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Biomedical subjects

M Boers

Publications and source records attributed to M Boers.

At least 19 recordsLinked to original sources
PubMed2003

Influence of glucocorticoids and disease activity on total and high density lipoprotein cholesterol in patients with rheumatoid arthritis.

BACKGROUND: Glucocorticoids induce hypercholesterolaemia, a cardiovascular risk factor, in patients with diseases other than rheumatoid arthritis (RA), but the data in RA are contradictory. OBJECTIVE: To determine the effects of antirheumatic treatment, including prednisolone (combination) therapy on total and high density lipoprotein (HDL) cholesterol levels in RA, taking disease activity into account. METHODS: HDL cholesterol and total cholesterol levels were determined in:(a) established RA (b) two cohorts with early active RA, (c) a previously conducted 56 week trial among patients with early RA comparing the value of intensive combination therapy (that included glucocorticoids) with sulfasalazine alone (COBRA trial). RESULTS: In established RA total cholesterol levels were only slightly raised, irrespective of disease activity. However, HDL cholesterol was significantly higher in patients in remission than in patients with active disease. In contrast, in active early RA at baseline total cholesterol was low normal: between 4.6 and 5.1 mmol/l in the different populations. The level of HDL cholesterol was highly dependent on the duration of storage. In both COBRA groups total cholesterol increased by a mean of 0.6 mmol/l. HDL cholesterol increased by more than 50% after treatment, leading to an improvement of the total cholesterol/HDL ratio (atherogenic index). This increase (and index improvement) was much more rapid in the group receiving combination treatment. A similar pattern was seen in the 2001 cohort with early RA. In all the groups with active disease HDL and total cholesterol levels correlated inversely with disease activity. CONCLUSION: In established, but especially in early RA, disease activity is accompanied by atherogenic lipid levels. This dyslipidaemia can be rapidly reversed by aggressive antirheumatic treatment including glucocorticoids.

Adult↗
PubMed2002

Early and aggressive treatment of rheumatoid arthritis patients affects the association of HLA class II antigens with progression of joint damage.

OBJECTIVE: The presence of certain HLA class II antigens is strongly associated with the progression of joint destruction in rheumatoid arthritis (RA). Such antigens may be more effective than other class II antigens in inducing the formation of autoreactive T cells after presentation of (auto)antigens. We investigated whether early and aggressive treatment with disease-modifying antirheumatic drugs could modify this relationship. METHODS: We analyzed data from 2 studies of patients with early RA treated according to different strategies. The first study consisted of 2 cohorts, one (n = 109; median disease duration before treatment 4 months) was treated according to the pyramid strategy (initial nonsteroidal antiinflammatory drugs, followed by chloroquine [CQ] or sulfasalazine [SSZ] when necessary), and the other (n = 97; median disease duration before treatment 2 weeks) was immediately treated with CQ or SSZ. The second study comprised 155 patients (median disease duration 4 months) from the Combinatietherapie Bij Reumatoide Artritis (COBRA) trial, in which patients were randomly assigned to combination treatment with step-down prednisolone, methotrexate (MTX), and SSZ (n = 76) or with SSZ alone (n = 79). Prednisolone and MTX dosages were tapered and stopped after 28 and 40 weeks, respectively. The extent of joint damage was measured by the modified Sharp method. RESULTS: In the pyramid treatment cohort, the median increase in Sharp score after 2 years was 12 in patients positive for the shared epitope (SE) and 1 in SE- patients. In the immediate treatment cohort, the median increase was 3 in SE+ patients and 2 in SE- patients. In the SSZ group of the COBRA study, the median increase in Sharp score after 1 year was 11 in DR4+ patients and 3 in DR4- patients. In the combination treatment group, the median increase was 4 in DR4+ patients and 2 in DR4- patients. Significance was confirmed by multiple regression using log-transformed scores. CONCLUSION: Early and aggressive antirheumatic drug treatment affects the association of HLA class II alleles with progression of joint damage in RA.

Adult↗
PubMed2002

The use of placebo-controlled and non-inferiority trials for the evaluation of new drugs in the treatment of postmenopausal osteoporosis.

