Biomedical subjects

S Fredrikson

Publications and source records attributed to S Fredrikson.

At least 19 recordsLinked to original sources

PubMed2006

A population-based study of depressive symptoms in multiple sclerosis in Stockholm county: association with functioning and sense of coherence.

OBJECTIVES: To explore and analyse the prevalence of depressive symptoms in people with multiple sclerosis (PwMS), taking into account disease-related and sociodemographic factors, and also to analyse the association between depressive symptoms and functioning (tested and self-reported) and sense of coherence (SOC), respectively. METHODS: Home visits were made to a population-based sample of 166 PwMS. Data were obtained from structured, face-to-face interviews using the Beck Depression Inventory (BDI), the Sickness Impact Profile (SIP) and the SOC scale. A range of tests were also carried out for analyses of different aspects of functioning such as cognitive function, walking capacity and manual dexterity, and structured interviews examined activities of daily living and frequency of social/lifestyle activities. RESULTS: 19% (28/149) of the people were depressed (BDI > or = 13). Depressive symptoms were associated with worse self-reported functioning on the SIP and with poor memory function, but not with any of the other tests of functioning. Depressive symptoms were associated with weak SOC, but not with any of the disease-related or sociodemographic factors studied. CONCLUSION: The prevalence of depressive symptoms in a population-based sample of PwMS is high. Given the serious nature of depression and its association with worse self-reported functioning and weak SOC, attention to, and treatment of, mental-health problems and depression are strongly indicated in the clinical management of multiple sclerosis.

Activities of Daily Living↗

PubMed2006

Costs and quality of life of patients with multiple sclerosis in Europe.

OBJECTIVE: To assess overall resource consumption, work capacity and quality of life of patients with multiple sclerosis in nine European countries. METHODS: Information on resource consumption related to multiple sclerosis, informal care by relatives, productivity losses and overall quality of life (utility) was collected with a standardised pre-tested questionnaire from 13,186 patients enrolled in national multiple sclerosis societies or followed up in neurology clinics. Information on disease included disease duration, self-assessed disease severity and relapses. Mean annual costs per patient (Euro, 2005) were estimated from the societal perspective. RESULTS: The mean age ranged from 45.1 to 53.4 years, and all levels of disease severity were represented. Between 16% and 29% of patients reported experiencing a relapse in the 3 months preceding data collection. The proportion of patients in early retirement because of multiple sclerosis ranged from 33% to 45%. The use of direct medical resources (eg, hospitalisation, consultations and drugs) varied considerably across countries, whereas the use of non-medical resources (eg, walking sticks, wheel chairs, modifications to house and car) and services (eg, home care and transportation) was comparable. Informal care use was highly correlated with disease severity, but was further influenced by healthcare systems and family structure. All types of costs increased with worsening disease. The total mean annual costs per patient (adjusted for gross domestic product purchasing power) were estimated at Euro 18,000 for mild disease (Expanded Disability Status Scale (EDSS) <4.0), Euro 36,500 for moderate disease (EDSS 4.0-6.5) and Euro 62,000 for severe disease (EDSS >7.0). Utility was similar across countries at around 0.70 for a patient with an EDSS of 2.0 and around 0.45 for a patient with an EDSS of 6.5. Intangible costs were estimated at around Euro 13,000 per patient.

Adult↗

PubMed2006

A case-control study of Guillain-Barré syndrome in Harbin, China.

We evaluated the putative factors for the onset of Guillain-Barré syndrome (GBS) in Harbin, China by a case-control study based on the information from GBS patients identified from a population-based incidence survey, which is the first study of this kind in China. Sixty-nine GBS patients were identified during a 1-year period from 1 October 1997 to 30 September 1998, and they were matched with 69 controls for gender and age (+/-5 years). GBS diagnosis was validated by senior neurologists and GBS patients were followed up for 6 months after onset. Odds ratio (OR) and 95% confidence intervals (CI) for each putative factor for the onset of GBS were calculated and compared between GBS cases and controls. Precedent respiratory infections within 2 months before onset were found to be significantly more frequent in GBS patients than in controls (OR = 1.68, 95% CI: 1.21-2.33). Although the number of cases with gastroenteritis among GBS patients was more than double of that in the controls, the difference was not statistically significant (OR = 2.25, 95% CI: 0.73-6.96). Other putative factors as well as characteristics regarding family situation, education level, occupation, etc., were not found to be statistically different between GBS patients and controls.

