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ABSTRACT: Quantitative electrocardiogram-gated single photon emission computed tomography (SPECT) myocardial imaging (QGS) is a means of providing functional information about the left ventricle and myocardial perfusion. However, the functional information derived 30 minutes post-stress may be different from the left ventricular (LV) function determined at rest. This study determined whether LV function post-stress would be different from LV function at rest in patients with an earlier myocardial infarction.
LV perfusion and ejection fraction (LVEF), were determined by means of both the rest and post-stress acquisition in 58 patients with an earlier myocardial infarction and in 23 patients with a low likelihood of coronary artery disease by using technetium-99m tetrofosmin and the QGS program. The interobserver and intraobserver variability of LVEF was excellent, within a margin of 2%. No significant differences in LVEF were observed between post-stress and rest in the 23 patients with a low likelihood of disease (DeltaLVEF, 0.04% +/- 3.2%, P = not significant). Conversely, the patients with an earlier myocardial infarction showed a significantly lower LVEF post-stress, compared with that at rest (DeltaLVEF, -1.9% +/- 4.2%, P =.002). In 33 patients (57%), the LVEF post-stress was 2% or more lower than the LVEF at rest. Furthermore, reversible ischemia, which was present in 16 patients (28%), did not interact with the DeltaLVEF post-stress, compared with the DeltaLVEF at rest (P = not significant). Parameters such as the stress modality (adenosine stress or exercise), the number of stenosed vessels, or the perfusion defect severity score did not influence the DeltaLVEF post-stress, compared with the DeltaLVEF at rest.
In patients with an earlier myocardial infarction, LV function post-stress may not represent the true resting LV function. Consequently, this result justifies the stratification of patients before starting the gated SPECT study. In patients with an earlier myocardial infarction, the gated acquisition should be performed during the rest study.
Journal of Nuclear Cardiology 04/2012; 8(1):10-8. · 2.67 Impact Factor
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ABSTRACT: A recent meta-analysis in this journal showed incidences between 3.4 and 33.9%. Studies performed by pharmacists and epidemiologists produced lower incidences than internists' studies. We reassessed the prevalence of iatrogenic admissions in a study of internists. Iatrogenic disease was defined as adverse drug reactions according to the World Health Organization Definition and complications induced by non-drug medical interventions. Subsequent admissions at the Departments of Medicine/Cardiology/Pulmonology in a 1,250 bed general hospital in the Netherlands from May 2007 to August 2007 were studied. 2,000 consecutive admissions were studied: 576 (29%, 26-32%) were classified as possibly iatrogenic; out of these 380 (19%, 17-22%) as definitely iatrogenic, out of whom 229 (12%, 10-14%) had already been classified as iatrogenic by the admitting physicians. Patients with cardiac disease, hypertension, gastrointestinal conditions, anticoagulant treatment and use of NSAIDs were, particularly, at risk of iatrogenic admission with percentages of 22 (16-24), 13 (11-18), 12 (9-15), and 7 (5-11) %. An independent predictor of iatrogenic admissions was age with an odds ratio of 1.27 per 10 years (p = 0.0001). 1. At least 19% of admissions to the Departments of Internal Medicine/Cardiology/Pulmonology, and, maybe, even percentages up to 29% were due to adverse drug effects. 2. A large difference between the numbers of iatrogenic admission according to the physicians in charge of admission and the investigators, 229 versus 380 patients, was observed. 3. Most often iatrogenic admissions were observed with cardiac disease, hypertension, gastrointestinal conditions, anticoagulant treatment, and use of NSAIDs.
International journal of clinical pharmacology and therapeutics 08/2010; 48(8):517-24. · 1.18 Impact Factor
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J J W Verschuren,
M L Sampietro,
D Pons,
S Trompet,
M M Ewing,
P H A Quax,
P de Knijff, A H Zwinderman,
R J de Winter,
R A Tio,
M P de Maat,
P A F M Doevendans,
J W Jukema
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ABSTRACT: Mixed results have been reported of matrix metalloproteinases (MMP) and their association with restenosis after percutaneous coronary intervention (PCI). The current study examines whether multiple single nucleotide polymorphisms (SNPs), covering the full genomic region of MMP2 and MMP3, were associated with restenosis in the GENDER study population.
