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1.
  • Murray, Alison E., et al. (författare)
  • Roadmap for naming uncultivated Archaea and Bacteria
  • 2020
  • Ingår i: Nature Microbiology. - : NATURE PUBLISHING GROUP. - 2058-5276. ; 5:8, s. 987-994
  • Tidskriftsartikel (refereegranskat)abstract
    • The assembly of single-amplified genomes (SAGs) and metagenome-assembled genomes (MAGs) has led to a surge in genome-based discoveries of members affiliated with Archaea and Bacteria, bringing with it a need to develop guidelines for nomenclature of uncultivated microorganisms. The International Code of Nomenclature of Prokaryotes (ICNP) only recognizes cultures as 'type material', thereby preventing the naming of uncultivated organisms. In this Consensus Statement, we propose two potential paths to solve this nomenclatural conundrum. One option is the adoption of previously proposed modifications to the ICNP to recognize DNA sequences as acceptable type material; the other option creates a nomenclatural code for uncultivated Archaea and Bacteria that could eventually be merged with the ICNP in the future. Regardless of the path taken, we believe that action is needed now within the scientific community to develop consistent rules for nomenclature of uncultivated taxa in order to provide clarity and stability, and to effectively communicate microbial diversity. In this Consensus Statement, the authors discuss the issue of naming uncultivated prokaryotic microorganisms, which currently do not have a formal nomenclature system due to a lack of type material or cultured representatives, and propose two recommendations including the recognition of DNA sequences as type material.
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2.
  • Patel, Riyaz S., et al. (författare)
  • Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium
  • 2019
  • Ingår i: Circulation. - 2574-8300. ; 12:4
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
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3.
  • Hibar, Derrek P., et al. (författare)
  • Novel genetic loci associated with hippocampal volume
  • 2017
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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4.
  • Thompson, Paul M., et al. (författare)
  • The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
  • 2014
  • Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
  • Tidskriftsartikel (refereegranskat)abstract
    • The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
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5.
  • Aronsson, Mattias, et al. (författare)
  • The cost-effectiveness of radiofrequency catheter ablation as first-line treatment for paroxysmal atrial fibrillation : results from a MANTRA-PAF substudy.
  • 2015
  • Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 17:1, s. 48-55
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: The aim of this prospective substudy was to estimate the cost-effectiveness of treating paroxysmal atrial fibrillation (AF) with radiofrequency catheter ablation (RFA) compared with antiarrhythmic drugs (AADs) as first-line treatment.METHODS AND RESULTS: A decision-analytic Markov model, based on MANTRA-PAF (Medical Antiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation) study data, was developed to study long-term effects and costs of RFA compared with AADs as first-line treatment. Positive clinical effects were found in the overall population, a gain of an average 0.06 quality-adjusted life years (QALYs) to an incremental cost of €3033, resulting in an incremental cost-effectiveness ratio of €50 570/QALY. However, the result of the subgroup analyses showed that RFA was less costly and more effective in younger patients. This implied an incremental cost-effectiveness ratio of €3434/QALY in ≤50-year-old patients respectively €108 937/QALY in >50-year-old patients.CONCLUSION: Radiofrequency catheter ablation as first-line treatment is a cost-effective strategy for younger patients with paroxysmal AF. However, the cost-effectiveness of using RFA as first-line therapy in older patients is uncertain, and in most of these AADs should be attempted before RFA (MANTRA-PAF ClinicalTrials.gov number; NCT00133211).
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6.
  • Baldvinsdóttir, Bryndís, et al. (författare)
  • Adverse events during endovascular treatment of ruptured aneurysms : A prospective nationwide study on subarachnoid hemorrhage in Sweden
  • 2023
  • Ingår i: BRAIN AND SPINE. - : Elsevier. - 2772-5294. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: A range of adverse events (AEs) may occur in patients with subarachnoid hemorrhage (SAH). Endovascular treatment is commonly used to prevent aneurysm re-rupture.Research question: The aim of this study was to identify AEs related to endovascular treatment, analyze risk factors for AEs and how AEs affect patient outcome.Material and methods: Patients with aneurysmal SAH admitted to all neurosurgical centers in Sweden during a 3.5-year period (2014-2018) were prospectively registered. AEs related to endovascular aneurysm treatment were thromboembolic events, aneurysm re-rupture, vessel dissection and puncture site hematoma. Potential risk factors for the AEs were analyzed using multivariate logistic regression. Functional outcome was assessed at one year using the extended Glasgow outcome scale.Results: In total, 1037 patients were treated for ruptured aneurysms. Of which, 715 patients were treated with endovascular occlusion. There were 115 AEs reported in 113 patients (16%). Thromboembolic events were noted in 78 patients (11%). Aneurysm re-rupture occurred in 28 (4%), vessel dissection in 4 (0.6%) and puncture site hematoma in 5 (0.7%). Blister type aneurysm, aneurysm smaller than 5 mm and endovascular techniques other than coiling were risk factors for treatment-related AEs. At follow-up, 230 (32%) of the patients had unfavorable outcome. Patients suffering intraprocedural aneurysm re-rupture were more likely to have unfavorable outcome (OR 6.9, 95% CI 2.3-20.9).Discussion and conclusion: Adverse events related to endovascular occlusion of a ruptured aneurysm were seen in 16% of patients. Aneurysm re-rupture during endovascular treatment was associated with increased risk of unfavorable functional outcome.
