| 220791. |
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| 220792. |
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| 220793. |
- Spelman, T., et al.
(författare)
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The association between disease activity and health-related quality of life in RRMS patients
- 2017
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Ingår i: Value in Health. - : ELSEVIER SCIENCE INC. - 1098-3015 .- 1524-4733. ; 20:9, s. A728-A728
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: Relapse-remitting multiple sclerosis (RRMS) is the most common disease course of multiple sclerosis (MS) patients. Disease activity (DA) has been shown to impact intermediate clinical outcomes including relapse rates and disease progression. However, it is unclear to what extent DA is related to ultimate health outcomes such as health-related quality of life (HRQoL). This study investigates the association between HRQoL and DA. Methods: Generic HRQoL was measured using the EQ-5D-3L utility instrument index value under the United Kingdom tariff. A cohort of 3496 adult RRMS patients enrolled in the Swedish population-based MS register during 1996-2015 (inclusive) was included from the date of first recorded EQ-5D-3L assessment (baseline). Patients were grouped according to DA within +/- 12 months of baseline. Active disease was the reference group, defined as 1+ relapse or T2 lesion. Two high disease activity groups were considered: HDA-R defined as 2+ relapses recorded within 1 year of each other, or Highly Active RRMS (HA-RRMS) defined as 9+ T2 lesions or 1+ gadolinium-enhanced T1 lesion. Patients not fulfilling any DA criteria were labelled unclassified. A general estimating equation was used to analyse the association between longitudinal EQ-5D-3L and disease activity group; adjusting for age, sex, proportion of time treated with disease modifying treatment (%DMT), and time since registry enrolment. Results: HA-RRMS was associated with a statistically significant decrease in EQ-5D-3L (coefficient -0.01, p=0.04). HDA-R and unclassified patients were not statistically significantly associated with EQ-5D-3L. Female sex and increasing age were significantly associated with decreasing EQ-5D-3L, while %DMT and time since registry enrolment were significantly associated with increasing EQ-5D-3L. Conclusions: HA-RRMS is associated with lower HRQoL over time, although it is unclear whether it is clinically significant. Additional data and modelling may be required to uncover the subtleties of the relationship between DA and HRQoL.
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| 220794. |
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| 220795. |
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| 220796. |
- Spelman, Tim, et al.
(författare)
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Treatment Escalation vs Immediate Initiation of Highly Effective Treatment for Patients with Relapsing-Remitting Multiple Sclerosis: Data from 2 Different National Strategies
- 2021
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 78, s. 1197-1204
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Treatment strategies for relapsing-remitting multiple sclerosis (RRMS) vary markedly between Denmark and Sweden. The difference in the association of these national strategies with clinical outcomes is unknown. Objective: To investigate the association of national differences in disease-modifying treatment (DMT) strategies for RRMS with disability outcomes. Design, Setting, and Participants: This cohort study used data on 4861 patients from the Danish and Swedish national multiple sclerosis (MS) registries from the date of index DMT initiation (between January 1, 2013, and December 31, 2016) until the last recorded visit at time of data extraction (October 2, 2019). Exposures: All MS-specific DMTs initiated during the observation period were included in the analysis. Main Outcomes and Measures: The primary study outcome was time to 24-week confirmed disability worsening. Secondary outcomes were 24-week confirmed disability improvement, milestone Expanded Disability Status Scale scores of 3 and 4, annualized relapse rate, time to first relapse, and treatment switching. Data were analyzed using inverse probability of treatment weighting-based models using a propensity score to weight and correct the comparison for the imbalance of confounders observed at baseline between the 2 countries. Results: A total of 2700 patients from the Swedish MS registry (1867 women [69.2%]; mean [SD] age, 36.1 [9.5] years) and 2161 patients from the Danish MS registry (1472 women [68.1%]; mean [SD] age, 37.3 [9.4 years]) started a first DMT between 2013 and 2016, were included in the analysis, and were observed for a mean (SD) of 4.1 (1.5) years. A total of 1994 Danish patients (92.3%) initiated a low to moderately effective DMT (teriflunomide, 907 [42.0%]) and 165 (7.6%) initiated a highly effective DMT, whereas a total of 1769 Swedish patients (65.5%) initiated a low to moderately effective DMT (teriflunomide, 64 [2.4%]) and 931 (34.5%) initiated a highly effective DMT. The Swedish treatment strategy was associated with a 29% reduction in the rate of postbaseline 24-week confirmed disability worsening relative to the Danish treatment strategy (hazard ratio, 0.71; 95% CI, 0.57-0.90; P =.004). The Swedish treatment strategy was also associated with a 24% reduction in the rate of reaching an expanded disability status scale score of 3 (hazard ratio, 0.76; 95% CI, 0.60-0.97; P =.03) and a 25% reduction in the rate of reaching an expanded disability status scale score of 4 (hazard ratio, 0.75; 95% CI, 0.61-0.96; P =.01) relative to Danish patients. Conclusions and Relevance: The findings of this study suggest that there is an association between differences in treatment strategies for RRMS and disability outcomes at a national level. Escalation of treatment efficacy was inferior to using more efficacious DMT as initial treatment.
