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Biomedical subjects

V de Groot

Publications and source records attributed to V de Groot.

8 recordsLinked to original sources

The usefulness of evaluative outcome measures in patients with multiple sclerosis.

To select the most useful evaluative outcome measures for early multiple sclerosis, we included 156 recently diagnosed patients in a 3-year follow-up study, and assessed them on 23 outcome measures in the domains of disease-specific outcomes, physical functioning, mental health, social functioning and general health. A global rating scale (GRS) and the Expanded Disability Status Scale (EDSS) were used as external criteria to determine the minimally important change (MIC) for each outcome measure. Subsequently, we determined whether the outcome measures could detect their MIC reliably. From these, per domain the outcome measure that was found to be most sensitive to changes (responsive) was identified. At group level, 11 outcomes of the domains of physical functioning, mental health, social functioning and general health could reliably detect the MIC. Of these 11, the most responsive measures per domain were the Medical Outcome Study 36 Short Form sub-scale physical functioning (SF36pf), the Disability and Impact Profile (DIP) sub-scale psychological, the Rehabilitation Activities Profile sub-scale occupation (RAPocc) and the SF36 sub-scale health, respectively. Overall, the most responsive measures were the SF36pf and the RAPocc. In individual patients, none of the measures could reliably detect the MIC. In sum, in the early stages of multiple sclerosis the most useful evaluative outcome measures for research are the SF36pf (physical functioning) and the RAPocc (social functioning).

Activities of Daily Living↗

The initial course of daily functioning in multiple sclerosis: a three-year follow-up study.

We studied the initial course of daily functioning in multiple sclerosis (MS). A cohort of 156 recently diagnosed patients was prospectively followed for three years (five measurements). Domains of interest were neurological deficits, physical functioning, mental health, social functioning and general health. An a priori distinction was made between a relapse onset group (n = 128) and a non-relapse onset group (n =28). At baseline, neurological deficits are relatively minor for most patients, 26.3% have aberrant physical functioning scores, 38.5% have aberrant social functioning scores, 9% have aberrant mental health scores and 25% have aberrant general health scores. The neurological deficits and physical functioning deteriorated significantly over time. This deterioration was more pronounced and clinically relevant in the non-relapse onset group only. Mental health showed a significant, but not clinically relevant deterioration over time. Social functioning and general health showed non-significant effects for time. It is concluded that in the initial stage of MS, when neurological deficits are relatively minor and mental health is relatively unaffected, patients in both groups experience limitations in daily functioning. Patients in the non-relapse onset group have progressive neurological symptoms that are accompanied by progressive limitations in physical functioning, but not by progressive limitations in the other domains.

Activities of Daily Living↗

Differences in cognitive impairment of relapsing remitting, secondary, and primary progressive MS.

OBJECTIVE: To investigate the cognitive skills of patients with relapsing remitting multiple sclerosis (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS) relative to healthy control subjects and to assess whether there is heterogeneity in the type of cognitive disabilities demonstrated by patients with different MS phenotypes. METHODS: RRMS patients (n = 108), SPMS patients (n = 71), PPMS patients (n = 55), and healthy control subjects (n = 67) underwent neuropsychological assessment with the Brief Repeatable Battery of Neuropsychological Tests. RESULTS: Relative to controls, cognitive performance of RRMS patients was deficient when tasks required higher-order working memory (WM) processes (Word List Generation, 10/36 Spatial Recall Test, Symbol Digit Modalities Test). PPMS and SPMS patients performed poorer than control subjects on all tasks. SPMS patients performed more poorly than PPMS patients when tasks required higher-order WM processes, except when speed of information processing played a relatively important role (Symbol Digit Modalities Test, Paced Auditory Serial Addition Test). Whereas RRMS patients generally performed better than the progressive subtypes, they showed relatively poor verbal fluency. CONCLUSION: MS patients with different disease courses have different cognitive profiles.

Adult↗

Spinal cord abnormalities in recently diagnosed MS patients: added value of spinal MRI examination.

