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| 2. |
- Ertzgaard, Per, 1958-
(author)
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Studies on Spasticity from an Interventional Perspective
- 2018
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Doctoral thesis (other academic/artistic)abstract
- This thesis focuses on interventional aspects of spasticity, but has a very holistic approach, grounded in the specialty of Rehabilitation medicine. This means capturing the effects of spasticity, on such a complex biological system as the human being, living in a psychosocial context affecting the situation. When evaluating spasticity there are a number of levels of evidence. The first of course, understanding what we mean with spasticity, where there unfortunately is no consensus. The second level is to study if our treatments affect spasticity in a positive direction. The third is to grasp if a decrease in spasticity improve or normalize patient’s movement patterns. The fourth level investigates if improvement in movement patterns improve patient’s ability to perform activities; and the fifth level, comprising whether this intervention improves life satisfaction. Finally, on a societal level, we wish to investigate whether the improvement in life satisfaction or health related quality of life would motivate society to fund the intervention.Paper I on Goal Attainment Scaling pointed out necessary aspects to consider when using this instrument. This relates, among other things, to the need of learning (“the art of”) goal setting and deciding the purpose of the measurements. Research and clinical use puts different demands on the instrument, for the latter time-efficiency and simplicity to use being most important. For research, it is important to be able to register deterioration, and this can be achieved using the 6-step version.In paper II, concerning validation of the portable motion system, we showed this system to be valid for short-term measurements and that the use of Exposure Variation Analysis (EVA) seems to be a valuable tool for graphically elucidating different movements. The equipment needs further development in handling long-term measurements (which is effectuated), and norms for normal movements in different activities has to be produced. The discriminative value of EVA needs confirmation in coming studies. For the future, there is the intriguing possibility of long-term measurements in patients’ every-day life, thereby getting objective measures on how our patients use their abilities, thus capturing the difference between what you can do and what you actually do.The results from paper III demonstrated a large inequality in Sweden regarding the accessibility of BoNT-A treatment for spasticity. We could also show that treatment with BoNT-A is sound from a health-economic perspective, accounting for the uncertainty of data via the sensitivity analysis. For the future, we need to explore if this inequality also exists for other modes of spasticity treatments, e.g. multidisciplinary spasticity treatment and ITB pumps, and in other countries.In paper IV evaluating multifocal TES, the results could not confirm efficacy with the treatment according to the protocol of the manufacturer. The results have to be interpreted with care, as low compliance and frequent adverse events made deduction not captured in the RCT study. Further studies are needed in a number of areas, e.g. what is the optimal stimulation frequency, what patients can gain from the treatment and how should adjunct treatment be organized.In this thesis, I have had the privilege to explore different methods of evaluating spasticity interventions from a multimodal perspective as a starting point in an effort to understand more of this intriguing phenomenon. Some of the research questions above are already in the “pipeline” for coming studies; others are to be planned by our research group and others.
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| 3. |
- Griswold, Max G., et al.
(author)
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Alcohol use and burden for 195 countries and territories, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016
- 2018
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In: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 392:10152, s. 1015-1035
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Journal article (peer-reviewed)abstract
- Background: Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older.Methods: Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health.Findings: Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2.2% (95% uncertainty interval [UI] 1.5-3.0) of age-standardised female deaths and 6.8% (5.8-8.0) of age-standardised male deaths. Among the population aged 15-49 years, alcohol use was the leading risk factor globally in 2016, with 3.8% (95% UI 3.2-4-3) of female deaths and 12.2% (10.8-13-6) of male deaths attributable to alcohol use. For the population aged 15-49 years, female attributable DALYs were 2.3% (95% UI 2.0-2.6) and male attributable DALYs were 8.9% (7.8-9.9). The three leading causes of attributable deaths in this age group were tuberculosis (1.4% [95% UI 1. 0-1. 7] of total deaths), road injuries (1.2% [0.7-1.9]), and self-harm (1.1% [0.6-1.5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27.1% (95% UI 21.2-33.3) of total alcohol-attributable female deaths and 18.9% (15.3-22.6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0.0-0.8) standard drinks per week.Interpretation: Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption.
