| 1. |
- Tseli, Elena, et al.
(författare)
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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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Ingår i: Systematic Reviews. - : BioMed Central (BMC). - 2046-4053. ; 6:1
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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.
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| 2. |
- Duan, Rui-Dong
(författare)
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Alkaline sphingomyelinase: An old enzyme with novel implications.
- 2006
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Ingår i: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. - : Elsevier BV. - 1388-1981. ; 1761:3, s. 281-291
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Forskningsöversikt (refereegranskat)abstract
- Alkaline sphingomyelinase (alk-SMase) is present in the intestinal tract and additionally human bile. It hydrolyses sphingomyelin in both intestinal lumen and the mucosal membrane in a specific bile salt dependent manner. The enzyme was discovered 36 years ago but got real attention only in the last decade, when sphingomyelin metabolism was realized to be a source of multiple lipid messengers, and when dietary sphingomyelin was found to inhibit colonic tumorigenesis in animals. The enzyme shares no structural similarity with other SMases and belongs to the nucleotide pyrophosphatase/phosphodiesterase family. The enzyme is of specific properties, such as bile salt dependency, trypsin resistance, high stability, and tissue specific expression. In the colon, the enzyme may play antiproliferative and antiinflammatory roles through generating ceramide, reducing the formation of lysophosphatidic acid, and inactivating platelet-activating factor. The enzyme is down regulated in human long-standing ulcerative colitis and colonic adenocarcinoma, and mutation of the enzyme has been found in colon cancer cells. In the small intestine, alk-SMase is the key enzyme for sphingomyelin digestion. The hydrolysis of sphingomyelin may affect the cholesterol uptake and have impact on sphingomyelin levels in plasma lipoproteins. The review summarizes the new information of alk-SMase from biochemical, cell and molecular biological studies in the last decade and evaluates its potential implications in development of colon cancer, inflammatory bowel diseases, and atherosclerosis. (c) 2006 Elsevier B.V. All rights reserved.
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| 3. |
- Ekegren, Titti, et al.
(författare)
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Clinical perspectives of high-resolution mass spectrometry-based proteomics in neuroscience: exemplified in amyotrophic lateral sclerosis biomarker discovery research.
- 2008
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Ingår i: Journal of mass spectrometry : JMS. - : Wiley. - 1076-5174 .- 1096-9888. ; 43:5, s. 559-71
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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).
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| 4. |
- Horn, Nina, et al.
(författare)
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Atp7a-regulated enzyme metalation and trafficking in the menkes disease puzzle
- 2021
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Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 9:4
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Forskningsöversikt (refereegranskat)abstract
- Copper is vital for numerous cellular functions affecting all tissues and organ systems in the body. The copper pump, ATP7A is critical for whole-body, cellular, and subcellular copper homeostasis, and dysfunction due to genetic defects results in Menkes disease. ATP7A dysfunction leads to copper deficiency in nervous tissue, liver, and blood but accumulation in other tissues. Site-specific cellular deficiencies of copper lead to loss of function of copper-dependent enzymes in all tissues, and the range of Menkes disease pathologies observed can now be explained in full by lack of specific copper enzymes. New pathways involving copper activated lysosomal and steroid sulfatases link patient symptoms usually related to other inborn errors of metabolism to Menkes disease. Additionally, new roles for lysyl oxidase in activation of molecules necessary for the innate immune system, and novel adapter molecules that play roles in ERGIC trafficking of brain receptors and other proteins, are emerging. We here summarize the current knowledge of the roles of copper enzyme function in Menkes disease, with a focus on ATP7A-mediated enzyme metalation in the secretory pathway. By establishing mechanistic relationships between copper-dependent cellular processes and Menkes disease symptoms in patients will not only increase understanding of copper biology but will also allow for the identification of an expanding range of copper-dependent enzymes and pathways. This will raise awareness of rare patient symptoms, and thus aid in early diagnosis of Menkes disease patients.
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| 5. |
- Kwakkenbos, Linda, et al.
