| 1. |
- Burkill, S., et al.
(författare)
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MS and the association of the DQB1*0302 allele with pain
- 2019
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 25:Suppl. 2, s. 437-438
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: There is an established association between multiple sclerosis (MS) and pain treatment, in particular neuropathic pain. Murine models have confirmed an association between carriage of the DQB1*0302 allele and development of neuropathic pain-like behavior after peripheral nerve injury. Observational studies in patients with spinal disc herniation identified an association between the DQB1*0302 allele and pain, indicating a possible link in humans. This HLA allele has not been previously investigated for its influence on susceptibility to pain in MS patients.Aim: To determine whether the DQB1*0302 genotype is associated with pain in MS patients or member of the general population without MS.Methods: Three Swedish studies (EIMS, GEMS and IMSE) were combined in which enrolled MS patients were matched with 1-2 randomly selected individuals without MS by sex, age and region of residence. Register data was obtained and prescriptions for pain and neuropathic pain were identified as proxy measures for pain. Blood samples were collected and genotyped. Individuals were included if genotype data were available (MS=3877, non-MS=4548). Logistic regression had pain medication use as the outcome, to examine associations with genotype, stratified by MS status.Results: Homo- or heterozygous MS patients with the DQB1*0302 allele had no significantly increased risk of pain (adjusted OR 1.02, 95% CI 0.85-1.23) or neuropathic pain (OR 1.14, 0.97-1.34) compared with MS patients without the allele. Non-MS comparators carrying at least one allele had an increased risk of pain (OR 1.18, 1.03-1.35). Additionally, a zygosity effect appeared present particularly for women in the non-MS cohort, as homozygous individuals had a higher risk of pain compared with heterozygotes. No association was observed for MS patients.Conclusions: The DQB1*0302 allele was associated with increased risk of pain among the non-MS cohort. Zygocity also impacted on pain risk in this cohort, particularly for women. The same was not observed in MS patients, for which no increased risk was detected. In view of previous data, immune functions seem to be involved in the development of pain and the observed associa-tion is likely due to peripheral nerve injuries or peripheral neu-ropathies. The allele was not associated with pain in the MS population, which often stems from CNS lesions.
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| 2. |
- Roshanisefat, H., et al.
(författare)
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All-cause mortality following a cancer diagnosis amongst multiple sclerosis patients : a Swedish population-based cohort study
- 2015
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Ingår i: European Journal of Neurology. - : Blackwell Publishing. - 1351-5101 .- 1468-1331. ; 22:7, s. 1074-1080
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: A reduced cancer risk amongst patients with multiple sclerosis (MS) has been reported. Theoretically, this could represent a genuine reduction in risk or, alternatively, diagnostic neglect', where cancer is undiagnosed when symptoms are misattributed to MS.Objective: Assess all-cause mortality risk following a cancer diagnosis in patients with MS compared with a cohort without MS.Patients: A cohort of MS patients (n=19364) and a cohort of the general population (n=192519) were extracted from national Swedish registers from 1969 to 2005. All-cause mortality after cancer in MS was compared with the general population. Poisson regression analysis was conducted in the MS and non-MS cohorts separately. The models were adjusted for follow-up duration, year at entry, sex, region and socioeconomic index. The two cohorts were combined and differences in mortality risk were assessed using interaction testing.Results: The adjusted relative risk (and 95% confidence interval) for all-cause mortality following a cancer diagnosis in MS patients (compared with MS patients without cancer) is 3.06 (2.86-3.27; n=1768) and amongst those without MS 5.73 (5.62-5.85; n=24965). This lower magnitude mortality risk in the MS patients was confirmed by multiplicative interaction testing (P<0.001).Conclusions: A consistent pattern of lower magnitude of all-cause mortality risk following cancer in MS patients for a range of organ-specific cancer types was found. It suggests that cancer diagnoses tend not to be delayed in MS and diagnostic neglect is unlikely to account for the reduced cancer risk associated with MS. The lower magnitude cancer risk in MS may be due to disease-associated characteristics or exposures.
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| 3. |
- Roshanisefat, H., et al.
