| 1. |
- Johansson, Viktoria, et al.
(författare)
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Multiple sclerosis and psychiatric disorders : comorbidity and sibling risk in a nationwide Swedish cohort
- 2014
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Ingår i: Multiple Sclerosis Journal. - Stockholm : Sage Publications. - 1352-4585 .- 1477-0970. ; 20:14, s. 1881-1891
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Psychiatric disorders are known to be prevalent in multiple sclerosis (MS).OBJECTIVE: The objective of this paper is to study comorbidity between MS and bipolar disorder, schizophrenia and depression in a nationwide cohort and to determine whether shared genetic liability underlies the putative association.METHODS: We identified ICD-diagnosed patients with MS (n = 16,467), bipolar disorder (n = 30,761), schizophrenia (n = 22,781) and depression (n = 172,479) in the Swedish National Patient Register and identified their siblings in the Multi-Generation Register. The risk of MS was compared in psychiatric patients and in matched unexposed individuals. Shared familial risk between MS and psychiatric disorders was estimated by sibling comparison.RESULTS: The risk of MS was increased in patients with bipolar disorder (hazard ratio (HR) 1.8, 95% confidence interval (CI) 1.6-2.2, p < 0.0001) and depression (HR 1.9, 95% CI 1.7-2.0, p < 0.0001). MS risk in schizophrenia was decreased (HR 0.6, 95% CI 0.4-0.9, p = 0.005). The association between having a sibling with a psychiatric disorder and developing MS was not significant.CONCLUSION: We found a strong positive association between MS and bipolar disorder and depression that could not be explained by genetic liability. The unexpected negative association between MS and schizophrenia might be spurious or indicate possible protective mechanisms that warrant further exploration.
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| 2. |
- Song, Jie, et al.
(författare)
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Similar familial risk in multiple sclerosis subgroups
- 2017
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Ingår i: Multiple Sclerosis. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1352-4585 .- 1477-0970.
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Tidskriftsartikel (refereegranskat)abstract
- Background: A subgroup of patients diagnosed with multiple sclerosis (MS) present with no oligoclonal bands (OCB) in the cerebrospinal fluid (CSF). Several studies report different clinical characteristics and genetic associations between the two groups. Objective: To investigate whether the OCB negative subgroup has a distinct etiology from band positive MS. Methods: Using nationwide registers to estimate familial risks, which reflect the genetic contribution of a disease. Results: Odds ratios of MS were similar for relatives to band positive and negative patients. Conclusion: From the perspective of familial liability, MS without OCB is etiologically closely related to the dominant subgroup of OCB positive MS.
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| 3. |
- Ahlgren, Cecilia, 1946, et al.
(författare)
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A nationwide survey of the prevalence of multiple sclerosis in immigrant populations of Sweden
- 2012
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Ingår i: Multiple Sclerosis. - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 18:8, s. 1099-1107
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Tidskriftsartikel (refereegranskat)abstract
- Background: In 2008, immigrants constituted 14% of the population of Sweden, a high-risk area for multiple sclerosis (MS). We investigated the largest Swedish immigrant populations for the prevalence of MS. Method: Data on foreign-born MS patients were retrieved from Swedish national health and population registers. We calculated observed versus expected numbers of MS patients and gender-and age-specific prevalence ratios (PR) between immigrant populations and the general population of Sweden and, where possible, of the countries of birth. Results: The 19 largest immigrant populations included 1327 MS patients. The global variation in MS prevalence was reflected in Sweden. The prevalence in immigrant populations who had moved to Sweden from countries with a lower MS risk was however higher than in their countries of birth. Notably, the MS prevalence in the population born in Iran was at least as high as in the general population of Sweden (men: PR = 1.10, 95% CI 0.81-1.46, p = 0.537, women: PR = 1.18, 95% CI 0.97-1.44, p = 0.855) and more than twice as high as in Isfahan, Iran (men: PR = 3.06 (95% CI 2.26-4.06), p < 0.001, women: PR = 2.21 (95% CI 1.81-2.68), p < 0.001). Conclusions: The MS prevalence increased in migrants who moved to Sweden from countries with a lower MS risk. In the Iranian immigrant population the prevalence exceeded that in the general population of Sweden. This indicates that Iranians carry genetic factors that contribute to a higher MS risk when environmental-lifestyle MS risk factors change.
