| 1. |
- Brand, Judith S, et al.
(författare)
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Risk of serious infections in multiple sclerosis patients by disease course and disability status : Results from a Swedish register-based study
- 2022
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Ingår i: Brain, behavior, & immunity - health. - : Elsevier. - 2666-3546. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Background and objectives: Serious infections are an emerging concern with increasing use of potent immunomodulation in multiple sclerosis (MS), but the extent to which MS disease features influence infectious susceptibility is poorly characterized. The objective of this study was to assess the associations of MS disease course and disability status with risk of serious infections.Methods: A cohort of 8660 MS patients was individually matched on age, sex and region of residence with 86,600 people without MS from the general population using national registers in Sweden. The study period was from 1996 to 2012, with follow-up until December 31, 2014. The main outcomes were infection as the underlying or contributory cause of death or infection-related hospital admission identified in the Cause of Death and Patient registers. MS disease course (relapsing-remitting or progressive disease) and Expanded Disability Status Scale (EDSS) score (six and over or below six) were extracted from the MS Register Hazard ratios (HRs) for any serious infection were estimated using flexible parametric models.Results: During a median follow-up of 9.6 years (interquartile range = 5.5-13.5 years), 1337 MS patients experienced a serious infection. Compared with individually matched people without MS, risk of serious infection was greater for progressive disease (HR = 3.80; 95% CI 3.52: 4.09) than relapsing-remitting disease (HR = 1.77; 95% CI: 1.62:1.93). A similar pattern of risk was seen for dichotomised EDSS score (HR = 4.26; 95% CI 3.87: 4.70 for EDSS 6.0-9.5 and HR = 1.30; 95% CI 1.1853: 1.43 for EDSS 0.0-5.5). Overall, associations with greater disability did not notably differ by immunomodulatory therapy use, but associations with lower disability were more pronounced in patients receiving these therapies.Conclusions: Disease course or EDSS score (which may be more readily available than MS course in some patients) should be considered in individual management and monitoring of MS patients, including assessing benefit-risk of therapies that influence general immune function.
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| 2. |
- Burkill, Sarah M., et al.
(författare)
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Pain and Painkiller Use Among Multiple Sclerosis Patients in Sweden
- 2017
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Ingår i: Pharmacoepidemiology and Drug Safety. - : John Wiley & Sons. - 1053-8569 .- 1099-1557. ; 26:Suppl. 2, s. 634-634
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Multiple sclerosis is an autoimmune disease which leads to demyelination and subsequent damage of axons and neurons. Pain is known to commonly affect MS patients, however the clinical characteristics of this pain are not fully described. Prescribed pain medication identifies more severe and chronic pain and different drug types can be used to identify other pain characteristics.Objectives: To assess whether MS patients in Sweden are at increased risk of receiving medication for pain relative to non-MS comparators. We aim to study overall pain, neuropathic pain, musculoskeletal pain and migraine.Methods: This cohort study using data on 5,555 MS patients in Sweden individually matched to 5,555 non-MS Swedish residents on sex, year of birth and place of residence at the time of MS diagnosis. We used Cox PH models using date of entry or 1stJuly 2006 as the beginning of follow up, whichever occurred later, and end of study was date of death, date of prescription of a painkiller or December 31st 2014, whichever occurred first. Painkillers were identified through relevant ATC codes. For neuropathic pain, pregabalin, gabapentin, amitriptyline, capsaicin or nortriptyline were used for identification, and for migraine prescriptions of anti-migraine preparations were included in the outcome. Musculoskeletal pain was identified primarily through topical products for joint and muscular pain.Results: Cox PH models showed MS patients to be at a 2.43 (CI 2.31–2.55) times increased risk of being prescribed any painkiller. The risk increased to 5.63 (CI 5.03–6.31) for neuropathic painkillers, however there was no significant difference for musculoskeletal painkillers (RR = 0.92 (CI 0.79–1.07)). MS patients were at a 1.28 (CI 1.10-1.50) times increased risk of being prescribed anti-migraine preparations. Restricting the data to MS patients showed that exposure to neuropathic painkillers was present in 32.8% of MS patients, and is associated with lower educational attainment and female sex. Conclusions: MS patients are at significantly increased risk of pain overall, with a particularly elevated risk for neuropathic pain. It seems that lower educational attainment and female sex are risk factors of neuropathic pain. However, the reason for this is not fully understood.*We would like to acknowledge the funding from the Science for Life - Astra Zeneca collaborative grant that supported this research
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| 3. |
- Burkill, Sarah, et al.
