Michael Wiberg

Multiple sclerosis: a study of chemokine receptors and regulatory T cells in relation to MRI variables

Magnetic resonance imaging (MRI) remains the most valuable tool for monitoring disease activity and progression in patients with multiple sclerosis (MS), a chronic demyelinating disease of the central nervous system (CNS) with presumably autoimmune etiology. Chemokine receptors have been implicated in MS as key molecules directing inflammatory cells into the CNS. Regulatory (CD4+CD25+) T cells (Tr cells) are important in suppressing autoimmunity, and their absolute or functional deficit could be expected in MS. In the present study, venous blood was obtained from MS patients concurrent with MRI examination of the brain, and expression of chemokine receptors CCR1, CCR2, CCR5, CXCR3 and CXCR4 by CD4 T cells and monocytes, proportions of Tr cells, as well as expression of CD45RO, CD95, CTLA‐4, HLA‐DR and interleukin (IL)‐10 by Tr cells and non‐Tr (CD25−) CD4 T cells was analyzed by flow cytometry. Surface expression of CXCR3 by CD4 T cells was downregulated in the group of patients with high lesion load (LL) on T2‐weighted images and gadolinium (Gd)‐enhancing lesions on T1‐weighted images, compared to the group with high LL and no Gd‐enhancing lesions, and to the group with low LL, suggesting internalization of CXCR3 due to the release of its chemokine ligand (IP‐10/CXCL10) from active MS lesions. Proportions of Tr cells amongst all CD4 T cells, and expression of IL‐10 by Tr cells were increased in the patients with high LL and Gd‐enhancing lesions. These results suggest that there is correlation between MRI parameters, chemokine receptor expression and the status of circulating Tr cells in MS, but further studies need to discriminate between pathogenetically relevant and bystander phenomena.

High prevalence of sickness absence and disability pension among multiple sclerosis patients : a nationwide population-based study.

Introduction: Although multiple sclerosis (MS) often implies substantial disability, there is little knowledge about sick leave and disability pension among MS patients. Objectives: The purpose of this study was to estimate the prevalence rates of sick leave and disability pension among MS patients and to explore how socio-demographics are associated with such rates. Methods: The register data of all people who lived in Sweden in 2005 and were 16–64 years old was used to identify 9721 MS patients and matched controls. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated and effect modifications were evaluated with Wald X2 tests. Results: In 2005, 61.7% of the MS patients were on partial or full disability pension compared to 14.2% among the controls. Of the others, 36.8% had ≥1 sick-leave spell for >14 days during that year. Socio-demographics were similarly associated with sick leave and disability pension among MS patients and controls, with the noteworthy exceptions that female gender and immigration status were less potent risk factors in the MS population (p<0.05). Conclusion: In spite of widespread access to modern health care including disease-modifying drugs, the majority of MS patients of working ages were on a disability pension. Strategies enabling MS patients to retain their footing in the labour market are needed.

Activities and sources of income after a period of long-term sick leave--a population-based prospective cohort study.

BackgroundThere is limited knowledge about what happens to people after long-term sick leave. The aim of this report was to conduct a prospective study of individuals who were on prolonged sick leave during a particular year, considering their activities and sources of income during subsequent years. To enable comparison of different time periods, we used three cohorts of individuals with different starting years.MethodsUsing data from national registers, three separate cohorts were constructed that included all people living in Sweden who were 20-64 years of age (>5 million) in the years 1995, 2000 and 2005, respectively. The individual members of the cohorts were classified into the following groups based on their main source of income and activity in 1995-2008: on long-term sick leave, employed, old-age pensioner, long-term unemployed, disability pensioner, on parental leave, social assistance recipient, student allowance recipient, deceased, or emigrated.ResultsMost individuals on long-term (> 6 months) sick leave in 1995 were not employed 13 years later. Only 11% of the women and 13% of the men were primarily in employment after 13 years. Instead, a wide range of alternatives existed, for example, many had been granted disability pension, and about 10% of the women and 17% of the men had died during the follow-up period. A larger proportion of those with long-term sick leave were back in employment when 2005 was the starting year for the follow-up.ConclusionsThe low future employment rates for people on long-term sick leave may seem surprising. There are several possible explanations for the finding: The disorders these people may have, might have entailed longstanding difficulties on the labor market. Besides, long-term absence from work, no matter what its causes were, might have worsen the chances of further employment. The economic cycles may also have been of importance. The improving labor market during later years seems to have improved the chances for employment among those earlier on long-term sick leave.