The GENetic DEterminants of Restenosis (GENDER) study enrolled 3104 consecutive patients after successful PCI. The primary endpoint was clinical restenosis, defined as target vessel revascularization (TVR), occurring in 9.8% of the patients. From the Hapmap database, 19 polymorphisms of MMP2 and 11 of MMP3 were selected. Furthermore, in a subpopulation, a genome-wide association analysis (GWA) was performed. No significant association was found with any of the investigated SNPs, including the previously reported 5A/6A polymorphism (rs3025058), with regard to TVR using single SNP analysis or haplotype analysis.
We found no significant association of MMP2 or MMP3 with TVR with this SNP-broad gene approach. Although we did not test all the known polymorphisms of these genes, using tagging analyses we examined those SNPs covering all known haplotypes of MMP2 and MMP3 to conclude that these genes do not correlate with a genetic risk of coronary restenosis after successful PCI.
Disease markers 01/2010; 29(5):265-73. · 1.64 Impact Factor
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ABSTRACT: Background. Repeated measurements in a single subject are generally more similar than unrepeated measurements in different subjects. Unrepeated analyses of repeated data cause underestimation of the treatment effects.Objective. To review methods adequate for the analysis of cardiovascular studies with repeated measures.Results. (1) For between-subjects comparisons, summary measures and random-effects mixedlinear models are possible. Examples of summary measures include the area under the curve of drug time-concentration and time-efficacy curves, maximal values, mean values, and changes from baseline. A problem is that precision is lost because averages, rather than individual data, are applied. Random-effects mixed-linear models, available in SPSS statistical software and other software programmes, provide better precision for that purpose. (2) For within-subjects comparisons, repeated-measures ANOVAs are available in SPSS and other software programmes. Subgroup factors such as gender differences and age class can be included.Discussion. For non-Gaussian data, Wilcoxon's and Friedman's tests are available, for binary data McNemar's tests can be used in case of two repeated observations. No standard methods are available for repeated binary measures with more than two observations. The purpose of this review was not to present a complete report but, rather, to underline that ample efforts should be made to account for the special nature of repeated measures. (Neth Heart J 2009;17:429-33.).
Netherlands heart journal: monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation 11/2009; 17(11):429-33. · 1.44 Impact Factor
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ABSTRACT: The use of drugs has expanded during the previous decade. However, earlier studies on patients admitted for adverse drugs effects (ADEs) have been heterogeneous. The objectives of this study were to assess the number of recent admissions to hospital due to ADEs and to assess the degree of heterogeneity in recent studies. Prospective studies published in the past decade were therefore pooled and compared with the pooled results from earlier studies. The pooled overall percentage in recent studies (n = 20) was 5.4% (5.0 - 5.8) and this did not significantly differ from that in the earlier studies (n = 21, pooled percentage 4.7%, 3.1 - 6.2). The studies were clinically very heterogeneous with percentages of ADEs between 3.4 and 33.2%. The nature of the patient group could be held largely responsible for the clinical heterogeneity observed.
International journal of clinical pharmacology and therapeutics 09/2009; 47(9):549-55. · 1.18 Impact Factor
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J S Rana,
M Cote,
J-P Després,
M S Sandhu,
P J Talmud,
E Ninio,
N J Wareham,
J J P Kastelein, A H Zwinderman,
K-T Khaw,
S M Boekholdt
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ABSTRACT: To evaluate the role of the inflammatory biomarkers C-reactive protein (CRP), myeloperoxidase, paraoxonase, secretory phospholipase A2 group IIA (sPLA2), lipoprotein-associated phospholipase A2, fibrinogen, macrophage chemoattractant protein-1 and adiponectin, in predicting the risk of coronary heart disease (CHD) among people estimated to be at intermediate risk according to the Framingham Risk Score (FRS).