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7.
  • Cole, Michelle J., et al. (författare)
  • Ten years of external quality assessment (EQA) of Neisseria gonorrhoeae antimicrobial susceptibility testing in Europe elucidate high reliability of data
  • 2019
  • Ingår i: BMC Infectious Diseases. - : BioMed Central. - 1471-2334. ; 19:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Confidence in any diagnostic and antimicrobial susceptibility testing data is provided by appropriate and regular quality assurance (QA) procedures. In Europe, the European Gonococcal Antimicrobial Susceptibility Programme (Euro-GASP) has been monitoring the antimicrobial susceptibility in Neisseria gonorrhoeae since 2004. Euro-GASP includes an external quality assessment (EQA) scheme as an essential component for a quality-assured laboratory-based surveillance programme. Participation in the EQA scheme enables any problems with the performed antimicrobial susceptibility testing to be identified and addressed, feeds into the curricula of laboratory training organised by the Euro-GASP network, and assesses the capacity of individual laboratories to detect emerging new, rare and increasing antimicrobial resistance phenotypes. Participant performance in the Euro-GASP EQA scheme over a 10 year period (2007 to 2016, no EQA in 2013) was evaluated.METHODS: Antimicrobial susceptibility category and MIC results from the first 5 years (2007-2011) of the Euro-GASP EQA were compared with the latter 5 years (2012-2016). These time periods were selected to assess the impact of the 2012 European Union case definitions for the reporting of antimicrobial susceptibility.RESULTS: dilutions of the modal MIC, respectively. The most common method used was Etest on GC agar base. There was a shift to using breakpoints published by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in the latter 5 years, however overall impact on the validity of results was limited, as the percentage categorical agreement and MIC concordance changed very little between the two five-year periods.CONCLUSIONS: The high level of comparability of results in this EQA scheme indicates that high quality data are produced by the Euro-GASP participants and gives confidence in susceptibility and resistance data generated by laboratories performing decentralised testing.
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9.
  • Cosedis Nielsen, Jens, et al. (författare)
  • Radiofrequency Ablation as Initial Therapy in Paroxysm Atrial Fibrillation
  • 2012
  • Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 367:17, s. 1587-1595
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThere are limited data comparing radiofrequency catheter ablation with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal atrial fibrillation.MethodsWe randomly assigned 294 patients with paroxysmal atrial fibrillation and no history of antiarrhythmic drug use to an initial treatment strategy of either radiofrequency catheter ablation (146 patients) or therapy with class IC or class III antiarrhythmic agents (148 patients). Follow-up included 7-day Holter-monitor recording at 3, 6, 12, 18, and 24 months. Primary end points were the cumulative and per-visit burden of atrial fibrillation (i.e., percentage of time in atrial fibrillation on Holter-monitor recordings). Analyses were performed on an intention-to-treat basis.ResultsThere was no significant difference between the ablation and drug-therapy groups in the cumulative burden of atrial fibrillation (90th percentile of arrhythmia burden, 13% and 19%, respectively; P=0.10) or the burden at 3, 6, 12, or 18 months. At 24 months, the burden of atrial fibrillation was significantly lower in the ablation group than in the drug-therapy group (90th percentile, 9% vs. 18%; P=0.007), and more patients in the ablation group were free from any atrial fibrillation (85% vs. 71%, P=0.004) and from symptomatic atrial fibrillation (93% vs. 84%, P=0.01). One death in the ablation group was due to a procedure-related stroke; there were three cases of cardiac tamponade in the ablation group. In the drug-therapy group, 54 patients (36%) underwent supplementary ablation.ConclusionsIn comparing radiofrequency ablation with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal atrial fibrillation, we found no significant difference between the treatment groups in the cumulative burden of atrial fibrillation over a period of 2 years.
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10.