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| 220797. |
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Spelmansböcker i Norden : Perspektiv på handskrivna notböcker
- 2019
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Samlingsverk (redaktörskap) (refereegranskat)abstract
- Spelmansböcker i Norden innehåller sju artiklar av nordiska forskare som presenterar och diskuterar ett särskilt slags musikaliskt källmaterial: personliga, handskrivna notböcker som till största del innehåller dansmusik. Denna typ av notböcker var huvudsakligen i bruk mellan 1600- och 1900-talen, bland annat i de nordiska länderna, och är en intressant källa för forskningen kring melodiers och dansers spridning i tid och rum samt mellan olika sociala samhällsskikt. Notböckernas innehåll har också inspirerat musiker till nya tolkningar av det historiska materialet.Artiklarna bygger på föredrag från en konferens på Linnéuniversitetet i Växjö 2017.
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| 220798. |
- Spelmink, Laura
(författare)
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Streptococcus pneumoniae and the host : activation, evasion and modulation of the human innate immune system
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Streptococcus pneumoniae is a major cause of severe infections such as pneumonia, septicemia and meningitis, but also a common colonizer of the nasopharynx in children. In most individuals colonization is harmless and eventually cleared by the immune system, but in rare cases pneumococci can reach deeper into the body and cause diseases. It is not understood why pneumococci cause infections in a few individuals while in most cases the bacteria are limited to the nasopharynx and eventually cleared. It is clear, however, that a well-orchestrated immune system is essential to prevent and limit pneumococcal infections. Macrophages are essential for an early clearance of pneumococci and dendritic cells are required to initiate appropriate adaptive responses. Both cell types were studied in this thesis. Cytokine secretion by dendritic cells directs the development of T-cells, and we studied the induction of IL-12 secretion by dendritic cells in response to pneumococci. We showed that pneumococcal RNA was recognized by TLR3, which together with the adapter molecule TRIF induced secretion of IL-12. Infection of dendritic cells with influenza A virus upregulated TLR3 expression which contributed to a more efficient detection of pneumococci and enhanced IL-12 secretion. We observed that the pneumococcal pore forming toxin pneumolysin had profound effects on cytokine responses in human dendritic cells and macrophages. We found a cell death independent inhibition of cytokine secretion in human dendritic cells and macrophages by pneumolysin expressing pneumococci. Interestingly however, cytokine secretion by macrophages derived from the human THP-1 cell line was enhanced in the presence of pneumolysin. We described pneumolysin mediated effects on these cell types and explored initial insight into the underlying mechanisms. Clearance of pneumococci by macrophages is supported by deposition of complement on the bacterial surface. The pneumococcal surface protein PspC binds human Factor H to evade opsonophagocytosis, and can also act as an adhesin. We characterized two variants of PspC proteins present in B6 clinical isolates. The two proteins showed differential expression patters on the bacterial surface and had distinct functions as Factor H binding protein or adhesin. Small changes in surface localization impaired the protein function, indicating the importance of correct surface expression. We tested the effects of vitamin D on the activation of dendritic cells by pneumococci and the induction of T-cell responses. Vitamin D supported dendritic cell maturation and skewed T-cell responses from an inflammatory to a regulatory phenotype. This work gives insight into the complex interactions between S. pneumoniae and human immune cells, and underlines the dynamic effects of pneumococcal virulence factors on the host. A thorough understanding of the activation and evasion of immune responses by pneumococci as well as the effects of immunomodulatory agents such as vitamin D is essential for the development of future treatment options and vaccine approaches.
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| 220799. |
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| 220800. |
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