(författare)
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Protocol for a scoping review to support development of a CONSORT extension for randomised controlled trials using cohorts and routinely collected health data
- 2018
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 8:8
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Forskningsöversikt (refereegranskat)abstract
- Introduction: Randomised controlled trials (RCTs) conducted using cohorts and routinely collected health data, including registries, electronic health records and administrative databases, are increasingly used in healthcare intervention research. The development of an extension of the CONsolidated Standards of Reporting Trials (CONSORT) statement for RCTs using cohorts and routinely collected health data is being undertaken with the goal of improving reporting quality by setting standards early in the process of uptake of these designs. To develop this extension to the CONSORT statement, a scoping review will be conducted to identify potential modifications or clarifications of existing reporting guideline items, as well as additional items needed for reporting RCTs using cohorts and routinely collected health data.Methods and analysis: In separate searches, we will seek publications on methods or reporting or that describe protocols or results from RCTs using cohorts, registries, electronic health records and administrative databases. Data sources will include Medline and the Cochrane Methodology Register. For each of the four main types of RCTs using cohorts and routinely collected health data, separately, two investigators will independently review included publications to extract potential checklist items. A potential item will either modify an existing CONSORT 2010, Strengthening the Reporting of Observational Studies in Epidemiology or REporting of studies Conducted using Observational Routinely collected health Data item or will be proposed as a new item. Additionally, we will identify examples of good reporting in RCTs using cohorts and routinely collected health data.Ethics and dissemination: The proposed scoping review will help guide the development of the CONSORT extension statement for RCTs conducted using cohorts and routinely collected health data.
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| 6. |
- Olsson, Anders, 1940-, et al.
(författare)
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Can LDL cholesterol be too low? Possible risks of extremely low levels
- 2017
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Ingår i: Journal of Internal Medicine. - : WILEY. - 0954-6820 .- 1365-2796. ; 281:6, s. 534-553
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Forskningsöversikt (refereegranskat)abstract
- Following the continuous accumulation of evidence supporting the beneficial role of reducing low-density lipoprotein cholesterol (LDL-C) levels in the treatment and prevention of atherosclerotic cardiovascular disease and its complications, therapeutic possibilities now exist to lower LDL-C to very low levels, similar to or even lower than those seen in newborns and nonhuman species. In addition to the important task of evaluating potential side effects of such treatments, the question arises whether extremely low LDL-C levels per se may provoke adverse effects in humans. In this review, we summarize information from studies of human cellular and organ physiology, phenotypic characterization of rare genetic diseases of lipid metabolism, and experience from clinical trials. Specifically, we emphasize the importance of the robustness of the regulatory systems that maintain balanced fluxes and levels of cholesterol at both cellular and organismal levels. Even at extremely low LDL-C levels, critical capacities of steroid hormone and bile acid production are preserved, and the presence of a cholesterol blood-brain barrier protects cells in the central nervous system. Apparent relationships sometimes reported between less pronounced low LDL-C levels and disease states such as cancer, depression, infectious disease and others can generally be explained as secondary phenomena. Drug-related side effects including an increased propensity for development of type 2 diabetes occur during statin treatment, whilst further evaluation of more potent LDL-lowering treatments such as PCSK9 inhibitors is needed. Experience from the recently reported and ongoing large event-driven trials are of great interest, and further evaluation including careful analysis of cognitive functions will be important. This is an article from the symposium: Risks and benefits of Extremely Low LDL Cholesterol.
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| 7. |
- Rasmusson, Lars, 1962, et al.
(författare)
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Bisphosphonate associated osteonecrosis of the jaw: an update on pathophysiology, risk factors, and treatment.
- 2014
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Ingår i: International Journal of Dentistry. - : Hindawi Publishing Corporation. - 1687-8728 .- 1687-8736.
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Forskningsöversikt (refereegranskat)abstract
- Osteonecrosis of the jaw in patients treated with bisphosphonates is a relatively rare but well known complication at maxillofacial units around the world. It has been speculated that the medication, especially long-term i.v. bisphosphonate treatment, could cause sterile necrosis of the jaws. The aim of this narrative review of the literature was to elaborate on the pathological mechanisms behind the condition and also to gather an update on incidence, risk factors, and treatment of bisphosphonate associated osteonecrosis of the jaw. In total, ninety-one articles were reviewed. All were published in internationally recognized journals with referee systems. We can conclude that necrotic lesions in the jaw seem to be following upon exposure of bone, for example, after tooth extractions, while other interventions like implant placement do not increase the risk of osteonecrosis. Since exposure to the bacterial environment in the oral cavity seems essential for the development of necrotic lesions, we believe that the condition is in fact chronic osteomyelitis and should be treated accordingly.
