacter pylori and nonsteroidal antiinflammatory drugs (NSAIDs) are the major ca... more Background: Helicobacter pylori and nonsteroidal antiinflammatory drugs (NSAIDs) are the major causes of gastroduodenal ulcers. Studies on the benefit of eradication of H. pylori in NSAID users yielded conflicting results. Objective: To investigate whether H. pylori eradication in patients on long-term NSAIDs reduces the incidence of gastroduodenal ulcers. Methods: Patients on long-term NSAID treatment and who are H. pylori positive

PLoS ONE, 2014

The 28-joint Disease Activity Score (DAS28) combines scores on a 28-tender and swollen joint coun... more The 28-joint Disease Activity Score (DAS28) combines scores on a 28-tender and swollen joint count (TJC28 and SJC28), a patient-reported measure for general health (GH), and an inflammatory marker (either the erythrocyte sedimentation rate [ESR] or the C-reactive protein [CRP]) into a composite measure of disease activity in rheumatoid arthritis (RA). This study examined the reliability of the DAS28 in patients with early RA using principles from generalizability theory and evaluated whether it could be increased by adjusting individual DAS28 component weights. Patients were drawn from the DREAM registry and classified into a "fast response" group (N = 466) and "slow response" group (N = 80), depending on their pace of reaching remission. Composite reliabilities of the DAS28-ESR and DAS28-CRP were determined with the individual components' reliability, weights, variances, error variances, correlations and covariances. Weight optimization was performed by minimizing the error variance of the index. Composite reliabilities of 0.85 and 0.86 were found for the DAS28-ESR and DAS28-CRP, respectively, and were approximately equal across patients groups. Component reliabilities, however, varied widely both within and between sub-groups, ranging from 0.614 for GH ("slow response" group) to 0.912 for ESR ("fast response" group). Weight optimization increased composite reliability even further. In the total and "fast response" groups, this was achieved mostly by decreasing the weight of the TJC28 and GH. In the "slow response" group, though, the weights of the TJC28 and SJC28 were increased, while those of the inflammatory markers and GH were substantially decreased. The DAS28-ESR and the DAS28-CRP are reliable instruments for assessing disease activity in early RA and reliability can be increased even further by adjusting component weights. Given the low reliability and weightings of the general health component across subgroups it is recommended to explore alternative patient-reported outcome measures for inclusion in the DAS28.

Arthritis Care & Research, 2014

Objective: Although treat-to-target (T2T) strategies are effective in early RA patients, importan... more Objective: Although treat-to-target (T2T) strategies are effective in early RA patients, important individual variations exist in the course towards remission. Growth mixture modeling (GMM) provides more insight into this heterogeneity by identifying subgroups of patients with similar response patterns. This study aimed to identify distinct trajectories of disease activity in early RA patients following a T2T strategy, during their first year. Methods: Data on various clinical and patient-reported measures were collected from the DREAM remission induction cohort. GMM was applied to examine the impact of T2T on subgroups characterized by different types of growth trajectories, as measured with the Disease Activity Score for 28 joints. Results: Three distinct trajectories of disease activity were found. The normative trajectory contained most patients (82.6%), showing a quickly decreasing disease activity, stabilizing at remission after 9 months. This group performed best on clinical and patient-reported measures over time and were more likely to be men. A smaller group (14.1%) also approached remission, but demonstrated a slower response to treatment. Finally, a minority (3.3%) showed no improvement after 1 year, despite an initial quick decrease in disease activity during the first months of treatment. Conclusion: Disease activity in early RA patients during the first year of a T2T strategy does not follow a linear pattern, nor is a single developmental trajectory applicable to all patients. Future studies should attempt to identify more specific risk factors for poor outcome to enable early identification of patients in need of alternative therapeutic approaches. © 2013 American College of Rheumatology.