  • Druwé, Patrick, et al. (författare)
  • Perception of inappropriate cardiopulmonary resuscitation by clinicians working in emergency departments and ambulance services : The REAPPROPRIATE international, multi-centre, cross sectional survey
  • 2018
  • Ingår i: Resuscitation. - : Elsevier. - 0300-9572 .- 1873-1570. ; 132, s. 112-119
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Cardiopulmonary resuscitation (CPR) is often started irrespective of comorbidity or cause of arrest. We aimed to determine the prevalence of perception of inappropriate CPR of the last cardiac arrest encountered by clinicians working in emergency departments and out-of-hospital, factors associated with perception, and its relation to patient outcome.Methods: A cross-sectional survey was conducted in 288 centres in 24 countries. Factors associated with perception of CPR and outcome were analyzed by Cochran-Mantel-Haenszel tests and conditional logistic models.Results: Of the 4018 participating clinicians, 3150 (78.4%) perceived their last CPR attempt as appropriate, 548 (13.6%) were uncertain about its appropriateness and 320 (8.0%) perceived inappropriateness; survival to hospital discharge was 370/2412 (15.3%), 8/481 (1.7%) and 8/294 (2.7%) respectively. After adjusting for country, team and clinician's characteristics, the prevalence of perception of inappropriate CPR was higher for a non-shockable initial rhythm (OR 3.76 [2.13-6.64]; P < .0001), a non-witnessed arrest (2.68 [1.89-3.79]; P < .0001), in older patients (2.94 [2.18-3.96]; P < .0001, for patients > 79 years) and in case of a "poor" first physical impression of the patient (3.45 [2.36-5.05]; P < .0001). In accordance, non-shockable and non-witnessed arrests were both associated with lower survival to hospital discharge (0.33 [0.26 - 0.41]; P < 0.0001 and 0.25 [0.15 - 0.41]; P < 0.0001, respectively), as were older patient age (0.25 [0.14 - 0.44]; P < 0.0001 for patients > 79 years) and a "poor" first physical impression (0.26 [0.19-0.35]; P < 0.0001).Conclusions: The perception of inappropriate CPR increased when objective indicators of poor prognosis were present and was associated with a low survival to hospital discharge. Factoring clinical judgment into the decision to (not) attempt CPR may reduce harm inflicted by excessive resuscitation attempts.
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11.
  • Gron, Kurt J., et al. (författare)
  • Archaeological cereals as an isotope record of long-term soil health and anthropogenic amendment in southern Scandinavia
  • 2021
  • Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791. ; 253
  • Tidskriftsartikel (refereegranskat)abstract
    • Maintaining soil health is integral to agricultural production, and the archaeological record contains multiple lines of palaeoclimatic and palaeoenvironmental proxy evidence that can contribute to the understanding and analysis of long-term trajectories of change that are key for contextualizing 21st century global environmental challenges. Soil is a capital resource and its nutrient balance is modified by agricultural activities, making it necessary to ensure soil productivity is maintained and managed through human choices and actions. Since prehistory this has always been the case; soil is a non-renewable resource within a human lifetime. Here, we present and interpret carbon and nitrogen isotope analysis of charred cereals from southern Scandinavia. Anthropogenic effects on soils are evident from the initiation of farming 6000 years ago, as is amendment to counteract its effects. The earliest cereals were planted on pristine soils, and by the late Neolithic, agriculture extensified. By the Iron Age it was necessary to significantly amend depleted soils to maintain crop yields. We propose that these data provide a record of soil water retention, net precipitation and amendment. From the start of the Neolithic there is a concurrent decrease in both Δ13C and δ15N, mitigated only by the replacement of soil organic content in the form of manure in the Iron Age. The cereal isotopes provide a record of trajectories of agricultural sustainability and anthropogenic adaptation for nearly the entire history of farming in the region.
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12.