Prospective case-control study nested in EPIC-Norfolk cohort.
Norfolk, UK.
Apparently healthy men and women aged 45-79 years.
Risk of future coronary artery disease.
For participants predicted to be at intermediate risk by the FRS, the highest c statistics were observed for FRS plus CRP (0.61, 95% CI 0.57 to 0.65) and for FRS plus sPLA2 (0.56, 95% CI 0.52 to 0.6). Net correct reclassification of cases and controls for each marker was assessed for people across the entire risk spectrum and again for people at intermediate risk only. The largest differences were observed for CRP, 12.0% net reclassification improvement in the entire risk spectrum and 28.4% net reclassification improvement in the intermediate-risk group and for sPLA2, the net reclassification improvement was 6.4% in the entire risk spectrum and 16.3% in the intermediate-risk group.
The discriminatory potential of inflammatory biomarkers was substantially different when analysed across the entire risk spectrum compared with the subgroup of people at intermediate risk.
Heart (British Cardiac Society) 08/2009; 95(20):1682-7. · 4.22 Impact Factor
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ABSTRACT: In clinical trials a fixed effects research model assumes that the patients selected for a specific treatment have the same true quantitative effect and that the differences observed are residual error. If, however, we have reasons to believe that certain patients respond differently from others, then the spread in the data is caused not only by the residual error but also by between-patient differences. The latter situation requires a random effects model.
To explain random effects models in analysis of variance and to give examples of studies qualifying for them.
If in a particular study the data are believed to be different from one assessing doctor to the other, and if we have no prior theory that 1 or 2 assessing doctors produced the highest scores, but rather expect there may be heterogeneity in the population of doctors at large, then a random effects model will be appropriate. For that purpose between-doctor variability is compared to within-doctor variability. If the data of 2 separate studies of the same new treatment are analyzed simultaneously, it will be safe to consider an interaction effect between the study number and treatment efficacy. If the interaction is significant, a random effects model with the study number as random variable, will be adequate. For that purpose the treatment effect is tested against the interaction effect. In a multicenter study the data are at risk of interaction between centers and treatment efficacy. If this interaction is significant, a random effects model with the health center as random variable, will be adequate. The treatment effect is tested not against residual but against the interaction. If in a crossover study a treatment difference is not observed, this may be due to random subgroup effects. A post-hoc random effects model, with patients effect as random variable, testing the treatment effect against treatments x patients interaction, will be appropriate.
Random effects research models enable the assessment of an entire sample of data for subgroup differences without need to split the data into subgroups. Clinical investigators, in general, are hardly aware of this possibility and, therefore, wrongly assess random effects as fixed effects leading to a biased interpretation of the data.
International journal of clinical pharmacology and therapeutics 09/2008; 46(8):421-7. · 1.18 Impact Factor
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Z de Jong,
M Munneke,
V Vilim, A H Zwinderman,
H M Kroon,
H K Ronday,
W F Lems,
B A C Dijkmans,
F C Breedveld,
T P M Vliet Vlieland,
J M W Hazes,
J Degroot
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ABSTRACT: To investigate the utility of serum COMP level measurements as a predictor of future damage of the weight-bearing (large) joints in RA patients participating in intensive exercise.
Data of the 281 completers of a 2-yr randomized controlled trial (Rheumatoid Arthritis Patients In Training; RAPIT) comparing the effects of usual care physical therapy with high-intensity weight-bearing exercises were analysed. The primary outcome variable was defined as the change in radiological joint damage (Larsen score) of the large joints. Potential predictors of outcome were defined: baseline and change in serum level of COMP after 3 months, baseline radiological damage of the large and small joints, number of months on glucocorticoids, change in disease activity and in physical capacity (aerobic fitness and muscle strength) after 2 yrs, and participation in the exercise group.