(författare)
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Mortality trends for multiple sclerosis patients in Sweden from 1968 to 2012
- 2017
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Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 89:6, s. 555-562
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess trends in mortality and causes of death for patients with multiple sclerosis (MS) relative to those without MS in Sweden.Methods: Patients with an MS diagnosis in Sweden between 1964 and 2012 were identified with the Patient Register and the Multiple Sclerosis Register. For this cohort study, each patient with MS (n = 29,617) was matched with 10 individuals without MS (n = 296,164) on sex, year of birth, vital status, and region of residence at the time of MS diagnosis with the Total Population Register. The Causes of Death Register was used to identify causes of death. Cox proportional hazard models were constructed to assess whether risk of mortality was increased for patients with MS.Results: The hazard ratio (HR) for patients with MS was 2.92 (95% confidence interval [CI] 2.86-2.99) for all-cause mortality over the entire study period. The largest differences between the cohorts were death resulting from respiratory (HR 5.07, 95% CI 4.87-5.26) and infectious (HR 4.07, 95% CI 3.70-4.47) diseases. Overall and for each specific cause, there have been improvements for the MS group and a subsequent reduction in the HR. The HR decreased from 6.52 (95% CI 5.79-7.34) for the period of 1968 to 1980 to 2.08 (95% CI 1.95-2.22) for the time period of 2001 to 2012. An interaction between time period and MS exposure showed that the decrease in mortality over time was statistically significant, with a larger decrease for patients with MS than their matched comparators.Conclusions: There has been a substantial improvement in mortality overall and for each specified cause of death for patients with MS compared with individuals without MS; however, large differences still remain.
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| 4. |
- Burkill, Sarah, et al.
(författare)
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Pharmacological Treatments Preceding Diagnosis Of Progressive Multifocal Leukencephalopathy
- 2016
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Ingår i: Pharmacoepidemiology and Drug Safety. - : Wiley-Blackwell. - 1053-8569 .- 1099-1557. ; 25:Suppl. 3, s. 496-497
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Progressive multifocal leukencephalopathy (PML) is a rare, often fatal viral disease, which affects the white matter of the brain. It is caused by John Cunningham (JC) polyomavirus, which is present in most people and is usually harm-less. For immunocompromised persons, such as those who are taking immunosuppressive treatments, the risk of JC virus causing PML is increased, although still rare. As PML diagnosis is not always accurate, epidemiology of PML, including the true incidence and patient characteristics, is incompletely described.Objectives: To identify pharmacological treatments preceding diagnosis of definitive, probable and possible PML, after excluding incorrect PML diagnoses by medical record review.Methods: Patients with a PML diagnosis in Sweden between 1988 and 2013 were identified through the Patient register using ICD 9 code 046D and ICD 10code A81.2 (n = 281). Medical records were reviewed and information on clinical characteristics and pharmacological treatments were collected. Each of the diagnoses was determined as definite PML, possible PML, probable PML or non-PML based on the consensus statement for the AAN neuroinfectious disease section published in 2013. (PMCID: 3662270).Results: Medical records for 251 patients (89%) were available and examined. In total, 84 (33%) of the 251 PML diagnoses were confirmed. For those with a record of being exposed to immunosuppressant drugs, 60 (65%) of the 92 records were confirmed as being definite PML. Among 12 patients exposed to rituximab 11 (92%) had definite and 1 (8%) had probable PML. For the 9 natalizumab users, 8 (89%) had definite PML and 1 (11%) was diagnosed incorrectly.Conclusions: A substantial proportion of PML diagnoses recorded in Sweden are incorrect, however amongst those exposed to immunosuppressants such as rituximab and natalizumab the majority of diagnoses are correct. Assessing immunosuppressive drug history could be an important part of the diagnostic processes for PML.
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| 5. |
- Burkill, Sarah, et al.
