Papers by Alfons Den Broeder
Clinical and experimental rheumatology, Jan 27, 2015
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Clinical and experimental rheumatology
Monitoring of disease activity using DAS28 is more effective than routine RA care, but the ESR me... more Monitoring of disease activity using DAS28 is more effective than routine RA care, but the ESR measurement is time consuming. Alternative rapid ESR determination methods can be used but effects on DAS28 classification are unknown. Alternative rapid ESR methods, including the Starrsed 30-minute mode and Alifax Roller Test-1TH, were compared to the Westergren method. Mean difference, limits of agreement (LoA) and intraclass correlation coefficients (ICC) were calculated. Based on these results, using a longitudinal design the percentage of DAS28 misclassification for the Alifax Roller Test-1TH was measured. The Alifax showed acceptable ICCs, but LoA were large. ICC was 0.67 (0.56-0.76), LoA -43;34. The longitudinal study on the Alifax (n=125) showed an ICC of 0.93, a kappa of 0.61, but disease activity was misclassified in 26% of the patients. Use of the ESR from the previous visit resulted in comparable levels of misclassification. ESR measured by automated analysers like Alifax show...
Annals of the Rheumatic Diseases, 2015
Osteoarthritis and Cartilage
Clinical and experimental rheumatology
To describe the results of a Numeric Rating Scale (NRS)-guided pharmacological pain management st... more To describe the results of a Numeric Rating Scale (NRS)-guided pharmacological pain management strategy in symptomatic knee and hip osteoarthritis (OA) in daily clinical practice. In this observational cohort study, standardised conservative treatment was offered to patients with symptomatic knee and/or hip OA referred to secondary care. Pain management was guided by a NRS for pain, aiming for NRS ≤4. The first step in pharmacological treatment was paracetamol (acetaminophen) in case of no recent use in adequate dose. In case of treatment failure, patients switched to a non-steroidal anti-inflammatory drug (NSAID) and eventually to a second NSAID, each after a 4-week trial period. Predictors for response to treatment were identified. Moreover, reasons for protocol violations were collected. Three-hundred and forty-seven patients were included. The proportion of patients that reached a response after paracetamol, first and second NSAID was 25% (59/234), 16% (31/190) and 11% (10/87), ...
Annals of the rheumatic diseases
1. Mladenovic V, Domljan Z, Rozman B, Jajic I, Mihajlovic D, Dordevic J, et al. Safety and effect... more 1. Mladenovic V, Domljan Z, Rozman B, Jajic I, Mihajlovic D, Dordevic J, et al. Safety and effectiveness of leflunomide in the treatment of patients with active rheumatoid arthritis. Results of a randomized, placebo-controlled, phase II study. Arthritis Rheum 1995;38:1595-603. 2. Kalgutkar AS, Nguyen HT, Vaz AD, Doan A, Dalvie DK, McLeod DG, et al. In vitro metabolism studies on the isoxazole ring scission in the anti-inflammatory agent lefluonomide to its active alpha-cyanoenol metabolite A771726: mechanistic similarities with the cytochrome P450-catalyzed dehydration of aldoximes. Drug Metab Dispos 2003;31:1240-50. 3. Bohanec Grabar P, Rozman B, Tomsic M, Suput D, Logar D, Dolzan V. Genetic polymorphism of CYP1A2 and the toxicity of leflunomide treatment in rheumatoid arthritis patients. Eur J Clin Pharmacol 2008:64:871-6. 4. Breedveld FC, Dayer JM. Leflunomide: mode of action in the treatment of rheumatoid arthritis. Ann Rheum Dis 2000;59:841-9. 5. Chonlahan J, Halloran MA, Hammonds A. Leflunomide and warfarin interaction: case report and review of the literature. Pharmacotherapy 2006;26:868-71. 6. Lim V, Pande I. Leflunomide can potentiate the anticoagulant effect of warfarin. BMJ 2002;325:1333.
Rheumatology (Oxford, England), Jan 23, 2015
The aim of this study was to investigate the association between a set of US features and radiogr... more The aim of this study was to investigate the association between a set of US features and radiographic and clinical progression of knee OA after 2 years of follow-up. A total of 125 patients fulfilling ACR clinical criteria for knee OA underwent US examination of the most symptomatic knee. The US protocol included assessment of synovial hypertrophy, joint effusion, infrapatellar bursitis, Baker's cyst, medial meniscus protrusion and cartilage thickness. Clinical progression was defined using the inverse Osteoarthritis Research Society International responder criteria or progression to total knee replacement. Radiological progression was defined as a ≥2 point increase in Altman score or progression to total knee replacement. Regression analyses were performed with baseline ultrasonographic features as independent variables and progression (two separate models for clinical progression and radiographic progression) as the dependent variable. A total of 31 (25%) patients fulfilled t...