In cross-sectional evaluation of baseline data, we found strong association between the high serum COMP level and current damage of the large joints. Serum COMP level at baseline, however, was not associated with an increased rate of radiological joint damage after 2 yrs of follow-up. Furthermore, neither interaction between baseline COMP level and participation in exercises, nor change in COMP level after 3 months of exercising were associated with future damage of the large joints.
Neither baseline serum COMP level nor its individual change after 3 months from start of intensive exercise predict longitudinal progression of damage of the large joints in this population.
Rheumatology (Oxford, England) 07/2008; 47(6):868-71. · 4.24 Impact Factor
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Y P M Goekoop-Ruiterman,
J K de Vries-Bouwstra,
C F Allaart,
D van Zeben,
P J S M Kerstens,
J M W Hazes, A H Zwinderman,
H K Ronday,
K H Han,
M L Westedt,
A H Gerards,
J H L M van Groenendael,
W F Lems,
M V van Krugten,
F C Breedveld,
B A C Dijkmans
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ABSTRACT: Several treatment strategies have proven value in the amelioration of rheumatoid arthritis (RA), but the optimal strategy for preventing long-term joint damage and functional decline is unclear. We undertook this study to compare clinical and radiographic outcomes of 4 different treatment strategies, with intense monitoring in all patients.
In a multicenter, randomized clinical trial, 508 patients were allocated to 1 of 4 treatment strategies: sequential disease-modifying antirheumatic drug monotherapy (group 1), step-up combination therapy (group 2), initial combination therapy with tapered high-dose prednisone (group 3), and initial combination therapy with the tumor necrosis factor antagonist infliximab (group 4). Treatment adjustments were made every 3 months in an effort to obtain low disease activity (a Disease Activity Score in 44 joints of < or =2.4).
Initial combination therapy including either prednisone (group 3) or infliximab (group 4) resulted in earlier functional improvement than did sequential monotherapy (group 1) and step-up combination therapy (group 2), with mean scores at 3 months on the Dutch version of the Health Assessment Questionnaire (D-HAQ) of 1.0 in groups 1 and 2 and 0.6 in groups 3 and 4 (P < 0.001). After 1 year, mean D-HAQ scores were 0.7 in groups 1 and 2 and 0.5 in groups 3 and 4 (P = 0.009). The median increases in total Sharp/Van der Heijde radiographic joint score were 2.0, 2.5, 1.0, and 0.5 in groups 1-4, respectively (P < 0.001). There were no significant differences in the number of adverse events and withdrawals between the groups.
In patients with early RA, initial combination therapy including either prednisone or infliximab resulted in earlier functional improvement and less radiographic damage after 1 year than did sequential monotherapy or step-up combination therapy.
Arthritis & Rheumatism 03/2008; 58(2 Suppl):S126-35. · 7.87 Impact Factor
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P S Monraats,
F A S Kurreeman,
D Pons,
V D K D Sewgobind,
F R de Vries, A H Zwinderman,
M P M de Maat,
P A Doevendans,
R J de Winter,
R A Tio,
J Waltenberger,
T W J Huizinga,
D Eefting,
P H A Quax,
R R Frants,
A van der Laarse,
E E van der Wall,
J W Jukema
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ABSTRACT: Genetic factors appear to be important in the process of restenosis after percutaneous coronary intervention (PCI), as well as in inflammation, a pivotal factor in restenosis. An important mediator in the inflammatory response is interleukin (IL)-10. Our aim was to study whether genetic variants in IL-10 predispose to the risk of restenosis. The GENetic DEterminants of Restenosis (GENDER) study included 3104 patients treated with successful PCI. Target vessel revascularization (TVR) was chosen as primary end point. Genotyping of the -2849G/A, -1082G/A, -592C/A and +4259A/G polymorphisms of the IL-10 gene was performed by MassArray platform. After adjusting for clinical variables, three polymorphisms significantly increased the risk of restenosis (-2849AA: relative risk (RR), 1.7, 95% confidence interval (CI), 1.2-2.5; -1082AA: RR, 1.4, 95% CI, 1.1-1.8 and +4259GG: RR, 2.0, 95% CI, 1.4-2.8). To further exclude possible involvement of neighboring genes due to LD in the IL-10 locus, additional polymorphisms were genotyped. The results reveal that association of the IL-10 gene with restenosis is independent of flanking genes. Our findings demonstrate that IL-10 is associated with restenosis and therefore support the hypothesis that anti-inflammatory genes also may be involved in developing restenosis. Furthermore, they may provide a new targeting gene for drug-eluting stents.