  • Jacobsson, Susanne, 1974-, et al. (författare)
  • WGS analysis and molecular resistance mechanisms of azithromycin-resistant (MIC >2 mg/L) Neisseria gonorrhoeae isolates in Europe from 2009 to 2014
  • 2016
  • Ingår i: Journal of Antimicrobial Chemotherapy. - Oxford, United Kingdom : Oxford University Press. - 0305-7453 .- 1460-2091. ; 71:11, s. 3109-3116
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To elucidate the genome-based epidemiology and phylogenomics of azithromycin-resistant (MIC >2 mg/L) Neisseria gonorrhoeae strains collected in 2009-14 in Europe and clarify the azithromycin resistance mechanisms.Methods: Seventy-five azithromycin-resistant (MIC 4 to >256 mg/L) N. gonorrhoeae isolates collected in 17 European countries during 2009-14 were examined using antimicrobial susceptibility testing and WGS.Results: Thirty-six N. gonorrhoeae multi-antigen sequence typing STs and five phylogenomic clades, including 4-22 isolates from several countries per clade, were identified. The azithromycin target mutation A2059G (Escherichia coli numbering) was found in all four alleles of the 23S rRNA gene in all isolates with high-level azithromycin resistance (n = 4; MIC ≥256 mg/L). The C2611T mutation was identified in two to four alleles of the 23S rRNA gene in the remaining 71 isolates. Mutations in mtrR and its promoter were identified in 43 isolates, comprising isolates within the whole azithromycin MIC range. No mutations associated with azithromycin resistance were found in the rplD gene or the rplV gene and none of the macrolide resistance-associated genes [mef(A/E), ere(A), ere(B), erm(A), erm(B), erm(C) and erm(F)] were identified in any isolate.Conclusions: Clonal spread of relatively few N. gonorrhoeae strains accounts for the majority of the azithromycin resistance (MIC >2 mg/L) in Europe. The four isolates with high-level resistance to azithromycin (MIC ≥256 mg/L) were widely separated in the phylogenomic tree and did not belong to any of the main clades. The main azithromycin resistance mechanisms were the A2059G mutation (high-level resistance) and the C2611T mutation (low- and moderate-level resistance) in the 23S rRNA gene.
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13.
  • Jansen, Willemijn J, et al. (författare)
  • Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
  • 2022
  • Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
  • Tidskriftsartikel (refereegranskat)abstract
    • One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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14.
  • Jons, Christian, et al. (författare)
  • The Medical Antiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial : clinical rationale, study design, and implementation
  • 2009
  • Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 11:7, s. 917-923
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: No large randomized multicentre trial has evaluated the efficacy of radiofrequency ablation (RFA) vs. anti-arrhythmic drug (AAD) therapy as a first-line treatment of paroxysmal atrial fibrillation (AF). METHODS AND RESULTS: The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation (MANTRA-PAF) trial is a randomized, controlled, parallel group, multicentre study designed to test whether catheter-based RFA is superior to optimized AAD therapy in suppressing relapse within 24 months of symptomatic and/or asymptomatic AF in patients with paroxysmal AF without prior AAD therapy. The primary endpoint is cumulative AF burden on repeated 7 days Holter monitoring. Secondary endpoints are: thromboembolic events, hospitalization due to arrhythmia, pro-arrhythmic events, procedure/treatment-related side effects, health economics, quality of life, and change in left ventricular function. Ten centres in Scandinavia and Germany are participating in the study. Enrolment was started in 2005 and as of November 2008, 260 patients have been enrolled into the study. It is expected that enrolment will end by March 2009, when 300 patients have been included. CONCLUSION: The MANTRA-PAF trial will determine whether catheter-based RFA is superior to optimized AAD therapy as a first-line treatment in suppressing long-term relapse of symptomatic and/or asymptomatic AF.
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15.
  • Jung, Christian, et al. (författare)
  • A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
  • 2019
  • Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery. 
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17.
  • Kaufmann, Tobias, et al. (författare)
  • Common brain disorders are associated with heritable patterns of apparent aging of the brain
  • 2019
  • Ingår i: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 22:10, s. 1617-
  • Tidskriftsartikel (refereegranskat)abstract
    • Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3-96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.
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18.
  • Kristensen, Steen D., et al. (författare)
  • Reperfusion therapy for ST elevation acute myocardial infarction 2010/2011 : current status in 37 ESC countries
  • 2014
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 35:29, s. 1957-1970
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion therapy in ST-elevation myocardial infarction (STEMI). We conducted this study to evaluate the contemporary status on the use and type of reperfusion therapy in patients admitted with STEMI in the European Society of Cardiology (ESC) member countries. Methods and results A cross-sectional descriptive study based on aggregated country-level data on the use of reperfusion therapy in patients admitted with STEMI during 2010 or 2011. Thirty-seven ESC countries were able to provide data from existing national or regional registries. In countries where no such registries exist, data were based on best expert estimates. Data were collected on the use of STEMI reperfusion treatment and mortality, the numbers of cardiologists, and the availability of PPCI facilities in each country. Our survey provides a brief data summary of the degree of variation in reperfusion therapy across Europe. The number of PPCI procedures varied between countries, ranging from 23 to 884 per million inhabitants. Primary percutaneous coronary intervention and thrombolysis were the dominant reperfusion strategy in 33 and 4 countries, respectively. The mean population served by a single PPCI centre with a 24-h service 7 days a week ranged from 31 300 inhabitants per centre to 6 533 000 inhabitants per centre. Twenty-seven of the total 37 countries participated in a former survey from 2007, and major increases in PPCI utilization were observed in 13 of these countries. Conclusion Large variations in reperfusion treatment are still present across Europe. Countries in Eastern and Southern Europe reported that a substantial number of STEMI patients are not receiving any reperfusion therapy. Implementation of the best reperfusion therapy as recommended in the guidelines should be encouraged.
