| 1. |
- Tour, Jeanette, et al.
(author)
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Gene-to-gene interactions regulate endogenous pain modulation in fibromyalgia patients and healthy controls-antagonistic effects between opioid and serotonin-related genes.
- 2017
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In: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 158:7, s. 1194-1203
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Journal article (peer-reviewed)abstract
- Chronic pain is associated with dysfunctional endogenous pain modulation, involving both central opioid and serotonergic (5-HT) signaling. Fibromyalgia (FM) is a chronic pain syndrome, characterized by widespread musculoskeletal pain and reduced exercise-induced hypoalgesia (EIH). In this study, we assessed the effects of 3 functional genetic polymorphisms on EIH in 130 patients with FM and 132 healthy controls. Subjects were genotyped regarding the mu-opioid receptor (OPRM1) gene (rs1799971), the serotonin transporter (5-HTT) gene (5-HTTLPR/rs25531), and the serotonin-1a receptor (5-HT1a) gene (rs6296). The patients with FM had increased pain sensitivity and reduced EIH compared with healthy controls. None of the polymorphisms had an effect on EIH on their own. We found significant gene-to-gene interactions between OPRM1 x 5-HTT and OPRM1 x 5-HT1a regarding activation of EIH, with no statistically significant difference between groups. Better EIH was found in individuals with genetically inferred strong endogenous opioid signaling (OPRM1 G) in combination with weak 5-HT tone (5-HTT low/5-HT1a G), compared with strong 5-HT tone (5-HTT high/5-HT1a CC). Based on the proposed mechanisms of these genetic variants, the findings indicate antagonistic interactions between opioid and serotonergic mechanisms during EIH. Moreover, despite different baseline pain level, similar results were detected in FM and controls, not supporting an altered interaction between opioid and 5-HT mechanisms as the basis for dysfunction of EIH in patients with FM. In summary, our results suggest that, by genetic association, the mu-opioid receptor interacts with 2 major serotonergic structures involved in 5-HT reuptake and release, to modulate EIH.
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| 2. |
- Tseli, Elena, et al.
(author)
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Predictors of multidisciplinary rehabilitation outcomes in patients with chronic musculoskeletal pain : protocol for a systematic review and meta-analysis
- 2017
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In: Systematic Reviews. - : BioMed Central (BMC). - 2046-4053. ; 6:1
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Research review (peer-reviewed)abstract
- BACKGROUND: Chronic musculoskeletal pain is a major public health problem. Early prediction for optimal treatment results has received growing attention, but there is presently a lack of evidence regarding what information such proactive management should be based on. This study protocol, therefore, presents our planned systematic review and meta-analysis on important predictive factors for health and work-related outcomes following multidisciplinary rehabilitation (MDR) in patients with chronic musculoskeletal pain.METHODS: We aim to perform a synthesis of the available evidence together with a meta-analysis of published peer-reviewed original research that includes predictive factors preceding MDR. Included are prospective studies of adults with benign, chronic (> 3 months) musculoskeletal pain diagnoses who have taken part in MDR. In the studies, associations between personal and rehabilitation-based factors and the outcomes of interest are reported. Outcome domains are pain, physical functioning including health-related quality of life, and work ability with follow-ups of 6 months or more. We will use a broad, explorative approach to any presented predictive factors (demographic, symptoms-related, physical, psychosocial, work-related, and MDR-related) and these will be analyzed through (a) narrative synthesis for each outcome domain and (b) if sufficient studies are available, a quantitative synthesis in which variance-weighted pooled proportions will be computed using a random effects model for each outcome domain. The strength of the evidence will be evaluated using the Grading of Recommendations, Assessment, Development and Evaluation.DISCUSSION: The strength of this systematic review is that it aims for a meta-analysis of prospective cohort or randomized controlled studies by performing an extensive search of multiple databases, using an explorative study approach to predictive factors, rather than building on single predictor impact on the outcome or on predefined hypotheses. In this way, an overview of factors central to MDR outcome can be made and will help strengthen the evidence base and inform a wide readership including health care practitioners and policymakers.SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016025339.
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| 3. |
- Cedervall, Ylva, et al.