(författare)
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Multiple sclerosis clinical course and cardiovascular disease risk : Swedish cohort study
- 2014
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Ingår i: European Journal of Neurology. - : Wiley-Blackwell. - 1351-5101 .- 1468-1331. ; 21:11, s. 1353-e88
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Cardiovascular disease (CVD) risk amongst multiple sclerosis (MS) patients appears raised, but few studies have examined CVD risk amongst an unselected MS patient group. MS course may be relevant for CVD risk. Our aim was to assess CVD risk and variation by course in MS patients.Methods: The Multiple Sclerosis Register identified 7667 patients who received an MS diagnosis between 1964 and 2005. They were matched by age, period, region and sex with 76045 members of the general population without MS using Swedish registers. Poisson regression compared the two cohorts to estimate the relative risk for CVD, overall, as well as grouped and individual CVD diagnoses.Results: MS patients had an increased adjusted relative risk (with 95% confidence intervals; number of MS cohort events) for CVD of 1.31 (1.22-1.41; n=847), with some variation by course: relapsing-remitting 1.38 (1.17-1.62; n=168); secondary progressive 1.30 (1.18-1.53; n=405) and primary progressive 1.15 (0.93-1.41; n=108). The association for the relapsing-remitting course was not significant after excluding the first year of follow-up. Overall incidence rates per 1000 person-years for CVD are 11.8 (11.06-12.66) for the MS cohort and 8.8 (8.60-9.05) for the non-MS cohort. The most pronounced association was for deep vein thrombosis: relapsing-remitting 2.16 (1.21-3.87; n=14), secondary progressive 3.41 (2.45-4.75; n=52) and primary progressive 3.57 (1.95-6.56; n=15). MS was associated with ischaemic stroke but largely during the first year of follow-up. MS was associated with a decreased relative risk for angina pectoris and atrial fibrillation.Conclusions: There is a significantly increased relative risk for CVD in MS, particularly for venous thromboembolic disorders in progressive MS, suggesting immobility as a possible factor. An increased frequency of ischaemic stroke in MS is most probably due to surveillance bias resulting from diagnostic investigations for MS. There is no increased relative risk for ischaemic heart disease in MS and atrial fibrillation appears to be less common than amongst the general population. Click for the corresponding questions to this CME article.
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| 4. |
- Roshanisefat, H., et al.
(författare)
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Shared genetic factors may not explain the raised risk of comorbid inflammatory diseases in multiple sclerosis
- 2012
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Ingår i: Multiple Sclerosis Journal. - London, United Kingdom : Sage Publications. - 1352-4585 .- 1477-0970. ; 18:10, s. 1430-1436
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Tidskriftsartikel (refereegranskat)abstract
- Background: Comorbid inflammatory conditions in multiple sclerosis (MS) patients suggest shared risks with MS.Objective: To estimate if the risk of immune-mediated disease in MS patients and their parents is increased.Methods: Swedish register data were analysed using Cox regression to estimate immune-mediated disease risk among 11284 fathers and 12006 mothers of MS patients, compared with 123158 fathers and 129409 mothers of index subjects without MS. Similar analyses were conducted among 20276 index subjects with MS and 203951 without.Results: Parents of patients with MS did not have a significantly altered immune-mediated disease risk. Patients with MS had a consistently raised risk for several immune-mediated diseases: ulcerative colitis, Crohn's disease, type 1 diabetes, psoriasis, polyarthritis nodosa and pemphigoid. The risk was more pronounced for diseases diagnosed subsequent to MS onset.Conclusion: The increased occurrence of other immune-mediated diseases in MS patients may not be due to shared genetic factors and surveillance bias is likely to be the main or possibly the entire explanation. If not entirely explained by surveillance bias, a modestly raised occurrence of comorbid diseases may be due to shared environmental risks or factors related to MS disease characteristics.
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| 5. |
- Smith, K. A., et al.
(författare)
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Burden of comorbid diseases among MS patients in Sweden
- 2019
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 25:Suppl. 2, s. 646-646
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: A raised risk for several comorbid diseases among MS patients has been identified. Most previous studies examined diseases separately rather than considering the overall burden of comorbidity. Multiple comorbidities may have important implica-tions for clinicians managing MS patients.Aims: To describe the lifetime burden of comorbid diseases among MS patients and the rate of these diseases compared with the general population in Sweden.Methods: MS patients identified using the MS Register and the Patient Register (PR) between 1964-2012 (n=25476) were matched by sex, age and county of residence with up to 10 general population comparators (n=251170). Prevalent and incident diag-noses of diseases other than MS for seven diseases categories were identified using the PR between 1987-2012. The total num-ber of comorbid diseases were compared using chi-square tests and prevalence rate ratios (PRR) were calculated. Hazard ratios (HR) were estimated using Cox regression and flexible non-para-metric survival models with age as the underlying time scale, MS as exposure, an additional comorbid disease as the outcome, adjusted for matching variables, education, number of previous comorbid diseases, and duration since study entry.Results: The proportion of MS patients with 1,2 or 3+ comorbid disease diagnoses was greater than in the comparison cohort across all age groups (p< 0.001). The largest PRR (range 1.22-9.99) were among younger age groups (6-18,19-40,41-60 years) in autoim-mune, cardiovascular, diabetes and seizure disease categories. Additionally, PRR were elevated in depression and respiratory dis-eases, but not for renal diseases. PRR between 61-80 and 81-100 years were reduced compared to younger groups across all comorbid diseases, but remained elevated for respiratory, seizure and renal dis-eases. The adjusted HR for an additional diagnosis in MS patients was 1.7 (95% CI 1.66-1.75). Flexible modelling showed signifi-cantly higher risk for all ages of an additional disease diagnosis in MS patients; twice the risk (95% CI 1.8-2.2) up to age 35 years and decreasing with age to 1.3 (95% CI 1.5-1.25) over age 80 years.Conclusions: MS patients in Sweden experience an increased burden of comorbidity and tend to be diagnosed with these dis-eases at an earlier age than the general population. This increased disease burden demonstrates the clinical reality of treating MS, indicating the need for integrated treatment approaches over sev-eral medical specialties.
