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Biomedical subjects

Maarten Boers

Publications and source records attributed to Maarten Boers.

At least 37 records · Page 2Linked to original sources
PubMed2004

Markers for type II collagen breakdown predict the effect of disease-modifying treatment on long-term radiographic progression in patients with rheumatoid arthritis.

OBJECTIVE: To investigate in a randomized clinical trial setting with an aggressive combination-therapy arm and a mild-monotherapy arm, whether therapy-induced changes in urinary C-terminal crosslinking telopeptide of type I collagen (CTX-I) and type II collagen (CTX-II) predict 5-year radiographic progression in patients with rheumatoid arthritis (RA). METHODS: Patients had participated in the COBRA (Combinatietherapie Bij Reumatoïde Artritis) trial comparing aggressive step-down combination therapy (the COBRA regimen, including temporary high-dose prednisolone, temporary low-dose methotrexate, and sulfasalazine [SSZ]) and mild monotherapy (SSZ). Urinary CTX-I and CTX-II levels were measured at baseline and 3, 6, 9, and 12 months after initiation of treatment. Radiographs were scored according to the modified Sharp/van der Heijde method (mean of 2 independent readers who were aware of the sequence). Individual long-term radiographic progression was estimated, using baseline radiographs and all radiographs obtained during the followup period, by simple linear regression analysis (curve fitting). RESULTS: Both COBRA therapy and SSZ monotherapy produced a significant decrease in urinary CTX-I and CTX-II levels at 3 months, and this decrease was amplified at 6 months. COBRA therapy suppressed CTX-II (change from baseline levels -36% and -43% at 3 and 6 months, respectively), but not CTX-I, significantly better than did SSZ (-17% and -21% at 3 and 6 months, respectively) at 3 and 6 months. The magnitude of the decrease in urinary CTX-II levels at 3 months significantly predicted long-term (5-year) radiographic progression (beta = 0.48 [95% confidence interval (95% CI) 0.13, 0.83]). This effect was independent of the change in disease activity and inflammation indices at 3 months. Patients whose CTX-II levels were normalized (<150 ng/mmoles of urinary creatinine) at 3 months had a significantly higher chance of radiographic stability (no progression over 5 years) than did patients whose CTX-II levels were increased both at baseline and at 3 months (odds ratio 4.5 [95% CI 1.5, 13]). CONCLUSION: The individual CTX-II response measured after 3 months of therapy in patients with active RA who had increased CTX-II levels at baseline independently predicts long-term radiographic progression. Urinary CTX-II levels may be used as early markers of treatment efficacy in patients with RA.

Adult↗
PubMed2004

The relationship between disease activity and radiologic progression in patients with rheumatoid arthritis: a longitudinal analysis.

OBJECTIVE: Radiologic progression in rheumatoid arthritis (RA) is considered the consequence of persistent inflammatory activity. To determine whether a change in disease activity is related to a change in radiologic progression in individual patients, we investigated the longitudinal relationship between inflammatory disease activity and subsequent radiologic progression. METHODS: The databases of the University Medical Center Nijmegen (UMCN) cohort and the Maastricht Combination Therapy in RA (COBRA) followup study cohort were analyzed. The UMCN cohort included 185 patients with early RA who were followed up for up to 9 years. Patients were assessed every 3 months for disease activity and every 3 years for radiologic damage. The COBRA cohort included 152 patients with early RA who were followed up for up to 6 years. Patients were assessed at least every year for disease activity and every 12 months for radiologic damage. Disease activity was assessed with the Disease Activity Score (DAS) (original DAS in the UMCN cohort, DAS28 in the COBRA cohort). Radiologic damage was measured by the Sharp/van der Heijde score in both cohorts. Data were analyzed with longitudinal regression analysis (generalized estimating equations [GEE]), using autoregression for longitudinal associations and radiologic damage as the dependent variable. Time, time(2) baseline predictors for radiologic progression and their interactions with time, as well as DAS/DAS28 (actual values or interval means and interval SDs of the means) were subsequently modeled as explanatory variables. RESULTS: Data analyzed by GEE showed a decrease in radiologic progression over time (regression coefficient for time(2) -1.0 [95% confidence interval -1.4, -0.6] in the UMCN cohort and -0.4 [95% confidence interval -0.8, 0.0] in the COBRA cohort). After adjustment for time effects and baseline predictors of radiologic progression and their interactions with time, a positive longitudinal relationship was indicated by autoregressive GEE between the mean interval DAS and radiologic progression in the UMCN cohort (regression coefficient 5.4 [95% confidence interval 2.1, 8.6]), and between the DAS28 and radiologic progression in the COBRA cohort (regression coefficient 1.4 [95% confidence interval 0.8, 2.0]). In the UMCN cohort, the SD of the mean interval DAS was independently longitudinally related to the radiologic progression over the same periods (regression coefficient 20.2 [95% confidence interval 7.2, 33.3]). In both cohorts, the longitudinal relationships between (fluctuations in) disease activity and radiologic progression were found selectively in rheumatoid factor (RF)-positive patients. CONCLUSION: Radiologic progression is not linear in individual patients. Fluctuations in disease activity are directly related to changes in radiologic progression, which supports the hypothesis that disease activity causes radiologic damage. This relationship might only exist in RF-positive patients.

