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Sökning: WFRF:(Christensen Robin)

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1.
  • Christensen, Robin, et al. (författare)
  • Effect of Weight Maintenance on Symptoms of Knee Osteoarthritis in Obese Patients: A Twelve-Month Randomized Controlled Trial 1
  • 2015
  • Ingår i: Arthritis Care and Research. - : Wiley. - 2151-4658 .- 2151-464X. ; 67:5, s. 640-650
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To compare results of obese patients with knee osteoarthritis (OA) who, after an intensive weight loss regimen, received 1 year of either dietary support (D), a knee-exercise program (E), or "no attention" (C; control group). Methods. We conducted a randomized, 2-phase, parallel-group trial. A total of 192 obese participants with knee OA were enrolled; the mean age was 62.5 years and 81% were women with a mean entry weight of 103.2 kg. In phase 1, all participants were randomly assigned to 1 of 3 groups and began a dietary regimen of 400-810 and 1,250 kcal/day for 16 weeks (2 8-week phases) to achieve a major weight loss. Phase 2 consisted of 52 weeks' maintenance in either group D, E, or C. Outcomes were changes from randomization in pain on a 100-mm visual analog scale, weight, and response according to the Outcome Measures in Rheumatology-Osteoarthritis Research Society International criteria. Results. Mean weight loss for phase 1 was 12.8 kg. After 1 year on maintenance therapy, the D group sustained a lower weight (11.0 kg, 95% confidence interval [95% CI] 9.0, 12.8 kg) than those in the E (6.2, 95% CI 4.4, 8.1 kg) and C (8.2, 95% CI 6.4, 10.1 kg) groups (P = 0.002 by analysis of covariance [ANCOVA]). Adherence was low in the E group. All groups had statistically significant pain reduction (D: 6.1; E: 5.6; and C: 5.5 mm) with no difference between groups (P = 0.98 by ANCOVA). In each group 32 (50%), 26 (41%), and 33 (52%) participants responded to treatment in the D, E, and C groups, respectively, with no statistically significant difference in the number of responders (P = 0.41). Conclusion. A significant weight reduction with a 1-year maintenance program improves knee OA symptoms irrespective of maintenance program.
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2.
  • Hudson, Lawrence N, et al. (författare)
  • The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
  • 2017
  • Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
  • Tidskriftsartikel (refereegranskat)abstract
    • The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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3.
  • Kanoni, Stavroula, et al. (författare)
  • Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
  • 2022
  • Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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5.
  • Bandholm, Thomas, et al. (författare)
  • Writing up your clinical trial report for a scientific journal : The REPORT trial guide for effective and transparent research reporting without spin
  • 2022
  • Ingår i: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 56:12, s. 683-691
  • Forskningsöversikt (refereegranskat)abstract
    • The REPORT guide is a 'How to' guide to help you report your clinical research in an effective and transparent way. It is intended to supplement established first choice reporting tools, such as Consolidated Standards of Reporting Trials (CONSORT), by adding tacit knowledge (ie, learnt, informal or implicit knowledge) about reporting topics that we have struggled with as authors or see others struggle with as journal reviewers or editors. We focus on the randomised controlled trial, but the guide also applies to other study designs. Topics included in the REPORT guide cover reporting checklists, trial report structure, choice of title, writing style, trial registry and reporting consistency, spin or reporting bias, transparent data presentation (figures), open access considerations, data sharing and more.
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6.
  • Bezemer, T. M., et al. (författare)
  • Divergent composition but similar function of soil food webs of individual plants: plant species and community effects
  • 2010
  • Ingår i: Ecology. - 0012-9658. ; 91:10, s. 3027-3036
  • Tidskriftsartikel (refereegranskat)abstract
    • Soils are extremely rich in biodiversity, and soil organisms play pivotal roles in supporting terrestrial life, but the role that individual plants and plant communities play in influencing the diversity and functioning of soil food webs remains highly debated. Plants, as primary producers and providers of resources to the soil food web, are of vital importance for the composition, structure, and functioning of soil communities. However, whether natural soil food webs that are completely open to immigration and emigration differ underneath individual plants remains unknown. In a biodiversity restoration experiment we first compared the soil nematode communities of 228 individual plants belonging to eight herbaceous species. We included grass, leguminous, and non-leguminous species. Each individual plant grew intermingled with other species, but all plant species had a different nematode community. Moreover, nematode communities were more similar when plant individuals were growing in the same as compared to different plant communities, and these effects were most apparent for the groups of bacterivorous, carnivorous, and omnivorous nematodes. Subsequently, we analyzed the composition, structure, and functioning of the complete soil food webs of 58 individual plants, belonging to two of the plant species, Lotus corniculatus (Fabaceae) and Plantago lanceolata (Plantaginaceae). We isolated and identified more than 150 taxa/groups of soil organisms. The soil community composition and structure of the entire food webs were influenced both by the species identity of the plant individual and the surrounding plant community. Unexpectedly, plant identity had the strongest effects on decomposing soil organisms, widely believed to be generalist feeders. In contrast, quantitative food web modeling showed that the composition of the plant community influenced nitrogen mineralization under individual plants, but that plant species identity did not affect nitrogen or carbon mineralization or food web stability. Hence, the composition and structure of entire soil food webs vary at the scale of individual plants and are strongly influenced by the species identity of the plant. However, the ecosystem functions these food webs provide are determined by the identity of the entire plant community.
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7.
  • Birkhofer, Klaus, et al. (författare)
  • Long-term organic farming fosters below and aboveground biota: Implications for soil quality, biological control and productivity
  • 2008
  • Ingår i: Soil Biology & Biochemistry. - : Elsevier BV. - 0038-0717. ; 40:9, s. 2297-2308
  • Tidskriftsartikel (refereegranskat)abstract
    • Organic farming may contribute substantially to future agricultural production worldwide by improving soil quality and pest control, thereby reducing environmental impacts of conventional farming. We investigated in a comprehensive way soil chemical, as well as below and aboveground biological parameters of two organic and two conventional wheat farming systems that primarily differed in fertilization and weed management strategies. Contrast analyses identified management related differences between "herbicide-free" bioorganic (BIOORG) and biodynamic (BIODYN) systems and conventional systems with (CONFYM) or without manure (CONMIN) and herbicide application within a long-term agricultural experiment (DOK trial, Switzerland). Soil carbon content was significantly higher in systems receiving farmyard manure and concomitantly microbial biomass (fungi and bacteria) was increased. Microbial activity parameters, such as microbial basal respiration and nitrogen mineralization, showed an opposite pattern, suggesting that soil carbon in the conventional system (CONFYM) was more easily accessible to microorganisms than in organic systems. Bacterivorous nematodes and earthworms were most abundant in systems that received farmyard manure, which is in line with the responses of their potential food sources (microbes and organic matter). Mineral fertilizer application detrimentally affected enchytraeids and Diptera larvae, whereas aphids benefited. Spider abundance was favoured by organic management, most likely a response to increased prey availability from the belowground subsystem or increased weed coverage. In contrast to most soil-based, bottom-up controlled interactions, the twofold higher abundance of this generalist predator group in organic systems likely contributed to the significantly lower abundance of aboveground herbivore pests (aphids) in these systems. Long-term organic farming and the application of farmyard manure promoted soil quality, microbial biomass and fostered natural enemies and ecosystem engineers, suggesting enhanced nutrient cycling and pest control. Mineral fertilizers and herbicide application, in contrast, affected the potential for top-down control of aboveground pests negatively and reduced the organic carbon levels. Our study indicates that the use of synthetic fertilizers and herbicide application changes interactions within and between below and aboveground components, ultimately promoting negative environmental impacts of agriculture by reducing internal biological cycles and pest control. On the contrary, organic farming fosters microbial and faunal decomposers and this propagates into the aboveground system via generalist predators thereby increasing conservation biological control. However, grain and straw yields were 23% higher in systems receiving mineral fertilizers and herbicides reflecting the trade-off between productivity and environmental responsibility. (C) 2008 Elsevier Ltd. All rights reserved.