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| 4. |
- Shi, Liu, et al.
(author)
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Dickkopf-1 Overexpression in vitro Nominates Candidate Blood Biomarkers Relating to Alzheimer's Disease Pathology.
- 2020
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In: Journal of Alzheimer's disease : JAD. - : IOS Press. - 1875-8908 .- 1387-2877. ; 77:3, s. 1353-1368
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Journal article (peer-reviewed)abstract
- Previous studies suggest that Dickkopf-1 (DKK1), an inhibitor of Wnt signaling, plays a role in amyloid-induced toxicity and hence Alzheimer's disease (AD). However, the effect of DKK1 expression on protein expression, and whether such proteins are altered in disease, is unknown.We aim to test whether DKK1 induced protein signature obtained in vitro were associated with markers of AD pathology as used in the amyloid/tau/neurodegeneration (ATN) framework as well as with clinical outcomes.We first overexpressed DKK1 in HEK293A cells and quantified 1,128 proteins in cell lysates using aptamer capture arrays (SomaScan) to obtain a protein signature induced by DKK1. We then used the same assay to measure the DKK1-signature proteins in human plasma in two large cohorts, EMIF (n = 785) and ANM (n = 677).We identified a 100-protein signature induced by DKK1 in vitro. Subsets of proteins, along with age and apolipoprotein E ɛ4 genotype distinguished amyloid pathology (A + T-N-, A+T+N-, A+T-N+, and A+T+N+) from no AD pathology (A-T-N-) with an area under the curve of 0.72, 0.81, 0.88, and 0.85, respectively. Furthermore, we found that some signature proteins (e.g., Complement C3 and albumin) were associated with cognitive score and AD diagnosis in both cohorts.Our results add further evidence for a role of DKK regulation of Wnt signaling in AD and suggest that DKK1 induced signature proteins obtained in vitro could reflect theATNframework as well as predict disease severity and progression in vivo.
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| 5. |
- Augutis, M, et al.
(author)
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Pediatric spinal cord injury in a subset of European countries.
- 2006
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In: Spinal Cord. - : Springer Science and Business Media LLC. - 1362-4393 .- 1476-5624. ; 44:2, s. 106-12
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Journal article (peer-reviewed)abstract
- STUDY DESIGN: Postal survey.SETTING: A total of 19 countries in Europe.OBJECTIVES: Firstly, to collect information about incidence and systems of care for pediatric spinal cord injury (pedSCI); including prevention, initial care and follow-up in a subset of European countries. Secondly, to initiate a network of involved professionals for exchange of information and development of research and care programs.METHODS: A short semi-structured questionnaire was sent to respondents working with spinal cord injury (SCI) in 19 countries in Europe.RESULTS: Only in Portugal and Sweden, is the incidence of pedSCI (fatal injuries included) established, that is 27 children/million children/year and 4.6 children/million children/year, respectively. For the other countries, the estimated incidence of pedSCI (nonfatal injuries) varied from 0.9 to 21.2 children/million children/year in the age group of 0-14 years. Although the incidence varies considerably, pedSCI is rare throughout Europe. The management differs between the countries depending on the age of the child and the local organization of health care.CONCLUSIONS: The survey confirms that pedSCI is rare. In order to establish high-quality standardized care, further integration of knowledge in this area is needed throughout Europe. The contacts initiated by this survey may be used to create an international network serving as a reference for health professionals, researchers and families, thereby possibly alleviating some of the unwanted variations of care identified in this study.
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| 6. |
- Augutis, M, et al.
(author)
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Pediatric spinal cord injury in Sweden : incidence, etiology and outcome.