Genes and Immunity 02/2007; 8(1):44-50. · 3.87 Impact Factor
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Journal of Internal Medicine 09/2006; 260(2):183-5. · 5.48 Impact Factor
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ABSTRACT: The objective of this study was to investigate the performance of multiple imputation of missing genotype data for unrelated individuals using the polytomous logistic regression model, focusing on different missingness mechanisms, percentages of missing data, and imputation models. A complete dataset of 581 individuals, each analysed for eight biallelic polymorphisms and the quantitative phenotype HDL-C, was used. From this dataset one hundred replicates with missing data were created, in different ways for different scenarios. The performance was assessed by comparing the mean bias in parameter estimates, the root mean squared standard errors, and the genotype-imputation error rates. Overall, the mean bias was small in all scenarios, and in most scenarios the mean did not differ significantly from 'no bias'. Including polymorphisms that are highly correlated in the imputation model reduced the genotype-imputation error rate and increased precision of the parameter estimates. The method works well for data that are missing completely at random, and for data that are missing at random. In conclusion, our results indicate that multiple imputation with the polytomous logistic regression model can be used for association studies to deal with the problem of missing genotype data, when attention is paid to the imputation model and the percentage of missing data.
Annals of Human Genetics 06/2006; 70(Pt 3):372-81. · 2.57 Impact Factor
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S M Boekholdt,
O W Souverein,
M W T Tanck,
G K Hovingh,
J A Kuivenhoven,
R I G Peters,
H Jansen,
P M H Schiffers,
E E van der Wall,
P A Doevendans,
P H Reitsma, A H Zwinderman,
J J P Kastelein,
J W Jukema
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ABSTRACT: It is assumed that the combined effects of multiple common genetic variants explain a large part of variation of high-density lipoprotein cholesterol (HDL-C) plasma levels, but little evidence exists to corroborate this assumption. It was our objective to study the contribution of multiple common genetic variants of HDL-C-related genes to variation of HDL-C plasma levels. A well-characterized cohort of 546 Caucasian men with documented coronary artery disease was genotyped for common functional variants in genes that control reverse cholesterol transport: ATP-binding cassette transporter A1, apolipoprotein A-I and apolipoprotein-E, cholesteryl ester transfer protein, hepatic lipase, lecithin : cholesterol-acyl transferase, lipoprotein lipase, and scavenger receptor class B type 1. Multivariate linear regression showed that these variants, in conjunction, explain 12.4% (95% confidence interval: 6.9-17.9%) of variation in HDL-C plasma levels. When the covariates smoking and body mass index were taken into account, the explained variation increased to 15.3% (9.4-21.2%), and when 10 two-way interactions were incorporated, this percentage rose to 25.2% (18.9-31.5%). This study supports the hypothesis that multiple, mildly penetrant, but highly prevalent genetic variants explain part of the variation of HDL-C plasma levels, albeit to a very modest extent. Multiple environmental and genetic influences on HDL-C plasma levels still have to be elucidated.
Clinical Genetics 04/2006; 69(3):263-70. · 3.13 Impact Factor
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ABSTRACT: Atherosclerosis is a slow disease process of arterial walls with onset decades prior to its clinical manifestations. Lifelong follow-up data may help to identify and understand the pathophysiology of this process. These longitudinal data are scarce. Using a standardized imaging and image analysis protocol, we acquired cross-sectional data of carotid and femoral arterial wall segments in populations at different cardiovascular disease risk.