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| 6. |
- Smith, K. A., et al.
(författare)
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Rapid discontinuation of baclofen as a treatment for spasticity among MS patients with incident and prevalent diagnoses
- 2022
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 28:Suppl. 3, s. 663-663
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Baclofen is the first line drug choice for spasticity; a common MS feature influencing function and quality of life. Its prescription and discontinuation patterns among persons with MS (pwMS) are described incompletely.Objective & Aim: To characterize baclofen prescription patterns in a nationwide cohort study of people with prevalent (pMS) and incident (iMS) MS.Method: Data was linked from the Swedish MS register and national health registers for PwMS aged 18-65 years at diagnosis. Baclofen initiation was identified using the Prescription Drug Register excluding prescriptions from 1 July 2005—30 June 2006 (1st year of the register) and before MS diagnosis, to identify new prescriptions. Follow-up was from first dispensation until discontinuation, 31 Dec 2014 or death. Discontinuation was defined as no renewed prescription within gaps of 90, 150, or 180 days from last dispensation. Failure functions were plotted and Cox regression estimated hazard ratios.Results: A total of 188 (10%) of iMS (N=1826) and 628 (19%) of pMS (N=3519) received a new baclofen prescription. Discontinuation among iMS and pMS was similar using different time gaps: 49% (CI 0.42-0.57) iMS and 51% (CI 0.48-0.56) pMS discontinued within 150 days and approx. 90% discontinued overall. Approx. 65% of individuals discontinued within 1-year and 80% by 2-years. iMS with progressive course were treated for longer than relapsing course, and though similar among pMS differences between courses were less evident. Stratifying by EDSS (0-2.5, 3.0-5.5 and 6+) at baclofen initiation showed that PwMS with higher EDSS persisted longer than EDSS 0-2.5 but discontinuation was high among all groups. Cox regression showed EDSS associated with discontinuation, with iMS of EDSS 3-5.5 and 6+ 72% (CI 0.44-1.16) and 61% (CI 0.35-1.05); pMS 78% (CI 0.59-1.03) and 65% (CI 0.49-0.85) less likely to discontinue. No other MS characteristics (duration, age, course, sex, diagnosis/onset age), depression or seizures were associated. Though not statistically significantly associated, females and those with a progressive course were less likely to discontinue.Conclusions: Baclofen has similarly high discontinuation rates among patients with iMS and pMS, possibly reflecting low tolerability or efficacy. Only increased disability indicated by higher EDSS was associated with longer baclofen persistence highlighting the need for more tolerable and efficacious pharmacological treatments for spasticity in PwMS.
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| 7. |
- Smith, K., et al.
(författare)
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Central nervous system infections in adolescence and MS risk after age 20 years
- 2020
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 26:3 Suppl., s. 42-42
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Infectious agents in MS etiology have been previously investigated. Theories of pathogenic mechanisms include molecular mimicry or activation of macrophages and natural killer cells with subsequent infiltration of the blood brain barrier. Epstein-Barr virus (EBV) infection often signaled by infectious mononucleosis (IM) is a notable MS risk factors, but other infections including Chlamydia pneumoniae, among others, are also associated with MS. Adolescence is a potentially critical period for susceptibility MS and asso-ciations with exposures in adolescence such as concussion, pneumonia, BMI, and EBV/IM have been found. No studies to our knowledge have examined CNS infection as a risk factor for MS.Objectives: To determine if CNS infection in childhood (age 0-11 years) or adolescence (age 11-20) is associated with MS risk after age 20 years.Methods: A cohort born in Sweden between 1970-1994 followed until 31 December 2014, was identified using the Total Population Register, excluding those diagnosed with MS before age 20 years (y) (N=2,422,969). ICD codes from the National Patient Register identified diagnoses of MS after age 20y (n=4,022) (two or more diagnoses), and CNS infection (bacterial and viral) before age 20y. Diagnoses of IM, pneumonia, and other bacterial or viral infections were identified. Infections were classified as present/absent at 0-10y or 11-20y. Cox regression was used to determine associations of CNS infection with MS, with follow-up from age 20y to first MS diagnosis, adjusting for gastrointestinal, genitourinary, respiratory, skin, other infections, sex and parental socioeconomic position.Results: CNS infection before age 11y was not associated with MS. CNS infection in adolescence was statistically significantly associated with increased MS risk producing an adjusted hazard ratio of 2.80 (95%CI 1.90-4.12). Excluding encephalomyelitis (as this includes acute disseminated encephalitis, often a precursor of MS) the estimate was 1.85 (95%CI 1.11-3.07): an accurate estimate of risk lies between these two hazard ratios. Further adjustment for other infec-tions did not alter the estimates notably.Conclusions: This novel finding of CNS infection in adolescence associated with MS risk suggests such infections may cause cellular damage in the CNS triggering autoimmune processes pertinent to multiple sclerosis pathogenesis. It also adds to the evidence of a critical susceptibility period in adolescence for MS initiation.
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