- 2003
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In: Spinal Cord. - : Springer Science and Business Media LLC. - 1362-4393 .- 1476-5624. ; 41:6, s. 328-36
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Journal article (peer-reviewed)abstract
- STUDY DESIGN: Retrospective descriptive study.OBJECTIVES: To assess incidence, causes and early outcome of traumatic spinal cord injury (SCI) among children in Sweden, thereby identifying high-risk groups and situations as a basis for preventative measures and improved care.METHODS: Data from population registers, County Habilitation Centers as well as from informal sources were used to estimate the incidence of SCI in Sweden during the years 1985-1996 among children aged 0-15 years. Contacts with the treating hospitals, reviews of medical records and/or personal interviews were used to verify primary data. In total, 92 children were thus identified.RESULTS: The incidence was found to be 4.6/million children/year (95% CI 3.6-5.5). When excluding prehospital fatalities, the incidence was 2.4 (95% CI 1.8-3.1). The main cause of injury among fatalities was traffic accidents. Associated injuries occurred in 41% of the children. Among survivors (10-15 years), sports-related injuries (43%) were as common a cause as traffic accidents (39%). The survivors were treated in 18 different hospitals.CONCLUSION: Pediatric SCI in Sweden is rare, presumably because of effective primary prevention. Preventative measures should be further differentiated for each age group of children in accordance with their differing risk profiles. In contrast to the effective preventative measures that have been implemented in Sweden, care of these patients is still too fractionated and decentralized for sufficient specialization to emerge.
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| 7. |
- Augutis, M, et al.
(author)
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Pediatric spinal cord injury in Sweden; how to identify a cohort of rare events.
- 2003
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In: Spinal Cord. - : Springer Science and Business Media LLC. - 1362-4393 .- 1476-5624. ; 41:6, s. 337-46
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Journal article (peer-reviewed)abstract
- STUDY DESIGN: Register study enhanced and verified by medical records and personal interviews and examinations.SETTINGS: Sweden.OBJECTIVES: To define a method of identifying a study population of rare events. To point out the relative importance of every step, an example is given of identifying persons who sustained traumatic spinal cord injury (SCI) in childhood.METHODS: Cases were identified in seven steps that all needed to be fulfilled, from definition of selection criteria through combination of several data sources, to the use of several verification methods.RESULTS: Initial screening by registers identified 384 possible cases, which however were found by subsequent analysis to include a large number of incorrect cases. At completion of all analytic steps, 35 living cases could be fully verified and 14 deceased cases could be partially verified.CONCLUSIONS: Registers offer a practical initial source for study population identification. The screening of International Classification of Diseases codes defining SCI only included less than 30% of 'true' SCIs. Subsequently, further refinement and quality control is necessary in order to ensure validity. Such further verification is time-consuming, but nevertheless necessary in order to verify a true cohort.
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| 8. |
- Augutis, Marika, et al.
(author)
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Psychosocial aspects of traumatic spinal cord injury with onset during adolescence : A qualitative study
- 2007
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In: Journal of Spinal Cord Medicine (JSCM). - : Informa UK Limited. - 1079-0268 .- 2045-7723. ; 30:Suppl1, s. 55-64
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Journal article (peer-reviewed)abstract
- BACKGROUND/OBJECTIVE: Spinal cord injury (SCI) occurring during adolescence poses additional challenges because of the concurrent age-specific bio-psychosocial development. Full understanding of the psychosocial dimensions of rehabilitation requires exploration of the patient perspective. The objective of this study was to focus on psychosocial factors from the patient perspective in persons who had previously sustained a SCI during early and mid-adolescence (11-15 years of age).METHODS: Twenty-four of the 28 persons who had sustained a SCI in Sweden from 1985 to 1996 participated in the study. Semistructured interviews were made an average of 10 years after injury. Narratives were analyzed qualitatively according to content analysis.RESULTS: Parents and peers were found to have formed a crucial network. Parents frequently acted as advocates in interactions with health care providers, as supporters, and as containers of sorrow, frustration, and anger. Peers acted as promoters of activity and identity development. However, health care providers were perceived as not making sufficient use of this network.CONCLUSIONS: Rehabilitation professionals might be encouraged to increase their knowledge of adolescence medicine to better meet the specific needs and demands of persons in this age group. It is further suggested that parents and peers be considered important partners in the joint rehabilitation effort.
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| 9. |
- Boito, Deneb, 1993-, et al.