(author)
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Timed Up-and-Go Dual-Task Testing in the Assessment of Cognitive Function : A Mixed Methods Observational Study for Development of the UDDGait Protocol
- 2020
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In: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 17:5
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Journal article (peer-reviewed)abstract
- New methods to screen for and identify early-stage dementia disorders are highly sought after. The purpose of this pilot study is to develop a study protocol for a dual-task test aimed at aiding the early detection of dementia disorders. We used the Timed Up-and-Go (TUG) test, which is a mobility task involving starting in a sitting position, standing up, walking three meters to cross a line on the floor, turning around, walking back and sitting down again. We combined TUG with the verbal task of naming different animals. Pilot study participants were 43 individuals with and without established dementia diagnoses who attended a clinic for memory assessment. Video-recorded test performances were systematically analysed. Deviant test performances concerning the interplay between test administration and participants' responses to the assessment instructions were revealed and led to refinements being made to the final study protocol. Exploration of the dual-task test outcome measures in a sub-sample of 22 persons, ten with and twelve without dementia, indicated that step-length and number of named animals after the turning point of the dual-task test might constitute appropriate measures for examining this kind of sample. We concluded that the refined study protocol is feasible for testing individuals undergoing initial memory assessments and healthy controls. Follow-up studies with larger samples are being carried out and will bring new knowledge to this area of research. It may also provide an opportunity for further studies exploring possibilities for broad clinical implementation.
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| 4. |
- Lawrence, Maggie, et al.
(author)
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Stroke secondary prevention, a non-surgical and non-pharmacological consensus definition: results of a Delphi study
- 2019
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In: BMC Research Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 12:1
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Evidence supporting lifestyle modification in vascular risk reduction is limited, drawn largely from primary prevention studies. To advance the evidence base for non-pharmacological and non-surgical stroke secondary prevention (SSP), empirical research is needed, informed by a consensus-derived definition of SSP. To date, no such definition has been published. We used Delphi methods to generate an evidence-based definition of non-pharmacological and non-surgical SSP. RESULTS: The 16 participants were members of INSsPiRE (International Network of Stroke Secondary Prevention Researchers), a multidisciplinary group of trialists, academics and clinicians. The Elicitation stage identified 49 key elements, grouped into 3 overarching domains: Risk factors, Education, and Theory before being subjected to iterative stages of elicitation, ranking, discussion, and anonymous voting. In the Action stage, following an experience-based engagement with key stakeholders, a consensus-derived definition, complementing current pharmacological and surgical SSP pathways, was finalised: Non-pharmacological and non-surgical stroke secondary prevention supports and improves long-term health and well-being in everyday life and reduces the risk of another stroke, by drawing from a spectrum of theoretically informed interventions and educational strategies. Interventions to self-manage modifiable lifestyle risk factors are contextualized and individualized to the capacities, needs, and personally meaningful priorities of individuals with stroke and their families.
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| 5. |
- Senek, Marina, et al.
(author)
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Levodopa/carbidopa microtablets in Parkinson's disease : a study of pharmacokinetics and blinded motor assessment
- 2017
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In: European Journal of Clinical Pharmacology. - Heidelberg, Germany : Springer. - 0031-6970 .- 1432-1041 .- 0014-2999. ; 73:5, s. 563-571
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Journal article (peer-reviewed)abstract
- Background: Motor function assessments with rating scales in relation to the pharmacokinetics of levodopa may increase the understanding of how to individualize and fine-tune treatments.Objectives: This study aimed to investigate the pharmacokinetic profiles of levodopa-carbidopa and the motor function following a single-dose microtablet administration in Parkinson’s disease.Methods: This was a single-center, open-label, single-dose study in 19 patients experiencing motor fluctuations. Patients received 150% of their individual levodopa equivalent morning dose in levodopa-carbidopa microtablets. Blood samples were collected at pre-specified time points. Patients were video recorded and motor function was assessed with six UPDRS part III motor items, dyskinesia score, and the treatment response scale (TRS), rated by three blinded movement disorder specialists.Results: AUC0–4/dose and Cmax/dose for levodopa was found to be higher in Parkinson’s disease patients compared with healthy subjects from a previous study, (p = 0.0008 and p = 0.026, respectively). The mean time to maximum improvement in sum of six UPDRS items score was 78 min (±59) (n = 16), and the mean time to TRS score maximum effect was 54 min (±51) (n = 15). Mean time to onset of dyskinesia was 41 min (±38) (n = 13).Conclusions: In the PD population, following levodopa/carbidopa microtablet administration in fasting state, the Cmax and AUC0–4/dose were found to be higher compared with results from a previous study in young, healthy subjects. A large between subject variability in response and duration of effect was observed, highlighting the importance of a continuous and individual assessment of motor function in order to optimize treatment effect.
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| 6. |
- Åberg, Anna Cristina, et al.