Seminars in Arthritis and Rheumatism, 2010

To discuss nonsteroidal anti-inflammatory drugs (NSAIDs), their history, development, mode of act... more To discuss nonsteroidal anti-inflammatory drugs (NSAIDs), their history, development, mode of action, toxicities, strategies for the prevention of toxicity, and future developments. Medline search for articles published up to 2007, using the keywords acetylsalicylic acid, aspirin, NSAIDs, cyclooxygenase 2, adverse effects, ulcer, and cardiovascular. NSAIDs are 1 of the oldest, most successful drugs known to modern medicine. They are effective for alleviating pain, fever, and inflammation by inhibiting prostaglandin synthesis. Aspirin, by its irreversible inhibition of blood platelet function, is also effective in the prevention of cardiovascular disease. NSAIDs may cause gastrointestinal ulcers, serious cardiovascular events, hypertension, acute renal failure, and worsening of preexisting heart failure. These adverse effects may be prevented by limiting NSAID dosage and duration and by performing individual risk assessments and treating patients accordingly. Those at risk for gastroduodenal ulcers may be treated with concomitant proton-pump inhibitors, misoprostol and/or COX-2 selective NSAIDs. Those at risk for cardiovascular events may be treated with naproxen and a proton-pump inhibitor or misoprostol, but should best avoid NSAID use altogether. Physicians should always prescribe the lowest effective dose for the shortest possible time and must take into account both the gastrointestinal and the cardiovascular risks of individual patients when prescribing NSAIDs.

PLoS ONE, 2014

Objective: To calibrate the Dutch-Flemish version of the PROMIS physical function (PF) item bank ... more Objective: To calibrate the Dutch-Flemish version of the PROMIS physical function (PF) item bank in patients with rheumatoid arthritis (RA) and to evaluate cross-cultural measurement equivalence with US general population and RA data.

Pharmaceuticals, 2010

While aspirin may offer protection, other non-aspirin non-steroidal antiinflammatory drugs (NSAID... more While aspirin may offer protection, other non-aspirin non-steroidal antiinflammatory drugs (NSAIDs) can cause serious cardiovascular side effects and complications. This has led to a general "black box" warning for cardiovascular adverse events for NSAIDs. This review explores the different mechanisms underlying the protective effects of aspirin, the NSAID associated renovascular effects causing hypertension, edema and heart failure, the cardiovascular effects causing myocardial infarction and stroke, and the possible deleterious interaction between NSAIDs and aspirin.

European Journal of Clinical Pharmacology, 2013

Nonsteroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid (ASA) are often prescribed... more Nonsteroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid (ASA) are often prescribed concurrently in patients with nociceptive pain and cardiovascular comorbidity. NSAIDs and ASA inhibit the same COX-enzymes, and thus may interact. ASA's cardioprotective antiplatelet effect is entirely COX-1 dependent. NSAIDs can be either non-COX-1 and COX-2 selective or COX-2 selective. The aim of this study was to examine the interaction between ASA and different selective and nonselective NSAIDs on thrombocyte function. Single-blind, prospective, placebo-controlled, ex vivo, serial crossover trial of 3-day cycles separated by washout periods of at least 12 days in 30 healthy volunteers, evaluating interaction on ASA's antithrombocyte effect by naproxen, ibuprofen, meloxicam, or etoricoxib taken 2 h before ASA. Ex vivo thrombocyte function, closure time (CT) in seconds, was measured using the Platelet Function Analyzer 100 (PFA-100). CT prolongation during a cycle reflects thrombocyte inhibitory effect. ASA nonresponse was defined as CT prolongation <40 % in the placebo cycle. ASA nonresponders were excluded. Wilcoxon signed-rank was used to evaluate NSAID effect on ASA-induced CT prolongation. Ibuprofen and naproxen inhibit ASA's antithrombocyte effect below the nonresponse threshold. Etoricoxib and meloxicam do not cause relevant change in ASA thrombocyte inhibition. Naproxen has an inherent weak thrombocyte inhibitory action below the ASA response threshold. COX-1 affinity determines the interaction between NSAIDs and ASA on thrombocyte adhesion and aggregation. Ibuprofen and naproxen, but not etoricoxib or meloxicam, taken 2 h before ASA, significantly inhibit ASA's antithrombocyte effect.

Drugs & Aging, 2007

of NSAIDs has become a major healthcare issue.