Registration of new agents for the treatment of postmenopausal osteoporosis has been based over the past few years on placebo-controlled phase III trials with the incidence of patients with new vertebral/nonvertebral fractures as the most usual primary endpoint. The use of a placebo in diseases where an active treatment is available has been a matter of debate following the update of the Declaration of Helsinki by the World Medical Association which questioned this trial design. Current regulatory recommendations within the European Union suggest that placebo-controlled trials are still the best option when assessing the efficacy and safety of new drugs intended for the treatment of postmenopausal osteoporosis. This suggestion seems to be in apparent contradiction with the current content of the Declaration of Helsinki. This paper addresses the ethics and feasibility of placebo-controlled trials in the treatment of postmenopausal osteoporosis, in the light of available therapeutic options, and discusses possible alternative approaches in those patients where placebo treatment could be deemed to be unethical. It is concluded that placebo-controlled trials remain the most efficient design to establish the efficacy and safety of a new agent for the treatment of postmenopausal osteoporosis. Such trials are feasible and ethically acceptable in patients with osteoporosis but without prevalent vertebral fractures. Conversely, in patients with prevalent vertebral fractures, placebo-controlled trials are ethically questionable and non-inferiority trials are more appropriate. A relative margin of non-inferiority of 20-30% is suggested, to be discussed on a case by case basis.

Aged↗
PubMed2002

Reproducibility and clinical value of 18F-fluorodeoxyglucose positron emission tomography in recurrent melanoma.

The purpose of this study was to assess the reproducibility and clinical impact of positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in patients with (suspected) recurrent melanoma. The clinical value of PET was prospectively measured in 58 consecutive patients referred for PET because of unresolved clinical questions after conventional work-up. Diagnostic understanding and therapy choice by referring physicians were evaluated before, directly after, and 6 months after PET. Observer agreement of PET readings was measured with respect to various parameters (interpretation, number and localization of lesions, 'clinically decisive' metastases), using intra-class correlation coefficients. FDG PET improved diagnostic understanding in 33 cases (57%). In six patients (10%), diagnostic understanding was solely based on PET information. According to the attending clinicians, PET contributed to a positive change of planned treatment in 23 patients (40%) and increased confidence in the chosen treatment in 23 (40%). Observer agreement of PET readings was very high (intra-class correlation coefficients were between 0.87 and 0.94). The diagnostic value related especially to the whole-body scan technique and the superior specificity, compared to conventional work-up. It is concluded that, in problematical cases with (suspected) recurrent melanoma, 18F-FDG PET had considerable impact on diagnostic understanding and management. Together with the excellent observer reliability, these results justify further studies to determine the optimal place of PET in routine diagnostic algorithms in recurrent melanoma.

Adult↗
PubMed2002

Rheumatoid factor measured by fluoroimmunoassay: a responsive measure of rheumatoid arthritis disease activity that is associated with joint damage.

OBJECTIVES: To determine whether rheumatoid factors (RFs), measured as continuous variables by time resolved fluoroimmunoassay, reflect disease activity in rheumatoid arthritis (RA). Further, to study the association of RFs and other disease activity parameters with radiological joint damage, especially in individual patients. METHODS: In active, early RA, IgM and IgA RFs, as well as erythrocyte sedimentation rate (ESR), C reactive protein (CRP), tender joint score, and swollen joint score were assessed regularly. At the study start and at 56 and 80 weeks, radiographs of hands and feet were assessed by the Sharp score (van der Heijde modification). Associations between RFs and disease activity parameters were studied. In addition, associations between radiographic damage and disease activity parameters (baseline and time integrated) were analysed by non-parametric tests and multiple regression analysis. The relation between time integrated disease activity parameters and radiological damage in individual patients was analysed and visualised. RESULTS: 155 patients were included. RF levels were strongly associated with the disease activity parameters (especially ESR and CRP) and with each other. All disease activity parameters, at baseline as well as time integrated parameters, were associated with (the progression of) radiographic damage. Moreover, in individual patients, a linear relationship between time integrated disease activity parameters and progression of radiological damage was seen. CONCLUSION: RFs, measured as continuous variables, can be considered as disease activity parameters in patients with RA. The level of RF at baseline and the exposure to RF over time is associated with radiological damage. In individual patients, there is a constant relation between disease activity and radiological damage.

Arthritis, Rheumatoid↗
PubMed2002

Standardised nomenclature for glucocorticoid dosages and glucocorticoid treatment regimens: current questions and tentative answers in rheumatology.

