| 1. |
- Schöll, Michael, 1980, et al.
(författare)
-
Biomarkers for tau pathology.
- 2019
-
Ingår i: Molecular and cellular neurosciences. - : Elsevier BV. - 1095-9327 .- 1044-7431. ; 97, s. 18-33
-
Forskningsöversikt (refereegranskat)abstract
- The aggregation of fibrils of hyperphosphorylated and C-terminally truncated microtubule-associated tau protein characterizes 80% of all dementia disorders, the most common neurodegenerative disorders. These so-called tauopathies are hitherto not curable and their diagnosis, especially at early disease stages, has traditionally proven difficult. A keystone in the diagnosis of tauopathies was the development of methods to assess levels of tau protein in vivo in cerebrospinal fluid, which has significantly improved our knowledge about these conditions. Tau proteins have also been measured in blood, but the importance of tau-related changes in blood is still unclear. The recent addition of positron emission tomography ligands to visualize, map and quantify tau pathology has further contributed with information about the temporal and spatial characteristics of tau accumulation in the living brain. Together, the measurement of tau with fluid biomarkers and positron emission tomography constitutes the basis for a highly active field of research. This review describes the current state of biomarkers for tau biomarkers derived from neuroimaging and from the analysis of bodily fluids and their roles in the detection, diagnosis and prognosis of tau-associated neurodegenerative disorders, as well as their associations with neuropathological findings, and aims to provide a perspective on how these biomarkers might be employed prospectively in research and clinical settings.
|
|
| 2. |
- Franks, P. W., et al.
(författare)
-
Technological readiness and implementation of genomic-driven precision medicine for complex diseases
- 2021
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 290:3, s. 602-620
-
Forskningsöversikt (refereegranskat)abstract
- The fields of human genetics and genomics have generated considerable knowledge about the mechanistic basis of many diseases. Genomic approaches to diagnosis, prognostication, prevention and treatment - genomic-driven precision medicine (GDPM) - may help optimize medical practice. Here, we provide a comprehensive review of GDPM of complex diseases across major medical specialties. We focus on technological readiness: how rapidly a test can be implemented into health care. Although these areas of medicine are diverse, key similarities exist across almost all areas. Many medical areas have, within their standards of care, at least one GDPM test for a genetic variant of strong effect that aids the identification/diagnosis of a more homogeneous subset within a larger disease group or identifies a subset with different therapeutic requirements. However, for almost all complex diseases, the majority of patients do not carry established single-gene mutations with large effects. Thus, research is underway that seeks to determine the polygenic basis of many complex diseases. Nevertheless, most complex diseases are caused by the interplay of genetic, behavioural and environmental risk factors, which will likely necessitate models for prediction and diagnosis that incorporate genetic and non-genetic data.
|
|
| 3. |
- Tseli, Elena, et al.
(författare)
-
Predictors of multidisciplinary rehabilitation outcomes in patients with chronic musculoskeletal pain : protocol for a systematic review and meta-analysis
- 2017
-
Ingår i: Systematic Reviews. - : BioMed Central (BMC). - 2046-4053. ; 6:1
-
Forskningsöversikt (refereegranskat)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.
|
|
| 4. |
- Johansson, Åsa, et al.