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19.
  • Lockmer, Sandra, et al. (författare)
  • Chemotherapy-Free Initial Treatment of Advanced Indolent Lymphoma Has Durable Effect With Low Toxicity : Results From Two Nordic Lymphoma Group Trials With More Than 10 Years of Follow-Up
  • 2018
  • Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 36:33, s. 3315-3323
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: For indolent lymphoma, the optimal timing, sequence, and choice of therapeutic regimens remain a matter of debate. In two Nordic Lymphoma Group randomized trials, symptomatic or clearly progressing patients were treated first line with a rituximab-containing regimen without chemotherapy. The purpose of this study was to assess long-term survival, risk of transformation, and need of new therapies.Methods: Data were collected at cross-sectional follow-up for 321 patients with indolent lymphoma (84% with follicular lymphomas [FL]) included in one of two Nordic Lymphoma Group trials (accrual 1998 to 1999 and 2002 to 2008). All patients received first-line therapy with one or two cycles of four weekly infusions of rituximab 375 mg/m(2), and 148 were randomly allocated to the addition of interferon alfa-2a. Follow-up data were retrieved from initial trial databases and medical records on repeated clinical evaluations.Results: At the end of follow-up, 73% of patients were alive, with a median follow-up after random assignment of 10.6 years. Among all, 36% (38% with FL) had never needed chemotherapy. For patients with FL who required new therapy within 24 months because of early disease progression, the 10-year survival rate was 59% versus 81% for those with longer remission. Interferon was not shown to improve long-term outcome. Transformation was diagnosed in 20% of all patients (2.4% per person-year) and in 18% with FL. An additional malignancy was found in 12%.Conclusion: Approximately one third of patients with symptomatic indolent lymphoma (30% with FL, 23% without FL) did not need new therapy in the long term after first-line rituximab without chemotherapy. In the entire cohort, 10-year survival was excellent with no major safety issues, which suggests that chemotherapy can be delayed safely in the majority of patients.
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20.
  • Mayes, Maureen D, et al. (författare)
  • Immunochip analysis identifies multiple susceptibility Loci for systemic sclerosis.
  • 2014
  • Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 94:1, s. 47-61
  • Tidskriftsartikel (refereegranskat)abstract
    • In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci.
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21.
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22.
  • Nielsen, Jens Cosedis, et al. (författare)
  • Long-term efficacy of catheter ablation as first-line therapy for paroxysmal atrial fibrillation : 5-year outcome in a randomised clinical trial.
  • 2017
  • Ingår i: Heart. - : BMJ Publishing Group Ltd. - 1355-6037 .- 1468-201X. ; 103:5, s. 368-376
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial compared radiofrequency catheter ablation (RFA) with antiarrhythmic drug therapy (AAD) as first-line treatment for paroxysmal atrial fibrillation (AF). Endpoint of ablation was elimination of electrical activity inside pulmonary veins. We present the results of the 5-year follow-up.METHODS: This pre-specified 5-year follow-up included assessment of any AF and symptomatic AF burden by one 7-day Holter recording and quality of life (QoL) assessment, using SF-36 questionnaire physical and mental component scores. Analysis was intention-to-treat. Imputation was used to compensate for missing Holter data.RESULTS: 245 of 294 patients (83%) randomised to RFA (n=125) or AAD (n=120) attended the 5-year follow-up, 227 with Holter recording. Use of class I or III AAD was more frequent in AAD group (N=61 vs 13, p<0.001). More patients in the RFA group were free from AF (126/146 (86%) vs 105/148 (71%), p=0.001, relative risk (RR) 0.82; 95% CI 0.73 to 0.93) and symptomatic AF (137/146 (94%) vs 126/148 (85%), p=0.015, χ(2) test, RR 0.91; 95% CI 0.84 to 0.98) in 7-day Holter recording. AF burden was significantly lower in the RFA group (any AF: p=0.003; symptomatic AF: p=0.02). QoL scores did not differ between randomisation groups. QoL scores remained improved from baseline (both components p<0.001), and did not differ from 2-year scores.CONCLUSIONS: At 5 years, the occurrence and burden of any AF and symptomatic AF were significantly lower in the RFA group than in the AAD group. Improved QoL scores observed after 2 years persisted after 5 years without between-group differences.TRIAL REGISTRATION NUMBER: NCT00133211; Results.