Adolescent↗

PubMed2006

Health-related quality of life in a population-based sample of people with multiple sclerosis in Stockholm County.

The aim of this descriptive, cross-sectional study was to analyse health-related quality of life (HRQoL) in a population-based sample of people with multiple sclerosis (PwMS) in Stockholm County, with respect to disease-related and sociodemographic factors and coping capacity. A further aim was to compare our results on HRQoL--collected by face-to-face interviews at home-visits--with the results from a study with a mail-surveyed sample of PwMS in Stockholm. Home visits were made to 166 PwMS with clinically definite MS. Data were obtained from structured interviews using the Sickness Impact Profile (SIP), EuroQol-5D (EQ-5D) and the Sense of Coherence Scale. HRQoL was widely affected, especially in home management, walking and recreation. Self-rated HRQoL was worse in PwMS, including those with milder disease and shorter disease duration, than in the general population. Factors that were independently associated with large impact on HRQoL were disease severity, work status and coping capacity. The EQ-5D score of PwMS was more favourable when assessed by face-to face interviews at home in our study than in the study using mailed questionnaires. The study gives detailed information on HRQoL and will contribute to the base needed for organizing health care services aimed at improving HRQoL of PwMS in Stockholm.

Adolescent↗

PubMed2006

Activities of daily living and social activities in people with multiple sclerosis in Stockholm County.

OBJECTIVE: To describe independence in personal and instrumental activities of daily living (ADL), and frequency of social/lifestyle activities in a population-based sample of people with multiple sclerosis in Stockholm. DESIGN: Population-based survey. SETTING: Data collection in home environment. SUBJECTS: One hundred and sixty-six people with multiple sclerosis. INTERVENTIONS: Data were collected using measurements and structured interviews. MAIN MEASURES: Independence in ADL was assessed by the Barthel Index; independence in personal and instrumental ADL by the Katz Extended ADL Index; and frequency of social/lifestyle activities by the Frenchay Activities Index. RESULTS: The mean age was 51 +/- 12 years in the included 166 people with multiple sclerosis, of whom 71% (n = 118) were women. Fifty-two per cent (n = 85) were independent in personal ADL, 30% (n = 50) in instrumental ADL, and 35% (n = 57) had normal frequency of social/lifestyle activities. Most frequently affected ADL items were cleaning indoors and outdoors transportation (62%, n = 102) and the social/lifestyle items of household maintenance (59%, n = 97), walking outside (59%, n = 97), heavy housework (61%, n = 100), and gardening (68%, n = 112). CONCLUSIONS: ADL and social/lifestyle activities were affected in two-thirds of people with multiple sclerosis in Stockholm. The most affected items were items that could be classified as mobility-related and physically demanding, underlining the importance of developing and using evidence-based exercise treatments and rehabilitation to increase independence in people with multiple sclerosis in Stockholm.

Activities of Daily Living↗

PubMed2006

Cognitive and motor function in people with multiple sclerosis in Stockholm County.

The aim of this study was to analyse cognitive and motor function in a population-based sample of people with multiple sclerosis (PwMS), taking into account both disease-related data and sociodemographic factors. Data were collected from 166 PwMS during home visits. Cognitive function was assessed by the Mini-Mental State Examination (MMSE), the Free Recall and Recognition of 12 Random Words Test (FRR12RWT), and the Symbol Digit Modalities Test (SDMT); manual dexterity by the Nine-Hole Peg Test (NHPT); global motor capacity by the Lindmark Motor Capacity Assessment; and walking capacity by a timed 10-metre walk. On cognitive tests, 55% (MMSE), 84% (FRR12RWT), and 45% (SDMT) of PwMS scored within the normal range; 27% of PwMS displayed normal manual dexterity, 9% had a maximal motorcapacity score, and 8% walked at normal speed. Factors associated with normal cognitive function were lower disability and higher education; lower disability and current employment were predictive of capacity to perform the NHPT and to walk 10 metres. In conclusion, cognitive function was normal in approximately half of the PwMS investigated, while a minority displayed normal manual dexterity and normal walking capacity. Thus, both disease severity and sociodemographic factors appear to influence cognitive and motor function in MS.

