| 1. |
- Bergman, Joakim, 1989-
(författare)
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Studies of the Biology of Intrathecal Treatment in Progressive MS
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Multiple Sclerosis (MS) is a chronic, inflammatory, autoimmune disease, affecting the central nervous system (CNS). About 85% of afflicted present with a relapsing-remitting form of the disease (RRMS), for which a breakthrough in treatment was made in 2008 with rituximab, an antibody directed towards CD20, a surface antigen on B-cells. These findings also contributed to cementing the importance of the B-cell’s role in MS pathophysiology. However, MS also exist as a progressive phenotype, affecting most MS patients either from onset or after a transition from RRMS, and for progressive MS the same treatment effect of anti-CD20 has not been observed. Still, studies have found follicle-like structures containing B-cells in meninges and subarachnoid space of the cortex in progressive MS brains, supporting the involvement of B-cells. Evidence also support the existence of a chronic, low-grade inflammatory process compartmentalised within the CNS that correlates with the progressive phase of MS, which may present a treatment barrier towards anti-CD20. Peripherally administrated therapeutic antibodies cross the intact blood-brain barrier with low efficiency with only 0.1-0.5% of the plasma concentration occurring in the cerebrospinal fluid (CSF). Intrathecal (IT) administration circumvents the blood-brain barrier, presenting an opportunity to better target the CNS B-cells.Aims: To evaluate the safety and feasibility of intrathecal anti-CD20 therapy with rituximab in progressive MS, its effect on disease progression through clinical parameters, and impact on biomarkers in CSF. Furthermore, this thesis aimed to evaluate the effect on biomarkers representative of cell injury related to insertion of a ventricular catheter for drug administration and to examine the interstitial milieu in the brain through microdialysis (MD).Methods: The thesis is based on the open-label, phase IIb, multicentre clinical trial Intrathecal Treatment Trial in Progressive Multiple Sclerosis (ITT-PMS; EudraCT 2008-002626-11), in which 23 participants received IT treatment with rituximab, and the extended follow-up study, ITT-PMS extension (EudraCT 2012-000721-53). All participants received a ventricular catheter and an Ommaya reservoir for drug administration through a neurosurgical procedure, and 10 participants received a MD catheter in parallel to the ventricular catheter for 10 days. The treatment effect was evaluated by regular clinical evaluations and analyses of CSF. The clinical outcome was evaluated through walking and upper-limb function tests, and by clinical evaluation scales. Levels of selected CSF biomarkers were analysed from the same time-points as the clinical evaluations.Results: After the completion of the extension trial, one clinical parameter (cognitive performance) showed improvement but could most likely be explained by a learning effect. Worsening of walking speed was observed, while the remaining clinical parameters showed no change. Two severe adverse events occurred in the form of low-virulent bacterial meningitis caused by Propionibacterium, but both were treated effectively with antibiotics without residual symptoms. A ‘spike’ was noticed in the level of lumbar CSF neurofilament light (NFL) following surgery but returned to pre-surgery baseline within 6-12 months. No change was observed for any of the other lumbar CSF biomarkers. No meaningful correlation of protein levels was observed when comparing MD samples, ventricular CSF, and lumbar CSF.Conclusions: Intrathecal treatment through intraventricular administration was well tolerated but not without risks. A continued progression was observed in gait impairment. The insertion of the ventricular catheter caused white matter injury, measured through an increase in NFL in lumbar CSF, in direct association with the surgical procedure. No impact was observed on other CSF biomarkers. There was a poor correlation between different CNS compartments regarding protein levels, arguing for caution in drawing conclusions about brain pathophysiology from lumbar CSF samples.
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| 2. |
- Niklasson, Joakim, 1989-, et al.