(author)
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MRI with generalized diffusion encoding reveals damaged white matter in patients previously hospitalized for COVID-19 and with persisting symptoms at follow-up
- 2023
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In: Brain Communications. - : Oxford University Press. - 2632-1297. ; 5:6
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Journal article (peer-reviewed)abstract
- There is mounting evidence of the long-term effects of COVID-19 on the central nervous system, with patients experiencing diverse symptoms, often suggesting brain involvement. Conventional brain MRI of these patients shows unspecific patterns, with no clear connection of the symptomatology to brain tissue abnormalities, whereas diffusion tensor studies and volumetric analyses detect measurable changes in the brain after COVID-19. Diffusion MRI exploits the random motion of water molecules to achieve unique sensitivity to structures at the microscopic level, and new sequences employing generalized diffusion encoding provide structural information which are sensitive to intravoxel features. In this observational study, a total of 32 persons were investigated: 16 patients previously hospitalized for COVID-19 with persisting symptoms of post-COVID condition (mean age 60 years: range 41–79, all male) at 7-month follow-up and 16 matched controls, not previously hospitalized for COVID-19, with no post-COVID symptoms (mean age 58 years, range 46–69, 11 males). Standard MRI and generalized diffusion encoding MRI were employed to examine the brain white matter of the subjects. To detect possible group differences, several tissue microstructure descriptors obtainable with the employed diffusion sequence, the fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity, microscopic anisotropy, orientational coherence (Cc) and variance in compartment’s size (CMD) were analysed using the tract-based spatial statistics framework. The tract-based spatial statistics analysis showed widespread statistically significant differences (P < 0.05, corrected for multiple comparisons using the familywise error rate) in all the considered metrics in the white matter of the patients compared to the controls. Fractional anisotropy, microscopic anisotropy and Cc were lower in the patient group, while axial diffusivity, radial diffusivity, mean diffusivity and CMD were higher. Significant changes in fractional anisotropy, microscopic anisotropy and CMD affected approximately half of the analysed white matter voxels located across all brain lobes, while changes in Cc were mainly found in the occipital parts of the brain. Given the predominant alteration in microscopic anisotropy compared to Cc, the observed changes in diffusion anisotropy are mostly due to loss of local anisotropy, possibly connected to axonal damage, rather than white matter fibre coherence disruption. The increase in radial diffusivity is indicative of demyelination, while the changes in mean diffusivity and CMD are compatible with vasogenic oedema. In summary, these widespread alterations of white matter microstructure are indicative of vasogenic oedema, demyelination and axonal damage. These changes might be a contributing factor to the diversity of central nervous system symptoms that many patients experience after COVID-19.
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| 10. |
- Budh Norrbrink, Cecilia, et al.
(author)
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Pain in a Swedish spinal cord injury population
- 2003
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In: Clinical Rehabilitation. - : SAGE Publications. - 0269-2155 .- 1477-0873. ; 17:6, s. 685-690
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Journal article (peer-reviewed)abstract
- Objective: To describe pain and associated variables in a prevalence group of persons with a sustained spinal cord injury (SCI) in the Swedish capital and its surroundings. Setting: Spinalis SCI Unit (outpatient clinic), Stockholm, Sweden. Design: Assessment over a 12-month period in a yearly health control. Subjects: Four hundred and fifty-six SCI patients. Results: Two hundred and ninety-one out of 456 SCI patients (63.7%) suffered from pain, and in 45.7% of these it was classified as being neurogenic. Aching pain was the most used descriptor (38.5%). The onset of pain was commonly within three months (73.5%). In 70.4% of patients pain occurred below the level of the lesion. Most patients identified pain as coming from one (55.0%) or two (28.2%) body regions. Rating of the general pain intensity on a visual analogue scale (VAS) was 46 out of 100 and rating of the worst pain intensity was 78 out of 100. Ninety-four out of 276 patients (32.3%) considered that their quality of life was significantly affected by pain. Conclusion: Pain was most common in patients with incomplete lesions (ASIA impairment grade D) and there was a correlation between pain and higher mean age at injury and between pain and female gender.
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