(author)
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Calculations of mechanisms for balance control during narrow and single-leg standing in fit older adults: A reliability study.
- 2011
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In: Gait & Posture. - : Elsevier BV. - 0966-6362 .- 1879-2219. ; 34:3, s. 352-7
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Journal article (peer-reviewed)abstract
- For older people balance control in standing is critical for performance of activities of daily living without falling. The aims were to investigate reliability of quantification of the usage of the two balance mechanisms M1 ‘moving the centre of pressure’ and M2 ‘segment acceleration’ and also to compare calculation methods based on a combination of kinetic (K) and kinematic (Km) data, (K–Km), or Km data only concerning M2. For this purpose nine physically fit persons aged 70–78 years were tested in narrow and single-leg standing. Data were collected by a 7-camera motion capture system and two force plates. Repeated measure ANOVA and Tukey's post hoc tests were used to detect differences between the standing tasks. Reliability was estimated by ICCs, standard error of measurement including its 95% CI, and minimal detectable change, whereas Pearson's correlation coefficient was used to investigate agreement between the two calculation methods. The results indicated that for the tasks investigated, M1 and M2 can be measured with acceptable inter- and intrasession reliability, and that both Km and K–Km based calculations may be useful for M2, although Km data may give slightly lower values. The proportional M1:M2 usage was approximately 9:1, in both anterio-posterior (AP) and medio-lateral (ML) directions for narrow standing, and about 2:1 in the AP and of 1:2 in the ML direction in single-leg standing, respectively. In conclusion, the tested measurements and calculations appear to constitute a reliable way of quantifying one important aspect of balance capacity in fit older people.
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| 7. |
- Westin, Jerker, et al.
(author)
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A new computer method for assessing drawing impairment in Parkinson's disease
- 2010
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In: Journal of Neuroscience Methods. - Amsterdam : Elsevier. - 0165-0270 .- 1872-678X. ; 190:1, s. 143-148
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Journal article (peer-reviewed)abstract
- A test battery, consisting of self-assessments and motor tests (tapping and spiral drawing tasks) was used on 9482 test occasions by 62 patients with advanced Parkinson's disease (PD) in a telemedicine setting. On each test occasion, three Archimedes spirals were traced. A new computer method, using wavelet transforms and principal component analysis processed the spiral drawings to generate a spiral score. In a web interface, two PD specialists rated drawing impairment in spiral drawings from three random test occasions per patient, using a modification of the Bain & Findley 10-category scale. A standardised manual rating was defined as the mean of the two raters’ assessments. Bland-Altman analysis was used to evaluate agreement between the spiral score and the standardised manual rating. Another selection of spiral drawings was used to estimate the Spearman rank correlations between the raters (r = 0.87), and between the mean rating and the spiral score (r = 0.89). The 95% confidence interval for the method's prediction errors was ±1.5 scale units, which was similar to the differences between the human raters. In conclusion, the method could assess PD-related drawing impairments well comparable to trained raters.
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| 8. |
- Aghanavesi, Somayeh, 1981-, et al.
(author)
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A multiple motion sensors index for motor state quantification in Parkinson's disease
- 2020
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In: Computer Methods and Programs in Biomedicine. - : Elsevier BV. - 0169-2607 .- 1872-7565. ; 189
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Journal article (peer-reviewed)abstract
- Aim: To construct a Treatment Response Index from Multiple Sensors (TRIMS) for quantification of motor state in patients with Parkinson's disease (PD) during a single levodopa dose. Another aim was to compare TRIMS to sensor indexes derived from individual motor tasks. Method: Nineteen PD patients performed three motor tests including leg agility, pronation-supination movement of hands, and walking in a clinic while wearing inertial measurement unit sensors on their wrists and ankles. They performed the tests repeatedly before and after taking 150% of their individual oral levodopa-carbidopa equivalent morning dose.Three neurologists blinded to treatment status, viewed patients’ videos and rated their motor symptoms, dyskinesia, overall motor state based on selected items of Unified PD Rating Scale (UPDRS) part III, Dyskinesia scale, and Treatment Response Scale (TRS). To build TRIMS, out of initially 178 extracted features from upper- and lower-limbs data, 39 features were selected by stepwise regression method and were used as input to support vector machines to be mapped to mean reference TRS scores using 10-fold cross-validation method. Test-retest reliability, responsiveness to medication, and correlation to TRS as well as other UPDRS items were evaluated for TRIMS. Results: The correlation of TRIMS with TRS was 0.93. TRIMS had good test-retest reliability (ICC = 0.83). Responsiveness of the TRIMS to medication was good compared to TRS indicating its power in capturing the treatment effects. TRIMS was highly correlated to dyskinesia (R = 0.85), bradykinesia (R = 0.84) and gait (R = 0.79) UPDRS items. Correlation of sensor index from the upper-limb to TRS was 0.89. Conclusion: Using the fusion of upper- and lower-limbs sensor data to construct TRIMS provided accurate PD motor states estimation and responsive to treatment. In addition, quantification of upper-limb sensor data during walking test provided strong results. © 2019
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| 9. |
- Thomas, Ilias, et al.