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23.
  • Pekka Raatikainen, M. J., et al. (författare)
  • Radiofrequency catheter ablation maintains its efficacy better than antiarrhythmic medication in patients with paroxysmal atrial fibrillation: On-treatment analysis of the randomized controlled MANTRA-PAF trial
  • 2015
  • Ingår i: International Journal of Cardiology. - : ELSEVIER IRELAND LTD. - 0167-5273 .- 1874-1754. ; 198, s. 108-114
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) is a randomized trial comparing radiofrequency catheter ablation (RFA) to antiarrhythmic drugs (AADs) as first-line treatment of paroxysmal atrial fibrillation (PAF). In order to eliminate the clouding effect of crossover we performed an on-treatment analysis of the data. Methods and results: Patients (n = 294) were divided into three groups: those receiving only the assigned therapy (RFA and AAD groups) and those receiving both therapies (crossover group). The primary end points were AF burden in 7-day Holter recordings at 3, 6, 12, 18, and 24 months and cumulative AF burden in all recordings. At 24 months, AF burden was significantly lower in the RFA (n = 110) than in the AAD (n = 92) and the crossover (n = 84) groups (90th percentile 1% vs. 10% vs. 16%, P = 0.007), and more patients were free from any AF (89% vs. 73% vs. 74%, P = 0.006). In the RFA, AAD and the crossover groups 63%, 59% and 21% (P less than 0.001) of the patients had no AF episodes in any Holter recording, respectively. Quality of life improved significantly in all groups. There were no differences in serious adverse events between the RFA, AAD and crossover groups (19% vs. 8% vs. 23%) (P = 0.10). Conclusions: In the treatment of antiarrhythmic therapy naive patients with PAF long-term efficacy of RFA was superior to AAD therapy. Thus, it is reasonable to offer RFA as first-line treatment for highly symptomatic patients who accept the risks of the procedure and are aware of frequent need for reablation(s). (C) 2015 Elsevier Ireland Ltd. All rights reserved.
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24.
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25.
  • Steen, Johanna, et al. (författare)
  • Recognition of Amino Acid Motifs, Rather Than Specific Proteins, by Human Plasma Cell-Derived Monoclonal Antibodies to Posttranslationally Modified Proteins in Rheumatoid Arthritis
  • 2019
  • Ingår i: Arthritis & Rheumatology. - : WILEY. - 2326-5191 .- 2326-5205. ; 71:2, s. 196-209
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Antibodies against posttranslationally modified proteins are a hallmark of rheumatoid arthritis (RA), but the emergence and pathogenicity of these autoantibodies are still incompletely understood. The aim of this study was to analyze the antigen specificities and mutation patterns of monoclonal antibodies (mAb) derived from RA synovial plasma cells and address the question of antigen cross-reactivity.Methods: IgG-secreting cells were isolated from RA synovial fluid, and the variable regions of the immunoglobulins were sequenced (n = 182) and expressed in full-length mAb (n = 93) and also as germline-reverted versions. The patterns of reactivity with 53,019 citrullinated peptides and 49,211 carbamylated peptides and the potential of the mAb to promote osteoclastogenesis were investigated.Results: Four unrelated anti-citrullinated protein autoantibodies (ACPAs), of which one was clonally expanded, were identified and found to be highly somatically mutated in the synovial fluid of a patient with RA. The ACPAs recognized >3,000 unique peptides modified by either citrullination or carbamylation. This highly multireactive autoantibody feature was replicated for Ig sequences derived from B cells from the peripheral blood of other RA patients. The plasma cell-derived mAb were found to target distinct amino acid motifs and partially overlapping protein targets. They also conveyed different effector functions as revealed in an osteoclast activation assay.Conclusion: These findings suggest that the high level of cross-reactivity among RA autoreactive B cells is the result of different antigen encounters, possibly at different sites and at different time points. This is consistent with the notion that RA is initiated in one context, such as in the mucosal organs, and thereafter targets other sites, such as the joints.
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26.
  • Steen Jensen, Camilla, et al. (författare)
  • Cerebrospinal Fluid Amyloid Beta and Tau Concentrations Are Not Modulated by 16 Weeks of Moderate- to High-Intensity Physical Exercise in Patients with Alzheimer Disease.