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8.
  • Christ, T. W., et al. (författare)
  • "Being a Risk" or "Being at Risk": Factors Shaping Negotiation of Concerns of Radicalization within Multiagency Collaboration in the Nordic Countries
  • 2024
  • Ingår i: Democracy & Security. - 1741-9166 .- 1555-5860. ; 20:1, s. 1-24
  • Tidskriftsartikel (refereegranskat)abstract
    • Multiagency collaboration between state and municipal actors such as schools, social services and the police is at the core of the Nordic countries' approach to preventing radicalization and violent extremism. Yet, assessment of reported concerns of radicalization differs across countries. This qualitative study analyze how professionals negotiate assessments to identify factors that shape whether a concern of radicalization develops into a perception of risk. We argue that differences in structural factors and "institutional logics" in addition to trustful relations between practitioners at the local level affect collaboration and shape the perception of the task when the assessments of concrete concerns are negotiated.
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10.
  • Christensen, Robin, et al. (författare)
  • Weight loss for overweight patients with knee or hip osteoarthritis
  • 2017
  • Ingår i: Cochrane Database of Systematic Reviews. - 1361-6137. ; 2017:11
  • Tidskriftsartikel (refereegranskat)abstract
    • This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To determine the benefits and harms associated with weight loss in overweight individuals with knee or hip osteoarthritis in terms of pain, physical function, quality of life, and safety. Further we will have an explicit focus on quality of the weight loss intervention (including magnitude and intensity) (Herbert 2005), to see whether there is a dose-response relationship at the trial (i.e. group) level.
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11.
  • Connolly, Stuart J., et al. (författare)
  • Andexanet for Factor Xa Inhibitor-Associated Acute Intracerebral Hemorrhage
  • 2024
  • Ingår i: New England Journal of Medicine. - 0028-4793. ; 390:19, s. 1745-1755
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Patients with acute intracerebral hemorrhage who are receiving factor Xa inhibitors have a risk of hematoma expansion. The effect of andexanet alfa, an agent that reverses the effects of factor Xa inhibitors, on hematoma volume expansion has not been well studied. Methods We randomly assigned, in a 1:1 ratio, patients who had taken factor Xa inhibitors within 15 hours before having an acute intracerebral hemorrhage to receive andexanet or usual care. The primary end point was hemostatic efficacy, defined by expansion of the hematoma volume by 35% or less at 12 hours after baseline, an increase in the score on the National Institutes of Health Stroke Scale of less than 7 points (scores range from 0 to 42, with higher scores indicating worse neurologic deficit) at 12 hours, and no receipt of rescue therapy between 3 hours and 12 hours. Safety end points were thrombotic events and death. Results A total of 263 patients were assigned to receive andexanet, and 267 to receive usual care. Efficacy was assessed in an interim analysis that included 452 patients, and safety was analyzed in all 530 enrolled patients. Atrial fibrillation was the most common indication for factor Xa inhibitors. Of the patients receiving usual care, 85.5% received prothrombin complex concentrate. Hemostatic efficacy was achieved in 150 of 224 patients (67.0%) receiving andexanet and in 121 of 228 (53.1%) receiving usual care (adjusted difference, 13.4 percentage points; 95% confidence interval [CI], 4.6 to 22.2; P=0.003). The median reduction from baseline to the 1-to-2-hour nadir in anti-factor Xa activity was 94.5% with andexanet and 26.9% with usual care (P<0.001). Thrombotic events occurred in 27 of 263 patients (10.3%) receiving andexanet and in 15 of 267 (5.6%) receiving usual care (difference, 4.6 percentage points; 95% CI, 0.1 to 9.2; P=0.048); ischemic stroke occurred in 17 patients (6.5%) and 4 patients (1.5%), respectively. There were no appreciable differences between the groups in the score on the modified Rankin scale or in death within 30 days. Conclusions Among patients with intracerebral hemorrhage who were receiving factor Xa inhibitors, andexanet resulted in better control of hematoma expansion than usual care but was associated with thrombotic events, including ischemic stroke. (Funded by Alexion AstraZeneca Rare Disease and others; ANNEXA-I ClinicalTrials.gov number, NCT03661528.).
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12.
  • Enghel, Florencia (författare)
  • Video letters, mediation and (proper) distance : A qualitative study of international development communication in practice
  • 2014
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This study scrutinizes the trajectory of an international development communication intervention aimed at mediating, rendering public and mobilizing processes of reconnection among estranged citizens across the former Yugoslavia. The intervention, which took place between 2000 and 2005 in the wider context of post-conflict international development assistance and peacebuilding operations in the region, was known as the Videoletters project. Centered on a documentary TV series aimed at promoting the reestablishment of relationships among ordinary people affected by ethno-political divisions, Videoletters was adopted by European bilateral funders for large-scale implementation and categorized as a “tool for reconciliation”.Starting from an understanding of communication as a right to which citizens are entitled, as a responsibility of practitioners and institutions, and as a capability that is socially distributed in unequal ways and has an ambiguous potential, the study looks into the contextualized potential and limitations of international development communication intervention to attend to the citizens that it is supposed to benefit. By providing rich empirical details about a process of intervention, the study argues in concrete terms for the study of development communication not as a presumably positive tool, but as an institutionally driven practice that may or may not strengthen conditions of justice, with consequences that will differ depending on the specificity of sociopolitical situations in time and space. Depending on contextual and institutional conditions and on the forms of mediation privileged/disregarded throughout the process, the deployment of a specific development communication intervention may/may not foster proper distance, and thus strengthen/weaken conditions of justice for the citizens under consideration, who are subject to the governance structure of international development assistance.By linking the practice of international development communication to a framework of justice, the study brings the political and ethical dimensions of said practice to the fore and contributes to a critical agenda for theorization and research that takes accountability into consideration and puts citizens at the center. 
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  • Fejrskov, Anja, et al. (författare)
  • Novel biomarker profiles to improve individual diagnosis and prognosis in patients with suspected inflammatory bowel disease : protocol for the Nordic inception cohort study (NORDTREAT)
  • 2024
  • Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 14:5
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, can be challenging to diagnose, and treatment outcomes are difficult to predict. In the NORDTREAT cohort study, a Nordic prospective multicentre study, we aim to identify novel molecular biomarkers of diagnostic value by assessing the diagnostic test accuracy (cross-sectionally), as well as the prognostic utility when used as prognostic markers in the long-term (cohort study). In the diagnostic test accuracy study, the primary outcome is a successful diagnosis using one or more novel index tests at baseline compared with the ECCO criteria as the reference standard. The composite outcome of the prognostic utility study is 'severe IBD' within 52 weeks from inclusion, defined as one or more of the following three events: IBD-related surgery, IBD-related hospitalisation or IBD-related death.METHODS AND ANALYSIS: We aim to recruit 800 patients referred on suspicion of IBD to this longitudinal observational study, a collaboration between 11 inclusion sites in Denmark, Iceland, Norway and Sweden. Inclusion will occur from February 2022 until December 2023 with screening and baseline visits for all participants and three outcome visits at weeks 12, 26 and 52 after baseline for IBD-diagnosed patients. Biological material (blood, faeces, biopsies, urine and hair), clinical data and lifestyle information will be collected during these scheduled visits.ETHICS AND DISSEMINATION: This study will explore novel biomarkers to improve diagnostic accuracy and prediction of disease progression, thereby improving medical therapy and the quality of life for patients with IBD.The study is approved by the Ethics Committee (DK: S-20200051, v1.4, 16.10.2021; IS: VSNb2021070006/03.01, NO: 193064; SE: DNR 2021-05090) and the Danish Data Protecting Agency (20/54594). Results will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences.CLINICAL TRIAL REGISTRATION NUMBER: NCT05414578; Pre-results.