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| 8. |
- Rosales, Roberto S., et al.
(författare)
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The methodological requirements for clinical examination and patient-reported outcomes, and how to test them
- 2020
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Ingår i: Journal of Hand Surgery: European Volume. - : SAGE Publications. - 1753-1934 .- 2043-6289. ; 45:1, s. 12-18
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Forskningsöversikt (refereegranskat)abstract
- This article presents the methodological requirements for clinical examination and patient-reported outcomes measurements. The assessment of any measurement for clinical research in hand surgery is difficult. A method of measuring a criterion could be 100% reliable but 100% invalid. Bias may be present in our assessment if we do not take into account the methodological requirements related to reliability, validity, and responsiveness of our measures. Reliability refers to intra-observer agreement, inter-observer agreement, or agreement between two methods of assessment, and, for patient-reported measures, internal consistency and test–retest reliability. Validity is the capability of a clinical method to measure what it proposes to measure. Assessing validity involves comparing a measure with one or more other measures, and, if possible, with a reference standard criterion. Responsiveness is the ability to detect important clinical change. The Consensus-based Standards for the Selection of Health Measurement Instruments provides the standards required for design and recommended statistical analyses of patient-reported outcome measures.
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| 9. |
- Stibrant Sunnerhagen, Katharina, 1957, et al.
(författare)
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Onset, time course and prediction of spasticity after stroke or traumatic brain injury.
- 2019
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Ingår i: Annals of physical and rehabilitation medicine. - : Elsevier BV. - 1877-0665 .- 1877-0657. ; 62:6, s. 431-434
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Forskningsöversikt (refereegranskat)abstract
- To describe spasticity from the onset of acquired brain injury, time course over the first year and factors associated with prediction of the development of spasticity.Recent relevant literature known to the authors, along with a complementary search yielding a total of 9 articles, represented the base for this scoping review.Spasticity can be seen in the first week after brain injury and is more common in the upper than lower extremity. The severity of upper-limb impairment is a major factor in the development of spasticity during the first year after stroke. The prevalence of severe spasticity seems to increase during the first year. The combination of reduced arm motor function and spasticity in an early phase (4 weeks post-stroke) is an important predictor of the development of severe spasticity after 12 months. Spontaneous reduction in spasticity was seldom reported but may occur, especially in mild forms of spasticity.Signs of spasticity can often be noted within the first 4 weeks after brain injury and is more common in the upper than lower extremity. Impaired sensorimotor function is a predictor. These findings highlight the importance to follow up patients with increased risk of developing severe spasticity to be able to start adequate spasticity treatment and prevent the negative consequences of spasticity. Understanding spasticity onset and progression also provides a basis for the development of effective therapies.
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| 10. |
- Banerjee, Debarshi, et al.
(författare)
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Adding nanotechnology to the metastasis treatment arsenal
- 2019
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Ingår i: TIPS - Trends in Pharmacological Sciences. - Cambridge, Massachusets : Elsevier. - 0165-6147 .- 1873-3735. ; 40:6, s. 403-418
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Forskningsöversikt (refereegranskat)abstract
- Metastasis is a major cause of cancer-related mortality, accounting for 90% of cancer deaths. The explosive growth of cancer biology research has revealed new mechanistic network information and pathways that promote metastasis. Consequently, a large number of antitumor agents have been developed and tested for their antimetastatic efficacy. Despite their exciting cytotoxic effects on tumor cells in vitro and antitumor activities in preclinical studies in vivo, only a few have shown potent antimetastatic activities in clinical trials. In this review, we provide a brief overview of current antimetastatic strategies that show clinical efficacy and review nanotechnology-based approaches that are currently being incorporated into these therapies to mitigate challenges associated with treating cancer metastasis.
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