  • 2016
  • Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 42:3-4, s. 146-158
  • Tidskriftsartikel (refereegranskat)abstract
    • Physical exercise may have some effect on cognition in patients with Alzheimer disease (AD). However, the underlying biochemical effects are unclear. Animal studies have shown that amyloid beta (Aβ), one of the pathological hallmarks of AD, can be altered with high levels of physical activity.The objective of this study was to elucidate the effect of 16 weeks of moderate- to high-intensity physical exercise on the biomarkers of AD, with special emphasis on the amyloidogenic pathway.From a total of 53 patients with AD participating in the Preserving Cognition, Quality of Life, Physical Health and Functional Ability in Alzheimer's Disease: The Effect of Physical Exercise (ADEX) study we analyzed cerebrospinal fluid samples for Aβ species, total tau (t-tau), phosphorylated tau (p-tau) and soluble amyloid precursor protein (sAPP) species. We also assessed the patients for apolipoprotein E ε4 (ApoE ε4) genotype.We found no effect of 16 weeks of physical exercise on the selected biomarkers, and no effect of ApoE ε4 genotype.Our findings suggest that the possible effect of physical exercise on cognition in patients with AD is not due to modulation of Aβ, t-tau, p-tau and sAPP species.
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27.
  • White, Harvey D, et al. (författare)
  • Darapladib for preventing ischemic events in stable coronary heart disease
  • 2014
  • Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 370:18, s. 1702-1711
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND:Elevated lipoprotein-associated phospholipase A2 activity promotes the development of vulnerable atherosclerotic plaques, and elevated plasma levels of this enzyme are associated with an increased risk of coronary events. Darapladib is a selective oral inhibitor of lipoprotein-associated phospholipase A2.METHODS:In a double-blind trial, we randomly assigned 15,828 patients with stable coronary heart disease to receive either once-daily darapladib (at a dose of 160 mg) or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the components of the primary end point as well as major coronary events (death from coronary heart disease, myocardial infarction, or urgent coronary revascularization for myocardial ischemia) and total coronary events (death from coronary heart disease, myocardial infarction, hospitalization for unstable angina, or any coronary revascularization).RESULTS:During a median follow-up period of 3.7 years, the primary end point occurred in 769 of 7924 patients (9.7%) in the darapladib group and 819 of 7904 patients (10.4%) in the placebo group (hazard ratio in the darapladib group, 0.94; 95% confidence interval [CI], 0.85 to 1.03; P=0.20). There were also no significant between-group differences in the rates of the individual components of the primary end point or in all-cause mortality. Darapladib, as compared with placebo, reduced the rate of major coronary events (9.3% vs. 10.3%; hazard ratio, 0.90; 95% CI, 0.82 to 1.00; P=0.045) and total coronary events (14.6% vs. 16.1%; hazard ratio, 0.91; 95% CI, 0.84 to 0.98; P=0.02).CONCLUSIONS:In patients with stable coronary heart disease, darapladib did not significantly reduce the risk of the primary composite end point of cardiovascular death, myocardial infarction, or stroke. (Funded by GlaxoSmithKline; STABILITY ClinicalTrials.gov number, NCT00799903.).
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28.
  • White, Harvey D., et al. (författare)
  • Survival with Cardiac-Resynchronization Therapy in Mild Heart Failure
  • 2014
  • Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 370:18, s. 1702-1711
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Elevated lipoprotein-associated phospholipase A(2) activity promotes the development of vulnerable atherosclerotic plaques, and elevated plasma levels of this enzyme are associated with an increased risk of coronary events. Darapladib is a selective oral inhibitor of lipoprotein-associated phospholipase A(2). Methods: In a double-blind trial, we randomly assigned 15,828 patients with stable coronary heart disease to receive either once-daily darapladib (at a dose of 160 mg) or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the components of the primary end point as well as major coronary events (death from coronary heart disease, myocardial infarction, or urgent coronary revascularization for myocardial ischemia) and total coronary events (death from coronary heart disease, myocardial infarction, hospitalization for unstable angina, or any coronary revascularization). Results: During a median follow-up period of 3.7 years, the primary end point occurred in 769 of 7924 patients (9.7%) in the darapladib group and 819 of 7904 patients (10.4%) in the placebo group (hazard ratio in the darapladib group, 0.94; 95% confidence interval [CI], 0.85 to 1.03; P=0.20). There were also no significant between-group differences in the rates of the individual components of the primary end point or in all-cause mortality. Darapladib, as compared with placebo, reduced the rate of major coronary events (9.3% vs. 10.3%; hazard ratio, 0.90; 95% CI, 0.82 to 1.00; P=0.045) and total coronary events (14.6% vs. 16.1%; hazard ratio, 0.91; 95% CI, 0.84 to 0.98; P=0.02). ConclusionsIn patients with stable coronary heart disease, darapladib did not significantly reduce the risk of the primary composite end point of cardiovascular death, myocardial infarction, or stroke. (Funded by GlaxoSmithKline; STABILITY ClinicalTrials.gov number, NCT00799903.)