(författare)
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Daily activity patterns in older adults receiving initial support : the association between daily steps and sitting in bouts of at least 60 min
- 2024
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Ingår i: BMC Geriatrics. - : BioMed Central (BMC). - 1471-2318. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Aging has a significant impact on health, underlining the importance of maintaining physical function and reducing time spent sitting among older adults. To understand how to reduce prolonged sitting or increase physical activity, factors related to the daily living and observed daily activity patterns should be explored. This study aimed to investigate the association between daily steps, self-rated health, physical activity, sedentary behavior, motivation to exercise and fear of falling among older adults receiving initial support. Method: Cross-sectional design with total population questionnaire data from adults aged ≥ 60 years (n = 917), living at home with initial support from municipal care in southern Sweden. The older adults were offered to participate in a follow-up study measuring daily activity patterns with accelerometers (n = 72). Linear regression was used to analyze associations between daily steps and possible predictors. Results: The linear model ($$ {R}^{2}= $$ 0.478) showed that sitting in unbroken bouts of > 60 min (β = -0.313, p < 0.05), walking independently outdoors (β = 0.301, p < 0.05), intending to increase physical activity (β = -0.294, p < 0.05), sex (β = 0.279, p < 0.05), relative autonomy index (β = 0.258, p < 0.05), fear of falling (β = -0.238, p < 0.05), and self-rated health (β = 0.213, p < 0.05) predicted daily steps. Conclusion: The model of predictors brings new understanding regarding daily steps among community-dwelling older adults. The association between sitting in bouts of > 60 min and daily steps is interesting as 35% of participants had a number of sitting bouts that on average, showed 30% less steps taken. Minimizing long sitting bouts and maintaining physical functioning to promote independence when walking outdoors can be tools for clinical practitioners devising interventions to break prolonged sitting among community-dwelling older adults. Future research should prioritize studying older adults’ outdoor walking independence, including its relation to walking with or without assistive devices and its impact on physical activity and sedentary behavior. © 2024, The Author(s).
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| 3. |
- Niklasson, Joakim, 1989-, et al.
(författare)
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Embodied navigation : the influence of lived experience on physical activity and sedentary behavior among older adults
- 2024
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Ingår i: International Journal of Qualitative Studies on Health and Well-being. - : Taylor & Francis. - 1748-2623 .- 1748-2631. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- PurposeThe impact of a sedentary lifestyle on health and well-being is well recognized. However, there is limited understanding of how a lifetime of physical activity and sedentary behaviour influences an active lifestyle in older adults. The aim of this study was to describe how lived experience of physical activity and sedentary behaviour impacts daily activities among older adults, from a life course perspective.MethodsQualitative content analysis was used; individual telephone interviews were conducted with fourteen older adults aged 71 to 92 years. The participants received initial support from community care and lived in ordinary housing in southern Sweden.ResultsThe interviews yielded one theme, "Navigating with an embodied activity compass," and two sub-themes: "Being guided by the past" and "Unveiling pathways through body awareness."ConclusionsOur study highlights how older adults' lived experiences of physical activity, with their connections to body awareness and acceptance, impact daily physical activity. These findings offer new knowledge for clinical practitioners balancing recommendations of sedentary behaviour and physical activity, to promote healthy daily physical activity among older adults. Future research and policies should consider the lived experiences of older adults when addressing public health matters related to sedentary behaviour and physical activity.
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| 4. |
- Niklasson, Joakim, 1989-, et al.
(författare)
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The meaning of sedentary behavior among older adults : a phenomenological hermeneutic study.
- 2023
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Ingår i: BMC Public Health. - : BioMed Central (BMC). - 1471-2458. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A sedentary lifestyle has implications for health and well-being. For healthy ageing, it is recommended to interrupt prolonged sitting; however, little is known about the meaning of sedentary behavior among older adults. The aim of this study was to understand the meaning of sedentary behavior among older adults with initial support from community care.METHODS: A phenomenological hermeneutics approach was used, and individual interviews were conducted with sixteen older adults aged 70 to 97 years, by phone and face to face. The older adults lived in ordinary housing in southern Sweden and received initial support from community care.RESULTS: The interviews yielded three key themes: Being sedentary is an unnatural part of life, having an ageing body means unwanted frailty, and having a sedentary lifestyle is based on conscious choices.CONCLUSION: Being sedentary means having a lack of physical activity and social interactions, resulting in wanting to be more physically active than sometimes possible. Clinical practitioners should bear in mind that becoming more sedentary is inevitable with an ageing body, but that older adults may have an innate desire to be as physically active as possible. A lifelong exposure to physical activity, the possibility of well-being found in sedentary activities and the impact of social networks should not be overlooked when creating clinical interventions to break unhealthy sedentary behavior among older adults. To increase the understanding of sedentary behavior among older adults, future research could focus on the impact of physical impairment on sedentary behavior and the relationship between sedentary behavior and physical activity throughout life.
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