In rheumatology and other medical specialties there is a discrepancy between the widespread use and the imprecise designation of glucocorticoid treatment regimens. Verbal descriptions of glucocorticoid treatment regimens used in various phases of diseases vary between countries and institutions. Given this background, a workshop under the auspices of the EULAR Standing Committee on International Clinical Studies including Therapeutic Trials was held to discuss this issue and to seek a consensus on nomenclature for glucocorticoid treatment. This report summarises the panel's discussion and recognises that answers derived from consensus conferences are not definitive. Nevertheless, recommendations on glucocorticoid treatment are presented that (1) reflect current and best knowledge available and (2) take into account current clinical practice. A question-answer rationale presentation style has been chosen to convey the messages, to summarise the meeting in a readable format, and to avoid dogmatism.

Drug Administration Schedule↗
PubMed2002

EMEA guidelines for trials in osteoporosis: design implications.

The design, execution and interpretation of trials that do not contain a placebo arm are a challenge. These issues are briefly discussed in the context of the new European guidelines for the study of drugs for the indication prevention and treatment of postmenopausal osteoporosis.

Bone Density↗
PubMed2001

American College of Rheumatology criteria for improvement in rheumatoid arthritis should only be calculated from scores that decrease on improvement.

OBJECTIVE: Change in a patient's condition is expressed as a percentage of the baseline value for a core set of measures in the American College of Rheumatology (ACR) improvement criteria for rheumatoid arthritis (RA), and this is used as the basis to decide whether a patient has improved. The result is dependent on whether the underlying measure has a score that increases or decreases on improvement. We examined the importance of this effect in the application of the ACR improvement criteria. METHODS: Data were obtained from the COBRA trial, in which 155 patients with early active RA had been randomized to receive either combination treatment with step-down prednisolone, methotrexate, and sulfasalazine or sulfasalazine alone. Patient and physician global assessments were recoded to reflect decreasing scores on improvement. The effects of this difference in scoring systems were compared among 3 response criteria levels (20%, 50%, and 70%) that are currently being used to assess improvement in RA clinical trials. RESULTS: Analyses showed that the effects of a decreasing, versus increasing, score on the designation of improvement cannot be ignored, especially at higher percentages of improvement (e.g., 50%, 70%). CONCLUSION: We recommend that percentage improvement in RA be calculated only on scores that decrease on improvement. When necessary, raw data should be recoded before the ACR improvement criteria are applied.

Anti-Inflammatory Agents↗
PubMed2001

Inflammation and damage in an individual joint predict further damage in that joint in patients with early rheumatoid arthritis.

UNLABELLED: OBJECTIVE; Several factors predict joint damage in early rheumatoid arthritis (RA). In the context of a trial in early RA, we studied the relationship between clinical signs in individual joints and their propensity to develop progressive damage. METHODS: The COBRA (Combinatietherapie Bij Reumatoide Artritis) multicenter trial compared the efficacy of prednisolone, methotrexate, and sulfasalazine against sulfasalazine alone in 155 patients with early RA. Two blinded observers interpreted radiographs in sequence (using the Sharp/Van der Heijde scoring system); in each center, one blinded observer performed clinical assessments every 3 months. The current analysis is based on clinical and radiologic data of the individual metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of 135 patients. Conditional stepwise logistic regression analyzed the relationship between damage (progression) and clinical signs at baseline and followup for each of these joints individually in each patient. RESULTS: Combination therapy strongly retarded the progression of damage. Progression was stronger in patients with rheumatoid factor, HLA-DR4, and high levels of disease activity at baseline. At baseline, 6% of the MCP and PIP joints showed damage; after 1 year, disease had progressed in 10% of these joints. Baseline damage, swelling, or pain in a joint independently and strongly predicted the progression of damage in that joint (P < 0.001). Each additional point in the swelling score (range 0-2) tripled the risk for subsequent progression. Each additional point on the Sharp scale (range 0-8 per joint) and each additional point on the pain scale (range 0-3) doubled the risk. The mean pain and swelling scores over the year were even stronger predictors of damage. CONCLUSION: Local expression of early RA disease activity, both at baseline and at 1-year followup, is strongly related to progression of damage in the individual joint.