Adult↗
PubMed2004

Null bar and null zone are better than the error bar to compare group means in graphs.

THE PROBLEM: Conventional graphs often include error bars around the group means. Regardless of what these bars depict, they are uninformative as to whether a difference between the groups is statistically significant. THE SOLUTION: This article suggests plotting the null bar or null zone: that is, the range or area in which the means of the two groups fall if the null hypothesis of no difference cannot be rejected. The bar and zone are simply derived from the confidence interval around the difference, obtained from the t-test.

Data Display↗
PubMed2004

The Sharp/van der Heijde method out-performed the Larsen/Scott method on the individual patient level in assessing radiographs in early rheumatoid arthritis.

OBJECTIVE: To test the reliability of two radiologic scoring methods in rheumatoid arthritis (RA)--the Sharp/van der Heijde (SvH) and the Larsen/Scott (LS)--with generalizability analyses. STUDY DESIGN AND SETTING: Films of 51 patients representing the spectrum of early RA were read by two raters for each method. The discriminative ability and responsiveness were expressed as: intraclass correlation coefficients (ICCs), two types of smallest detectable difference (SDD), and two types of smallest detectable change (SDC); reflecting measurement error when discriminating between or detecting changes within (1) individuals or (2) groups. They were calculated for (average) scores of one to three raters. RESULTS: The discriminative capacity (0.85-0.97) and responsiveness (0.91-0.97) were good when expressed by ICC. On the group level the SDDs and SDCs ranged between 0.6-3.3% of the max. obtainable score. On the individual level, the scores showed better reliability measured with the SvH (SDDs 2.0-3.4%) than with the LS (SDDs 5.3-9.2%). The SvH also assessed changes in scores in individuals with less measurement error (SDCs 1.3-2.2%) than the LS (SDCs 2.3-3.9%). CONCLUSION: For early RA patients, the SvH seems preferable if analyses on individual level are included.

Analysis of Variance↗
PubMed2004

Practice, efficacy, and costs of thyroid nodule evaluation: a retrospective study in a Dutch university hospital.

Fine-needle aspiration (FNA) of thyroid nodules has markedly reduced the role of thyroid scintigraphy. This is often limited to nondiagnostic or follicular (tumor) FNA classifications. In this study, we evaluated the efficacy and cost of such a strategy in a university center. From 1992-1998, 995 aspirations were done in 667 patients with palpable nodules. FNA was classified as malignant, suspicious, follicular, benign or inadequate. The Gold standard was surgery or extended follow-up, including physical examination, FNA, and/or ultrasound (US) with a time interval of half a year. Cost analysis was limited to operated patients. The first FNA yielded inadequate results in 28%, decreasing to 6% after 4 aspirations (n = 42). The other final classifications were: 76%, benign; 14%, follicular; 2%, suspicious; 1%, malignant (n = 7). Scintigraphy ((99m)Tc) suggested a hyperfunctioning autonomous nodule (adenoma) in 12% and 3% of the inadequate and follicular subset, respectively. Surgery for diagnostic reasons (n = 105) yielded 24 malignancies (23%): in 47% of suspicious, 12% of the follicular, and in all with malignant FNA. Postoperative morbidity occurred in 14 (5 laryngeal nerve paralyses) with benign histology. Major cost drivers were surgery and hospitalization: mean costs per patient amounting to Euro 3.311 in case of benign histology. We conclude that current work-up is still unable to prevent unnecessary surgery for benign thyroid nodules. Thyroid scintigraphy proved most productive in the inadequate FNA category. Improvement of the diagnostic process using immunohistochemistry and/or imaging is needed from the patient's and society's perspective.

