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H J Adèr

Publications and source records attributed to H J Adèr.

At least 19 recordsLinked to original sources
PubMed2003

[The importance of equivalence trials in showing the usefulness of treatments].

There are different kinds of randomised controlled trials: trials in which the superiority of a treatment can be demonstrated (superiority trials) and trials in which the equal efficacy of two treatments can be shown (equivalence trials). The main reason for performing an equivalence trial is that for many diseases and disorders an effective treatment already exists. Equivalence trials are appropriate when a new treatment offers some advantages over an existing treatment (less cost, greater safety, improved convenience or freedom of choice for the patient), in addition to the expected equal therapeutic effectiveness. The design of equivalence trials is to a large extent comparable to that of superiority trials, but there are some methodological differences. In equivalence trials, the null hypothesis and alternative hypothesis are interchanged, compared to superiority trials. In equivalence trials, an equivalence margin is defined for the different treatments. Clinical professionals decide on the equivalence margin beforehand on the basis of the clinical relevance. To demonstrate equivalence, the confidence interval of the difference between two treatments must lie completely within the equivalence margin. In equivalence trials, there are usually more patients needed: the smaller the equivalence margin, the more patients are needed. In equivalence trials, both per-protocol analyses and intention-to-treat analyses should be used to prove the equal therapeutic effectiveness of the treatments under study.

Clinical Trials as Topic↗
PubMed2003

Hemodynamic and metabolic effects after nifedipine and ritodrine tocolysis.

OBJECTIVES: The purpose of this study is to compare the hemodynamic and metabolic changes after ritodrine and nifedipine tocolysis. METHODS: For an open randomized study, patients with preterm labor (N=185) were allocated to groups to receive ritodrine intravenously (N=90) or nifedipine orally (N=95). RESULTS: The mean diastolic blood pressure was significantly lower in the ritodrine group 24 h (65+/-12 vs. 70+/-8, P=0.001) and 48 h (65+/-12 vs. 71+/-8, P=0.004) after starting tocolysis compared with the nifedipine group. Mean maternal heart rate was significantly higher in the ritodrine group 24 h (105+/-17 vs. 86+/-13, P<0.0001) and 48 h (100+/-21 vs. 85+/-12, P<0.0001) after starting tocolysis compared with the nifedipine group. Mean fasting glucose levels were higher (6.68+/-2.53 vs. 4.93+/-1.23, P=0.0016), while mean potassium levels were lower (3.52+/-0.84 vs. 3.81+/-0.45, P=0.04) in the ritodrine group 48 h after starting tocolysis compared with the nifedipine group. CONCLUSIONS: Use of nifedipine for preterm labor is associated with a lower incidence of adverse hemodynamic and metabolic changes compared with ritodrine after 24 and 48 h of tocolysis. In our opinion nifedipine is the preferred drug of choice for the treatment of preterm labor.

Adult↗
PubMed2003

How morphometric analysis of metastatic load predicts the (un)usefulness of PET scanning: the case of lymph node staging in melanoma.

BACKGROUND: In primary cutaneous melanoma, the sentinel node (SN) biopsy is an accurate method for the staging of the lymph nodes. Positron emission tomography (PET) has been suggested as a useful alternative. However, the sensitivity of PET may be too low to detect SN metastases, which are often small. AIM: To predict the value of PET for initial lymph node staging in melanoma based on morphometric analysis of SN metastatic load, without exposing patients to PET. MATERIALS AND METHODS: In 59 SN positive patients with melanoma, the sizes of tumour deposits in the SNs and subsequent dissection specimens were measured by morphometry and correlated with the detection limits of current and future PET scanners. RESULTS: The median tumour volume within the basin was 0.15 mm(3) (range, 0.0001-118.86). Seventy per cent of these deposits were smaller than 1 mm(3). State of the art PET scanners that have a resolution of about 5 mm would detect only 15-49% of positive basins. Logistic regression analysis revealed no pretest indicators identifying patients expected to have a positive PET. However, the SN tumour load was a significant and single predictor of the presence of PET detectable residual tumour. CONCLUSION: Morphometric analysis of metastatic load predicts that PET scanning is unable to detect most metastatic deposits in sentinel lymph nodes of patients with melanoma because the metastases are often small. Therefore, the SN biopsy remains the preferred method for initial regional staging.

Adolescent↗
PubMed2002

Seasonal variation in immune measurements and MRI markers of disease activity in MS.