Sources and level of income among individuals with multiple sclerosis compared to the general population: A nationwide population-based study:

Introduction: Multiple sclerosis (MS) is associated with reduced work capacity, but there is limited knowledge about MS patients’ sources of income. Objectives: The purpose of this study was to elucidate MS patients’ earnings and social benefits compared to those of the general population. Methods: From nationwide registers of all residents in Sweden aged 21–64 years in 2010 (n=5,291,764), those with an MS diagnosis (n=13,979) were compared to a propensity score matched reference group (n=69,895). Descriptive statistics and regression models were used to estimate the percentage difference between the MS patients and the matched references regarding the following annual incomes: earnings, disability pension, sickness absence, disability allowance, unemployment compensation and social assistance. Results: Both MS patients and the matched references received most of their income from earnings followed by disability pension and sickness absence. MS patients that were diagnosed in 2010 had 15% lower earnings than the matched references, while MS patients diagnosed before 2005 had 38% lower earnings. Corresponding figures regarding summed social benefits were 33% and 130% higher for MS patients, respectively. Conclusion: The results indicate that MS patients are overrepresented, in relative and absolute terms, regarding health-related benefits and have lower levels of earnings. However, the redistributing welfare systems appear to financially compensate the MS patients considerably.

Earnings and Financial Compensation from Social Security Systems Correlate Strongly with Disability for Multiple Sclerosis Patients.

Background Multiple sclerosis (MS) patients earn lower incomes and receive higher benefits. However, there is limited knowledge of how this is correlated with their disability. Objective To elucidate sources and levels of income among MS patients with different disability, assessed with the Expanded Disability Status Scale. Methods A total of 7929 MS patients aged 21–64 years and living in Sweden in 2010 were identified for this cross-sectional study. Descriptive statistics, logistic and truncated linear regression models were used to estimate differences between MS patients regarding earnings, disability pension, sickness absence, disability allowance, unemployment compensation, and social assistance. Results The average level of earnings was ten times lower and the average level of health- related benefits was four times higher when comparing MS patients with severe and mild disability. MS patients with severe disability had on average SEK 166,931 less annual income from earnings and SEK 54,534 more income from benefits compared to those with mild disability. The combined average income for MS patients was 35% lower when comparing patients in the same groups. The adjusted risk ratio for having earnings among MS patients with severe disability compared to the patients with mild disability was 0.33 (95% CI 0.29–0.39), while the risk ratio for having benefits was 1.93 (95% CI 1.90–1.94). Conclusions Disease progression affects the financial situation of MS patients considerably. Correlations between higher disability and patient income were observed, suggesting that earnings and benefits could be used as measures of MS progression and proxies of disability.

Sickness absence and subsequent disposable income: A population-based cohort study

Aims: Studies show a negative association between an absence from work due to disease of injury (sickness absence (SA)) and subsequent earnings; however, little is known about the association between SA and an individuals’ subsequent overall economic welfare. Our primary objective was to evaluate individuals’ disposable income (DI) following a spell of SA. Our secondary objective was to examine if the potential association between SA and DI differs, depending on the diagnosis given to that sickness or the duration of the SA spell. Methods: We used a cohort based on a linked individual register database that includes all individuals living in Sweden from 2001 to 2005, aged 30–54. DI was measured 2–6 years after a spell of SA and compared with a propensity score-matched reference group (individuals without SA in 2005). Each year of follow-up during 2007–2011 was estimated by linear regression for three different forms of exposure: SA (yes/no), diagnosis specific (cancer, circulatory, injuries, musculoskeletal or mental illnesses), and by duration of the SA spell (15–29, 30–89, 90–179 or > 179 days). Results: Individuals with SA during 2005 had 4% lower disposable income in subsequent years than the reference group. Our results were similar across diagnoses, except for mental diagnoses, where disposable income was 7–10% lower than the reference group; and for cancer, where we found only a marginal difference among those with SA and the reference group. Furthermore, DI was negatively associated with the SA spell duration. Conclusions: SA was associated with lower subsequent DI, 2–6 years after a SA spell, especially after a mental illness diagnosis and if the SA was for longer spells.

Costs of illness of multiple sclerosis in Sweden: a population-based register study of people of working age

BackgroundMultiple sclerosis (MS) causes work disability and healthcare resource use, but little is known about the distribution of the associated costs to society.ObjectivesWe estimated the cost of illness (COI) of working-aged individuals with MS, from the societal perspective, overall and in different groups.MethodsA population-based study was conducted, using data linked from several nationwide registers, on 14,077 individuals with MS, aged 20–64 years and living in Sweden. Prevalence-based direct and indirect costs in 2010 were calculated, including costs for prescription drug use, specialized healthcare, sick leave, and disability pension.ResultsThe estimated COI of all the MS patients were SEK 3950 million, of which 75% were indirect costs. MS was the main diagnosis for resource use, causing 38% of healthcare costs and 67% of indirect costs. The distribution of costs was skewed, in which less than 25% of the patients accounted for half the total COI.ConclusionsIndirect costs contributed to approximately 75% of the estimated overall COI of MS patients of working age in Sweden. MS was the main diagnosis for more than half of the estimated COI in this patient group. Further studies are needed to gain knowledge on development of costs over time during the MS disease course.