Activities of Daily Living↗

PubMed2004

Genes in the HLA class I region may contribute to the HLA class II-associated genetic susceptibility to multiple sclerosis.

In order to analyze whether loci in the human leukocyte antigen (HLA) class I region may contribute to the HLA class II-associated genetic susceptibility to multiple sclerosis (MS), we examined selected microsatellite markers in 177 Nordic sib-pair families, 222 British sib-pair families, 323 sporadic Norwegian MS patients and 386 Norwegian controls. All samples were, in addition, genotyped for the HLA-DR DQ haplotype, and the Norwegian case-control samples were also typed for HLA-A and -B loci. In the Norwegian sporadic MS patients association was seen with HLA-A, HLA-B, and with the D6S265 marker, located 100 kb centromeric to HLA-A. Associations with HLA-A and D6S265 loci were also suggested when restricting the analysis to HLA-DR15 haplotypes. In the sib-pair data a similar trend was seen with marker D6S265. Higher genotypic relative risk (GRR) was found for individuals who carry both HLA-DR15 and -A3 (GRR = 15), compared to those who carry only HLA-DR15 (GRR = 7), only HLA-A3 (GRR = 3) or none of these alleles (GRR = 1). The highest risk was conferred by a combination of HLA-DR15 and -A3 (odds ratio (OR) = 5.2). These results suggest that HLA-A or a gene in linkage disequilibrium with it may contribute to the HLA class II-associated genetic susceptibility to MS.

Case-Control Studies↗

PubMed2003

Cost-utility of interferon beta1b in the treatment of patients with active relapsing-remitting or secondary progressive multiple sclerosis.

Economic evaluations of treatments for multiple sclerosis have focused either on relapsing-remitting or secondary progressive disease. None has addressed specifically the question of how treatments affect disease progression from diagnoses to severe disability; however, in both clinical and economic terms this is one of the key questions. This study therefore created a disease model that includes both relapsing and progressive multiple sclerosis and covers the full range of disease severity. In addition, the issue of covariates influencing the cost per QALY and the uncertainty in the estimates is addressed. The model is based on our earlier approach using a Markov model, where disease progression is measured as functional disability (EDSS), costs and utilities associated with different disability levels, and outcome expressed as QALY. Treatment is based on a subgroup of patients with active disease in two placebo-controlled clinical trials and open-label extensions with interferon-beta(1b) in relapsing-remitting or secondary progressive multiple sclerosis, and natural history data are used for the extrapolation beyond the trials. Disease progression (transition probabilities) was estimated using a probit model controlling for differences in patient and disease characteristics, and costs and utilities for different disability levels are taken from large population-based observational studies. Results are presented for Sweden and compared to the United Kingdom. When treatment is given for 36 months (adjusted for compliance) and no further effect is included, the cost per QALY is EURO 7800 (direct, indirect, and informal care costs included, discounted at 3%) over 10 years. The total number of QALYs increases from 3.45 in the no-treatment group to 3.64 in the treatment group. When treatment is prolonged to 54 months, the cost per QALY is EURO 38,700. Using the full range of costs and utilities, the probability that the cost per QALY over a 20-year time-frame is below EURO 50,000 for patients starting treatment at EDSS 3.0 is 80%. In view of the progression of MS over many years models are required to estimate the cost-effectiveness of new treatments. The model proposed here allows estimating disease progression, costs, and QALYs for patients with different characteristics and types of MS, and it can be adapted to different countries. It can hence be used to assess the cost-effectiveness of a defined intervention, such as interferon-beta(1b).

Journal Article↗

PubMed2003

Multiple sclerosis in Stockholm County. A pilot study exploring the feasibility of assessment of impairment, disability and handicap by home visits.