BACKGROUND: The exact mechanisms by which T cells contribute to MS progression are not known. Recently, the results of cross-sectional studies suggested seasonal variation of both interferon (IFN)-gamma production and the number of active MRI lesions in MS. OBJECTIVE: To investigate whether seasonal fluctuations of IFN-gamma and active MRI lesions could be confirmed and whether any correlations could be detected. METHODS: Data were analyzed from a group of 28 MS patients in whom detailed longitudinal monitoring of both immune function and MRI measurements had taken place. RESULTS: Significant seasonal variation was observed in T-cell activation as measured by the ability of T cells to secrete the pro-inflammatory cytokines tumor necrosis factor-alpha and IFN-gamma. Maximum values were found in samples obtained during autumn. Even though clear fluctuations were observed, no significant seasonal variation could be detected in the number of active MRI lesions. Fluctuations of in vitro IFN-gamma secretion correlated weakly with changes in active MRI lesions. CONCLUSIONS: The finding of seasonal variation of immune function in serially MRI-monitored MS patients suggests an environmental role in T-cell activation.

Adult↗
PubMed2002

Information processing characteristics in subtypes of multiple sclerosis.

The purpose of this study was to evaluate information processing characteristics in patients with multiple sclerosis (MS). We selected 53 patients with MS and 58 matched healthy controls. Using computerized tests, we investigated focused, divided, sustained attention, and executive function, and attempted to pinpoint deficits in attentional control to peripheral or central processing stages. The results substantiate the hypothesis that the slowing of attention-demanding (controlled) information processing underlying more complex cognitive skills is general, i.e. irrespective of type of controlled processing, with MS patients being 40% slower than controls. MS patients may suffer from focused, and divided and sustained attention deficits, as well as from compromised central processing stages, with secondary progressive (SP) patients showing the most extensive range of deficits, closely followed by primary progressive (PP) patients, while relapsing-remitting (RR) patients appear to be much less affected. General slowing appears to be highest in PP and SP type MS patients (50% slower) versus relapsing-remitting MS (24% slower). In contrast to most previous results, (complex) processing speed appeared to be robustly correlated with severity of MS as measured by the expanded disability status scale and with disease duration. Patients did much less differ in accuracy of processing from controls, suggesting the importance of using time strategies in planning everyday life and job activities to compensate for or alleviate MS-related speed handicaps.

Activities of Daily Living↗
PubMed2002

Prevalence of and risk factors for HIV infection in blood donors and various population subgroups in Ethiopia.

The aim was to determine the prevalence of HIV infection and risk factors for HIV infection in various population subgroups in Ethiopia. Serum panels from blood donors (n = 2610), from various population subgroups in Ethiopia were tested for anti-HIV-1/2 by ELISA. All ELISA repeatedly reactive samples were subjected for confirmation by immunoblot (IB) and anti-HIV-1 and anti-HIV-2 specific ELISAs. 155/2610 (5.9%) blood donors were HIV-1 infected. Of pregnant women, 84/797 (10.5%) were HIV-1 infected, and 1/797 (0.1%) was HIV-2 infected. 1/240 (0.4%) individuals from the rural population were HIV-1 infected. 198/480 (41.3%) female attendees, and 106/419 (25.3%) male attendees at sexual transmitted disease (STD) clinics were HIV-1 infected. One (0.2%) male, and 2 (0.4%) female STD patients were infected with both HIV-1 and HIV-2. It was concluded that the prevalence of HIV-1 infection varied from 0.4% among urban residents to 25.3-41.3% among STD attendees. There is a low prevalence of HIV-2 present in Ethiopian subjects. Risky sexual behaviour is significantly associated with HIV-infection in Ethiopia.

Adolescent↗
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

Multiple sclerosis functional composite: impact of reference population and interpretation of changes.

The Multiple sclerosis functional composite (MSFC) has been recommended as a clinical outcome measure to be used in future MS trials. A specific characteristic of the MSFC is that it is defined as a measure of impairment relative to a reference population. Using different reference populations affects actual MSFC scores. If the selection of a reference population also has an effect on sensitivity to change of the MSFC, comparison of data from clinical trials will be almost impossible when different reference populations are used We studied the effect of the selection of a reference population on the outcome of a trial by simulating 343 intervention trials and comparing results obtained by using three different reference populations: two previously published MS patient populations and a healthy population. Scores of the healthy population were collected in the first part of the study. The effects of sex, age and education level on test scores of healthy subjects were studied as well. In the healthy controls, sex, age and education level had a different impact on individual test scores of MSFC components and overall MSFC score. Our study shows that, with the use of the MSFC, the selection of different reference populations does not affect the trial statistics and significance, but it does affect comparability of results between different trials, and complicates the dinical interpretation of any observed change.

