| 1. |
- Allen-Philbey, Kimberley, et al.
(författare)
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Subcutaneous cladribine to treat multiple sclerosis : experience in 208 patients
- 2021
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Ingår i: Therapeutic Advances in Neurological Disorders. - : SAGE Publications. - 1756-2856 .- 1756-2864. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To report on safety and effectiveness of subcutaneous cladribine (Litak®) in multiple sclerosis (MS) patients. Methods: Litak® was offered to MS-patients irrespective of disease course. Litak® 10 mg was administered for 3–4 days during week 1. Based on lymphocyte count at week 4, patients received another 0–3 doses at week 5. A second course was administered 11 months later. Follow-up included adverse events, relapses, expanded disability status scale (EDSS), 9-hole-peg and Timed-25-foot-walking tests, no-evidence-of-disease-activity (NEDA), no-evidence-of-progression-or-active-disease (NEPAD), MRI, cerebrospinal fluid (CSF) neurofilament light chain (NfL), and lymphocyte counts. Results: In all, 208 patients received at least one course of treatment. Age at baseline was 44 (17–72) years and EDSS 0–8.5. Cladribine was generally well tolerated. One myocardial infarction, one breast cancer, and three severe skin reactions occurred without long-term sequelae. Two patients died (one pneumonia, one encephalitis). Lymphopenia grade 3 occurred in 5% and grade 4 in 0.5%. In 94 out of 116 pwMS with baseline and follow-up (BaFU) data after two treatment courses, EDSS remained stable or improved. At 18 months, 64% of patients with relapsing MS and BaFU data (n = 39) had NEDA. At 19 months, 62% of patients with progressive MS and BaFU data (n = 13) had NEPAD. Of n = 13 patients whose CSF-NfL at baseline was elevated, 77% were normalised within 12 months. Conclusions: Litak® was well tolerated. Effectiveness in relapsing MS appeared similar to cladribine tablets and was encouraging in progressive MS. Our data suggest cladribine may be safe and effective in MS-patients irrespective of their disease stage.
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| 2. |
- Beecham, Ashley H, et al.
(författare)
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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
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Tidskriftsartikel (refereegranskat)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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| 3. |
- Bladh, Stina, et al.
(författare)
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Psychometric performance of a generic walking scale (Walk-12G) in Multiple Sclerosis and Parkinson's disease
- 2012
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Ingår i: Journal of Neurology. - Heidelberg : Springer Berlin/Heidelberg. - 0340-5354 .- 1432-1459. ; 259:4, s. 729-738
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Tidskriftsartikel (refereegranskat)abstract
- Walking difficulties are common in neurological and other disorders, as well as among the elderly. There is a need for reliable and valid instruments for measuring walking difficulties in everyday life since existing gait tests are clinician rated and focus on situation specific capacity. The Walk-12G was adapted from the 12-item multiple sclerosis walking scale as a generic patient-reported rating scale for walking difficulties in everyday life. The aim of this study is to examine the psychometric properties of the Walk-12G in people with multiple sclerosis (MS) and Parkinson’s disease (PD). The Walk-12G was translated into Swedish and evaluated qualitatively among 25 people with and without various neurological and other conditions. Postal survey (MS, n = 199; PD, n = 189) and clinical (PD, n = 36) data were used to test its psychometric properties. Respondents considered the Walk-12G relevant and easy to use. Mean completion time was 3.5 min. Data completeness was good (<5% missing item responses) and tests of scaling assumptions supported summing item scores to a total score (corrected item-total correlations >0.6). Coefficient alpha and test–retest reliabilities were >0.9, and standard errors of measurement were 2.3–2.8. Construct validity was supported by correlations in accordance with a priori expectations. Results are similar to those with previous Walk-12G versions, indicating that scale adaptation was successful. Data suggest that the Walk-12G meets rating scale criteria for clinical trials, making it a valuable complement to available gait tests. Further studies involving other samples and application of modern psychometric methods are warranted to examine the scale in more detail.
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| 4. |
- Hagell, Peter, et al.
(författare)
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Measuring the impact of drug-induced dyskinesias in Parkinson’s disease : the PDYS-26 revisited
- 2018
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Ingår i: International Conference on Probabilistic Models for Measurement.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: Drug-induced dyskinesias (DID) are a common long-term complication of dopaminergic drug therapy for Parkinson’s disease (PD). The 26-item PD dyskinesia scale (PDYS-26) is a patient-reported rating scale intended to quantify the everyday impact of DID. However, its measurement properties have not been scrutinized since its development some 10 years ago.AIM: To examine the measurement properties of the PDYS-26 using Rasch Measurement Theory (RMT).DESIGN: The PDYS-26 was administered to people with PD and varying degrees of DID recruited from six Swedish (n=172) and three British (n=150) outpatient movement disorder clinics. RMT analyses were conducted using the RUMM2030 software.RESULTS: RMT model fit was generally good with only three items exhibiting relatively minor misfit. Response categories worked as intended and targeting was acceptable and reliability was 0.96. There was no differential item functioning (DIF) by age, PD duration or time, but three items exhibited DIF by country and one by sex, neither of which appear to notably bias person measurement. Item hierarchy review suggested a variable of dubious clinical/theoretical coherence. Therefore, a recently proposed three-dimensional reduced (21-item) PDYS version was explored. Results were similar to those from the original scale but with improved conceptual coherence, albeit with close to a 2- to 3-fold decrease in measurement precision. SUMMARY AND IMPLICATIONS: The PDYS-26 appears useful for measuring the impact of DID, and yields sufficiently invariant measurement across core patient subgroups. Scale reconceptualization improves the meaning of scores, but at the cost of measurement uncertainty.
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| 5. |
- Hagell, Peter, et al.
(författare)
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Measuring the impact of drug-induced dyskinesias in Parkinson’s disease : the PDYS-26 revisited
- 2018
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: Drug-induced dyskinesias (DID) are a common long-term complication of dopaminergic drug therapy for Parkinson’s disease (PD). The 26-item PD dyskinesia scale (PDYS-26) is a patient-reported rating scale intended to quantify the everyday impact of DID. However, its measurement properties have not been scrutinized since its development some 10 years ago. AIM: To examine the measurement properties of the PDYS-26 using Rasch Measurement Theory (RMT). DESIGN: The PDYS-26 was administered to people with PD and varying degrees of DID recruited from six Swedish (n=172) and three British (n=150) outpatient movement disorder clinics. RMT analyses were conducted using the RUMM2030 software. RESULTS: RMT model fit was generally good with only three items exhibiting relatively minor misfit. Response categories worked as intended and targeting was acceptable and reliability was 0.96. There was no differential item functioning (DIF) by age, PD duration or time, but three items exhibited DIF by country and oneby sex, neither of which appear to notably bias person measurement. Item hierarchy review suggested a variable of dubious clinical/theoretical coherence. Therefore, a recently proposed three-dimensional reduced (21-item) PDYS version was explored. Results were similar to those from the original scale but with improved conceptual coherence, albeit with close to a 2- to 3-fold decrease in measurement precision. SUMMARY AND IMPLICATIONS: The PDYS-26 appears useful for measuring the impact of DID, and yields sufficiently invariant measurement across core patient subgroups. Scale reconceptualization improves the meaning of scores, but at the cost of measurement uncertainty.
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| 6. |
- Sawcer, Stephen, et al.
(författare)
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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