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14.
  • Furukawa, Toshi A., et al. (författare)
  • Dismantling, optimising, and personalising internet cognitive behavioural therapy for depression : a systematic review and component network meta-analysis using individual data
  • 2021
  • Ingår i: Lancet psychiatry. - London, United Kingdom : Elsevier. - 2215-0374 .- 2215-0366. ; 8:6, s. 500-511
  • Forskningsöversikt (refereegranskat)abstract
    • Findings We identified 76 RCTs, including 48 trials contributing individual participant data (11 704 participants) and 28 trials with aggregate data (6474 participants). The participants' weighted mean age was 42.0 years and 12 406 (71%) of 17 521 reported were women. There was suggestive evidence that behavioural activation might be beneficial (iMD -1.83 [95% credible interval (CrI) -2.90 to -0.80]) and that relaxation might be harmful (1.20 [95% CrI 0.17 to 2.27]). Baseline severity emerged as the strongest prognostic factor for endpoint depression. Combining human and automated encouragement reduced dropouts from treatment (incremental odds ratio, 0.32 [95% CrI 0.13 to 0.93]). The risk of bias was low for the randomisation process, missing outcome data, or selection of reported results in most of the included studies, uncertain for deviation from intended interventions, and high for measurement of outcomes. There was moderate to high heterogeneity among the studies and their components. 511
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  • Gøtzsche-Astrup, Oluf, et al. (författare)
  • Trust in interagency collaboration: The role of institutional logics and hybrid professionals
  • 2023
  • Ingår i: Journal of Professions and Organization. - : Oxford University Press (OUP). - 2051-8803 .- 2051-8811. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Interagency collaboration among social workers, teachers, and police is key to countering violent extremism in the Nordic countries by securing comprehensive assessment of cases of concern. Yet, previous research indicates that different institutional logics—perceptions of fundamental goals, strategies, and grounds for attention in efforts to counter violent extremists—exist across professions and challenge collaboration and trust building in practice. In this article, we empirically investigate these claims across social workers (n=1,105), teachers (n=1,387), and police (n=1,053) in four Nordic countries: Denmark, Sweden, Norway, and Finland. Using results from online surveys with professionals, we investigate the distribution of a ‘societal security logic’ and a ‘social care logic’ across professions and the degree to which these institutional logics translate into mutual trust. Through a comparison of institutional logics among practitioners with and without practical experience of interagency collaboration, we investigate whether and how institutional logics tend to mix and merge in hybrid organizational spaces. We conclude that differences in institutional logics across professions are differences in degree rather than in kind, but that such differences are important in shaping mutual trust and that experiences of interagency collaboration are correlated with a convergence toward a ‘social care logic’ conception of countering violent extremism.
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  • Hare, Kristoffer B., et al. (författare)
  • Arthroscopic partial meniscectomy in middle-aged patients with mild or no knee osteoarthritis: a protocol for a double-blind, randomized sham-controlled multi-centre trial
  • 2013
  • Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Arthroscopic partial meniscectomy has been shown to be of no benefit to patients with concomitant knee osteoarthritis, but the optimal treatment of a degenerative meniscus tear in patients with mild or no knee osteoarthritis is unknown. This article describes the rationale and methodology of a randomized sham-controlled trial to assess the benefit of arthroscopic partial meniscectomy of a medial meniscus tear in patients with mild or no knee osteoarthritis. The objective of the study is to test whether the benefit from arthroscopic partial meniscectomy in patients with knee pain, medial meniscus lesion and mild/no knee osteoarthritis, is greater after arthroscopic partial meniscectomy than following sham surgery. Methods: We will conduct a randomized controlled trial of treatment for degenerative meniscus tears in middle-aged patients (aged 35-55 years) with an MRI-verified medial meniscus lesion and mild or no knee radiographic osteoarthritis (grade 0-2 on the Kellgren & Lawrence scale). Patients will be randomized to receive either conventional arthroscopic partial meniscectomy or a sham surgery procedure. The primary outcome will be the KOOS5 derived from the 'Knee Injury and Osteoarthritis Outcome Score' at 2 years follow-up. Secondary outcomes at 2 years will include all five individual subscales of the KOOS, a global perceived effect score, the Short-Form-36 health status score, EQ-5D for economic appraisal and objective tests of muscle strength and physical function. Radiographic knee osteoarthritis will be evaluated at 5 years. Discussion: Demonstration of no additional benefit from arthroscopic partial meniscectomy on pain and function should lead to a change in clinical care of patients with a degenerative meniscus tear. The results of this study will provide empirical evidence for the potential benefit/harm of arthroscopic partial meniscectomy compared to a masked sham-therapeutics intervention.
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  • Hultcrantz, Monica, et al. (författare)
  • The GRADE Working Group clarifies the construct of certainty of evidence
  • 2017
  • Ingår i: Journal of Clinical Epidemiology. - : Pergamon Press. - 0895-4356 .- 1878-5921. ; 87, s. 4-13
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To clarify the grading of recommendations assessment, development and evaluation (GRADE) definition of certainty of evidence and suggest possible approaches to rating certainty of the evidence for systematic reviews, health technology assessments, and guidelines. Study Design and Setting: This work was carried out by a project group within the GRADE Working Group, through brainstorming and iterative refinement of ideas, using input from workshops, presentations, and discussions at GRADE Working Group meetings to produce this document, which constitutes official GRADE guidance. Results: Certainty of evidence is best considered as the certainty that a true effect lies on one side of a specified threshold or within a chosen range. We define possible approaches for choosing threshold or range. For guidelines, what we call a fully contextualized approach requires simultaneously considering all critical outcomes and their relative value. Less-contextualized approaches, more appropriate for systematic reviews and health technology assessments, include using specified ranges of magnitude of effect, for example, ranges of what we might consider no effect, trivial, small, moderate, or large effects. Conclusion: It is desirable for systematic review authors, guideline panelists, and health technology assessors to specify the threshold or ranges they are using when rating the certainty in evidence. (C) 2017 The Authors. Published by Elsevier Inc.
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  • Jelenkovic, Aline, et al. (författare)
  • Zygosity Differences in Height and Body Mass Index of Twins From Infancy to Old Age : A Study of the CODATwins Project
  • 2015
  • Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 18:5, s. 557-570
  • Tidskriftsartikel (refereegranskat)abstract
    • A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m(2) in childhood and adolescence and up to 0.2 kg/m(2) in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
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21.