Drug, Healthcare and Patient Safety, 2010

Diabetes, Obesity and Metabolism, 2001

Aim: The b 3 -adrenergic receptor (b 3 -AR) is suspected to play a key role in the regulation of ... more Aim: The b 3 -adrenergic receptor (b 3 -AR) is suspected to play a key role in the regulation of energy balance by increasing lipolysis and thermogenesis. A mutation in the b 3 -AR gene (Trp64Arg) has been associated with the capacity of weight gain and with early onset of noninsulin dependent diabetes mellitus (type 2 diabetes). In this study we investigated the prevalence of the two b 3 -AR alleles in a Caucasian population and studied the association between the b 3 -AR genotype and metabolic disorders (obesity and type 2 diabetes). Methods: Genomic DNA extracted from peripheral blood leucocytes of 200 Caucasian subjects (137 subjects with and 63 subjects without type 2 diabetes). The MvaI polymorphism of b 3 -AR, which detects the Trp64Arg mutation, was determined by polymerase chain reaction (PCR). We studied the correlation between the Trp64Arg mutation and the body mass index (b.m.i. kg/m 2 ). Results: There was no signi®cant difference between the patients with type 2 diabetes and control subjects in the frequency of the Arg64 allele (5.5% and 4.8%, respectively). Within the group of type 2 diabetes patients were 14 subjects with the Trp64Arg mutation (b.m.i., mean T s.d.: 31 T 8.5 kg/m 2 ) and 123 without the mutation (b.m.i. 29 T 4.8). There was no association between the b 3 -AR gene polymorphism and sex, obesity, blood pressure, glycohaemoglobin concentration, proteinuria. Conclusion: Our results suggest that the Trp64Arg mutation is not a major determinant of metabolic disorders (type 2 diabetes, obesity) and chronic complications of type 2 diabetes in a Dutch population.

Current Opinion in Rheumatology, 2013

This era of early aggressive treatment of rheumatoid arthritis (RA) calls for criteria that allow... more This era of early aggressive treatment of rheumatoid arthritis (RA) calls for criteria that allow timely classification of patients at risk of persistent erosive disease. We review how the new American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria meet up to this challenge. The new 2010 ACR/EULAR classification criteria for RA were developed using initiation of methotrexate as anchor in a population with undifferentiated arthritis. Many studies from different countries have now been published that have addressed the performances of these new criteria. The goal of earlier classification of RA seems to be met with the new criteria, but exclusion of other diagnoses is essential. Increased sensitivity comes at the price of loss of specificity and indiscriminate use of these classification criteria as a diagnostic tool carries the risk of overtreatment.

Clinical Rheumatology, 2014

This paper aims to examine the interchangeability of the disease activity score in 28 joints (DAS... more This paper aims to examine the interchangeability of the disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) and DAS28-CRP scores in a diverse sample of rheumatoid arthritis (RA) patients and to evaluate generalizability over gender, age, and disease duration. A sample of 682 patients was drawn from the DREAM registry. Agreement between the two DAS28 scores was analyzed using the intraclass correlation coefficient (ICC), Bland Altman plots, and a matrix of classification agreement over DAS28 disease activity categories. Despite a strong linear correlation between the DAS28 scores and a high ICC value of 0.931, a considerable lack of individual agreement could be observed, with Bland-Altman 95% limits of agreement ranging between -0.85 and +1.25 points. On average, DAS28-CRP scores were 0.20 points lower than DAS28-ESR scores, and data stratification on age and gender showed that this systematic bias was most severe in older women (0.39 points). The overall classification agreement across DAS28 categories was 76.69%, with the agreement being lowest (35.37%) in the low disease activity group. Patients were more easily classified as being in remission when using the DAS28-CRP measure. DAS28-ESR and DAS28-CRP scores are not interchangeable within individuals. The DAS28-CRP tends to yield lower values of disease activity than the DAS28-ESR, resulting in substantial classification differences.