(författare)
-
Precision medicine in complex diseases - : Molecular subgrouping for improved prediction and treatment stratification
- 2023
-
Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 1365-2796 .- 0954-6820. ; 294:4, s. 378-396
-
Forskningsöversikt (refereegranskat)abstract
- Complex diseases are caused by a combination of genetic, lifestyle, and environmental factors and comprise common noncommunicable diseases, including allergies, cardiovascular disease, and psychiatric and metabolic disorders. More than 25% of Europeans suffer from a complex disease, and together these diseases account for 70% of all deaths. The use of genomic, molecular, or imaging data to develop accurate diagnostic tools for treatment recommendations and preventive strategies, and for disease prognosis and prediction, is an important step toward precision medicine. However, for complex diseases, precision medicine is associated with several challenges. There is a significant heterogeneity between patients of a specific disease-both with regards to symptoms and underlying causal mechanisms-and the number of underlying genetic and nongenetic risk factors is often high. Here, we summarize precision medicine approaches for complex diseases and highlight the current breakthroughs as well as the challenges. We conclude that genomic-based precision medicine has been used mainly for patients with highly penetrant monogenic disease forms, such as cardiomyopathies. However, for most complex diseases-including psychiatric disorders and allergies-available polygenic risk scores are more probabilistic than deterministic and have not yet been validated for clinical utility. However, subclassifying patients of a specific disease into discrete homogenous subtypes based on molecular or phenotypic data is a promising strategy for improving diagnosis, prediction, treatment, prevention, and prognosis. The availability of high-throughput molecular technologies, together with large collections of health data and novel data-driven approaches, offers promise toward improved individual health through precision medicine.
|
|
| 5. |
- Munoz-Novoa, Maria, et al.
(författare)
-
Upper Limb Stroke Rehabilitation Using Surface Electromyography: A Systematic Review and Meta-Analysis
- 2022
-
Ingår i: Frontiers in Human Neuroscience. - : Frontiers Media SA. - 1662-5161. ; 16
-
Forskningsöversikt (refereegranskat)abstract
- Background: Upper limb impairment is common after stroke, and many will not regain full upper limb function. Different technologies based on surface electromyography (sEMG) have been used in stroke rehabilitation, but there is no collated evidence on the different sEMG-driven interventions and their effect on upper limb function in people with stroke. Aim: Synthesize existing evidence and perform a meta-analysis on the effect of different types of sEMG-driven interventions on upper limb function in people with stroke. Methods: PubMed, SCOPUS, and PEDro databases were systematically searched for eligible randomized clinical trials that utilize sEMG-driven interventions to improve upper limb function assessed by Fugl-Meyer Assessment (FMA-UE) in stroke. The PEDro scale was used to evaluate the methodological quality and the risk of bias of the included studies. In addition, a meta-analysis utilizing a random effect model was performed for studies comparing sEMG interventions to non-sEMG interventions and for studies comparing different sEMG interventions protocols. Results: Twenty-four studies comprising 808 participants were included in this review. The methodological quality was good to fair. The meta-analysis showed no differences in the total effect, assessed by total FMA-UE score, comparing sEMG interventions to non-sEMG interventions (14 studies, 509 participants, SMD 0.14, P 0.37, 95% CI –0.18 to 0.46, I2 55%). Similarly, no difference in the overall effect was found for the meta-analysis comparing different types of sEMG interventions (7 studies, 213 participants, SMD 0.42, P 0.23, 95% CI –0.34 to 1.18, I2 73%). Twenty out of the twenty-four studies, including participants with varying impairment levels at all stages of stroke recovery, reported statistically significant improvements in upper limb function at post-sEMG intervention compared to baseline. Conclusion: This review and meta-analysis could not discern the effect of sEMG in comparison to a non-sEMG intervention or the most effective type of sEMG intervention for improving upper limb function in stroke populations. Current evidence suggests that sEMG is a promising tool to further improve functional recovery, but randomized clinical trials with larger sample sizes are needed to verify whether the effect on upper extremity function of a specific sEMG intervention is superior compared to other non-sEMG or other type of sEMG interventions.
|
|
| 6. |
- Canevelli, Marco, et al.
(författare)
-
Race reporting and disparities in clinical trials on Alzheimer's disease : A systematic review
- 2019
-
Ingår i: Neuroscience and Biobehavioral Reviews. - : Elsevier BV. - 0149-7634 .- 1873-7528. ; 101, s. 122-128
-
Forskningsöversikt (refereegranskat)abstract
- Introduction: Race is an important health determinant and should adequately be considered in research and drug development protocols targeting Alzheimer's disease (AD).Methods: A systematic review of available randomized controlled trials (RCTs) on the currently marketed treatments for AD was conducted with the aim of 1) documenting the reporting of race, and 2) exploring the impact of race on the efficacy and safety/tolerability of the considered medications.Results: Overall, 59.2% of the 49 retained RCTs reported information concerning the race of participants. Only a striking minority of enrolled patients was constituted of blacks and Hispanics. None on the retained studies reported results on the efficacy and safety/tolerability of the tested treatment separately for racial groups nor performed sensitivity analyses accounting for the race of participants.Discussion: Race has insufficiently been reported in previous interventional studies on AD. Its potential association with the effectiveness and safety/tolerability of the tested medications has completely been neglected.
|
|
| 7. |
- Tseli, Elena, et al.