  • Justice, Anne E., et al. (författare)
  • Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution
  • 2019
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 452-469
  • Tidskriftsartikel (refereegranskat)abstract
    • Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
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  • Jørgensen, Tanja Schjødt, et al. (författare)
  • EQ-5D utility, response and drug survival in rheumatoid arthritis patients on biologic monotherapy : A prospective observational study of patients registered in the south Swedish SSATG registry
  • 2017
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Biologic agents have dramatically changed treatment of rheumatoid arthritis (RA). To date only scarce head-To-head data exist especially when the biological therapies are given as monotherapy without concomitant disease modifying drugs (DMARDs). Thus the objective of the current study is to evaluate treatment response of all available biological therapies with special focus on utility (EQ-5D-3L) and drug survival of biologic DMARDs (bDMARDs) prescribed as monotherapy in RA patients in southern Sweden. Materials and methods All RA patients registered in a regional database as initiating bDMARD as monotherapy, i.e. without concomitant conventional synthetic DMARDs (csDMARDs), from 1st of January 2006 through 31st of December 2012, were included. Patients were followed from initiation of the first dose of bDMARD monotherapy treatment until withdrawal from treatment, loss of follow-up or 31st of December 2012. Descriptive statistics for utility (EQ-5D-3L), effectiveness, and drug survival of bDMARD monotherapy were calculated. Results During the study period, a total of 554 patients were registered in SSATG as initiating bDMARD monotherapy. Most of the patients were women (81%), with a mean age of 57 years. The average disease duration was more than 12 years, and on average the patients had previously been treated with approximately four different csDMARDs. Fifty-five percent of the patients were initiating their first bDMARD, 26% their second, and 19% their third or more. At baseline the average EQ-5D-3L was 0.34. Most patients had moderate to high disease activity, with a mean DAS28 of 5.0, and were substantially disabled, with an average HAQ score of 1.4. At 6 months follow-up, the EQ-5D-3L in patients still on the biologic drug had increased by mean 0.23 (SD 0.4) with no differences between type of bDMARD (p = 0.49). The mean change in EQ-5D-3L ranged from 0.11 (rituximab and infliximab) to 0.42 (tocilizumab). Although the changes were numerically different, no distinct pattern favored any particular bDMARD for EQ-5D-3L (p = 0.49) or other clinical outcomes. Overall, DAS28 defined remission and low disease activity were achieved in 20% and 43% of patients, respectively. Drug survival rates were statistically significantly different between bDMARDs (p = 0.01), with the highest rates observed for rituximab, followed by etanercept. After failing first course of anti-TNF, patients switching to another mode of action had significantly higher drug survival than those switching to a second course of anti-TNF therapy (p = 0.02). Conclusions Utility (EQ-5D-3L) increased after 6 months of all bDMARD treatments in monotherapy, indicating improvement of patients' quality of life. After failure of anti-TNF treatment in monotherapy, switching to another mode of action may be associated with better drug survival than starting a second TNF-inhibitor.
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24.
  • Kotonen, Tommi, et al. (författare)
  • “When neo-Nazis march on Norwegian streets, you hear a lot of Swedish”: Pan-Nordic and transnational dimensions of right-wing extremism
  • 2023
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • This report constitutes the first comprehensive review of right-wing extremism (RWE) in the Nordics (Denmark, Finland, Norway, and Sweden). In it, a team of 13 leading researchers have compiled and reviewed academic texts written about the topic. The result is a descriptive and analytical report of how the Nordic RWE milieu has developed from 1918 until today, with a specific focus on the pan-Nordic and transnational dimensions of the milieu. In the report, we also compile the practices used to prevent RWE in the Nordics, and analyze how well they are situated to handle the threat RWE poses to society. 
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25.
  • Kraja, Aldi T., et al. (författare)
  • New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475000 Individuals
  • 2017
  • Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 1942-325X .- 1942-3268. ; 10:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Background - Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association.Methods and Results - Here, we augment the sample with 140886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, approximate to 475000), and the other in the subset of individuals of European descent (approximate to 423000). Twenty-one SNVs were genome-wide significant (P<5x10(-8) ) for BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP), rs7437940 (AFAP1), rs13303 (missense, STAB1), and rs1055144 (7p15.2). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, SYNPO2L) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at DBH) was genome-wide significant.Conclusions - We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up.
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26.
  • Kristensen, Lars Erik, et al. (författare)
  • Is Swollen to Tender Joint Count Ratio a New and Useful Clinical Marker for Biologic Drug Response in Rheumatoid Arthritis? Results From a Swedish Cohort
  • 2014
  • Ingår i: Arthritis Care and Research. - : Wiley. - 2151-4658 .- 2151-464X. ; 66:2, s. 173-179
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveTo study the impact of swollen to tender joint count ratio (STR) and other baseline characteristics on treatment response to a first course of anti-tumor necrosis factor (anti-TNF) therapy in rheumatoid arthritis (RA) patients. MethodsPatients with RA initiating their first course of anti-TNF treatment were included in a structured clinical followup protocol. Based on pragmatic thresholds and plausibility, patients were categorized as having low (STR <0.5), moderate (0.5 STR 1.0), or high (STR >1.0) joint count ratios. The data were collected and followed during the period of March 1999 through December 2010. ResultsA total of 2,507 patients were included in the study (median age 56 years, 78% women). Of these patients, 344 (14%) had a low STR, 1,180 (47%) had a moderate STR, and 983 (39%) had a high STR. According to these STR thresholds, 23% of patients (95% confidence interval [95% CI] 18-29%) with low, 39% (95% CI 35-43%) with moderate, and 40% (95% CI 36-44%) with high STR achieved the American College of Rheumatology criteria for 50% improvement (ACR50) response at 6 months after initiation. Correlation tests showed that STR was associated with ACR50 response independent of both swollen and tender joint counts. Logistic regression analysis consistently showed that moderate STR, high STR, not using prednisolone, high baseline Disease Activity Score in 28 joints, and low baseline Health Assessment Questionnaire scores were significantly associated with favorable ACR50 response with odds ratios of 1.93 (P < 0.01), 2.82 (P < 0.01), 0.65 (P < 0.01), 1.49 (P < 0.01), and 0.47 (P < 0.01), respectively. ConclusionSTR is a new and feasible predictor of treatment response in RA. RA patients with a moderate to high STR have a 2- to 3-fold increased likelihood of responding according to ACR50 criteria.
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27.
  • Laugesen, Monika, et al. (författare)
  • Smoking Cessation Rates among Patients with Rheumatoid Arthritis and Osteoarthritis Following the 'Gold Standard Programme' (GSP): : A Prospective Analysis from the Danish Smoking Cessation Database
  • 2022
  • Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1660-4601. ; 19:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Smoking cessation may be very difficult, even if smoking aggravates the prognosis of a disease, which has been shown to be the case for persons with rheumatoid arthritis (RA). In contrast, an association in patients with osteoarthritis (OA) is still disputed. The primary objective was to compare smokers diagnosed with RA and OA to controls, regarding smoking cessation rates after following the intensive ‘Gold Standard Programme’ (GSP). Secondary objectives included the identification of significant prognostic factors for successful quitting. (2) Methods: In total, 24,652 patients were included in this prospective cohort study, after attending the national GSP for smoking cessation intervention 2006–2016, as registered in the Danish Smoking Cessation Database. Data were linked to the National Patient Register. Hereof, 227 patients (1%) were diagnosed with seropositive RA and 2899 (12%) with OA. Primary outcome was continuous abstinence six months after the planned quitting date. (3) Results: In total, 16,969 (69%) of the patients participated in the follow-up interviews. The adjusted odds ratios for successful quitting were similar to the control group for both RA (1.28, 95% CI: 0.90–1.80) and OA patients (0.92, 0.82–1.03). The outermost, strongest positive factor for successful quitting was compliance, defined as attending ≥75% of the meetings.To a lesser degree, attending an individual intervention was a positive predictor, while being heavy smokers, disadvantaged smokers, women, living with a smoker, and if GSP was recommended by health professionals were negative predictors. (4) Conclusions: The odds ratios for quitting were similar to controls for both RA and OR patients. Additional research is needed to determine effectiveactions towards increased attendance at the programmes.