Clinical Trials as Topic↗
PubMed2001

Isotropic 3D fast FLAIR imaging of the brain in multiple sclerosis patients: initial experience.

The application of image registration and subtraction to detect change in multiple sclerosis (MS) disease burden on serial MR scans benefits from the use of isotropic voxels. An optimised 3D fast fluid-attenuated inversion recovery (FLAIR) sequence with 1.2- and 1.8-mm cubic voxels was compared with a 2D T2 SE sequence using standard 3-mm slices. Three-dimensional fast FLAIR and T2 SE series were obtained in 20 MS patients and 15 controls. Whole brain acquisition times for the 1.2- and 1.8-mm FLAIR were 21 and 10.5 min, respectively, for the interleaved T2 SE 16 min. Brain lesions were marked in consensus by two radiologists and the CNR was calculated in ten lesions. The mean number of lesions detected with the 1.2-mm FLAIR sequence was 115 +/- 76, compared with 85 +/- 59 for the T2 SE series ( p<0.001). The 1.8-mm FLAIR detected only 73 +/- 46 lesions. The CNR of the 1.2-mm FLAIR was significantly better than the T2 SE ( p<0.01), but not as good as the 1.8-mm FLAIR. In conclusion, isotropic 3D fast FLAIR using 1.2-mm cubic voxels is superior to the 2D T2 SE in the detection of brain lesions in MS patients. The isotropic 1.8-mm FLAIR is faster and has better contrast characteristics but lacks sensitivity.

Adult↗
PubMed2001

Optimizing the association between disability and biological markers in MS.

OBJECTIVE: Axonal damage is an important feature of MS pathology and the likely substrate of development of progressive disability. Brain volume measurement on MRI can be used as an overall marker of tissue damage and axonal loss. The authors studied the relation of brain volume measurements with the MS Functional Composite (MSFC) in an attempt to improve the clinico-radiologic association. METHODS: In 137 patients with MS (80 relapsing-remitting [RR], 36 secondary progressive [SP], and 21 primary progressive [PP]) and 12 healthy controls, a brain MRI scan was obtained. Patients also underwent MSFC and Expanded Disability Status Scale (EDSS) assessments. MRI analysis included determination of hypointense T1- and hyperintense T2-weighted lesion load, and two brain volume measurements: 1) the parenchymal fraction (PF): whole brain parenchyma/intracranial volume; and 2) the ventricular fraction (VF): ventricular volume/whole brain parenchyma. RESULTS: The median PF was smaller and the median VF larger in the patient group (0.81 for PF and 0.029 for VF) than in the control group (0.87 for PF, p < 0.001; and 0.013 for VF, p < 0.01). For the patient population, moderate correlations were found between brain volume measurements and MSFC (0.36 for PF and -0.40 for VF). Patients with short disease duration showed a correlation of MSFC with both brain and lesion volume measurements on MRI, whereas patients with long disease duration only showed a correlation with brain volume measurements. CONCLUSION: Brain volume measurements are correlated with disability as assessed by the MSFC. Although in the early phase of the disease the amount of focal demyelination is important, the residual brain volume seems to be more relevant in determining disability in later phases of the disease.

Adolescent↗
PubMed2001

Active MRI lesion appearance in MS patients is preceded by fluctuations in circulating T-helper 1 and 2 cells.

BACKGROUND: The role of T cell subpopulations and their ability to produce immunoregulatory cytokines has been extensively studied in multiple sclerosis (MS). However, the exact mechanisms by which T cells and cytokines contribute to disease activity remain to be clarified. OBJECTIVES: To analyze the longitudinal relation between markers of T cell activation and differentiation and disease activity in MS patients. METHODS: During a period of 9 months, clinical disease activity was scored, monthly MRI scans were performed, and blood was taken for immune measurements in a group of 13 untreated clinically definite MS patients. RESULTS: Disease activity, as measured by the occurrence of active MRI lesions, is associated with a significant transient decrease in both T cells producing interferon-gamma (IFN-gamma) and T cells producing interleukin (IL)-4. CONCLUSIONS: Our results suggest that MRI-documented disease activity is associated with a transient decrease in circulating cytokine producing T cells, possibly due to the migration of activated T cells into the CNS.

Adult↗
PubMed2001

Magnetization transfer histogram parameters reflect all dimensions of MS pathology, including atrophy.