B-mode ultrasound intima-media thickness (IMT) data of carotid and femoral arteries were acquired in individuals at high cardiovascular disease risk: 44 young adolescents with familial hypercholesterolemia (FH), 248 adult FH patients and 184 patients with coronary artery disease (CAD), as well as in disease free unaffected individuals, 44 young adolescents, 26 middle-aged adults and 48 senior adults.
Per patient combined average IMT (SD) and % of lesions in the high risk populations were 0.55 (0.05) mm, 0.1%, 0.86 (0.18) mm, 15%, and 0.9 (0.18) mm, 18%, respectively. In the unaffected groups these values were 0.53 (0.03) mm, 0%, 0.59 (0.07) mm, 0%, and 0.77 (0.12) mm, 8%. Of all arterial segments, the far wall of the common femoral artery (CFA) of the FH patients exhibited the highest absolute IMT (1.12 [0.61] mm), the most rapid estimated IMT increase since adolescence (+0.58 mm) and the highest percentage of lesions (39% of CFA measurements).
Regardless of location, carotid and femoral arterial walls increase in thickness with age and cardiovascular disease risk. This increase in thickness and prevalence of lesions is not similarly distributed among anatomical segments. The strong preponderance in arterial wall segments with the highest estimated atherosclerosis progression indicates the existence of a threshold value beyond which plaque formation is greatly increased. In the set of arterial locations we studied, this process might be best represented by the far wall of the CFA.
International angiology: a journal of the International Union of Angiology 01/2006; 24(4):359-65. · 1.65 Impact Factor
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ABSTRACT: Clinical investigators, although they are generally familiar with testing differences between averages, have difficulty testing differences between variabilities.
To give examples of situations where variability is more relevant than averages and to describe simple methods for testing such data.
Examples include: (1) testing drugs with small therapeutic indices, (2) testing variability in drug response, (3) assessing pill diameters or pill weights, (4) comparing patient groups for variability in patient characteristics, (5) assessing the variability in duration of clinical treatment, (6) finding the best method for patient assessment. Various fields of research, particularly in clinical pharmacology, make use of test procedures that implicitly, address the variability in the data. Tests specially designed for testing variability in data include the chi2-test for one sample, the F-test for 2 samples and Bartlett's or Levene's test for 3 or more samples. Additional methods include (1) the comparison of confidence intervals, and (2) testing confidence intervals against prior defined intervals of therapeutic tolerance or equivalence. Many of these tests are available in Excel and other statistical software programs and one such program is described.
In the analysis of clinical data the variability in the data is often more important than averages. Eight simple methods for assessment variability are described to illustrate the value and importance of putting more emphasis on and this parameter.
International journal of clinical pharmacology and therapeutics 12/2005; 43(11):536-42. · 1.18 Impact Factor
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S M Boekholdt,
F M Sacks,
J W Jukema,
J Shepherd,
D J Freeman,
A D McMahon,
F Cambien,
V Nicaud,
G J de Grooth,
P J Talmud, [......],
H Kauma,
S Kakko,
M J Savolainen,
M Arca,
A Montali,
S Liu,
H J Lanz, A H Zwinderman,
J A Kuivenhoven,
J J P Kastelein
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ABSTRACT: Several studies have reported that the cholesteryl ester transfer protein (CETP) TaqIB gene polymorphism is associated with HDL cholesterol (HDL-C) levels and the risk of coronary artery disease (CAD), but the results are inconsistent. In addition, an interaction has been implicated between this genetic variant and pravastatin treatment, but this has not been confirmed.