Heterogeneity of sickness absence and disability pension trajectories among individuals with MS

Background The variability of progression of multiple sclerosis (MS) suggests that MS is a heterogeneous entity. Objective The objective of this article is to determine whether sickness absence (SA) and disability pension (DP) could be used to identify groups of patients with different progression courses. Methods We analyzed mean-annual net months of SA/DP, five years prior to MS diagnosis, until the year of diagnosis, and five years after for 3543 individuals diagnosed 2003–2006, by modeling trajectory subgroups. Results Five different groups were identified, revealing substantial heterogeneity among MS patients. Before diagnosis, 74% had a flat trajectory, while the remaining had a sharply increasing degree of SA/DP. After diagnosis, 95% had a flat or marginally increasing trajectory, although at various SA/disability pension (DP) levels, whereas a small group of 5% had decreasing SA/DP. A majority had few or no SA/DP months throughout the 11-year study period. Higher age and a lower educational level were associated with an unfavorable trajectory (p values <0.01). Conclusions There’s a considerable heterogeneity of MS progression in terms of SA/DP. Compared with other measures of disability, sickness-absence and disability pension offer a continuous variable that can be assigned to every individual for each time period without missing data. To what extent the SA/DP measure reflects classical MS outcome-measures as well as how correlated it is with co-morbidities and working-conditions needs to be investigated further.

Sickness absence due to gastroesophageal reflux diagnoses: a nationwide Swedish population-based study.

Abstract Objective. Gastroesophageal reflux disease (GERD) is a major public health problem in the Western world. No previous population-based nationwide study has, however, examined the occurrence of sickness absence due to GERD diagnoses, that is, the aim of this study. Material and methods. Nationwide population-based study based on Swedish registers including all 4,764,843 individuals registered as living in Sweden in 31 December 2004 and 31 December 2005, aged 20–64 years, not on disability or old age pension. Reimbursed sickness absence due to reflux diagnoses (ICD-10), that is, GERD (K21), esophagitis (K20), and heartburn (R12), was studied separately and combined. In analyses stratified by sociodemographic factors, inpatient/specialized outpatient care, antireflux surgery, and prescribed reflux medications those sickness absent in 2005 due to reflux diagnoses were compared to those sickness absent due to non-reflux diagnoses and to those with no sickness benefits 2005. Results. In total, 627 individuals had at least one prevalent sick-leave spell due to reflux diagnoses in 2005, of which GERD was the most common diagnosis. Of these, almost half (45%) was absent for ≥ 28 reimbursed sick-leave days due to reflux diagnoses. The proportions of low socioeconomic status (SES), inpatient and outpatient care due to tumors, mental disorders, circulatory disorders, GERD, antireflux surgery, and reflux medications were higher among those sickness absent due to reflux diagnoses compared to those with no sickness benefits. Conclusions. In this nationwide population-based study a high proportion of those sickness absent due to reflux diagnoses was on long-term sick leave, a finding that warrants attention.

How does work disability of patients with MS develop before and after diagnosis? A nationwide cohort study with a reference group.

Objectives We compared work disability of patients with multiple sclerosis (MS) from 5 years before with 5 years after diagnosis, with that of matched controls, and analysed whether progression in work disability among patients with MS was associated with sociodemography. Design Population-based cohort study. Setting The adult Swedish general population. Participants Residents aged 24–57 diagnosed with MS (n=3685) in 2003–2006 and 18 425 matched controls without MS. Primary and secondary outcome measures Annual net days of sickness absence (SA) and disability pension (DP), used as a proxy for work disability, followed from 5 years before to 5 years after diagnosis (ie, T−5–T+5). For patients with MS, regression was used to identify sociodemographic factors related to progression in work disability. Results Work disability of patients with MS increased gradually between T−5 and T−1 (mean: 46–82 days) followed by a sharp increase (T+1, 142 days), after which only a marginal increase was observed (T+5, 149 days). The matched controls had less work disability, slightly increasing during the period to a maximum of ∼40 days. Men with MS had a sharper increase in work disability before diagnosis. High educational level was associated with less progression in work disability before and around diagnosis. Conclusions Patients with MS had more work disability days also 5 years before diagnosis. Several sociodemographic variables were associated with the absolute level and the progression in SA and DP.