(författare)
-
Prognostic Factors for Physical Functioning After Multidisciplinary Rehabilitation in Patients With Chronic Musculoskeletal Pain : A Systematic Review and Meta-Analysis
- 2019
-
Ingår i: The Clinical Journal of Pain. - : Lippincott Williams & Wilkins. - 0749-8047 .- 1536-5409. ; 35:2, s. 148-173
-
Forskningsöversikt (refereegranskat)abstract
- OBJECTIVES: This systematic review aimed to identify and evaluate prognostic factors for long-term (≥6 mo) physical functioning in patients with chronic musculoskeletal pain following multidisciplinary rehabilitation (MDR).MATERIALS AND METHODS: Electronic searches conducted in MEDLINE, PsycINFO, EMBASE, CINAHL, Web of Science, and Cochrane CENTRAL revealed 25 original research reports, published 1983-2016, (n=9436). Potential prognostic factors relating to initial pain and physical and psychological functioning were synthesized qualitatively and quantitatively in random effects meta-analyses. The level of evidence (LoE) was evaluated with Grading of Recommendations Assessment, Development and Evaluation (GRADE).RESULTS: Pain-related factors (intensity and chronicity) were not associated with function/disability at long-term follow-up, odds ratio (OR)=0.84; 95% confidence interval (CI), 0.65-1.07 and OR=0.97; 95% CI, 0.93-1.00, respectively (moderate LoE). A better function at follow-up was predicted by Physical factors; higher levels of initial self-reported functioning, OR=1.07; 95% CI, 1.02-1.13 (low LoE), and Psychological factors; low initial levels of emotional distress, OR=0.77; 95% CI, 0.65-0.92, low levels of cognitive and behavioral risk factors, OR=0.85; 95% CI, 0.77-0.93 and high levels of protective cognitive and behavioral factors, OR=1.49; 95% CI, 1.17-1.90 (moderate LoE).DISCUSSION: While pain intensity and long-term chronicity did not predict physical functioning in chronic pain patients after MDR, poor pretreatment physical and psychological functioning influenced the prognosis negatively. Thus, treatment should further target and optimize these modifiable factors and an increased focus on positive, psychological protective factors may perhaps provide an opening for yet untapped clinical gains.
|
|
| 8. |
- Ekegren, Titti, et al.
(författare)
-
Clinical perspectives of high-resolution mass spectrometry-based proteomics in neuroscience: exemplified in amyotrophic lateral sclerosis biomarker discovery research.
- 2008
-
Ingår i: Journal of mass spectrometry : JMS. - : Wiley. - 1076-5174 .- 1096-9888. ; 43:5, s. 559-71
-
Forskningsöversikt (refereegranskat)abstract
- Biomarker discovery is a central application in today's proteomic research. There is an urgent need for valid biomarkers to improve diagnostic tools and treatment in many disorders, such as the rapidly progressing neurodegenerative disorder amyotrophic lateral sclerosis (ALS) that has a fatal outcome in about 3 years and yet no curative treatment. Screening for clinically relevant biomarkers puts high demands on high-throughput, rapid and precise proteomic techniques. There is a large variety in the methods of choice involving mainly gel-based approaches as well as chromatographic techniques for multi-dimensional protein and peptide separations followed by mass spectrometry (MS) analysis. This special feature article will discuss some important aspects of MS-based clinical proteomics and biomarker discovery in the field of neurodegenerative diseases and ALS research respectively, with the aim to provide a prospective view on current and future research aspects in the field. Furthermore, examples for application of high-resolution MS-based proteomic strategies for ALS biomarker discovery will be demonstrated with two studies previously reported by our group. These studies include among others, utilization of capillary liquid chromatography-Fourier transform ion cyclotron resonance mass spectrometry (LC-FTICR-MS) for advanced protein pattern classification in cerebrospinal fluid (CSF) samples of ALS patients as well as highly sensitive protein identification in minimal amounts of postmortem spinal cord tissue and laser micro-dissected motor neurons using FT-ICR-MS in conjunction with nanoflow LC coupled to matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (LC-MALDI-TOF-TOF-MS).