A meta-analysis was performed on individual patient data from 7 large, population-based studies (each >500 individuals) and 3 randomized, placebo-controlled, pravastatin trials. Linear and logistic regression models were used to assess the relation between TaqIB genotype and HDL-C levels and CAD risk. After adjustment for study, age, sex, smoking, body mass index (BMI), diabetes, LDL-C, use of alcohol, and prevalence of CAD, TaqIB genotype exhibited a highly significant association with HDL-C levels, such that B2B2 individuals had 0.11 mmol/L (0.10 to 0.12, P<0.0001) higher HDL-C levels than did B1B1 individuals. Second, after adjustment for study, sex, age, smoking, BMI, diabetes, systolic blood pressure, LDL-C, and use of alcohol, TaqIB genotype was significantly associated with the risk of CAD (odds ratio=0.78 [0.66 to 0.93]) in B2B2 individuals compared with B1B1 individuals (P for linearity=0.008). Additional adjustment for HDL-C levels rendered a loss of statistical significance (P=0.4). Last, no pharmacogenetic interaction between TaqIB genotype and pravastatin treatment could be demonstrated.
The CETP TaqIB variant is firmly associated with HDL-C plasma levels and as a result, with the risk of CAD. Importantly, this CETP variant does not influence the response to pravastatin therapy.
Circulation 02/2005; 111(3):278-87. · 14.74 Impact Factor
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Z de Jong,
M Munneke, A H Zwinderman,
H M Kroon,
K H Ronday,
W F Lems,
B A C Dijkmans,
F C Breedveld,
T P M Vliet Vlieland,
J M W Hazes,
T W J Huizinga
[show abstract]
[hide abstract]
ABSTRACT: To investigate the effect of long term high intensity weightbearing exercises on radiological damage of the joints of the hands and feet in patients with rheumatoid arthritis (RA).
Data of the 281 completers of a 2 year randomised controlled trial comparing the effects of usual care physical therapy (UC) with high intensity weightbearing exercises were analysed for the rate of radiological joint damage (Larsen score) of the hands and feet. Potential determinants of outcome were defined: disease activity, use of drugs, change in physical capacity and in bone mineral density, and attendance rate at exercise sessions.
After 2 years, the 136 participants in high intensity weightbearing exercises developed significantly less radiological damage than the 145 participants in UC. The mean (SD) increase in damage was 3.5 (7.9) in the exercise group and 5.7 (10.2) in the UC group, p = 0.045. Separate analysis of the damage to the hands and feet suggests that this difference in rate of increase of damage is more pronounced in the joints of the feet than in the hands. The rate of damage was independently associated with less disease activity, less frequent use of glucocorticoids, and with an improvement in aerobic fitness.
The progression of radiological joint damage of the hands and feet in patients with RA is not increased by long term high intensity weightbearing exercises. These exercises may have a protective effect on the joints of the feet.
Annals of the Rheumatic Diseases 12/2004; 63(11):1399-405. · 8.73 Impact Factor
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ABSTRACT: Cisplatin-induced toxicities are mainly caused by the formation of free radicals, leading to oxidative organ damage. Plasma concentrations of antioxidants decrease significantly during cisplatin chemotherapy for cancer. Forty-eight cancer patients treated with cisplatin-based chemotherapy were randomised in a double-blind manner to receive either supplementation with vitamin C, vitamin E and selenium dissolved in a beverage or to receive a placebo beverage. Primary outcome measures were the amount of nephrotoxicity and ototoxicity induced by cisplatin. No significant differences were found between the two study groups with respect to these primary outcome measures. However, patients who achieved the highest plasma concentrations of the three antioxidant micronutrients had significantly less loss of high-tone hearing. In addition, significant correlations were found between the reduced/oxidised vitamin C ratio and malondialdehyde (MDA), markers of oxidative stress, and cisplatin-induced ototoxicity and nephrotoxicity. The lack of protection against cisplatin-induced toxicities in patients in the intervention arm may be related to poor compliance and/or inadequate supplementation. Supplementation with a higher dose (intensity) and in combination with other antioxidants should be investigated further.