Annals of the Rheumatic Diseases, 2013
ABSTRACT Background Anti-nuclear antibodies (ANA) are found in patients with (non)-rheumatic dise... more ABSTRACT Background Anti-nuclear antibodies (ANA) are found in patients with (non)-rheumatic diseases and in healthy controls, with 30% positives in the latter group.1 ANA testing is useful in diagnosing auto-immune diseases, especially in Systemic Lupus Erythematodus (SLE), Systemic Sclerosis (SSc), polymyositis (PM), dermatomyositis (DM), Mixed Connective Tissue Disorder (MCTD) and Sjögren Syndrome (SS).1 For the correct use of diagnostic tests knowledge about disease prevalence and test characteristics is essential. Many physicians find this difficult to apply, often leading to overuse of tests.2,3 Objectives To assess the characteristics of ANA testing in patients visiting the rheumatology outpatient clinic of the Sint Maartenskliniek, the Netherlands, before and after a targeted intervention. Methods The number, result and final diagnosis of all ANA tests done by rheumatologists working at the clinic between 1-1-2010 and 31-1-2012 (25 months) were compared with the ANA’s done after the intervention (1-7-2012 and 31-10-2012; 4 months). To make comparison possible the absolute ANA count was corrected for the number of new patients seen at the outpatient clinic in the same period. The intervention consisted of a one-hour, group wise training in which the results from the pre-intervention period were given together with general background information on the correct ANA use. Directly afterwards all doctors received individual information on their own ANA tests in comparison with their peers. Results In the pre-intervention period 2696 ANAs were requested by 14 rheumatologists in 2673 unique patients (mean age 53 ±15 years, 74% women); 62% were negative. The most frequent final diagnoses were undifferentiated artralgia/myalgia (20%), rheumatoid arthritis (19%) and fibromyalgia (8%); 7% had an ANA-associated disease (SLE, SSc, PM, DM, MCTD, SS). In the four months after the intervention 127 ANA’s were requested by the same rheumatologists in 125 unique patients (mean age 48 ±17 years, 81% women); 56% were negative. When corrected for number of new patients seen, on average 0.42 (SD ±0.15) ANA per new patient was done in the pre-intervention period and 0.15 (SD ±0.15) in the post-intervention period (p= 0.00), resulting in a decrease of 64% (figure 1). The distribution of the final diagnoses did not change. Conclusions The finding that our single session intervention resulted in a sizable reduction in number of ANA’s requested, while inter-individual variation and final diagnoses remained unchanged, suggests that excessive usage was reduced without a reduction in appropriate use. References References Disclosure of Interest None Declared
Annals of the Rheumatic Diseases, 2013
ABSTRACT Background The level of radiographic knee osteoarthritis (OA) is only moderately associa... more ABSTRACT Background The level of radiographic knee osteoarthritis (OA) is only moderately associated with the level of pain. As OA is a disease of the entire joint, ultrasonography (US) of cartilage and soft tissue structures might provide more insight in the complex process of pain in knee OA(1). Objectives To investigate the cross sectional association between US findings and pain in knee OA. Methods A single centre cross sectional observational study was performed. A total of 180 patients fulfilling the American College of Rheumatology clinical criteria for knee OA underwent US examination of the most symptomatic knee. The previously validated US protocol (2) comprised inflammatory (synovial hypertrophy, joint effusion, infrapatellar bursitis and Baker’s cyst), and mechanical aspects(medial meniscus protrusion, cartilage thickness). On inclusion, clinical data, data on pain (Knee injury and Osteoarthritis Outcome Score (KOOS) and Numerated Rating Scale (NRS) and knee X-rays were collected. Correlations between the different US features were tested. To evaluate the association between US features and pain, regression analysis was performed. Results The study participants were predominantly female (67%). Mean age was 57 ± 9.2 years and the predominant Kellgren and Lawrence score was II (0-IV). The mean NRS was 6.1± 1.7 indicating moderate to high pain levels. The US findings were: (n,%): joint effusion : 30 (16.7%), synovial hypertrophy: 37 (20.6%), meniscal protrusion: 111 (61.7%), infrapatellar bursitis 10 (5.6%) Baker’s cyst: 47 (26.1%). Cartilage thickness measures were (mean, SD) 1.75 (0.56) mm, 2.26 (0.67) mm and 1.86 (0.50) mm respectively. Small statistically significant associations among US features were found for the three measures of cartilage thickness (r:0.45-0.50) and between synovial hypertrophy and joint effusion (V: 0.18). Regression analysis showed no association between US features and the level of knee pain. Post hoc analyses for inflammatory and mechanical symptoms yielded the same results. Conclusions In this cohort of 180 patients with painful knee OA no association between US features and the level of knee pain was found. The