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28.
  • Lee, Francis, et al. (författare)
  • Algorithms as folding : Reframing the analytical focus
  • 2019
  • Ingår i: Big Data and Society. - : SAGE PUBLICATIONS INC. - 2053-9517. ; 6:2
  • Tidskriftsartikel (refereegranskat)abstract
    • This article proposes an analytical approach to algorithms that stresses operations of folding. The aim of this approach is to broaden the common analytical focus on algorithms as biased and opaque black boxes, and to instead highlight the many relations that algorithms are interwoven with. Our proposed approach thus highlights how algorithms fold heterogeneous things: data, methods and objects with multiple ethical and political effects. We exemplify the utility of our approach by proposing three specific operations of folding-proximation, universalisation and normalisation. The article develops these three operations through four empirical vignettes, drawn from different settings that deal with algorithms in relation to AIDS, Zika and stock markets. In proposing this analytical approach, we wish to highlight the many different attachments and relations that algorithms enfold. The approach thus aims to produce accounts that highlight how algorithms dynamically combine and reconfigure different social and material heterogeneities as well as the ethical, normative and political consequences of these reconfigurations.
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29.
  • Mahajan, Anubha, et al. (författare)
  • Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes
  • 2018
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:4, s. 559-571
  • Tidskriftsartikel (refereegranskat)abstract
    • We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10−7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent ‘false leads’ with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.
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30.
  • Marouli, Eirini, et al. (författare)
  • Rare and low-frequency coding variants alter human adult height
  • 2017
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
  • Tidskriftsartikel (refereegranskat)abstract
    • Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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31.
  • Miglio, A., et al. (författare)
  • PLATO as it is : A legacy mission for Galactic archaeology
  • 2017
  • Ingår i: Astronomical Notes - Astronomische Nachrichten. - : WILEY-V C H VERLAG GMBH. - 0004-6337 .- 1521-3994. ; 338:6, s. 644-661
  • Tidskriftsartikel (refereegranskat)abstract
    • Deciphering the assembly history of the Milky Way is a formidable task, which becomes possible only if one can produce high-resolution chrono-chemo-kinematical maps of the Galaxy. Data from large-scale astrometric and spectroscopic surveys will soon provide us with a well-defined view of the current chemo-kinematical structure of the Milky Way, but it will only enable a blurred view on the temporal sequence that led to the present-day Galaxy. As demonstrated by the (ongoing) exploitation of data from the pioneering photometric missions CoRoT, Kepler, and K2, asteroseismology provides the way forward: solar-like oscillating giants are excellent evolutionary clocks thanks to the availability of seismic constraints on their mass and to the tight age-initial mass relation they adhere to. In this paper we identify five key outstanding questions relating to the formation and evolution of the Milky Way that will need precise and accurate ages for large samples of stars to be addressed, and we identify the requirements in terms of number of targets and the precision on the stellar properties that are needed to tackle such questions. By quantifying the asteroseismic yields expected from PLATO for red giant stars, we demonstrate that these requirements are within the capabilities of the current instrument design, provided that observations are sufficiently long to identify the evolutionary state and allow robust and precise determination of acoustic-mode frequencies. This will allow us to harvest data of sufficient quality to reach a 10% precision in age. This is a fundamental prerequisite to then reach the more ambitious goal of a similar level of accuracy, which will be possible only if we have at hand a careful appraisal of systematic uncertainties on age deriving from our limited understanding of stellar physics, a goal that conveniently falls within the main aims of PLATO's core science. We therefore strongly endorse PLATO's current design and proposed observational strategy, and conclude that PLATO, as it is, will be a legacy mission for Galactic archaeology.
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32.
  • Mishra, A., et al. (författare)
  • Stroke genetics informs drug discovery and risk prediction across ancestries
  • 2022
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
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33.
  • Morville, Anne-Le, et al. (författare)
  • Activity of Daily Living Performance amongst Danish Asylum Seekers : A cross-sectional study
  • 2014
  • Ingår i: Journal on Rehabilitation of Torture Victims and Prevention of Torture. - Copenhagen : International Rehabilitation Council for Torture Victims. - 1018-8185 .- 1997-3322. ; 24:1, s. 49-64
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The aim of this study was to evaluate the extent of Activities of Daily Living (ADL) ability impairment in newly arrived Danish asylum seekers. It was hypothesized that exposure to trauma and torture would negatively influence ADL performance and that measures of ADL ability would be lower in individuals exposed to torture as compared to the non-tortured.Subjects: Forty-three newly arrived asylum seekers aged 20-50 years, from Iran, Afghanistan and Syria, were consecutively included in the study.Method: ADL ability was assessed with the observation-based test Assessment of Motor and Process Skills (AMPS). Interviews were based on questionnaires about torture exposure, WHO-5 Wellbeing Index, Major Depression Inventory and Pain Detect Questionnaire. All participants were interviewed and tested using a linguistic interpreter.Results: Thirty three (77%) participants reported exposure to torture. The tortured did not differ significantly from the nontortured on measures of ADL ability (two-sample t-tests: Motor, p= 0.36; Process, p= 0.82). ADL performance impairment was observed in the overall study sample. Twelve had motor and 15 process ability measures below age norms and 2 below both AMPS motor and process cut-offs for effortless and efficient ADL performance. There were statistically significant - weak to moderate - correlations between self-reported psychological distress, VAS average pain, pain distribution and the AMPS measures.Conclusion: The study results supported significant ADL ability impairment in tortured as well as non-tortured newly arrived asylum seekers. Implementation of performance-based evaluation of ADL ability as part of the initial medical screening of this particular population should be considered.
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34.
  • Naghavi, Mohsen, et al. (författare)
  • Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
  • 2015
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 385:9963, s. 117-171
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specifi c all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specifi c causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute diff erences between countries decreased but relative diff erences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative diff erences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specifi c mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.
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35.
  • Nguyen, Thanh N, et al. (författare)
  • Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.
  • 2023
  • Ingår i: Neurology. - 1526-632X. ; 100:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
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36.
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37.
  • Palmowski, Andriko, et al. (författare)
  • The Effect of Low-Dose Glucocorticoids Over Two Years on Weight and Blood Pressure in Rheumatoid Arthritis : Individual Patient Data From Five Randomized Trials
  • 2023
  • Ingår i: Annals of Internal Medicine. - 0003-4819 .- 1539-3704. ; 176:9, s. 1181-1189
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Weight gain and hypertension are well known adverse effects of treatment with high-dose glucocorticoids. Objective: To evaluate the effects of 2 years of low-dose glucocorticoid treatment in rheumatoid arthritis (RA). Design: Pooled analysis of 5 randomized controlled trials with 2-year interventions allowing concomitant treatment with disease-modifying antirheumatic drugs. Setting: 12 countries in Europe. Patients: Early and established RA. Intervention: Glucocorticoids at 7.5 mg or less prednisone equivalent per day. Measurements: Coprimary end points were differences in change from baseline in body weight and mean arterial pressure after 2 years in intention-to-treat analyses. Difference in the change of number of antihypertensive drugs after 2 years was a secondary end point. Subgroup and sensitivity analyses were done to assess the robustness of primary findings. Results: A total of 1112 participants were included (mean age, 61.4 years [SD, 14.5]; 68% women). Both groups gained weight in 2 years, but glucocorticoids led, on average, to 1.1 kg (95% CI, 0.4 to 1.8 kg; P < 0.001) more weight gain than the control treatment. Mean arterial pressure increased by about 2 mm Hg in both groups, with a between-group difference of -0.4 mm Hg (CI, -3.0 to 2.2 mm Hg; P = 0.187). These results were consistent in sensitivity and subgroup analyses. Most patients did not change the number of antihypertensive drugs, and there was no evidence of differences between groups. Limitation: Body composition was not assessed, and generalizability to non-European regions may be limited. Conclusion: This study provides robust evidence that low-dose glucocorticoids, received over 2 years for the treatment of RA, increase weight by about 1 kg but do not increase blood pressure.