European Journal of Cancer 08/2004; 40(11):1713-23. · 5.54 Impact Factor
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ABSTRACT: To examine the outcome expectations of RA patients, rheumatologists, and physiotherapists regarding high intensity exercise programmes compared with conventional exercise programmes.
An exercise outcome expectations questionnaire was administered to 807 RA patients, 153 rheumatologists, and 624 physiotherapists. The questionnaire consisted of four statements regarding positive and negative outcomes of high intensity exercise programmes and four similar statements for conventional exercise programmes. A total expectation score for both conventional and high intensity exercise was calculated, ranging from -2 (very negative expectation) to 2 (very positive expectation).
The questionnaire was returned by 662 RA patients (82%), 132 rheumatologists (86%), and 467 physiotherapists (75%). The mean (95% confidence interval) scores for high intensity exercise programmes were 0.30 (0.25 to 0.34), 0.68 (0.62 to 0.74), and -0.06 (-0.15 to 0.02), and for conventional exercise programmes were 0.99 (0.96 to 1.02), 1.13 (1.09 to 1.17), and 1.27 (1.21 to 1.34) for RA patients, rheumatologists, and physiotherapists, respectively. In all three respondent groups, the outcome expectations of high intensity exercise were significantly less positive than those of conventional exercise programme.
Despite the existing evidence regarding the effectiveness and safety of high intensity exercise programmes, RA patients, rheumatologists, and physiotherapists have more positive expectations of conventional exercise programmes than of high intensity exercise programmes. Physiotherapists were the least positive about outcomes of high intensity exercise programmes while rheumatologists were the most positive. To help the implementation of new insights in the effectiveness of physical therapy modalities in rheumatology, the need for continuous education of patients, rheumatologists and physiotherapists is emphasised.
Annals of the Rheumatic Diseases 08/2004; 63(7):804-8. · 8.73 Impact Factor
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B. E. E. M. van den Borne,
R. B. M. Landewé,
I. Houkes,
F. Schild,
P. C. W. van der Heyden,
J. M. W. Hazes,
J. P. Vandenbroucke, A. H. Zwinderman,
H. S. Goei The,
F. C. Breedveld,
H. J. Bernelot Moens,
P. M. Kluin,
B. A. C. Dijkmans
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ABSTRACT: Objective
To evaluate the cyclosporin A (CSA)-attributed risk of developing malignancies in general and malignant lymphoproliferative diseases (LPDs) and skin cancers in particular, as well as the CSA-attributed incidence of mortality in patients with rheumatoid arthritis (RA).Methods
In a retrospective, controlled cohort study, the incidence of malignancies and mortality was evaluated in 208 CSA-treated patients with RA compared with 415 matched control patients with RA between 1984 and 1995. Patients were followed up for a median of 5.0 years (range 1.4-12.0).ResultsForty-eight cases of malignancy (8 in the CSA group and 40 in the control group; relative risk [RR] 0.40, 95% confidence interval [95% CI] 0.19-0.84) were identified, of which 8 were malignant LPDs (2 CSA versus 6 control; RR 0.67, 95% CI 0.14-3.27) and 14 were skin cancers (2 CSA versus 12 control; RR 0.33, 95% CI 0.08-1.47). Seventy-three patients died (16 CSA versus 57 control; RR 0.56, 95% CI 0.33-0.95) due primarily to cardiovascular diseases (4 CSA versus 22 control; RR 0.36, 95% CI 0.13-1.04) or a malignancy (3 CSA versus 8 control; RR 0.67, 95% CI 0.18-2.43). Proportional hazards regression analysis with correction for potential confounding factors did not significantly change the results.Conclusion
The study findings suggest that CSA treatment in RA patients does not increase the risk of malignancies in general or the risk of malignant LPDs or skin cancers in particular. Moreover, the incidence of mortality in CSA-treated RA patients was comparable to that in matched control RA patients.
Arthritis & Rheumatism 05/2004; 41(11):1930 - 1937. · 7.87 Impact Factor