Arthritis Research & Therapy, 2007

Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is hampered by gastrointestinal ulc... more Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is hampered by gastrointestinal ulcer complications, such as ulcer bleeding and perforation. The efficacy of proton-pump inhibitors in the primary prevention of ulcer complications arising from the use of NSAIDs remains unproven. Selective cyclooxygenase-2 (COX-2) inhibitors reduce the risk for ulcer complications, but not completely in high-risk patients. This study determines which patients are especially at risk for NSAID ulcer complications and investigates the effectiveness of different preventive strategies in daily clinical practice. With the use of a nested case-control design, a large cohort of NSAID users was followed for 26 months. Cases were patients with NSAID ulcer complications necessitating hospitalisation; matched controls were selected from the remaining cohort of NSAID users who did not have NSAID ulcer complications.

Annals of the Rheumatic Diseases, 2011

Annals of the Rheumatic Diseases, 2013

Annals of Neurology, 1995

Preferential loss of basal ganglia neurons and terminals occurs in Huntington's disease (HD). Ter... more Preferential loss of basal ganglia neurons and terminals occurs in Huntington's disease (HD). Terminals of preproenkephalin medium-size spiny neurons are more vulnerable than terminals of preprotachykinin neurons, but the peptidergic neurons of origin have not yet been shown to die preferentially. We sought to determine, in the striatum, whether preproenkephalin neurons were lost to a greater extent than preprotachykinin neurons and to determine whether there were decreases in specific messenger RNA (mRNA) levels of preproenkephalin, preprotachykinin, and calbindin D28k. We found a grade-related decrease in the number of preprotachykinin-and calbindin D28k-labeled neurons per measuring field in the caudate nucleus of patients with HD. Three measures of the neuronal level of preprotachykinin mRNA were all significantly reduced (6-65% of control values) in HD caudate nucleus. No decline in calbindin D28k mRNA levels per neuron were found in HD striata compared to control striata. We found a greater loss of preproenkephalin neurons per field than preprotachykinin neurons per field in the caudate nucleus of HD brains compared to control brains. Preprotachykinin neurons are lost in HD in a grade-related manner and surviving preprotachykinin neurons are impaired in function. However, preproenkephalin neurons are lost to a greater extent than preprotachykinin neurons, which may explain preferential changes found in projection regions of the striatum. Declines in neuropeptide mRNA may be specific in HD, since calbindin D28k mRNA levels were unchanged. Alterations in the levels of expression of preproenkephalin and preprotachykinin mRNA may be direct or indirect effects of the HD mutation.

AIDS, 2000

The treatment of HIV patients with highly active antiretroviral therapy (HAART) is associated wit... more The treatment of HIV patients with highly active antiretroviral therapy (HAART) is associated with the occurrence of peripheral lipodystrophy, low total body fat, visceral abdominal fat accumulation, hyperlipidaemia and insulin resistance. This syndrome implies a ...

Arthritis Care & Research, 2014

To evaluate the reliability of a crosswalk, developed in The Netherlands, between the Health Asse... more To evaluate the reliability of a crosswalk, developed in The Netherlands, between the Health Assessment Questionnaire (HAQ) disability index (DI) and the Short Form 36 physical functioning scale (PF-10) in a sample of patients with various rheumatic diseases in the US. Baseline data from patients with rheumatoid arthritis (RA; n = 29,020), fibromyalgia (FM; n = 3,776), and systemic lupus erythematosus (SLE; n = 1,609) participating in the National Data Bank for Rheumatic Diseases were analyzed. Reliability of the crosswalk was evaluated by calculating intraclass correlation coefficients (ICCs), and agreement between observed and predicted scores was evaluated using the Bland-Altman approach. RESULTS. The crosswalk produced reliable conversions for both the HAQ DI (ICC range 0.70-0.77) and PF-10 (ICC range 0.73-0.78) in all 3 disease groups. The mean difference between observed and expected scores was close to zero in US patients with RA. For all 3 disease groups, the limits of agreement were fairly wide and conversion at the level of individual patients is not recommended. The crosswalk produced reliable conversions at the group level in a crosscultural setting and can be used to convert HAQ DI to PF-10 scores and vice versa in US patients with RA, FM, or SLE.