OBJECTIVE: A pilot study performed within Stockholm County to evaluate the feasibility of collecting data using a comprehensive evaluation package administered in the home environment to assess impairment, disability and handicap in order to explore the consequences of multiple sclerosis (MS). DESIGN: Home visits to 26 purposefully selected MS patients with different levels of disability, in both ordinary and sheltered living. The comprehensive evaluation package included: biographical data, Mini-Mental State Examination, Free Recall and Recognition of 12 Random Words Test, Symbol Digit Modalities Test, Beck Depression Index, Lindmark Motor Capacity Assessment, time to walk 10 metres, Nine-hole Peg Test, Barthel ADL Index, Katz Extended ADL Index, Frenchay Activities Index, Sickness Impact Profile and frequency of falls and injurious falls. RESULTS: This pilot study demonstrates that the proposed methods can be used to evaluate MS patients differing in levels of disability and forms of living. The data collection method, based on home visits, was well accepted by the patients, their spouses and salaried personal assistants and could be performed within 2-2 1/2 hours. CONCLUSIONS: The evaluation package used in this pilot study is suitable for use in population-based studies and it should provide comprehensive information on the impact and consequences of MS on patients, and should contribute to the identification of areas in which the provision of rehabilitation and health care services needs to be improved.

Activities of Daily Living↗

PubMed2002

Multiple sclerosis in Stockholm County. A pilot study of utilization of health-care resources, patient satisfaction with care and impact on family caregivers.

Multiple sclerosis (MS) is a progressive, incurable neurological disease with a large impact on the person/people with MS (PwMS), the family of the PwMS, medical resources and the community. We have explored the feasibility of calculating utilization of health-care resources within Stockholm County and evaluated methods for interviewing PwMS and family caregivers in their homes. Home visits were made to 26 PwMS with different levels of disability, both in ordinary and sheltered living. Questionnaires assessing patient satisfaction, the use of technical aids and home adaptations, help from municipal and family caregivers, and health-related quality of life were administered in the form of structured interviews. Utilization of health-care resources was evaluated with the help of an available computerized register. The study shows that the chosen methods are feasible for PwMS, irrespective of level of disability or form of living. They are well accepted by both PwMS and family caregivers and need only minor modifications in order to be suitable for a population-based study.

Adult↗

PubMed2002

A genome-wide screen for linkage in Nordic sib-pairs with multiple sclerosis.

Genetic factors influence susceptibility to multiple sclerosis but the responsible genes remain largely undefined, association with MHC class II alleles being the only established genetic feature of the disease. The Nordic countries have a high prevalence of multiple sclerosis, and to further explore the genetic background of the disease, we have carried out a genome-wide screen for linkage in 136 sibling-pairs with multiple sclerosis from Denmark, Finland, Norway and Sweden by typing 399 microsatellite markers. Seventeen regions where the lod score exceeds the nominal 5% significance threshold (0.7) were identified-1q11-24, 2q24-32, 3p26.3, 3q21.1, 4q12, 6p25.3, 6p21-22, 6q21, 9q34.3, 10p15, 10p12-13, 11p15.5, 12q21.3, 16p13.3, 17q25.3, 22q12-13 and Xp22.3. Although none of these regions reaches the level of genome-wide significance, the number observed exceeds the 10 that would be expected by chance alone. Our results significantly add to the growing body of linkage data relating to multiple sclerosis.

Denmark↗

PubMed2001

The T cell regulator gene SH2D2A contributes to the genetic susceptibility of multiple sclerosis.

The T cell specific adapter protein (TSAd) encoded by the SH2D2A gene is involved in the control of T cell activation. The gene is located in the 1q21 region, which has been implicated in susceptibility to experimental allergic encephalomyelitis in the mouse. We therefore evaluated whether a polymorphic GA repeat (GA(13)-GA(33)) within the promoter region of the SH2D2A gene shows association to multiple sclerosis (MS). The frequency of the short alleles GA(13-16) was increased among 313 Norwegian MS patients compared to 277 healthy controls (0.332 vs 0.249, OR 1.5, Pc = 0.03). Transmission disequilibrium analysis in 146 Scandinavian families with at least two affected sibs showed increased transmission of GA(16) to MS patients. No linkage or association of MS to four genetic markers flanking the SH2D2A gene was observed. After activation of naive CD4(+) T cells, T cells homozygous for MS associated short alleles displayed lower level of TSAd ex vivo than T cells carrying at least one long allele, which were not associated to MS. Since the SH2D2A protein modulates T cell activation, this may be a mechanism for how short SH2D2A alleles confer susceptibility to develop MS.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Linkage analysis suggests a region of importance for multiple sclerosis in 3p14-13.