Biopsy, Needle↗
PubMed2004

Costs of treating bleeding and perforated peptic ulcers in The Netherlands.

OBJECTIVE: Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs includes perforations and bleeds. Several preventive strategies are being tested for cost-effectiveness, but little is known about the costs of the complications they are trying to prevent. We estimated the direct costs of hospital treatment of bleeding and perforated ulcers in a university hospital, from data in discharge letters and the hospital management information system. METHODS: Eligible patients had been treated in the VU University Medical Center between January 1997 and August 2000 for an ulcer bleed or perforation (International Classification of Diseases code 531-4). Resource use comprised hospitalization days and diagnostic and therapeutic interventions. Insurance claim prices determined the costs from the payers' perspective. In a secondary analysis we excluded resource use that was clearly related to the treatment of comorbid illness. RESULTS: Fifty-three patients with a bleeding (n = 35) or perforated ulcer (n = 15) or both (n = 3) were studied, including 14 with comorbidity; 22 complications occurred in the stomach, 29 in the duodenum, one in both stomach and duodenum, and one after partial gastrectomy. A simultaneous bleed and perforation was most expensive (26,000 euro), followed by perforation (19,000 euro) and bleeding (12,000 euro). A bleed in the duodenum was more expensive than in the stomach (13,000 euro vs 10,000 euro), while the opposite was seen for perforations (13,000 euro vs 21,000 euro). Comorbidity increased costs substantially: even after correction for procedures unrelated to the ulcer complication, comorbidity more than doubled the costs of treatment. CONCLUSION: Treatment of complicated ulcers is expensive, especially in patients with comorbid conditions.

Adult↗
PubMed2004

Variability of precision in scoring radiographic abnormalities in rheumatoid arthritis by experienced readers.

OBJECTIVE: To determine the extent of precision and sources of variability among experts on scoring radiographic abnormalities in rheumatoid arthritis. METHODS: Radiographic scores from 6 datasets in which 2 or more readers had scored film sets were analyzed. Datasets included scores by 11 different readers, 6 of whom scored films by both the Larsen (global) and Sharp (composite) methods. Scores of each possible combination of 2 readers were compared in calculating the smallest detectable difference (SDD) on raw scores and on scores normalized for each individual reader (nSDD). Intraclass correlation (ICC), Pearson's r, and the correlation between differences in score and their mean scores were determined. Agreement on progression of radiographic damage scores was also examined. RESULTS: Variability among readers was greater than previous studies suggested. Agreement was better for intra- than interreader comparisons; average intrareader SDD was 24.4 for the composite method and 9.0 for the global. The larger SDD for the composite method reflect their greater range of possible scores. When normalized scores were used to adjust for the range difference, there was minimal difference in the SDD; nSDD was 10.1 for the composite method, 8.0 for the global. Interreader variability was larger: SDD of 53.7 for the composite method and 23.3 for the global; nSDD 12.9 and 14.4, respectively. ICC varied between 0.465 and 0.999, with all but one value below 0.925 occurring in composite scores with a range below 100. Differences in repeated scores were frequently associated with the mean of those scores and this was greater for inter- than for intrareader comparisons. Agreement between progression scores showed a similar pattern. The SDD was better for intrareader comparisons and smaller for global scores: compare 13.7 (composite, intrareader) and 5.4 (global, intrareader) to 18.1 (composite, interreader) and 8.7 (global, interreader). The ICC was lower for progression scores than for raw scores, averaging between 0.661 and 0.885. CONCLUSION: The variability in scoring radiographic abnormalities is considerable among this group of 11 expert readers. This has important implications for power calculations in comparison studies such as therapeutic trials and for cross-trial comparisons. The correlation between the difference in repeated scores and their means indicates systematic error (bias), which, if corrected, may improve the detection of treatment effects when using a responder-type analysis. These and other design and analysis issues are discussed.