|
|
| 9. |
- Broström, Anders, et al.
(författare)
-
Quality of life among patients with restless legs syndrome : A systematic review and meta-analysis
- 2024
-
Ingår i: Journal of clinical neuroscience. - : Elsevier. - 0967-5868 .- 1532-2653. ; 122, s. 80-91
-
Forskningsöversikt (refereegranskat)abstract
- Objective: The primary aim was to estimate the pooled mean score of quality of life (QoL) (total, mental and physical health components) among patients with Restless Legs Syndrome (RLS).Secondary aims were to assess: (I) QoL differences for RLS vs. control groups, (II) heterogeneity and possible sources; and (III) moderating variables.Methods: Studies identified in PubMed, Scopus, Web of Science, and ProQuest between January 2000 and December 2022 were included. Methodological quality was assessed with Newcastle Ottawa Scale. The protocol was pre-registered (PROSPERO, CRD42023387318).Results: Twenty-seven studies (20121 participants, 12 countries) were included. The corrected pooled estimated mean score of QoL was 47.92 (27 studies, CI 95 %: 43.11 to 52.72, range 0–100, i.e., low–high QoL) and was marginally affected by publication year (increased 0.89 by each year, p = 0.12). The corrected pooled estimated mean score of the mental health component was 47.32 (17 studies, 95 % CI: 43.12 to 51.51, range 0–100) and influenced by RLS instrument (decreased with recent versions, p = 0.05). The corrected pooled estimated mean score of the physical health component was 39.08 (17 studies, 95 % CI: 33.05 to 45.10, range 0–100), with no statistically significant moderator. The pooled estimated QoL scores were statistically significantly lower in RLS patients compared to control groups with standardized mean difference (SMD) of −0.78, −0.57 and −0.50 respectively for overall QoL (24 studies), physical and mental health components (14 studies). Total QoL SMD was affected by proportion of women.Conclusion: Low QoL was revealed among RLS patients, which was statistically significantly reduced compared to control groups.
|
|
| 10. |
- Linton, Steven J., 1952-, et al.
(författare)
-
The effect of the work environment on future sleep disturbances : a systematic review
- 2015
-
Ingår i: Sleep Medicine Reviews. - : W. B. Saunders. - 1087-0792 .- 1532-2955. ; 23:Oktober, s. 10-19
-
Forskningsöversikt (refereegranskat)abstract
- Workers often attribute poor sleep to factors at work. Despite the large number of workers with sleep disturbances, there is a lack of consensus on the relationship between the work environment and sleep. The purpose of this systematic review therefore was to conduct a comprehensive evaluation. To this end, we employed standardized methods to systematically locate, review, and tabulate the results of prospective or randomized studies of the impact of work factors on sleep disturbances. From the 7981 articles located in five databases, 24 fulfilled our inclusion criteria and formed the base of the review including meta-analyses of the effect sizes. Results showed that the psychosocial work variables of social support at work, control, and organizational justice were related to fewer sleep disturbances, while high work demands, job strain, bullying, and effort-reward imbalance were related to more future sleep disturbances. Moreover, working a steady shift was associated with disturbances while exiting shift work was associated with less disturbed sleep. We conclude that psychosocial work factors and the scheduling of work have an impact on sleep disturbances and this might be utilized in the clinic as well as for planning work environments. Future research needs to employ better methodology and focus on underlying mechanisms.
|
|