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| 4. |
- Ahlgren, Cecilia, 1946, et al.
(författare)
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High nationwide prevalence of multiple sclerosis in Sweden.
- 2011
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 17:8, s. 901-8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Few nationwide multiple sclerosis (MS) prevalence studies have been published. In Scandinavia, the nationwide MS prevalence was 173/100,000 in Denmark 2005 and 100/100,000 in Iceland 1990. Objective: Our aim with the present study was to determine the first population-based nationwide MS prevalence in Sweden, based on observed, registered patients and to investigate the presence of a north-south gradient of MS prevalence. Methods: By linking the Swedish National Patient Register, the Swedish Multiple Sclerosis Registry and the Swedish Total Population Register we obtained the number of patients who were diagnosed with MS before 2009, and who were registered, alive and resident in Sweden on the prevalence date 31 December 2008. We calculated the gender-specific nationwide MS prevalence in 1-year age intervals. The relationship between MS risk and latitude was studied in a logistic regression model including all individuals in the population of Sweden. Results: The number of registered MS patients in 2008 was 17,485 out of the Swedish population of 9,256,347. The overall MS prevalence was 188.9/100,000 (95% CI 186.1-191.7), 113.4 (95% CI 110.3-116.5) for men and 263.6 (95% CI 258.9-268.3) for women. The female to male ratio was 2.35:1. The prevalence of MS significantly increased for each degree of north latitude with 1.5% in men (p = 0.013) and 1% in women (p = 0.015). Conclusions: The MS prevalence of 188.9/100,000 in Sweden is among the highest nationwide prevalence estimates in the world. In Sweden, the risk of MS increases with increasing north latitude for both men and women.
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| 5. |
- Ahlgren, Cecilia, 1946, et al.
(författare)
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High risk of MS in Iranian immigrants in Gothenburg, Sweden.
- 2010
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Ingår i: Multiple sclerosis journal. - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 16:9, s. 1079-1082
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In this study we investigated the risk of multiple sclerosis (MS) in migrants who had moved from Iran to Gothenburg, Sweden. METHODS: Patients born in Iran were retrieved from a population-based cohort, which included 534 MS and clinically isolated syndrome patients, born 1959-1990, aged 10-39 years at disease onset in Gothenburg. The expected versus observed number of migrants from Iran was calculated. RESULTS: The MS risk in the Iranian migrants in Gothenburg was several times higher than in Isfahan, Iran (hazard ratio 3.88, 95% confidence interval 2.17-6.40). Compared with the general population of Gothenburg, the observed number of 17 Iranian patients was higher than the expected value of 9.89 (hazard ratio 1.72, 95% confidence interval 1.00-2.75). CONCLUSION: Migration from a medium-risk to a high-risk area may increase the MS risk to that of the high-risk area.
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| 6. |
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| 7. |
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| 8. |
- Alping, P., et al.
(författare)
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Effectiveness of initial MS treatments in the COMBAT-MS trial : injectables, dimethyl fumarate, natalizumab and rituximab
- 2021
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 27:Suppl. 2, s. 21-22
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Direct comparisons across multiple disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS) are valuable in clinical decision making. COMBAT-MS (NCT03193866) is an observational drug trial capturing data on clinical relapses, lesions on magnetic resonance imaging (MRI), Expanded Disability Status Scale (EDSS), and drug survival, at all Swedish university clinics.Objective: Compare the effectiveness of the most common initial MS therapies in Sweden.Methods: All first-ever MS treatments with injectables (INJ, interferon-β/glatiramer acetate), dimethyl fumarate (DMF), natalizumab (NTZ), and rituximab (RTX), started 2011-01-01 to 2020-12-14, were identified with prospectively recorded outcome data in the Swedish MS Register. Follow-up continued even if the therapy ended. Missing data were imputed using multiple imputation and potential confounding was adjusted for using stabilized inverse probability of treatment weighting with baseline variables: age, sex, MS duration, geographical region, EDSS, and relapses. All comparisons are made against RTX.Results: We included 1936 first-ever therapy episodes: 856 INJ, 341 DMF, 270 NTZ, and 469 RTX. Baseline characteristics differed by DMT, with natalizumab having the youngest patients, shortest MS duration, and the most previous relapses.After adjustment, the hazard ratio (HR) for first relapse vs RTX was for INJ 5.9 (95% confidence interval 3.7; 