OBJECTIVE: The most recent diagnostic criteria for multiple sclerosis (MS) ascertain that findings from spinal cord MRI can be used to demonstrate dissemination in space. Because little is known about the prevalence and characteristics of cord lesions early in the disease, the authors studied the prevalence of spinal cord abnormalities in patients with early-stage MS and assessed their impact on diagnostic classification. METHODS: The brains and spinal cords of 104 recently diagnosed patients with MS were examined. Median interval between first symptom and diagnosis was 18.4 months. The brain MRI protocol included before and after gadolinium axial T1-weighted conventional spin-echo sequences and dual-echo spin-echo images. For spinal cord MRI, sagittal cardiac-triggered dual-echo T2-weighted and sagittal T1-weighted spin-echo images were included. Clinical assessment for each patient included age, sex, clinical signs for spinal cord involvement, and Expanded Disability Status Scale. RESULTS: Abnormal cord MRIs were found in 83% of patients, usually with only focal lesions. Diffuse cord abnormalities were found in 13% of patients, although in isolation they were found in only three patients. Focal cord lesions were often multiple (median number, 3.0), small (median, 0.8 vertebral segments), and primarily (56.4%) situated in the cervical spinal cord. In 68 of 104 patients (65.4%), two or more focal lesions were visible on spinal cord images. The criteria for dissemination in space, as defined in the McDonald criteria for the brain, were met in only 66.3% of the patients. This percentage increased to 84.6% when spinal cord MRI abnormalities were also included. CONCLUSION: Spinal cord abnormalities are prevalent in patients with early-stage MS, have distinct morphologic characteristics, and help to determine dissemination in space at time of diagnosis.

Adult↗

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↗

Concurrent validity of the MS Functional Composite using MRI as a biological disease marker.

INTRODUCTION: The MS Functional Composite (MSFC), a recently developed outcome measure for MS clinical trials measuring three dimensions (ambulation/leg function, arm/hand function, and cognition), was applied to 134 patients with MS to study the concurrent validity, using MRI measurements as a biological disease marker. The results were compared to correlations between the traditionally applied Expanded Disability Status Scale (EDSS) and MRI measurements in the same patients. METHODS: The assessments of MSFC and EDSS were performed in combination with brain MRI. MRI consisted of T1- and T2-weighted images, from which the hypointense and hyperintense lesion loads were quantified. RESULTS: The MSFC score ranged from -2.54 to 0.99. The median EDSS was 3.0 (interquartile range [IQR] 1.5 to 6.0). The median T2-weighted lesion load was 8.4 cm(3) (IQR 3.4 to 19.8) and the median T1-weighted lesion load was 1.1 cm(3) (IQR 0.3 to 3.2). Correlations between the MSFC and both T1 (-0.24) and T2 (-0.25) lesion loads were demonstrated, but not between the EDSS and both MRI parameters. Significant correlations between MSFC components and T1 and T2 lesion loads existed for cognitive function and arm/hand function, but not for ambulation. If relapse-onset patients (relapsing-remitting and secondary progressive) were combined, the correlation between MSFC and MRI parameters became stronger for both T1 (-0.37) and T2 lesion loads (-0.35). CONCLUSIONS: The authors present the concurrent validity of the MSFC with a biological disease marker by showing correlations with MRI. Specifically, they demonstrate significant correlations with cognition and arm/hand function assessments, domains that are not well represented in the EDSS.

Adolescent↗

MS functional composite: relation to disease phenotype and disability strata.

OBJECTIVE: The MS Functional Composite (MSFC), a recently developed outcome measure for clinical trials, was applied to 240 patients with MS to explore its utility in different subgroups of MS and for comparison with the Expanded Disability Status Scale (EDSS). METHOD: Three clinical dimensions were examined: arm/hand function, leg function/ambulation, and cognition. Predictions of relative scores on the MSFC and its components in three major MS phenotypes (relapsing-remitting, primary progressive, and secondary progressive) and three strata of disability were developed and tested. Also, correlations with EDSS were calculated and the effect of an external reference population was assessed. RESULTS: Mean MSFC score was positive in the relapsing-remitting (0.4) and mildly disabled (0.4) groups and negative in the secondary progressive (-0.3), primary progressive (-0.4), and moderately (-0.07) and severely disabled (-1.0) groups. The correlation between EDSS and MSFC was strong (-0.68). EDSS correlated strongly with ambulation in secondary and primary progressive patients and severely disabled patients, moderately with arm/hand function for all analyzed groups, and not at all with cognition. Comparison with an external reference population showed changes in MSFC- and Z-scores, but did not result in altered differences between the subgroups. CONCLUSION: Our prospective study in subgroups of MS confirmed and extended the construct validity of the MSFC. The MSFC also showed good concurrent validity with the EDSS, and includes information about cognition.

Adolescent↗