results in this study are in line with limited previous research, that also failed to demonstrate a robust cross sectional association between US features and the level pain in knee OA, although some differences between patients with and without knee pain in OA have been found. This cohort somewhat distinguishes itself from other cohorts in relatively high pain levels and moderate radiological damage. Longitudinal extension of the study will further assess whether US features can be predictive for future signs and symptoms of knee OA, and what the course is of US abnormalities in knee OA. References Disclosure of Interest None Declared Background The level of radiographic knee osteoarthritis (OA) is only moderately associated with the level of pain. As OA is a disease of the entire joint, ultrasonography (US) of cartilage and soft tissue structures might provide more insight in the complex process of pain in knee OA(1). Objectives To investigate the cross sectional association between US findings and pain in knee OA. Methods A single centre cross sectional observational study was performed. A total of 180 patients fulfilling the American College of Rheumatology clinical criteria for knee OA underwent US examination of the most symptomatic knee. The previously validated US protocol (2) comprised inflammatory (synovial hypertrophy, joint effusion, infrapatellar bursitis and Baker’s cyst), and mechanical aspects(medial meniscus protrusion, cartilage thickness). On inclusion, clinical data, data on pain (Knee injury and Osteoarthritis Outcome Score (KOOS) and Numerated Rating Scale (NRS) and knee X-rays were collected. Correlations between the different US features were tested. To evaluate the association between US features and pain, regression analysis was performed. Results The study participants were predominantly female (67%). Mean age was 57 ± 9.2 years and the predominant Kellgren and Lawrence score was II (0-IV). The mean NRS was 6.1± 1.7 indicating moderate to high pain levels. The US findings were: (n,%): joint effusion : 30 (16.7%), synovial hypertrophy: 37 (20.6%), meniscal protrusion: 111 (61.7%), infrapatellar bursitis 10 (5.6%) Baker’s cyst: 47 (26.1%). Cartilage thickness measures were (mean, SD) 1.75 (0.56) mm, 2.26 (0.67) mm and 1.86 (0.50) mm respectively. Small statistically significant associations among US features were found for the three measures of cartilage thickness (r:0.45-0.50) and between synovial hypertrophy and joint effusion (V: 0.18). Regression analysis showed no association between US features and the level of knee pain. Post hoc analyses for inflammatory and mechanical symptoms yielded the same results. Conclusions In this cohort of 180 patients with painful knee OA no association between US features and the level of knee pain…
BMJ (Clinical research ed.), 2015
To evaluate whether a disease activity guided strategy of dose reduction of two tumour necrosis f... more To evaluate whether a disease activity guided strategy of dose reduction of two tumour necrosis factor (TNF) inhibitors, adalimumab or etanercept, is non-inferior in maintaining disease control in patients with rheumatoid arthritis compared with usual care. Randomised controlled, open label, non-inferiority strategy trial. Two rheumatology outpatient clinics in the Netherlands, from December 2011 to May 2014. 180 patients with rheumatoid arthritis and low disease activity using adalimumab or etanercept; 121 allocated to the dose reduction strategy, 59 to usual care. Disease activity guided dose reduction (advice to stepwise increase the injection interval every three months, until flare of disease activity or discontinuation) or usual care (no dose reduction advice). Flare was defined as increase in DAS28-CRP (a composite score measuring disease activity) greater than 1.2, or increase greater than 0.6 and current score of at least 3.2. In the case of flare, TNF inhibitor use was res...
European Journal of Hospital Pharmacy: Science and Practice, 2012
Clinical and experimental rheumatology
To investigate the predictive value of ultrasound (US) characteristics for the effect of intra-ar... more To investigate the predictive value of ultrasound (US) characteristics for the effect of intra-articular glucocorticoids in knee osteoarthritis (OA). In this prospective cohort study, 62 patients with symptomatic knee OA (clinical knee OA criteria, pain>4 on a Numerical Rating Scale (NRS; 0-10)) received an intra-articular glucocorticoid injection (40 mg triamcinolone acetonide). Patients with NRS pain ≤4 at 4 weeks were defined as responders. On inclusion, demographics, clinical data (body mass index, local swelling) knee x-rays and knee injury and Osteoarthritis Outcome Score (KOOS) questionnaire were collected. Six US features were assessed including: effusion, synovial hypertrophy, Baker's cyst, infrapatellar bursitis, meniscal protrusion and cartilage thickness. Stepwise multiple logistic regression analyses with forward selection were conducted to identify possible predictors. At 4 weeks, 42% of the study participants reached a NRS ≤4; an effect comparable to existing l...
Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society, 2014
Imaging of (peri)articular structures and inflammation with Ultrasonography (US) during the cours... more Imaging of (peri)articular structures and inflammation with Ultrasonography (US) during the course of osteoarthritis (OA) might contribute to knowledge about early diagnosis of OA, prognosis and possibly the effect of disease modifying drugs. Our goal was to identify the prevalence of distinct patterns (stable vs fluctuating) in a set of US features in a cohort of patients receiving standard multimodal treatment for knee OA at T = 0, T = 3 months and T = 12 months. This was a prospective, explorative study including 55 patients fulfilling the American College of Rheumatology clinical criteria for knee OA. Six US features were investigated including: effusion, synovial proliferation, infrapatellar bursitis, meniscal protrusion, Baker's cyst and cartilage thickness at three time points during 1 year. A composite inflammatory score was composed. Overall prevalence was assessed as well as individual patterns which were appointed as stable or unstable. Inflammation like effusion and ...
BMC infectious diseases, 2014
Q fever is caused by the intracellular bacterium Coxiella burnetii. Initial infection can present... more Q fever is caused by the intracellular bacterium Coxiella burnetii. Initial infection can present as acute Q fever, while a minority of infected individuals develops chronic Q fever endocarditis or vascular infection months to years after initial infection. Serology is an important diagnostic tool for both acute and chronic Q fever. However, since immunosuppressive drugs may hamper the humoral immune response, diagnosis of Q fever might be blurred when these drugs are used. A 71-year-old Caucasian male was diagnosed with symptomatic acute Q fever (based on positive C. burnetii PCR followed by seroconversion) while using anti-tumor necrosis factor-α (anti-TNFα) drugs for rheumatoid arthritis (RA). He was treated for two weeks with moxifloxacin. After 24 months of follow-up, the diagnosis of probable chronic Q fever was established based on increasing anti-C. burnetii phase I IgG antibody titres in a immunocompromised patient combined with clinical suspicion of endocarditis. At the ti...
The Journal of rheumatology, 2002
To assess the pharmacokinetics, safety profile, and efficacy of the fully human anti-tumor necros... more To assess the pharmacokinetics, safety profile, and efficacy of the fully human anti-tumor necrosis factor-alpha (anti-TNF-alpha) monoclonal antibody adalimumab (D2E7) in patients with long-standing, active rheumatoid arthritis (RA). This was a randomized, double blind, placebo controlled study of single intravenous injections of ascending doses (0.5 to 10 mg/kg) of adalimumab in 5 cohorts of 24 patients each (18 adalimumab and 6 placebo in all cohorts except the 0.5 mg/kg cohort of 17 adalimumab, 7 placebo). A total of 120 patients participated (adalimumab 89, placebo 31). The clinical response was measured by changes in composite scores defined by the criteria of the European League Against Rheumatism (EULAR) and the American College of Rheumatology. Single doses of adalimumab showed a rapid onset of clinical effect (24 hours to 1 week), with peak efficacy at 1 to 2 weeks that was sustained for at least 4 weeks and for as long as 3 months in some patients. EULAR response was seen ...