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38.
  • Pihl, Kenneth, et al. (författare)
  • Less improvement following meniscal repair compared with arthroscopic partial meniscectomy : a prospective cohort study of patient-reported outcomes in 150 young adults at 1- and 5-years’ follow-up
  • 2021
  • Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 92:5, s. 589-596
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose — Meniscal repair may reduce long-term risk of knee osteoarthritis compared with arthroscopic partial meniscectomy (APM), whereas patient-reported outcomes may be poorer at short term than for APM. We compared patient-reported outcomes in young adults undergoing meniscal repair or APM up to ∼5 years after surgery. Patients and methods — We included 150 patients aged 18–40 years from the Knee Arthroscopy Cohort Southern Denmark (KACS) undergoing meniscal repair or APM. Between-group differences in change in a composite of 4 of 5 Knee injury and Osteoarthritis Outcome Score (KOOS) subscales (pain, symptoms, sport and recreation, and quality of life—KOOS4) from baseline, 12, and 52 weeks, and a median of 5 years (range 4–6 years) were analyzed using adjusted mixed linear models, with 52 weeks being the primary endpoint. Results — 32 patients had meniscal repair (mean age 26 [SD 6]), and 118 patients underwent APM (mean age 32 [SD 7]). The repair and APM groups improved in KOOS4 from before to 52 weeks after surgery (least square means 7 and 19, respectively; adjusted mean difference –12, [95% CI –19 to –4] in favor of APM). Both groups improved further from 52 weeks to 5 years after surgery with the difference in KOOS4 scores between the groups remaining similar. Interpretation — Patients having meniscal repair experienced less improvements in patient-reported outcomes from baseline to 52 weeks and 5 years post-surgery. The findings highlight the need for randomized trials comparing these interventions in terms of patient-reported outcomes and knee OA development.
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39.
  • Rejler, Martin, et al. (författare)
  • Nordic inflammatory bowel disease treatment strategy trial : protocol for the NORDTREAT randomised controlled biomarker-strategy trial
  • 2024
  • Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 14:7
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: The absence of reliable prognostic markers poses a challenge to the management of inflammatory bowel disease (IBD). Patients with aggressive disease may not receive sufficient treatment with conventional 'step-up' therapy, whereas a top-down approach may expose patients with indolent disease to unnecessary treatment-related toxicity. The objective of the Nordic IBD treatment strategy trial (NORDTREAT) is to assess the feasibility of personalised therapy by stratifying patients according to a prognostic serum protein signature at diagnosis.METHODS AND ANALYSIS: NORDTREAT is a multicentre, biomarker-strategy design, open-label controlled trial. After screening consent, eligible patients are randomised (1:1) into one of two groups: a group with access to the protein signature and a group without access. In the access to protein signature group, patients displaying a protein signature suggestive of an increased risk of an aggressive disease course will be treated in line with a top-down treatment algorithm (anti-tumour necrosis factor agent with/without an immunomodulator). In contrast, those with a protein signature indicative of indolent disease will be excluded from the trial. Patients not in the access group receive treatment based on clinical management. This traditional management involves a stepwise escalation of treatment as determined by the investigator after failure of first-line treatment. After 52 weeks, outcomes are assessed in the subgroup of patients with a protein profile indicating a potentially severe disease trajectory. The primary endpoint is a composite of the proportion of patients with corticosteroid-free clinical and endoscopic remission at week 52. Surgical intervention due to IBD during follow-up will be defined as treatment failure.ETHICS AND DISSEMINATION: Ethical approval has been obtained, and recruitment is underway at sites in four participating Nordic countries (Denmark, Iceland, Norway and Sweden). Following trial completion and data analysis, the trial results will be submitted for publication in peer-reviewed journals and presented at international conferences.TRIAL REGISTRATION NUMBER: NCT05180175; Pre-results. EudraCT number: 2019-002942-19.
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40.
  • Roelsgaard, Ida Kristiane, et al. (författare)
  • The effect of an intensive smoking cessation intervention on disease activity in patients with rheumatoid arthritis : Study protocol for a randomised controlled trial
  • 2017
  • Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 18:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Rheumatoid arthritis (RA) is a chronic, inflammatory rheumatic disease with the potential to induce significant disability. Patients with RA are at increased risk of cardiovascular diseases (CVD). Smokers with RA tend to experience more pain and fatigue, higher disease activity, more erosive joint destruction and a lower health-related quality of life (HR-QoL) than non-smokers. It remains to be determined whether these effects can be reduced by smoking cessation. This randomised controlled trial (RCT) in patients with RA aims to examine the effect of intensive smoking cessation intervention (motivational counselling combined with tailored nicotine replacement therapy) versus standard care on smoking cessation, and consequently on disease activity. Secondary objectives are to explore the effect on flare, risk factors for CVD, lung function, physical function, HR-QoL, pain and fatigue in patients with RA. Methods: This will be a multicentre, open label, two arm, parallel group, RCT, including 150 daily smokers with RA, being in remission or having low-moderate disease activity (DAS28 ≤ 5.1). The intervention group (n = 75) will receive five counselling sessions with a trained smoking cessation counsellor based on the principles of motivational counselling. Furthermore, intervention patients will be offered nicotine replacement therapy tailored to individual needs. Participants randomised to the control group will receive standard care. The co-primary outcome is a hierarchical endpoint, which will be evaluated at 3 months follow-up and will include (1) self-reported smoking cessation biochemically validated by exhaled carbon monoxide and (2) achievement of EULAR clinical response (an improvement in DAS28 of > 0.6). Follow-up visits will be performed at 3, 6 and 12 months post-intervention. Discussion: This trial will reveal whether intensive smoking cessation counselling helps smokers with RA to achieve continuous smoking cessation and whether, as a concomitant benefit, it will reduce their RA disease activity. The trial aims to generate high quality evidence for the feasibility of a health promotion intervention for smokers with RA. Trial registration: ClinicalTrials.gov, identifier: NCT02901886. Registered on 10 September 2016. Recruitment status updated on 10th October 2016.
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41.