9.5), DMF 2.8 (1.7; 4.8), and NTZ 1.8 (1.0; 3.3). Similarly, the relative three-year lesion rate was for INJ 6.06 (3.75; 9.80), DMF 3.52 (2.01; 6.17), and NTZ 2.03 (1.14; 3.64). EDSS differences at three years were only marginally different: INJ 0.25 (0.06; 0.44), DMF 0.05 (-0.16; 0.26), and NTZ 0.00 (-0.23; 0.24). In contrast, HR for treatment discontinuation was marked: INJ 32.5 (19.0; 55.7), DMF 20.2 (11.5; 35.4), and NTZ 16.2 (8.9; 29.5).Conclusions: In treatment-naïve patients, RTX was associated with the lowest risk of relapses and MRI lesions, and by far the lowest probability of switching to a second therapy. In contrast, EDSS at 3 years was similar for RTX, DMF, and NTZ, and only slightly higher for INJ. The apparent difference in effectiveness between NTZ and RTX could possibly be explained by the vulnerable period after switching from NTZ, mainly due to JC virus positivity. These findings underscore the importance of tracking long-term outcomes from first DMT start, while considering subsequent therapy switches.
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| 9. |
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| 10. |
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| 11. |
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| 12. |
- Anna Karin, Hedström, et al.
(författare)
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The impact of bariatric surgery on disease activity and progression of multiple sclerosis : A nationwide matched cohort study
- 2022
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 28:13, s. 2099-2105
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Surgical outcomes in patients with multiple sclerosis (MS) following metabolic surgery appear to be similar compared to those of the general bariatric population.OBJECTIVE: To study the impact of metabolic surgery on the clinical course of MS.METHODS: Using data from the Scandinavian Obesity Surgery Registry and the Swedish Multiple Sclerosis register, we compared disease outcomes in 122 cases of MS who had undergone metabolic surgery with those of 122 cases of MS without surgery, matched by a two-staged Propensity score match, including age at disease onset, sex, MS phenotype, body mass index, and preoperative severity of MS as measured by the Expanded Disability Status Scale.RESULTS: The time to 6-month confirmed disability progression during the first five years postbaseline was shorter among the surgical patients (hazard ratio (HR) = 2.31, 95% confidence interval (CI) = 1.09-4.90; p = 0.03). No differences were observed regarding postoperative annual relapse rate (p = 0.24) or time to first postoperative relapse (p = 0.52).CONCLUSION: Although metabolic surgery appears to be a safe and efficient treatment of obesity in patients with MS, the clinical course of the disease might be negatively affected. Long-term nutritional follow-up after surgery and supplementation maintenance are crucial, particularly among those with preoperative deficits.
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| 13. |
- Arrambide, G, et al.
(författare)
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Aggressive multiple sclerosis (2): Treatment
- 2020
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 26:9, s. 1045-1063
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Tidskriftsartikel (refereegranskat)abstract
- The natural history of multiple sclerosis (MS) is highly heterogeneous. A subgroup of patients has what might be termed aggressive MS. These patients may have frequent, severe relapses with incomplete recovery and are at risk of developing greater and permanent disability at the earlier stages of the disease. Their therapeutic window of opportunity may be narrow, and while it is generally considered that they will benefit from starting early with a highly efficacious treatment, a unified definition of aggressive MS does not exist and data on its treatment are largely lacking. Based on discussions at an international focused workshop sponsored by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), we review our current knowledge about treatment of individuals with aggressive MS. We analyse the available evidence, identify gaps in knowledge and suggest future research needed to fill those gaps. A companion paper details the difficulties in developing a consensus about what defines aggressive MS.
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| 14. |
- Augutis, Kristin, et al.
(författare)
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Cerebrospinal fluid biomarkers of β-amyloid metabolism in multiple sclerosis.
- 2013
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 19:5, s. 543-52
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid precursor protein (APP) and amyloid β (Aβ) peptides are intensely studied in neuroscience and their cerebrospinal fluid (CSF) measurements may be used to track the metabolic pathways of APP in vivo. Reduced CSF levels of Aβ and soluble APP (sAPP) fragments are reported in inflammatory diseases, including multiple sclerosis (MS); but in MS, the precise pathway of APP metabolism and whether it can be affected by disease-modifying treatments remains unclear.