Purpose: Fears and beliefs have been shown to be important prognostic factors for low back pain p... more Purpose: Fears and beliefs have been shown to be important prognostic factors for low back pain patients but are usually not recorded in OA. We aimed to develop a questionnaire assessing fears and beliefs of patients regarding knee OA. Methods: To generate items of the pre-questionnaire, the extensive document reporting a qualitative analysis of interviews with 81 patients with knee OA was sent to 10 experts and a Delphi procedure was adopted. A forward-backward translation technique was used to provide an English version of the pre-questionnaire. Eighty physicians (64 general practitioners, 16 rheumatologists) recruited 566 patients with knee OA to test the pre-questionnaire. An item reduction was performed according to metric properties of each item (floor and ceiling effects, percentage of missing answers, correlations with other items). Reliability of the questionnaire was tested by use of Chronbach a coefficient. Construct validity was tested by use of divergent validity, and exploratory and confirmatory factor analyses. Results: In total, 137 items were extracted from the analysis of the qualitative study and three Delphi rounds were needed to obtain consensus on a 25-items pre-questionnaire assessing fears and beliefs of patients regarding knee OA. Consensuses were easily found for English and French versions of the pre-questionnaire. Files of 524 patients were available for analysis and the item reduction process leaded to an 11-item questionnaire (range 0-99). Chronbach coefficient was 0.85 (95% CI 0.83-0.87). Divergent validity was observed with knee pain score (r = 0.38), WOMAC function score (r = 0.52), and physical and mental scores of the SF-12 (r = 0.36 and 0.38, respectively). Exploratory factor analysis extracted 4 main factors with Eigen values of 6.51, 2.19, 1.60, and 1.37 explaining 45% of the variance. Each factor was easily characterized, factor 1 (3-items) representing fears and beliefs about daily living activities, factor 2 (4-items) fears and beliefs about physicians, factor 3 (2-items) fears and beliefs about the disease, and factor 4 (2-items) fears and beliefs about sports and leisure activities. Confirmatory factor analyses confirmed that intra-factor correlations were higher than inter factors ones. Conclusions: We propose a new 11-items questionnaire assessing patients' fears and beliefs concerning knee OA with good content and construct validities. Test-retest reliability and sensitivity to change should now be tested before clinical use.
Annals of the Rheumatic Diseases
BMJ Open, 2012
Objectives: To evaluate the feasibility and potential effectiveness of a 12-week, non-pharmacolog... more Objectives: To evaluate the feasibility and potential effectiveness of a 12-week, non-pharmacological multidisciplinary intervention in patients with generalised osteoarthritis (GOA).
Annals of the rheumatic diseases, Jan 17, 2015
Predictive performance of cardiovascular disease (CVD) risk calculators appears suboptimal in rhe... more Predictive performance of cardiovascular disease (CVD) risk calculators appears suboptimal in rheumatoid arthritis (RA). A disease-specific CVD risk algorithm may improve CVD risk prediction in RA. The objectives of this study are to adapt the Systematic COronary Risk Evaluation (SCORE) algorithm with determinants of CVD risk in RA and to assess the accuracy of CVD risk prediction calculated with the adapted SCORE algorithm. Data from the Nijmegen early RA inception cohort were used. The primary outcome was first CVD events. The SCORE algorithm was recalibrated by reweighing included traditional CVD risk factors and adapted by adding other potential predictors of CVD. Predictive performance of the recalibrated and adapted SCORE algorithms was assessed and the adapted SCORE was externally validated. Of the 1016 included patients with RA, 103 patients experienced a CVD event. Discriminatory ability was comparable across the original, recalibrated and adapted SCORE algorithms. The Hosm...
Patient Preference and Adherence, 2014
and community care, radboud University Medical centre, nijmegen, the netherlands; 4 niVel (nether... more and community care, radboud University Medical centre, nijmegen, the netherlands; 4 niVel (netherlands institute for health services research), Background: This is the first cross-sectional study that aims to examine associations between beliefs about medication and non-adherence in patients with rheumatoid arthritis (RA) using disease-modifying antirheumatic drugs, taking potential psychological confounders into account. Methods: Eligible patients (diagnosed with RA for 1 year or 18 years, using greater than or equal to one disease-modifying antirheumatic drug) were included by their rheumatologist during regular outpatient visits between September 2009 and September 2010. Included patients received questionnaires. The Beliefs about Medicines Questionnaire was used to measure the perceived need to take medication (necessity beliefs), the concerns about taking medication (concern beliefs), general medication beliefs, and attitudes toward taking medication. Medication non-adherence (no/yes) was measured using the Compliance Questionnaire Rheumatology (CQR). Associations between beliefs and non-adherence, and the influence of demographical, clinical, and psychological factors (symptoms of anxiety/depression, illness cognitions, self-efficacy) were assessed using logistic regression. Results: A total of 580 of the 820 eligible patients willing to participate were included in the analyses (68% female, mean age 63 years, 30% non-adherent to their medication). Weaker necessity beliefs (OR [odds ratio]: 0.8, 95% CI [confidence interval]: 0.8-0.9) and an unfavorable balance between necessity and concern beliefs (OR: 0.9, 95% CI: 0.9-1.0) were associated with CQR non-adherence. Also, having an indifferent attitude toward medication (no/yes) was associated with CQR non-adherence (OR: 5.3, 95% CI: 1.1-25.8), but the prevalence of patients with an indifferent attitude toward medication was low. The associations were barely confounded by demographical, clinical, and psychological factors.
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Papers by Alfons Den Broeder