  • Roos, Ewa M., et al. (författare)
  • Better outcome from arthroscopic partial meniscectomy than skin incisions only? A sham-controlled randomised trial in patients aged 35-55 years with knee pain and an MRI-verified meniscal tear
  • 2018
  • Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 8:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Compare arthroscopic partial meniscectomy to a true sham intervention. Methods Sham-controlled superiority trial performed in three county hospitals in Denmark comparing arthroscopic partial meniscectomy to skin incisions only in patients aged 35-55 years with persistent knee pain and an MRIconfirmed medial meniscus lesion. A computer-generated table of random numbers generated two comparison groups. Participants and outcome assessors were blinded to group allocation. Exclusions were locking knees, highenergy trauma or severe osteoarthritis. Outcomes were collected at baseline, 3 and 24 months. We hypothesised no difference between groups. The primary outcome was the between-group difference in change from baseline to 2 years in the mean score across all five normalised Knee injury and Osteoarthritis Outcome Score (KOOS) subscales (KOOS5). Results Forty-four patients (of the estimated 72) underwent randomisation; 22 in each group. Sixteen participants (36%) were non-blinded and eight participants (36%) from the sham group crossed over to the surgery group prior to the 2-year follow-up. At 2 years, both groups reported clinically relevant improvements (surgery 21.8, skin incisions only 13.6), the mean difference between groups was 8.2 in favour of surgery, which is slightly less than the cut-off of 10 prespecified to represent a clinically relevant difference; judged by the 95% CI (-3.4 to 19.8), a possibility of clinically relevant difference could not be excluded. In total, nine participants experienced 11 adverse events; six in the surgery group and three in the skin-incisions-only group. Conclusion We found greater improvement from arthroscopic partial meniscectomy compared with skin incisions only at 2 years, with the statistical uncertainty of the between-group difference including what could be considered clinically relevant. Because of the study being underpowered, nearly half in the sham group being non-blinded and one-Third crossing over to surgery, the results cannot be generalised to the greater patient population.
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42.
  • Sebastian, Sujeesh, et al. (författare)
  • Antibiotic containing bone cement in prevention of hip and knee prosthetic joint infections : A systematic review and meta-analysis
  • 2020
  • Ingår i: Journal of Orthopaedic Translation. - : Elsevier BV. - 2214-031X. ; 23, s. 53-60
  • Forskningsöversikt (refereegranskat)abstract
    • Background: Prosthetic joint infection (PJI) is the most serious total joint arthroplasty (TJA) complication despite several aseptic and antiseptic preventive measures. There is no clear evidence or even consensus, whether antibiotic-loaded bone cement (ALBC) should be used, in addition to systemic short-term routine antibiotic prophylaxis, to reduce the risk of PJI in primary TJA. We aimed to analyze the efficacy of ALBC for prevention of PJI in patients undergoing primary TJA. Methods: We searched systematically for randomized controlled trials (RCTs) in PubMed, Scopus, Embase, Web of Science and Cochrane library. Two reviewers independently screened potentially eligible studies according to predefined selection criteria and assessed the risk of bias using a modified version of the Cochrane risk of bias tool. PJI was prespecified as the primary outcome of interest. The meta-analyses were based on risk ratios using random-effects model per default. For the purpose of sensitivity, the corresponding fixed effects model odds ratios were calculated with the use of the Peto method as well. To evaluate a potential difference in effect sizes using different types (subgroups) of antibiotics used in bone cement, and at different follow-up periods, we performed stratified meta-analyses. Results: Thirty-seven studies were eligible for the systematic review and qualitative synthesis, and 9 trials (6507 total joint arthroplasties) were included in this meta-analysis. Overall ALBC significantly reduced the risk of PJI following primary TJAs (RRs, 0.36; 95% CIs, 0.16 to 0.80; P = 0.01) with a moderate degree of inconsistency (I2 = 47%). Based on stratified meta-analyses the use of gentamicin appeared to have a better effect (P = 0.0005) in the total hip arthroplasty. Pooled data of different antibiotics used in knee arthroplasties showed a significant association of cefuroxime (RRs, 0.08; 95% CIs, 0.01 to 0.63; P = 0.02). Further, ALBCs significantly reduced the PJI at one and two years of follow-up (P = 0.03 and P = 0.005 respectively). Conclusions: The evidence suggests that ALBCs are effective in reducing the PJI following primary TJA; i.e. between 20 and 84% reduced risk. However, the clear limitations of the available trial evidence highlight the need for joint-specific confirmatory trials, that will need to be designed as cluster-randomized trials of clinics in countries with well-functioning arthroplasty registries. The translational potential of this article: This meta-analysis highlights the prophylactic potential of ALBCs in lowering the risk of infection following primary hip or knee arthroplasties but emphasizes the need for more recent confirmatory trials.
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43.
  • Shoamanesh, Ashkan, et al. (författare)
  • Factor XIa inhibition with asundexian after acute non-cardioembolic ischaemic stroke (PACIFIC-Stroke) : an international, randomised, double-blind, placebo-controlled, phase 2b trial
  • 2022
  • Ingår i: The Lancet. - 0140-6736. ; 400:10357, s. 997-1007
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Asundexian (Bayer AG, Leverkusen, Germany), an oral small molecule factor XIa (FXIa) inhibitor, might prevent thrombosis without increasing bleeding. Asundexian's effect for secondary prevention of recurrent stroke is unknown. Methods: In this randomised, double-blind, placebo-controlled, phase 2b dose-finding trial (PACIFIC-Stroke), patients with acute (within 48 h) non-cardioembolic ischaemic stroke were recruited from 196 hospitals in 23 countries. Patients were eligible if they were aged 45 years or older, to be treated with antiplatelet therapy, and able to have a baseline MRI (either before or within 72 h of randomisation). Eligible participants were randomly assigned (1:1:1:1), using an interactive web-based response system and stratified according to anticipated antiplatelet therapy (single vs dual), to once daily oral asundexian (BAY 2433334) 10 mg, 20 mg, or 50 mg, or placebo in addition to usual antiplatelet therapy, and were followed up during treatment for 26–52 weeks. Brain MRIs were obtained at study entry and at 26 weeks or as soon as possible after treatment discontinuation. The primary efficacy outcome was the dose–response effect on the composite of incident MRI-detected covert brain infarcts and recurrent symptomatic ischaemic stroke at or before 26 weeks after randomisation. The primary safety outcome was major or clinically relevant non-major bleeding as defined by International Society on Thrombosis and Haemostasis criteria. The efficacy outcome was assessed in all participants assigned to treatment, and the safety outcome was assessed in all participants who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04304508, and is now complete. Findings: Between June 15, 2020, and July 22, 2021, 1880 patients were screened and 1808 participants were randomly assigned to asundexian 10 mg (n=455), 20 mg (n=450), or 50 mg (n=447), or placebo (n=456). Mean age was 67 years (SD 10) and 615 (34%) participants were women, 1193 (66%) were men, 1505 (83%) were White, and 268 (15%) were Asian. The mean time from index stroke to randomisation was 36 h (SD 10) and median baseline National Institutes of Health Stroke Scale score was 2·0 (IQR 1·0–4·0). 783 (43%) participants received dual antiplatelet treatment for a mean duration of 70·1 days (SD 113·4) after randomisation. At 26 weeks, the primary efficacy outcome was observed in 87 (19%) of 456 participants in the placebo group versus 86 (19%) of 455 in the asundexian 10 mg group (crude incidence ratio 0·99 [90% CI 0·79–1·24]), 99 (22%) of 450 in the asundexian 20 mg group (1·15 [0·93–1·43]), and 90 (20%) of 447 in the asundexian 50 mg group (1·06 [0·85–1·32]; t statistic –0·68; p=0·80). The primary safety outcome was observed in 11 (2%) of 452 participants in the placebo group versus 19 (4%) of 445 in the asundexian 10 mg group, 14 (3%) of 446 in the asundexian 20 mg group, and 19 (4%) of 443 in the asundexian 50 mg group (all asundexian doses pooled vs placebo hazard ratio 1·57 [90% CI 0·91–2·71]). Interpretation: In this phase 2b trial, FXIa inhibition with asundexian did not reduce the composite of covert brain infarction or ischaemic stroke and did not increase the composite of major or clinically relevant non-major bleeding compared with placebo in patients with acute, non-cardioembolic ischaemic stroke. Funding: Bayer AG.