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| 15. |
- Axelsson, Markus, 1975, et al.
(författare)
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Immunosuppressive therapy reduces axonal damage in progressive multiple sclerosis.
- 2014
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - London, United Kingdom : SAGE Publications. - 1477-0970 .- 1352-4585. ; 20:1, s. 43-50
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In progressive multiple sclerosis (PMS), disease-modifying therapies have not been shown to reduce disability progression. OBJECTIVE: The impact from immunosuppressive therapy in PMS was explored by analyzing cerebrospinal fluid (CSF) biomarkers of axonal damage (neurofilament light protein, NFL), astrogliosis (glial fibrillary acidic protein, GFAP), and B-cell regulation (CXCL13). METHODS: CSF was obtained from 35 patients with PMS before and after 12-24 months of mitoxantrone (n=30) or rituximab (n=5) treatment, and from 14 age-matched healthy control subjects. The levels of NFL, GFAP, and CXCL13 were determined by immunoassays. RESULTS: The mean NFL level decreased by 51% (1781 ng/l, SD 2018 vs. 874 ng/l, SD 694, p=0.007), the mean CXCL13 reduction was 55% (9.71 pg/ml, SD 16.08, vs. 4.37 pg/ml, SD 1.94, p=0.008), while GFAP levels remained unaffected. Subgroup analysis showed that the NFL reduction was confined to previously untreated patients (n=20) and patients with Gd-enhancing lesions on magnetic resonance imaging (n=12) prior to study baseline. CONCLUSIONS: Our data imply that 12-24 months of immunosuppressive therapy reduces axonal damage in PMS, particularly in patients with ongoing disease activity. Determination of NFL levels in CSF is a potential surrogate marker for treatment efficacy and as endpoint in phase II trials of MS.
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| 16. |
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| 17. |
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| 18. |
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| 19. |
- Baarnhielm, M, et al.
(författare)
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Fatty fish intake is associated with decreased occurrence of multiple sclerosis
- 2014
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 20:6, s. 726-732
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Tidskriftsartikel (refereegranskat)abstract
- High vitamin D levels have been associated with a decreased risk of developing multiple sclerosis (MS). The most important source of dietary vitamin D is fatty fish. Objective: The objective of this paper is to investigate the association between fish consumption and the risk of MS, including the interaction between fish intake and ultraviolet radiation (UVR) exposure habits. Methods: This study is based on the project Epidemiological Investigation of MS (EIMS), which is a Swedish population-based case-control study. The analysis included 1879 incident cases of MS and 4135 controls. Subjects who reported high fatty fish intake were compared regarding occurrence of MS with those who reported low intake by calculating odds ratio (OR) with 95% confidence interval (CI). Results: Frequent fatty fish intake was associated with decreased occurrence of MS (adjusted OR 0.82 (95% CI 0.68-0.98). There was no significant association between intake of lean fish and MS. Conclusion: Fatty fish intake might decrease the risk for MS. A hypothetical explanation is that intake of fatty fish may compensate for vitamin D deficiency that is associated with increased MS risk.
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| 20. |
- Barletta, VT, et al.
(författare)
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Evidence of diffuse cerebellar neuroinflammation in multiple sclerosis by 11C-PBR28 MR-PET
- 2020
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 26:6, s. 668-678
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Tidskriftsartikel (refereegranskat)abstract
- Activated microglia, which can be detected in vivo by 11C-PBR28 positron emission tomography (PET), represent a main component of MS pathology in the brain. Their role in the cerebellum is still unexplored, although cerebellar involvement in MS is frequent and accounts for disability progression. Objectives: We aimed at characterizing cerebellar neuroinflammation in MS patients compared to healthy subjects by combining 11C-PBR28 MRI-Positron Emission Tomography (MR-PET) with 7 Tesla (T) MRI and assessing its relationship with brain neuroinflammation and clinical outcome measures. Methods: Twenty-eight MS patients and 16 healthy controls underwent 11C-PBR28 MR-PET to measure microglia activation in normal appearing cerebellum and lesions segmented from 7 T scans. Patients were evaluated using the Expanded Disability Status Scale and Symbol Digit Modalities Test. 11C-PBR28 binding was assessed in regions of interest using 60–90 minutes standardized uptake values normalized by a pseudo-reference region in the brain normal appearing white matter. Multilinear regression was used to compare tracer uptake in MS and healthy controls and assess correlations with clinical scores. Results: In all cerebellar regions examined, MS patients showed abnormally increased tracer uptake, which correlated with cognitive and neurological disability. Conclusion: Neuroinflammation is widespread in the cerebellum of patients with MS and related to neurological disability and cognitive impairment.