Health and Quality of Life Outcomes, 2015

This paper demonstrates the mechanism of a multidimensional computerized adaptive test (CAT) to m... more This paper demonstrates the mechanism of a multidimensional computerized adaptive test (CAT) to measure fatigue in patients with rheumatoid arthritis (RA). A CAT can be used to precisely measure patient-reported outcomes at an individual level as items are consequentially selected based on the patient's previous answers. The item bank of the CAT Fatigue RA has been developed from the patients' perspective and consists of 196 items pertaining to three fatigue dimensions: severity, impact and variability of fatigue. The CAT Fatigue RA was completed by fifteen patients. To test the CAT's working mechanism, we applied the flowchart-check-method. The adaptive item selection procedure for each patient was checked by the researchers. The estimated fatigue levels and the measurement precision per dimension were illustrated with the selected items, answers and flowcharts. The CAT Fatigue RA selected all items in a logical sequence and those items were selected which provided the most information about the patient's individual fatigue. Flowcharts further illustrated that the CAT reached a satisfactory measurement precision, with less than 20 items, on the dimensions severity and impact and to somewhat lesser extent also for the dimension variability. Patients' fatigue scores varied across the three dimensions; sometimes severity scored highest, other times impact or variability. The CAT's ability to display different fatigue experiences can improve communication in daily clinical practice, guide interventions, and facilitate research into possible predictors of fatigue. The results indicate that the CAT Fatigue RA measures precise and comprehensive. Once it is examined in more detail in a consecutive, elaborate validation study, the CAT will be available for implementation in daily clinical practice and for research purposes.

Helicobacter, 2007

Background: Helicobacter pylori and nonsteroidal antiinflammatory drugs (NSAIDs) are the major ca... more Background: Helicobacter pylori and nonsteroidal antiinflammatory drugs (NSAIDs) are the major causes of gastroduodenal ulcers. Studies on the benefit of eradication of H. pylori in NSAID users yielded conflicting results. Objective: To investigate whether H. pylori eradication in patients on long-term NSAIDs reduces the incidence of gastroduodenal ulcers. Methods: Patients on long-term NSAID treatment and who are H. pylori positive

PLoS ONE, 2014

The 28-joint Disease Activity Score (DAS28) combines scores on a 28-tender and swollen joint coun... more The 28-joint Disease Activity Score (DAS28) combines scores on a 28-tender and swollen joint count (TJC28 and SJC28), a patient-reported measure for general health (GH), and an inflammatory marker (either the erythrocyte sedimentation rate [ESR] or the C-reactive protein [CRP]) into a composite measure of disease activity in rheumatoid arthritis (RA). This study examined the reliability of the DAS28 in patients with early RA using principles from generalizability theory and evaluated whether it could be increased by adjusting individual DAS28 component weights. Patients were drawn from the DREAM registry and classified into a "fast response" group (N = 466) and "slow response" group (N = 80), depending on their pace of reaching remission. Composite reliabilities of the DAS28-ESR and DAS28-CRP were determined with the individual components' reliability, weights, variances, error variances, correlations and covariances. Weight optimization was performed by minimizing the error variance of the index. Composite reliabilities of 0.85 and 0.86 were found for the DAS28-ESR and DAS28-CRP, respectively, and were approximately equal across patients groups. Component reliabilities, however, varied widely both within and between sub-groups, ranging from 0.614 for GH ("slow response" group) to 0.912 for ESR ("fast response" group). Weight optimization increased composite reliability even further. In the total and "fast response" groups, this was achieved mostly by decreasing the weight of the TJC28 and GH. In the "slow response" group, though, the weights of the TJC28 and SJC28 were increased, while those of the inflammatory markers and GH were substantially decreased. The DAS28-ESR and the DAS28-CRP are reliable instruments for assessing disease activity in early RA and reliability can be increased even further by adjusting component weights. Given the low reliability and weightings of the general health component across subgroups it is recommended to explore alternative patient-reported outcome measures for inclusion in the DAS28.