Adult↗
PubMed2001

Combination treatment in autoimmune diseases. Methodology of combination trials.

Even with the limited number of antirheumatic agents available, theoretical considerations lead to an almost infinite number of combination strategies. This article outlines possible strategies based on the primary choice between maximization of efficacy or minimization of toxicity. Strategies are illustrated with examples from trial experience in the field of rheumatoid arthritis.

Antirheumatic Agents↗
PubMed2001

Second primary tumors in hereditary retinoblastoma: a register-based study, 1945-1997: is there an age effect on radiation-related risk?

OBJECTIVE: The aim of this study is to evaluate the influence of age at external beam irradiation (EBRT) on the occurrence of second primary tumors (SPTs) inside and outside the irradiation field in hereditary retinoblastoma patients. DESIGN: Cross-sectional study. PARTICIPANTS: The study included 263 hereditary retinoblastoma patients born in The Netherlands between 1945 and 1997. METHODS: A national register-based follow-up cohort study was performed on hereditary retinoblastoma patients. Information on therapy, age at irradiation, and location of SPT was obtained from the register. The Kaplan-Meier method calculated cumulative incidences of SPT in three subgroups: irradiation before (early EBRT) and after 12 months of age (late EBRT), and no irradiation. The Mantel-Cox method determined the statistical significance of differences between the cumulative incidence curves. MAIN OUTCOME MEASURES: Development of SPT inside and outside a precisely defined irradiation field in relation to age at irradiation. Our definition excluded pineoblastoma as SPT, because they constitute part of a trilateral retinoblastoma; in addition, they lie outside the field of irradiation. RESULTS: The cumulative incidence of SPT at the age of 25 years was 22% (95% confidence intervals 13%-34%) in the early EBRT group, 3% (0%-14%) in the late EBRT group, and 5% (1%-16%) in the nonirradiated group (Mantel-Cox overall: P = 0.001; between early and late EBRT, P = 0.04). However, in early irradiated patients, the incidence of SPTs inside and outside the irradiation field was similar (11%), and the difference between early and late EBRT in incidence of SPT inside the field of irradiation was less prominent than overall (11% vs. 3%: P = 0.37). Sensitivity analysis showed the results depended on the way SPT, irradiation field, and, especially, pineoblastomas are defined. CONCLUSIONS: Hereditary retinoblastoma confers an increased risk for the development of SPT, especially in patients treated with EBRT before the age of 12 months. However, the presence of similar numbers of SPTs inside and outside the irradiation field suggests that irradiation is not the cause. In other words, this study does not show an age effect on radiation-related risk. Rather, early EBRT is probably a marker for other risk factors of SPT.

Adolescent↗
PubMed2001

Toward less futile surgery in non-small cell lung cancer? A randomized clinical trial to evaluate the cost-effectiveness of positron emission tomography.

Non-small cell lung cancer can be cured if the patient is medically operable and the tumor resectable. Current diagnostic strategies are aimed to detect tumor deposits that preclude resection with curative intent. However, these strategies are rather inefficient, resulting in a large number of futile invasive procedures. In the early 1990s positron emission tomography (PET) showed promising results at its introduction in the clinic, especially in oncology. A large number of accuracy studies have reported that PET is superior to conventional imaging. However, whether PET ultimately improves patient outcome should ideally be assessed by means of a randomized controlled trial. No such design has been applied to evaluate PET in oncology so far. The PLUS study was designed to compare the current strategy of conventional methods with a strategy where PET was added after completion of noninvasive techniques. Patients considered operable by the physician at this point were then randomly assigned to PET and further consequences or to standard procedures of mediastinoscopy or thoracotomy. Primary outcome events were futile thoracotomies. The trial randomized 188 patients from nine hospitals in 1 year. Patient enrollment has been stopped and data collection is in progress. The results will be published in 2001. Control Clin Trials 2001;22:89-98

Aged↗
PubMed2001

Rheumatoid arthritis. Treatment of early disease.

Treatment of rheumatoid arthritis (RA) is changing with the rapid increase of information on the efficacy of old and new antirheumatic agents. This article provides an opinionated review of the data currently available and makes a case for rapid and aggressive treatment of all patients with RA as early as possible. In the future, corticosteroids will be an important component of such treatment strategies.

Antirheumatic Agents↗