INTRODUCTION: Magnetization transfer ratio (MTR) histogram analysis can be used as a method for quantifying overall disease burden in MS. We studied correlations between MTR histogram and clinical parameters in MS subgroups. Contrary to earlier studies we placed special emphasis on the lower MTR range, to explore the effect of partial volume averaging effects with CSF. METHODS: Seventy-nine patients with MS [26 primary progressive (PP), and 53 'relapse-onset', including 26 secondary progressive (SP)], and 23 healthy individuals were studied. MR imaging included 3 mm 2D gradient-echo images with and without an off-resonance MT pulse. According to the visually determined cut-off, histogram parameters were classified as parenchymal or CSF-related variables. Clinical measurements included the Expanded Disability Status Scale (EDSS) as a measure of global impairment/disability and the Paced Auditory Serial Addition Test (PASAT) as a measure of cognition. RESULTS: SP MS patients differed from the other subgroups on many MTR variables, originating from both the lower and the higher MTR range. CSF-related low MTRs were clearly over-represented in SP patients, and showed a significant distinction between the SP and PP MS group. In the total group, as well as in the relapse-onset patients, significant correlations were found between MTR parameters and clinical parameters. No associations were found in the PP group. CONCLUSION: This explorative study suggests that MTR histogram analysis can distinguish between MS patients and controls, and best identifies the SP phenotype, partly as a result of increased CSF volume (atrophy). In addition, we show that MTR histogram analysis gives information about the level of impairment and disability in patients with a 'relapse-onset' course of MS, and therefore provides a useful tool to monitor the evolution of the disease in these patients.

Adult↗
PubMed2001

Hypointense lesions on T1-weighted spin-echo magnetic resonance imaging: relation to clinical characteristics in subgroups of patients with multiple sclerosis.

CONTEXT: Hypointense lesions on T1-weighted spin-echo magnetic resonance images (T1 lesions) represent destructive multiple sclerosis (MS) lesions, consisting of axonal loss and matrix destruction. These lesions are being used as a secondary outcome measure in phase III clinical trials. Clinical determinants of T1 lesions may differ between subgroups of patients with MS and subsequently may have implications for the selection of patients for clinical trials. OBJECTIVE: To determine if clinical characteristics of patients with MS are related to T1 lesion volume. DESIGN: A survey of 138 patients with MS (52 with relapsing-remitting MS, 44 with secondary progressive MS, and 42 with primary progressive MS). SETTING: The Magnetic Resonance Center for Multiple Sclerosis Research, University Hospital "Vrije Universiteit," Amsterdam, the Netherlands. MAIN OUTCOME MEASURES: Type of MS, Expanded Disability Status Scale (EDSS) score, sex, age at first symptoms, and T1 lesion volume. RESULTS: Patients with secondary progressive MS have the highest T1 lesion volume. Patients with relapsing-remitting MS have a lower T1/T2 ratio than patients with secondary progressive MS and patients with primary progressive MS. In patients with relapsing-remitting MS and secondary progressive MS, T1 lesion volume relates to disease duration and EDSS score, while in patients with primary progressive MS sex is important. A trend toward higher T1 lesion volume was shown for male patients with primary progressive MS when compared with female patients with primary progressive MS (1.0 cm(3) vs 0.3 cm(3), P=.03); a trend toward higher T1 lesion volume was found with age at onset in patients with relapsing-remitting MS and in patients with primary progressive MS. CONCLUSIONS: In patients with MS different clinical characteristics associate with T1 lesion volume, suggesting a more destructive type of lesions in certain subgroups. A possible sex difference in (destructive) lesion development on magnetic resonance imaging should be evaluated in more detail, preferably in a cohort.

Adult↗
PubMed2001

Improved interobserver agreement for visual detection of active T2 lesions on serial MR scans in multiple sclerosis using image registration.

The aim of this study was to analyse the effect of image registration on interobserver agreement in the visual detection of active multiple sclerosis (MS) lesions from serial magnetic resonance (MR) scans. T2W spin-echo MR scans (3-mm slices) of 16 MS patients participating in a treatment trial were selected. For each patient, two pairs of scans were used: an original (i. e., non-registered) and a registered pair. For the original pair, baseline and month 6 were used, and for the registered pair month 3 and 9. For registration an automatic matching algorithm based on Mutual Information was used. Six observers identified active lesions on both original and registered scans. Kappa values were calculated to assess interobserver agreement. Reslicing caused a slight blurring of the images, but near perfect registration. The kappa value of 0.35 +/- 0.07 for new lesions on original images improved to 0.62 (+/- 0.06) by registration (p = 0.004). For enlarging lesions on original images it was extremely poor (kappa 0.11 +/- 0.05), and did not benefit much by registration (kappa 0.20 +/- 0.11). Thus, image registration improved interobserver agreement for visual detection of new lesions. For enlarging lesions, registration improved agreement but still not to a satisfactory level.