Arthritis Care & Research, 2014

Objective: Although treat-to-target (T2T) strategies are effective in early RA patients, importan... more Objective: Although treat-to-target (T2T) strategies are effective in early RA patients, important individual variations exist in the course towards remission. Growth mixture modeling (GMM) provides more insight into this heterogeneity by identifying subgroups of patients with similar response patterns. This study aimed to identify distinct trajectories of disease activity in early RA patients following a T2T strategy, during their first year. Methods: Data on various clinical and patient-reported measures were collected from the DREAM remission induction cohort. GMM was applied to examine the impact of T2T on subgroups characterized by different types of growth trajectories, as measured with the Disease Activity Score for 28 joints. Results: Three distinct trajectories of disease activity were found. The normative trajectory contained most patients (82.6%), showing a quickly decreasing disease activity, stabilizing at remission after 9 months. This group performed best on clinical and patient-reported measures over time and were more likely to be men. A smaller group (14.1%) also approached remission, but demonstrated a slower response to treatment. Finally, a minority (3.3%) showed no improvement after 1 year, despite an initial quick decrease in disease activity during the first months of treatment. Conclusion: Disease activity in early RA patients during the first year of a T2T strategy does not follow a linear pattern, nor is a single developmental trajectory applicable to all patients. Future studies should attempt to identify more specific risk factors for poor outcome to enable early identification of patients in need of alternative therapeutic approaches. © 2013 American College of Rheumatology.

Seminars in Arthritis and Rheumatism, 2010

To discuss nonsteroidal anti-inflammatory drugs (NSAIDs), their history, development, mode of act... more To discuss nonsteroidal anti-inflammatory drugs (NSAIDs), their history, development, mode of action, toxicities, strategies for the prevention of toxicity, and future developments. Medline search for articles published up to 2007, using the keywords acetylsalicylic acid, aspirin, NSAIDs, cyclooxygenase 2, adverse effects, ulcer, and cardiovascular. NSAIDs are 1 of the oldest, most successful drugs known to modern medicine. They are effective for alleviating pain, fever, and inflammation by inhibiting prostaglandin synthesis. Aspirin, by its irreversible inhibition of blood platelet function, is also effective in the prevention of cardiovascular disease. NSAIDs may cause gastrointestinal ulcers, serious cardiovascular events, hypertension, acute renal failure, and worsening of preexisting heart failure. These adverse effects may be prevented by limiting NSAID dosage and duration and by performing individual risk assessments and treating patients accordingly. Those at risk for gastroduodenal ulcers may be treated with concomitant proton-pump inhibitors, misoprostol and/or COX-2 selective NSAIDs. Those at risk for cardiovascular events may be treated with naproxen and a proton-pump inhibitor or misoprostol, but should best avoid NSAID use altogether. Physicians should always prescribe the lowest effective dose for the shortest possible time and must take into account both the gastrointestinal and the cardiovascular risks of individual patients when prescribing NSAIDs.

PLoS ONE, 2014

Objective: To calibrate the Dutch-Flemish version of the PROMIS physical function (PF) item bank ... more Objective: To calibrate the Dutch-Flemish version of the PROMIS physical function (PF) item bank in patients with rheumatoid arthritis (RA) and to evaluate cross-cultural measurement equivalence with US general population and RA data.

Pharmaceuticals, 2010

While aspirin may offer protection, other non-aspirin non-steroidal antiinflammatory drugs (NSAID... more While aspirin may offer protection, other non-aspirin non-steroidal antiinflammatory drugs (NSAIDs) can cause serious cardiovascular side effects and complications. This has led to a general "black box" warning for cardiovascular adverse events for NSAIDs. This review explores the different mechanisms underlying the protective effects of aspirin, the NSAID associated renovascular effects causing hypertension, edema and heart failure, the cardiovascular effects causing myocardial infarction and stroke, and the possible deleterious interaction between NSAIDs and aspirin.