Arthritis, Rheumatoid↗
PubMed2004

Indirect and total costs of early rheumatoid arthritis: a randomized comparison of combined step-down prednisolone, methotrexate, and sulfasalazine with sulfasalazine alone.

OBJECTIVE: To describe the effect of indirect costs for patients with early rheumatoid arthritis (RA) within the COBRA trial (Combinatietherapie Bij Reumatoide Artritis) on the cost-effectiveness of both therapies. Analyses of the efficacy and direct costs of the treatments have already been reported. METHODS: Patients with early RA selected for the 56-week trial were randomly assigned to prednisolone, methotrexate, and sulfasalazine (the COBRA combination) (n = 76, tapered after 28 weeks) or to sulfasalazine (SSZ; n = 79, of which 78 patients were evaluable) alone. The main efficacy outcomes were a pooled index and radiographic damage score in hands and feet, and utilities. Direct and indirect costs were measured (from a societal perspective) by means of cost diaries and interviews completed by patients during the intervention phase and the followup phase, each lasting 28 weeks. Differences in mean costs between groups and cost-utility ratios were evaluated by applying nonparametric bootstrapping techniques. RESULTS: In the first 28 weeks, indirect costs per patient totaled US $2,578 and US $3,638 for COBRA and SSZ therapy, respectively (p = 0.09). The total costs were $5,931 and $7,853, respectively (p < 0.05). These differences were lost in the second 28 weeks. For the total period the mean total costs per patient were $10,262 and $12,788, respectively (p = 0.11). Sensitivity analyses showed robustness of the data. The point estimate of the cost per quality-adjusted life-year based on the rating scale was negative at $-385, suggesting dominance of COBRA (more effect at lower cost). CONCLUSION: COBRA therapy adds additional disease control (improvements in disease activity, physical function, and rate of damage progression) at lower or equal cost compared to SSZ in early RA.

Adult↗
PubMed2003

Cost-effectiveness of FDG-PET in staging non-small cell lung cancer: the PLUS study.

Currently, up to 50% of the operations in early-stage non-small cell lung cancer (NSCLC) are futile owing to the presence of locally advanced tumour or distant metastases. More accurate pre-operative staging is required in order to reduce the number of futile operations. The cost-effectiveness of fluorine-18 fluorodeoxyglucose positron emission tomography ((18)FDG-PET) added to the conventional diagnostic work-up was studied in the PLUS study. Prior to invasive staging and/or thoracotomy, 188 patients with (suspected) NSCLC were randomly assigned to conventional work-up (CWU) and whole-body PET or to CWU alone. CWU was based on prevailing guidelines. Pre-operative staging was followed by 1 year of follow-up. Outcomes are expressed in the percentage of correctly staged patients and the associated costs. The cost price of PET varied between 736 and 1,588 depending on the (hospital) setting and the procurement of (18)FDG commercially or from on-site production. In the CWU group, 41% of the patients underwent a futile thoracotomy, whereas in the PET group 21% of the thoracotomies were considered futile ( P=0.003). The average costs per patient in the CWU group were 9,573 and in the PET group, 8,284. The major cost driver was the number of hospital days related to recovery from surgery. Sensitivity analysis on the cost and accuracy of PET showed that the results were robust, i.e. in favour of the PET group. The addition of PET to CWU prevented futile surgery in one out of five patients with suspected NSCLC. Despite the additional PET costs, the total costs were lower in the PET group, mainly due to a reduction in the number of futile operations. The additional use of PET in the staging of patients with NSCLC is feasible, safe and cost saving from a clinical and from an economic perspective.

Aged↗
PubMed2003

Incidence of retinoblastoma in children born after in-vitro fertilisation.

Every year, 3000 women in the Netherlands are treated with in-vitro fertilisation (IVF), and results from studies suggest that the offspring of these women do not have a heightened risk of cancer. Between November, 2000, and February, 2002, we diagnosed retinoblastoma in five patients born after IVF. To calculate the relative risk of the disease, we assumed that the proportion of children conceived by IVF in the Netherlands is between 1.0 and 1.5%, and that the five patients who we diagnosed with the disease represent all new cases in the Netherlands during that period. Relative risks for retinoblastoma were significantly raised (7.2 [95% CI 2.4-17.0], and 4.9 [1.6-11.3], for 1% and 1.5% rates, respectively). This possible association of an increased risk of retinoblastoma in a population-based study needs to be established.