(författare)
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The association between multiple sclerosis and pain medications
- 2019
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Ingår i: Pain. - : Lippincott Williams & Wilkins. - 0304-3959 .- 1872-6623. ; 160:2, s. 424-432
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Tidskriftsartikel (refereegranskat)abstract
- Patients with multiple sclerosis (MS) are at greater risk of pain than people without the disease; however, the occurrence and characteristics of pain among these patients are incompletely described. We aimed to assess characteristics of pain amongst MS patients using MS patients who were recruited to participate in 3 studies in Sweden (n = 3877) and were matched with individuals without MS (n = 4548) by sex, year of birth, and region of residence. The Prescribed Drugs Register identified prescribed pain medication, overall and restricted to those given 4 or more prescriptions in 1 year to assess chronic pain. Anatomical therapeutic chemical codes classified whether pain was neuropathic, musculoskeletal, or migraine. Cox-proportional hazard models were used to estimate associations. Our findings showed patients with MS were at increased risk of pain treatment, with a hazard ratio (HR) of 2.52 (95% confidence interval 2.38-2.66). The largest magnitude HR was for neuropathic pain (5.73, 5.07-6.47) for which 34.2% (n = 1326) of the MS and 7.15% (n = 325) of the non-MS cohort were prescribed a treatment. The HR for chronic pain treatment was 3.55 (3.27-3.84), indicating an increased effect size relative to any pain treatment. Chronic neuropathic pain showed the largest HR at 7.43 (6.21-8.89). Neuropathic pain was shown to be the primary mechanism leading to increased risk of pain in patients with MS.
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| 6. |
- Burkill, Sarah, et al.
(författare)
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The DQB1* 03:02 Genotype and Treatment for Pain in People With and Without Multiple Sclerosis
- 2020
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Ingår i: Frontiers in Neurology. - : Frontiers. - 1664-2295. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Murine models have demonstrated that the major histocompatibility complex (MHC) is associated with pain-like behavior in peripheral nerve injury, however, the same association has not been shown when considering injury to the central nervous system (CNS), which more closely mimics the damage to the CNS experienced by MS patients. Previous research has indicated the DQB1*03:02 allele of the class II HLA genes as being associated with development of neuropathic pain in persons undergoing inguinal hernia surgery or with lumbar spinal disk herniation. Whether this HLA allele plays a part in susceptibility to pain, has not, as far as we are aware, been previously investigated. This study utilizes information on DQB1*03:02 alleles as part of the EIMS, GEMS, and IMSE studies in Sweden. It also uses register data for 3,877 MS patients, and 4,548 matched comparators without MS, to assess whether the DQB1*03:02 allele is associated with prescribed pain medication use, and whether associations with this genotype differ depending on MS status. Our results showed no association between the DQB1*03:02 genotype and pain medication in MS patients, with an adjusted odds ratio (OR) of 1.02 (95% CI 0.85-1.24). In contrast, there was a statistically significant association of low magnitude in individuals without MS [adjusted OR 1.18 (95% CI 1.03-1.35)], which provides support for HLA influence on susceptibility to pain in the general population. Additionally, the effect of zygosity was evident for the non-MS cohort, but not among MS patients, suggesting the DQB1*03:02 allele effect is modified by the presence of MS.
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| 7. |
- Hiyoshi, Ayako, 1972-, et al.