Four genomic screens for linkage in multiple sclerosis (MS) have been reported. They confirmed the established role of the human leucocyte antigen (HLA) complex genes in MS and, in addition, suggested the importance of a few other chromosomal segments. Here we report evidence for the importance of 3p14-13 region identified by suggestive linkage in genomic screens from Canada and the United Kingdom. When studying 146 Nordic MS multiplex families, mostly affected sib-pairs, with eight microsatellite markers, spanning a 36-cM region, we observed a two-point non-parametric linkage (NPL) score of 2.39 (P = 0.007) by the GENEHUNTER package for marker D3S1285 and a multipoint NPL score of 1.20 in the same region. Association studies in Swedish MS patients revealed modest allelic associations of uncertain significance not supported by transmission analysis. Analysis of the trinucleotide repeat sequence of the SCA7 gene in Swedish index cases did not reveal expansions. We conclude that support was obtained for the location of a gene or genes with importance for MS susceptibility in 3p14-13 region.

Alleles↗

PubMed2001

Altered phenotype and function of blood dendritic cells in multiple sclerosis are modulated by IFN-beta and IL-10.

Multiple sclerosis (MS) is assumed to result from autoaggressive T cell-mediated immune responses, in which T helper type 1 (Th1) cells producing cytokines, e.g. IFN-gamma and lymphotoxin promote damage of oligodendrocyte-myelin units. Dendritic cells (DCs) as potent antigen presenting cells initiate and orchestrate immune responses. Whether phenotype and function of DCs with respect to Th1 cell promotion are altered in MS, are not known. This study revealed that blood-derived DCs from MS patients expressed low levels of the costimulatory molecule CD86. In addition, production of IFN-gamma by blood mononuclear cells (MNCs) was strongly enhanced by DCs derived from MS patients. IFN-beta and IL-10 inhibited the costimulatory capacity of DCs in mixed lymphocyte reaction (MLR) and showed additive effects on suppression of IL-12 production by DCs. Correspondingly, DCs pretreated with IFN-beta and IL-10 significantly suppressed IFN-gamma production by MNCs. IFN-beta in vitro also upregulated CD80 and, in particular, CD86 expression on DCs. In vitro, anti-CD80 antibody remarkably increased, while anti-CD86 antibody inhibited DC-induced IL-4 production in MLR. We conclude that DC phenotype and function are altered in MS, implying Th1-biased responses with enhanced capacity to induce Th1 cytokine production. In vitro modification of MS patients' DCs by IFN-beta and IL-10 could represent a novel way of immunomodulation and of possible usefulness for future immunotherapy of MS.

Adult↗

PubMed2001

Costs, quality of life and disease severity in multiple sclerosis: a cross-sectional study in Sweden.

This study assessed the cost to society of multiple sclerosis (MS) in Sweden in 1998. The cost-of-illness method, based on the human capital theory, was used as the theoretical framework. The study used a cross-sectional approach, in which resource utilization data and quality-of-life data (utilities) were collected at a single time point. The total cost of MS was estimated at 4868 MSEK, or 586 MEUR, giving an annual cost of 442 500 SEK, or 53 250 EUR, per patient (1USD = 9.73 SEK, 1 EUR = 8.31 SEK, as of 21 September 2000). Direct costs accounted for about 67% of total cost, and they were dominated by the cost of personal assistants and drugs. Indirect costs (loss of production) accounted for about 33% of total costs. To these economic costs, intangible costs of 2702 MSEK (325 MEUR) should be added as well. Direct, indirect and informal care costs all rose significantly with increased disability and were higher during a relapse. Quality of life declined substantially with increased disability and was lower during a relapse. Multiple sclerosis was found to be associated with much higher costs to society than has been ascertained by former studies. The study also revealed a strong correlation between severity of the disease and quality of life. These results are crucial for further studies on the cost-effectiveness of new treatments aimed at preventing relapses and reducing progression of the disease.