European Journal of Clinical Pharmacology, 2013

Nonsteroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid (ASA) are often prescribed... more Nonsteroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid (ASA) are often prescribed concurrently in patients with nociceptive pain and cardiovascular comorbidity. NSAIDs and ASA inhibit the same COX-enzymes, and thus may interact. ASA's cardioprotective antiplatelet effect is entirely COX-1 dependent. NSAIDs can be either non-COX-1 and COX-2 selective or COX-2 selective. The aim of this study was to examine the interaction between ASA and different selective and nonselective NSAIDs on thrombocyte function. Single-blind, prospective, placebo-controlled, ex vivo, serial crossover trial of 3-day cycles separated by washout periods of at least 12 days in 30 healthy volunteers, evaluating interaction on ASA's antithrombocyte effect by naproxen, ibuprofen, meloxicam, or etoricoxib taken 2 h before ASA. Ex vivo thrombocyte function, closure time (CT) in seconds, was measured using the Platelet Function Analyzer 100 (PFA-100). CT prolongation during a cycle reflects thrombocyte inhibitory effect. ASA nonresponse was defined as CT prolongation <40 % in the placebo cycle. ASA nonresponders were excluded. Wilcoxon signed-rank was used to evaluate NSAID effect on ASA-induced CT prolongation. Ibuprofen and naproxen inhibit ASA's antithrombocyte effect below the nonresponse threshold. Etoricoxib and meloxicam do not cause relevant change in ASA thrombocyte inhibition. Naproxen has an inherent weak thrombocyte inhibitory action below the ASA response threshold. COX-1 affinity determines the interaction between NSAIDs and ASA on thrombocyte adhesion and aggregation. Ibuprofen and naproxen, but not etoricoxib or meloxicam, taken 2 h before ASA, significantly inhibit ASA's antithrombocyte effect.

Drugs & Aging, 2007

of NSAIDs has become a major healthcare issue.

Drug, Healthcare and Patient Safety, 2010

Diabetes, Obesity and Metabolism, 2001

Aim: The b 3 -adrenergic receptor (b 3 -AR) is suspected to play a key role in the regulation of ... more Aim: The b 3 -adrenergic receptor (b 3 -AR) is suspected to play a key role in the regulation of energy balance by increasing lipolysis and thermogenesis. A mutation in the b 3 -AR gene (Trp64Arg) has been associated with the capacity of weight gain and with early onset of noninsulin dependent diabetes mellitus (type 2 diabetes). In this study we investigated the prevalence of the two b 3 -AR alleles in a Caucasian population and studied the association between the b 3 -AR genotype and metabolic disorders (obesity and type 2 diabetes). Methods: Genomic DNA extracted from peripheral blood leucocytes of 200 Caucasian subjects (137 subjects with and 63 subjects without type 2 diabetes). The MvaI polymorphism of b 3 -AR, which detects the Trp64Arg mutation, was determined by polymerase chain reaction (PCR). We studied the correlation between the Trp64Arg mutation and the body mass index (b.m.i. kg/m 2 ). Results: There was no signi®cant difference between the patients with type 2 diabetes and control subjects in the frequency of the Arg64 allele (5.5% and 4.8%, respectively). Within the group of type 2 diabetes patients were 14 subjects with the Trp64Arg mutation (b.m.i., mean T s.d.: 31 T 8.5 kg/m 2 ) and 123 without the mutation (b.m.i. 29 T 4.8). There was no association between the b 3 -AR gene polymorphism and sex, obesity, blood pressure, glycohaemoglobin concentration, proteinuria. Conclusion: Our results suggest that the Trp64Arg mutation is not a major determinant of metabolic disorders (type 2 diabetes, obesity) and chronic complications of type 2 diabetes in a Dutch population.

Current Opinion in Rheumatology, 2013

This era of early aggressive treatment of rheumatoid arthritis (RA) calls for criteria that allow... more This era of early aggressive treatment of rheumatoid arthritis (RA) calls for criteria that allow timely classification of patients at risk of persistent erosive disease. We review how the new American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria meet up to this challenge. The new 2010 ACR/EULAR classification criteria for RA were developed using initiation of methotrexate as anchor in a population with undifferentiated arthritis. Many studies from different countries have now been published that have addressed the performances of these new criteria. The goal of earlier classification of RA seems to be met with the new criteria, but exclusion of other diagnoses is essential. Increased sensitivity comes at the price of loss of specificity and indiscriminate use of these classification criteria as a diagnostic tool carries the risk of overtreatment.