(författare)
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Myopia in late adolescence and subsequent multiple sclerosis among men
- 2023
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Ingår i: Multiple Sclerosis and Related Disorders. - : Elsevier. - 2211-0348 .- 2211-0356. ; 71
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Risk factors such as low vitamin D level has been implicated in the etiology of multiple sclerosis (MS) and may be relevant to myopia, such that there may be an association between myopia and MS.METHODS: Using linked Swedish national register data, we conducted a cohort study of men who were born in Sweden between 1950 and 1992, lived in Sweden between 1990 and 2018, and enrolled in military conscription assessment (n = 1,847,754). Myopia was defined based on the spherical equivalent refraction measured at conscription assessment, around age 18 years. Multiple sclerosis was identified using the Patient Register. Cox regression produced hazard ratios (HR) with 95% confidence intervals (95% CI), with adjustment for demographic and childhood socioeconomic characteristics and residential region. Due to changes in the assessment of refractive error, the analysis was stratified into two groups by the year of conscription assessment: 1969-1997 and 1997-2010.RESULTS: Among 1,559,859 individuals during a maximum of 48 years of follow-up from age 20 to 68 years (44,715,603 person-years), there were 3,134 MS events, and the incidence rate 7.0 (95% CI [6.8, 7.3] per 100,000 person-years). Among individuals with conscription assessments during 1997-2010, there were 380 MS events. There was no evidence of an association between myopia and MS, with HR 1.09 (95% CI 0.83, 1.43). Among individuals who underwent conscription assessment in 1969-1997, there were 2754 MS events. After adjusting for all covariates, there was no evidence of an association between myopia and MS (HR 0.99 [95% CI 0.91, 1.09]).CONCLUSION: Myopia in late adolescence is not associated with a subsequent raised risk of MS and thus there does not appear to be important shared risk factors.
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| 8. |
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| 9. |
- Iacobaeus, Ellen, et al.
(författare)
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The national incidence of PML in Sweden, 1988-2013
- 2018
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Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 90:6, s. E498-E506
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the incidence of progressive multifocal leukoencephalopathy (PML) and patient characteristics in Sweden between 1988 and 2013.Methods: All PML diagnoses in Sweden between 1988 and 2013 were identified in the National Patient Register. Information to validate the diagnosis and patient characteristics was obtained from medical records.Results: Medical record review classified 108 out of 250 patients (43%) as definite (n = 84), probable (n = 4), or possible (n = 20) PML according to diagnostic criteria. Accurate diagnoses were more common in records obtained from neurology departments (82% of patients seen in neurology departments) compared with other departments (31%) (p < 0.001). The incidence of PML increased from a largely stable level at 0.026 (95% confidence interval [CI] 0.021-0.031) per 100,000 individuals per year during 1988-2010 to 0.11 (95% CI 083-0.137) during 2011-2013, during which time there was a notable increase (p < 0.001). Hematologic malignancies (n = 34), HIV/AIDS (n = 33), and autoimmune disease (n = 23) were the most common underlying diseases. Treatment with a monoclonal antibody prior to PML diagnosis was identified in 26 patients.Conclusion: An increased incidence of PML in Sweden was observed and coincided with the prior use of monoclonal antibody treatment. The high level of misdiagnosis emphasizes the importance of immediate contact with a neurology center upon suspicion of PML.
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| 10. |
- Montgomery, Scott, 1961-, et al.
(författare)
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Concussion in adolescence and risk of multiple sclerosis
- 2017
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Ingår i: Annals of Neurology. - : John Wiley & Sons. - 0364-5134 .- 1531-8249. ; 82:4, s. 554-561
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess whether concussion in childhood or adolescence is associated with subsequent multiple sclerosis (MS) risk. Previous research suggests an association, but methodological limitations included retrospective data collection and small study populations.Methods: The national Swedish Patient Register (hospital diagnoses) and MS Register were used to identify all MS diagnoses up to 2012 among people born since 1964, when the Patient Register was established. The 7,292 patients with MS were matched individually with 10 people without MS by sex, year of birth, age/vital status at MS diagnosis, and region of residence (county), resulting in a study population of 80,212. Diagnoses of concussion and control diagnoses of broken limb bones were identified using the Patient Register from birth to age 10 years or from age 11 to 20 years. Conditional logistic regression was used to examine associations with MS.Results: Concussion in adolescence was associated with a raised risk of MS, producing adjusted odds ratios (95% confidence intervals) of 1.22 (1.05-1.42, p=0.008) and 2.33 (1.35-4.04, p=0.002) for 1 diagnosis of concussion and >1 diagnosis of concussion, respectively, compared with none. No notable association with MS was observed for concussion in childhood, or broken limb bones in childhood and adolescence.Interpretation: Head trauma in adolescence, particularly if repeated, is associated with a raised risk of future MS, possibly due to initiation of an autoimmune process in the central nervous system. This further emphasizes the importance of protecting young people from head injuries. Ann Neurol 2017;82:554-561
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