(author)
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Using measurements from wearable sensors for automatic scoring of Parkinson's disease motor states : Results from 7 patients
- 2017
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In: 2017 39th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC). - New York : IEEE. - 1094-687X. - 9781509028092 - 9781509028108 ; , s. 131-134
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Conference paper (peer-reviewed)abstract
- The objective of this study was to investigate the validity of an objective gait measure for assessment of different motor states of advanced Parkinson's disease (PD) patients. Seven PD patients performed a gait task up to 15 times while wearing sensors on their upper and lower limbs. Each task was performed at specific points during a test day, following a single dose of levodopa-carbidopa. At the time of the tasks the patients were video recorded and three movement disorder experts rated their motor function on three clinical scales: a treatment response scale (TRS) that ranged from −3 (very bradykinetic) to 0 (ON) to +3 (very dyskinetic), a dyskinesia score that ranged from 0 (no dyskinesia) to 4 (extreme dyskinesia), and a bradykinesia score that ranged from 0 (no bradykinesia) to 4 (extreme bradykinesia). Raw accelerometer and gyroscope data of the sensors were processed and analyzed with time series analysis methods to extract features. The utilized features quantified separate limb movements as well as movement symmetries between the limbs. The features were processed with principal component analysis and the components were used as predictors for separate support vector machine (SVM) models for each of the three scales. The performance of each model was evaluated in a leave-one-patient out setting where the observations of a single patient were used as the testing set and the observations of the other 6 patients as the training set. Root mean square error (RMSE) and correlation coefficients for the predictions showed a good ability of the models to map the sensor data into the rating scales. There were strong correlations between the SVM models and the mean ratings of TRS (0.79; RMSE=0.70), bradykinesia score (0.79; RMSE=0.47), and bradykinesia score (0.78; RMSE=0.46). The results presented in this paper indicate that the use of wearable sensors when performing gait tasks can generate measurements that have a good correlation to subjective expert assessments.
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| 10. |
- Åhman, Hanna Bozkurt, et al.
(author)
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Dual-task performance and neurodegeneration : Correlations between timed up-and-go dual-task test outcomes and Alzheimer's disease cerebrospinal fluid biomarkers
- 2019
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In: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 71:Suppl 1, s. S75-S83
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Journal article (peer-reviewed)abstract
- BACKGROUND: Tools to identify individuals at preclinical stages of dementia disorders are needed to enable early interventions. Alterations in dual-task performance have been detected early in progressive neurodegenerative disorders. Hence, dual-task testing may have the potential to screen for cognitive impairment caused by neurodegeneration. Exploring correlations between dual-task performance and biomarkers of neurodegeneration is therefore of interest.OBJECTIVE: To investigate correlations between Timed Up-and-Go dual-task (TUGdt) outcomes and Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers amyloid-β 42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau).METHODS: This cross-sectional cohort study included 90 participants (age range 49-84 years) undergoing memory assessment, who were subsequently diagnosed with AD, other dementia disorders, mild cognitive impairment, or subjective cognitive impairment. TUG combined with "Naming Animals" (TUGdt NA) and "Months Backwards" (TUGdt MB), respectively, were used to assess dual-task performance. The number of correct words and time taken to complete the tests were measured. The CSF biomarkers were analysed by ELISA. Spearman's rank correlation was used for analyses between TUGdt outcomes (TUGdt NA and TUGdt MB), and CSF biomarkers, adjusted for age, gender, and educational level.RESULTS: The number of correct words, as well as the number of correct words/10 s during TUGdt NA correlated negatively to CSF t-tau and p-tau. No correlations were found between any time scores and CSF biomarkers.CONCLUSION: The correlations between TUGdt NA and t-tau and p-tau may indicate that neurodegeneration affects dual-task performance. Longitudinal studies are needed to further explore dual-task testing in screening for cognitive impairment due to neurodegeneration.
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