Ambulatory Care↗

PubMed2000

Multiple sclerosis: pro- and anti-inflammatory cytokines and metalloproteinases are affected differentially by treatment with IFN-beta.

Interferon-beta (IFN-beta) has a beneficial influence on the course of multiple sclerosis (MS) and has become standard treatment of this disease, though its mechanisms of action are incompletely understood. This study examines the effect of IFN-beta treatment on the cytokines IL-6, TNF-alpha, IFN-gamma and IL-10; the metalloproteinases MMP-3, -7 and -9 and the tissue inhibitor of metalloproteinase-1 (TIMP-1). IFN-beta treatment resulted in decreased numbers of mononuclear cells (MNC) secreting IL-6 and TNF-alpha and expressing mRNA of MMP-3 and MMP-9 compared to pretreatment levels. On the contrary, numbers of IL-10 secreting MNC and TIMP-1 mRNA expressing were augmented during IFN-beta therapy. Whether the down-regulatory effects on pro-inflammatory and upregulatory effects on anti-inflammatory molecules are a direct result of IFN-beta on the immune system or secondary to clinical stabilization of MS pathology induced by IFN-beta remains to be evaluated.

Cells, Cultured↗

PubMed2000

Cost-utility analysis of interferon beta-1b in secondary progressive multiple sclerosis.

OBJECTIVES: Interferon beta-1b has recently become available for the treatment of secondary progressive multiple sclerosis (SPMS). This study aims at estimating the cost-effectiveness of this new treatment that has been shown in a clinical trial to reduce the progression of the disease. Effectiveness is measured as the number of quality-adjusted life-years (QALYs) gained from the reduction in progression. Because the clinical trial period will only capture part of the treatment's effect in terms of QALYs gained, since benefits achieved during the trial will have an effect beyond it, the cost-effectiveness analysis involves modeling over the longer term using complementary data. METHODS: A Markov model with states based on disability expressed by EDSS scores was used. Transition probabilities were calculated directly from clinical trial data for the first 3 years and then extrapolated to 10 years. Mean costs and utilities for each Markov state were calculated from a population-based cross-sectional study in Sweden. RESULTS: The incremental cost per QALY is SEK 342,700 (US $39,250; US $1 = SEK 8.73, March 10, 2000) when all costs (direct, informal care, and indirect) are included (discounted 3%). When indirect costs are excluded, the cost per QALY is SEK 542,000 ($62,100). CONCLUSIONS: Cost-effectiveness analysis in SPMS requires that the effect of treatment beyond clinical trials be included. Also, analysis should be done from a societal perspective, since many of the costs occur outside the healthcare system. The cost-utility ratios estimated in this analysis are at or below the mean threshold value indicated in a recent survey of health economists ($60,000).

Adjuvants, Immunologic↗

PubMed2000

Epidemiological surveillance of Guillain-Barré syndrome in Sweden, 1996-1997. Network members of the Swedish GBS Epidemiology Study Group.

OBJECTIVES: To set up an epidemiological surveillance system of Guillain-Barré syndrome (GBS) in Sweden and to evaluate the pilot practice of the system for 2 years. MATERIAL AND METHODS: A network of neurologists reported incident patients with a GBS diagnosis among a general population of 4.5 million inhabitants in Sweden during 1996 1997. Historical GBS data from the national hospital in-patient registry were used for predicting incidences and controlling under-reporting. RESULTS: One hundred and seventeen cases were reported. No alarm signals were identified during the study period. A re-analysis of data in 1996 revealed: 1) a higher than expected incidence in the population aged below 40 years in January, and 2) 27% under-reporting mainly associated to one hospital and to GBS patients hospitalized outside neurological departments. Threshold values for GBS incidences among the general and selected populations were obtained from corrected data. CONCLUSION: - The Swedish Network for GBS Surveillance can provide immediate support for epidemiological evaluation of suspected outbreaks or increased GBS incidence.

Adult↗