Clinical Rheumatology, 2014

This paper aims to examine the interchangeability of the disease activity score in 28 joints (DAS... more This paper aims to examine the interchangeability of the disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) and DAS28-CRP scores in a diverse sample of rheumatoid arthritis (RA) patients and to evaluate generalizability over gender, age, and disease duration. A sample of 682 patients was drawn from the DREAM registry. Agreement between the two DAS28 scores was analyzed using the intraclass correlation coefficient (ICC), Bland Altman plots, and a matrix of classification agreement over DAS28 disease activity categories. Despite a strong linear correlation between the DAS28 scores and a high ICC value of 0.931, a considerable lack of individual agreement could be observed, with Bland-Altman 95% limits of agreement ranging between -0.85 and +1.25 points. On average, DAS28-CRP scores were 0.20 points lower than DAS28-ESR scores, and data stratification on age and gender showed that this systematic bias was most severe in older women (0.39 points). The overall classification agreement across DAS28 categories was 76.69%, with the agreement being lowest (35.37%) in the low disease activity group. Patients were more easily classified as being in remission when using the DAS28-CRP measure. DAS28-ESR and DAS28-CRP scores are not interchangeable within individuals. The DAS28-CRP tends to yield lower values of disease activity than the DAS28-ESR, resulting in substantial classification differences.

Arthritis Research & Therapy, 2007

Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is hampered by gastrointestinal ulc... more Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is hampered by gastrointestinal ulcer complications, such as ulcer bleeding and perforation. The efficacy of proton-pump inhibitors in the primary prevention of ulcer complications arising from the use of NSAIDs remains unproven. Selective cyclooxygenase-2 (COX-2) inhibitors reduce the risk for ulcer complications, but not completely in high-risk patients. This study determines which patients are especially at risk for NSAID ulcer complications and investigates the effectiveness of different preventive strategies in daily clinical practice. With the use of a nested case-control design, a large cohort of NSAID users was followed for 26 months. Cases were patients with NSAID ulcer complications necessitating hospitalisation; matched controls were selected from the remaining cohort of NSAID users who did not have NSAID ulcer complications.

Annals of the Rheumatic Diseases, 2011

Annals of the Rheumatic Diseases, 2013

Annals of Neurology, 1995

Preferential loss of basal ganglia neurons and terminals occurs in Huntington's disease (HD). Ter... more Preferential loss of basal ganglia neurons and terminals occurs in Huntington's disease (HD). Terminals of preproenkephalin medium-size spiny neurons are more vulnerable than terminals of preprotachykinin neurons, but the peptidergic neurons of origin have not yet been shown to die preferentially. We sought to determine, in the striatum, whether preproenkephalin neurons were lost to a greater extent than preprotachykinin neurons and to determine whether there were decreases in specific messenger RNA (mRNA) levels of preproenkephalin, preprotachykinin, and calbindin D28k. We found a grade-related decrease in the number of preprotachykinin-and calbindin D28k-labeled neurons per measuring field in the caudate nucleus of patients with HD. Three measures of the neuronal level of preprotachykinin mRNA were all significantly reduced (6-65% of control values) in HD caudate nucleus. No decline in calbindin D28k mRNA levels per neuron were found in HD striata compared to control striata. We found a greater loss of preproenkephalin neurons per field than preprotachykinin neurons per field in the caudate nucleus of HD brains compared to control brains. Preprotachykinin neurons are lost in HD in a grade-related manner and surviving preprotachykinin neurons are impaired in function. However, preproenkephalin neurons are lost to a greater extent than preprotachykinin neurons, which may explain preferential changes found in projection regions of the striatum. Declines in neuropeptide mRNA may be specific in HD, since calbindin D28k mRNA levels were unchanged. Alterations in the levels of expression of preproenkephalin and preprotachykinin mRNA may be direct or indirect effects of the HD mutation.

AIDS, 2000

The treatment of HIV patients with highly active antiretroviral therapy (HAART) is associated wit... more The treatment of HIV patients with highly active antiretroviral therapy (HAART) is associated with the occurrence of peripheral lipodystrophy, low total body fat, visceral abdominal fat accumulation, hyperlipidaemia and insulin resistance. This syndrome implies a ...