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44.
  • Silventoinen, Karri, et al. (författare)
  • The CODATwins Project : The Cohort Description of Collaborative Project of Development of Anthropometrical Measures in Twins to Study Macro-Environmental Variation in Genetic and Environmental Effects on Anthropometric Traits
  • 2015
  • Ingår i: Twin Research and Human Genetics. - : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 18:4
  • Tidskriftsartikel (refereegranskat)abstract
    • For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
  •  
45.
  • Surendran, Praveen, et al. (författare)
  • Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
  • 2020
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
  •  
46.
  • Surendran, Praveen, et al. (författare)
  • Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension
  • 2016
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:10, s. 1151-1161
  • Tidskriftsartikel (refereegranskat)abstract
    • High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used -1/4155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.
  •  
47.
  • Thorlund, Jonas Bloch, et al. (författare)
  • Knee Arthroscopy Cohort Southern Denmark (KACS): protocol for a prospective cohort study
  • 2013
  • Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 3:10, s. 003399-003399
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Meniscus surgery is a high-volume surgery carried out on 1 million patients annually in the USA. The procedure is conducted on an outpatient basis and the patients leave the hospital a few hours after surgery. A critical oversight of previous studies is their failure to account for the type of meniscal tears. Meniscus tears can be categorised as traumatic or non-traumatic. Traumatic tears (TT) are usually observed in younger, more active individuals in an otherwise healthy' meniscus and joint. Non-traumatic tears (NTT) (ie, degenerative tears) are typically observed in the middle-aged (35-55years) and older population but the aetiology is largely unclear. Knowledge about the potential difference of the effect of arthroscopic meniscus surgery on patient symptoms between patients with traumatic and NTT is sparse. Furthermore, little is known about the natural time course of patient perceived pain, function and quality of life after meniscus surgery and factors affecting these outcomes. The aim of this prospective cohort study is to investigate the natural time course of patient-reported outcomes in patients undergoing meniscus surgery, with particular emphasis on the role of type of symptom onset. Methods/design This prospective cohort study enrol patients assigned for meniscus surgery. At the baseline (PRE surgery), patient characteristics are assessed using an email-based questionnaire also comprising several validated questionnaires assessing general health, knee-specific characteristics and patient's expectations of the surgery. Follow-up will be conducted at 12 and 52weeks after meniscus surgery. The major outcomes will be differences in changes, from before to 52weeks after surgery, in each of the five domains on the Knee injury and Osteoarthritis Outcome Score (KOOS) between patients undergoing surgery for traumatic compared with non-traumatic meniscus tears. Dissemination The study findings will be disseminated in peer-reviewed journals and presented at national and international conferences. Trial registration number ClinicalTrials.gov Identifier: NCT01871272.
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48.
  • Thorlund, Jonas Bloch, et al. (författare)
  • Patient reported outcomes in patients undergoing arthroscopic partial meniscectomy for traumatic or degenerative meniscal tears : comparative prospective cohort study
  • 2017
  • Ingår i: BMJ. - : BMJ. - 0959-8138 .- 1756-1833. ; 356
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To compare patient reported outcomes from before surgery to 52 weeks after surgery between individuals undergoing arthroscopic partial meniscectomy for traumatic meniscal tears and those for degenerative meniscal tears.DESIGN: Comparative prospective cohort study.SETTING: Four public orthopaedic departments in the Region of Southern Denmark. Participants were recruited between 1 February 2013 and 31 January 2014, and at one of the original four hospitals from 1 February 2014 to 31 January 2015.PARTICIPANTS: Individuals selected from Knee Arthroscopy Cohort Southern Denmark, aged 18-55, and undergoing arthroscopic partial meniscectomy for a traumatic or degenerative meniscal tear (defined by a combination of age and symptom onset).INTERVENTIONS: Both participant groups underwent arthroscopic partial meniscectomy for a meniscal tear, with operating surgeons recording relevant information on knee pathology. Patient reported outcomes were recorded via online questionnaires.MAIN OUTCOME MEASURES: Primary outcome was the average between-group difference in change on four of five subscales of the knee injury and osteoarthritis outcome score (KOOS). The four subscales covered pain, symptoms, sport and recreational function, and quality of life (KOOS4). A 95% confidence interval excluding differences greater than 10 KOOS points between groups was interpreted as absence of a clinically meaningful difference. Analyses adjusted for age, sex, and body mass index.RESULTS: 397 eligible adults (42% women) with a traumatic or degenerative meniscal tear (n=141, mean age 38.7 years (standard deviation 10.9); n=256, 46.6 years (6.4); respectively) were included in the main analysis. At 52 weeks after arthroscopic partial meniscectomy, 55 (14%) patients were lost to follow-up. Statistically, participants with degenerative meniscal tears had a significantly larger improvement in KOOS4 scores than those with traumatic tears (adjusted between-group difference -5.1 (95% confidence interval -8.9 to -1.3); P=0.008). In the analysis including KOOS4 score at all time points, a significant time-by-group interaction was observed in both the unadjusted (P=0.025) and adjusted analysis (P=0.024), indicating better self-reported outcomes in participants with degenerative tears. However, the difference between groups was at no time point considered clinically meaningful.CONCLUSIONS: These results question the current tenet that patients with traumatic meniscal tears experience greater improvements in patient reported outcomes after arthroscopic partial meniscectomy than patients with degenerative tears.Trial registration ClinicalTrials.gov identifier NCT01871272.
  •  
49.
  • Turcot, Valerie, et al. (författare)
  • Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
  • 2018
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
  •  
50.
  • Wouters, Anke, et al. (författare)
  • Association Between Time From Stroke Onset and Fluid-Attenuated Inversion Recovery Lesion Intensity Is Modified by Status of Collateral Circulation.
  • 2016
  • Ingår i: Stroke: a journal of cerebral circulation. - 1524-4628. ; 47, s. 1018-1018
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND PURPOSE:In patients with acute stroke, the intensity of a fluid-attenuated inversion recovery (FLAIR) lesion in the region of diffusion restriction is associated with time from symptom onset. We hypothesized that collateral status as assessed by the hypoperfusion intensity ratio could modify the association between time from stroke onset and FLAIR lesion intensity.METHODS:From the AX200 for ischemic stroke trial, 141 patients had appropriate FLAIR, diffusion-weighted imaging, and perfusion-weighted imaging. In the region of nonreperfused core, we calculated voxel-based relative FLAIR (rFLAIR) signal intensity. The hypoperfusion intensity ratio was defined as the ratio of the Tmax >10 s lesion over the Tmax >6 s lesion volume. A hypoperfusion intensity ratio threshold of ≤0.4 was used to dichotomize good versus poor collaterals. We studied the interaction between collateral status on the association between time from symptom onset and FLAIR intensity.RESULTS:Time from symptom onset was associated with the rFLAIR intensity in the region of nonreperfused core (B=1.05; 95% confidence interval, 1.0-1.1). We identified an interaction between this association and collateral status; an association was present between time and rFLAIR intensity in patients with poor collaterals (r=0.53), but absent in patients with good collaterals (r=0.17; P=0.04).CONCLUSIONS:Our findings show that the relationship between time from symptom onset and rFLAIR lesion intensity depends on collateral status. In patients with good collaterals, the development of an rFLAIR-positive lesion is less dependent on time from symptom onset compared with patients with poor collaterals.
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