Adult↗
PubMed2001

Insulin-treated diabetes patients with fear of self-injecting or fear of self-testing: psychological comorbidity and general well-being.

OBJECTIVE: To examine psychological functioning and self-management behaviours of Dutch adult patients with insulin-requiring diabetes mellitus suffering from extreme fear of self-injecting (FSI) and/or fear of self-testing (FST). METHODS: A cross-sectional survey was performed in a sample of insulin-treated diabetes patients (n=1275; 51.1% male; age 49.7+/-15.8 years; 58.0% Type 1 diabetes), assessing FSI and FST. Patients completed the questionnaires concerning trait/state anxiety, depression, fear of hypoglycemia, diabetes-related distress, diabetes self-care activities, and general well-being. Comparisons were made on these measures between patients with extremely high scores on FSI and/or FST (> or = 95th percentile) and the other patients. Patients with extreme scores on FSI and/or FST were invited to take part in a second survey to assess the prevalence of major depression, common fears/phobias, and psychoneuroticism. RESULTS: People with extreme FSI/ FST scores, as compared to the other patients, reported higher levels of trait/state anxiety and depression. This group also reported more fear of hypoglycaemia and diabetes-related distress, had lower levels of general well-being, and reported less frequent self-monitoring of blood glucose. The second survey showed 11.1% of patients with extreme FSI/FST reporting scores indicating major depression. Prevalence of scores greater than or equal to the high scores on phobias (38.0-63.3%) and psychoneuroticism (27.8%) were consistently higher than norm group prevalences. DISCUSSION: Extreme levels of FSI and/or FST are associated with high diabetes-related distress, poor general well-being, and psychological comorbidity, as well as poorer adherence to the diabetes treatment regimen. It is concluded that patients with extreme FSI/FST are often burdened with more than this specific phobia.

Adult↗
PubMed2001

Effects of cognitive behavioural group training (CBGT) in adult patients with poorly controlled insulin-dependent (type 1) diabetes: a pilot study.

A substantial group of patients with type 1 diabetes has difficulty adhering to the treatment regimen, and as a consequence is at increased risk of developing microvascular complications. Cognitive behavioural interventions may help these patients to cope more effectively with their diabetes. We developed a 4 weeks cognitive behavioural group training (CBGT) for patients with type 1 (insulin-dependent) diabetes in persistent poor glycaemic control, to help them overcome negative beliefs and attitudes towards diabetes and improve their self-care behaviours. Feasibility and efficacy of CBGT were tested in a non-randomised prospective study in 24 poorly-controlled type 1 diabetes patients (mean age 35.2+/-11.1years; 15 female; mean HbA(1c) 9.3% (+/-1.2)), with assessments at 3 and 6 months follow-up. The programme was delivered in small groups (n=6-8), by a team of a diabetes nurse specialist and a psychologist. Primary outcome measures were glycosylated haemoglobin (HbA(1c)), diabetes-related emotional distress (PAID) and psychological well-being (WBQ-12). Changes in diabetes self-care activities (DSCI) were documented, along with perceived barriers in diabetes questionniare (BDQ) and fear of hypoglycaemia survey (HFS). Data were analysed using repeated measures analysis of variance. The CBGT proved to be feasible in this selected group of patients and was well appreciated. Following CBGT, mean HbA(1c) dropped by 0.8% at 6 months from baseline, while emotional well-being was preserved. It is concluded that CBGT is a promising intervention that deserves further evaluation in randomised controlled trials.

Adult↗
PubMed2001

Variance components of two-dimensional strain parameters in the left-ventricular heart wall obtained by magnetic resonance tagging.

This study quantifies variance components of two-dimensional strains in the left-ventricular heart wall assessed by magnetic resonance (MR) tagging in 18 healthy xxvolunteers. For a 7-mm tagging grid and homogeneous strain analysis, the intersubject variability and measurement error were estimated, as well as the intra- and interobserver variability. The variance components were calculated for the mean strain of a circumferential sector. The results show that the measurement error was almost equal to the intra-observer variability. With four circumferential sectors of 90 degrees each, approximately 65% of the total variance in epsilonr and epsilonc was due to intersubject variability, the remaining 35% was due to measurement error. With 12 sectors of 30 degrees each, the intersubject variability and measurement error both contributed 50% to the total variance. With 18 sectors of 20 degrees each, only 40% of the total variance was due to intersubject variability. The total variability increased with the number of sectors and therefore the number of sectors used in a study will be a trade-off between segment size (defining spatial resolution) and variability.

Analysis of Variance↗