Child, Preschool↗
PubMed2003

Radiologic features in juvenile idiopathic arthritis: a first step in the development of a standardized assessment method.

OBJECTIVE: To describe radiologic features of patients with juvenile idiopathic arthritis (JIA) in a standardized manner, to test the reliability and feasibility of this description, and to correlate these features with clinical signs as a first step in the development of a standardized assessment method. METHODS: The placebo-controlled study of sulfasalazine in patients with oligoarticular, extended oligoarticular, and polyarticular JIA performed by the Dutch Juvenile Idiopathic Arthritis Study Group yielded the data for this study. All trial entry radiographs (clinically involved joints and contralateral joints) were scored (in consensus by a skeletal radiologist and pediatric rheumatologist) for the presence of swelling, osteopenia, joint space narrowing, growth abnormalities, subchondral bone cysts, erosions, and malalignment. RESULTS: Data on 67 of 69 patients were analyzed. The mean age was 9.1 years (range 2.5-17.6 years), and the median disease duration was 24 months (range 5-176 months). Thirteen percent of the patients were IgM rheumatoid factor (IgM-RF) positive, and 16% were HLA-B27 positive. All 68 clinically evaluated joints were included in the maximum of 19 radiographed joints (or joint groups) per patient. The mean number of radiographed joints per patient was 7 (range 2-15); knees, hands, ankles, and feet were most frequently affected. Fifty-eight patients (87%) had radiologic abnormalities in at least one joint (soft-tissue swelling in 63% of patients, growth disturbances in 48%, joint space narrowing in 28%, and erosions in 15%). In total, half of the radiographs of the clinically involved joints showed radiologic abnormalities, including two-thirds of the radiographs of the clinically affected hands and knees. Univariate analysis revealed a good correlation between the overall articular (clinical) severity and the presence of radiologic abnormalities (odds ratio [OR] 1.38, P < 0.0001). Multivariate analysis showed increased ORs for the presence of radiologic abnormalities and IgM-RF positivity (OR 4.6, P = 0.005) or HLA-B27 positivity (OR 3.0, P = 0.004). In general, reproducibility of the radiologic scoring method was good (mean kappa coefficient of 0.74 [range 0.40-0.86]), although there were scoring discrepancies for swelling, osteopenia, and growth disturbances. The scoring took 10-20 minutes per patient. CONCLUSION: Our model of describing and scoring radiologic abnormalities of radiographed joints in JIA was feasible, mostly reproducible, correlated well with the overall articular severity score, and added substantial new information not available on clinical examination.

Adolescent↗
PubMed2003

Cost effectiveness and cost utility of acetylcysteine versus dimethyl sulfoxide for reflex sympathetic dystrophy.

OBJECTIVE: To determine the cost effectiveness and cost utility of acetylcysteine versus dimethyl sulfoxide (DMSO) for patients with reflex sympathetic dystrophy (RSD), from a societal viewpoint. DESIGN: An economic evaluation was conducted alongside a double-dummy, double-blind, randomised, controlled trial. Patients were followed for 1 year. The primary outcome measure was the Impairment-level Sum Score (ISS). Utilities were determined by the EuroQOL instrument (EQ-5D). Both cost-effectiveness and cost-utility analyses were performed. Differences in mean direct, indirect and total costs were estimated. Corresponding 95% confidence intervals were calculated by bootstrapping techniques. RESULTS: Both groups (DMSO, n = 64; acetylcysteine, n = 67) showed relevant improvement; no differences in effects were found. Only the total direct costs were significantly lower in the DMSO group for the period of 0-52 weeks. The incremental cost-effectiveness ratios showed that, in general, DMSO generated fewer costs and more effects compared with acetylcysteine. Post-hoc subgroup analyses on cost effectiveness suggested that patients with warm RSD could be best treated with DMSO and patients with cold RSD with acetylcysteine. These results were based on small subsamples. CONCLUSION: In general, DMSO is the preferred treatment for patients with RSD.

Acetylcysteine↗