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| 21. |
- Beiske, A G, et al.
(författare)
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Health-related quality of life in secondary progressive multiple sclerosis.
- 2007
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 13:3, s. 386-92
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Tidskriftsartikel (refereegranskat)abstract
- Common disability scales in multiple sclerosis (MS) are often weighted towards physical disability. Non-motor symptoms such as depression, fatigue and pain substantially influence wellbeing in MS. Health-related quality of life (HRQoL) measures the broader impact of MS and might indicate less obvious disease burdens. We analysed HRQoL, using the Nottingham Health Profile Part I (NHP-I), among 345 secondary progressive MS (SPMS) patients participating in a randomized trial of interferon-beta1a (IFN-beta1a), 22 mug subcutaneously weekly, or matching placebo. The results did not reveal any beneficial effect of IFN-beta1a in any outcome measure. NHP-I sub- and sum scores were compared for 217 population controls and correlated with demographic and clinical disease variables. SPMS patients had lower NHP-I sum and all subscores than the controls. Patients experiencing disease progression reported worse NHP-I sum scores. Increased fatigue, Expanded Disability Status Scale (EDSS) and Arm Index scores were independently associated with reduction in several NHP-I subscores. SPMS patients had significantly lower HRQoL than controls and physical disability (EDSS and Arm Index), disease progression and fatigue strongly influenced this. MS.
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| 22. |
- Beiske, A. G., et al.
(författare)
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Health-related quality of life in secondary progressive multiple sclerosis
- 2007
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Ingår i: Multiple Sclerosis Journal. - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 13:3, s. 386-392
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Tidskriftsartikel (refereegranskat)abstract
- Common disability scales in multiple sclerosis (MS) are often weighted towards physical disability. Non-motor symptoms such as depression, fatigue and pain substantially influence wellbeing in MS. Health-related quality of life (HRQoL) measures the broader impact of MS and might indicate less obvious disease burdens. We analysed HRQoL, using the Nottingham Health Profile Part I (NHP-I), among 345 secondary progressive MS (SPMS) patients participating in a randomized trial of interferon-beta 1a (IFN-beta 1a), 22 mu g subcutaneously weekly, or matching placebo. The results did not reveal any beneficial effect of IFN-beta 1a in any outcome measure. NHP-I sub- and sum scores were compared for 217 population controls and correlated with demographic and clinical disease variables. SPMS patients had lower NHP-I sum and all subscores than the controls. Patients experiencing disease progression reported worse NHP-I sum scores. Increased fatigue, Expanded Disability Status Scale (EDSS) and Arm Index scores were independently associated with reduction in several NHP-I subscores. SPMS patients had significantly lower HRQoL than controls and physical disability (EDSS and Arm Index), disease progression and fatigue strongly influenced this. MS influenced subdimensions such as pain, sleep and emotional reactions. Increased focus on optimizing symptomatic treatment and psychosocial patient care could improve patients' HRQoL.
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| 23. |
- Bergkvist, My, et al.
(författare)
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No evidence for genetic linkage between development of multiple sclerosis and components of the IFN system and the JAK-STAT pathway.
- 2004
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Ingår i: Multiple Sclerosis Journal. - : SAGE Publications. - 1477-0970 .- 1352-4585. ; 10:1, s. 87-88
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS). Several observations suggest that the interferon system may be of interest in the study of MS development. To investigate whether polymorphism in components of the IFN system and the JA K-STAT pathway influence susceptibility to MS, we performed a linkage analysis between polymorphic loci in or close to the IFN gamma, IFN gamma recepto r, IFN alpha/beta recepto r, JA K 1, STAT 1 and STAT 3 genes in 27 Swedish families with at least two members having MS. Tests for transmission disequilibrium and nonparametric linkage analysis gave negative results. We found no evidence for linkage between MS and any of these loci.
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| 25. |
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