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29.
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30.
  • Ahmad Kiadaliri, Aliasghar, et al. (författare)
  • Predicting Changes in Cardiovascular Risk Factors in Type 2 Diabetes in the Post-UKPDS Era: Longitudinal Analysis of the Swedish National Diabetes Register
  • 2013
  • Ingår i: Journal of Diabetes Research. - : Hindawi Limited. - 2314-6745 .- 2314-6753. ; 2013
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the current study was to provide updated time-path equations for risk factors of type-2-diabetes-related cardiovascular complications for application in risk calculators and health economic models. Observational data from the Swedish National Diabetes Register were analysed using Generalized Method of Moments estimation for dynamic panel models ( , aged 25–70 years at diagnosis in 2001–2004). Validation was performed using persons diagnosed in 2005 ( ). Results were compared with the UKPDS outcome model. The value of the risk factor in the previous year was the main predictor of the current value of the risk factor. People with high (low) values of risk factor in the year of diagnosis experienced a decreasing (increasing) trend over time. BMI was associated with elevations in all risk factors, while older age at diagnosis and being female generally corresponded to lower levels of risk factors. Updated time-path equations predicted risk factors more precisely than UKPDS outcome model equations in a Swedish population. Findings indicate new time paths for cardiovascular risk factors in the post-UKPDS era. The validation analysis confirmed the importance of updating the equations as new data become available; otherwise, the results of health economic analyses may be biased.
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31.
  • Ahmad Kiadaliri, Aliasghar, et al. (författare)
  • Towards Renewed Health Economic Simulation of Type 2 Diabetes: Risk Equations for First and Second Cardiovascular Events from Swedish Register Data
  • 2013
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Predicting the risk of future events is an essential part of health economic simulation models. In pursuit of this goal, the current study aims to predict the risk of developing first and second acute myocardial infarction, heart failure, non-acute ischaemic heart disease, and stroke after diagnosis in patients with type 2 diabetes, using data from the Swedish National Diabetes Register. Material and Methods Register data on 29,034 patients with type 2 diabetes were analysed over five years of follow up (baseline 2003). To develop and validate the risk equations, the sample was randomly divided into training (75%) and test (25%) subsamples. The Weibull proportional hazard model was used to estimate the coefficients of the risk equations, and these were validated in both the training and the test samples. Results In total, 4,547 first and 2,418 second events were observed during the five years of follow up. Experiencing a first event substantially elevated the risk of subsequent events. There were heterogeneities in the effects of covariates within as well as between events; for example, while for females the hazard ratio of having a first acute myocardial infarction was 0.79 (0.70–0.90), the hazard ratio of a second was 1.21 (0.98–1.48). The hazards of second events decreased as the time since first events elapsed. The equations showed adequate calibration and discrimination (C statistics range: 0.70–0.84 in test samples). Conclusion The accuracy of health economic simulation models of type 2 diabetes can be improved by ensuring that they account for the heterogeneous effects of covariates on the risk of first and second cardiovascular events. Thus it is important to extend such models by including risk equations for second cardiovascular events.
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32.
  • Alhede, Christina, et al. (författare)
  • Antiarrhythmic medication is superior to catheter ablation in suppressing supraventricular ectopic complexes in patients with atrial fibrillation
  • 2017
  • Ingår i: International Journal of Cardiology. - : ELSEVIER IRELAND LTD. - 0167-5273 .- 1874-1754. ; 244, s. 186-191
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Supraventricular ectopic complexes (SVEC) originating in the pulmonary veins are known triggers of atrial fibrillation (AF) which led to the development of pulmonary vein isolation for AF. However, the long-term prevalence of SVEC after catheter ablation (CA) as compared to antiarrhythmic medication (AAD) is unknown. Our aims were to compare the prevalence of SVEC after AAD and CA and to estimate the association between baseline SVEC burden and AF burden during 24 months of follow-up. Methods: Patients with paroxysmal AF (N = 260) enrolled in the MANTRA PAF trial were treated with AAD (N = 132) or CA (N = 128). At baseline and 3, 6, 12, 18 and 24 months follow-up patients underwent 7-day Holter monitoring to assess SVEC and AF burden. We compared SVEC burden between treatments with Wilcoxon sum rank test. Results: Patients treated with AAD had significantly lower daily SVEC burden during follow-up as compared to CA (AAD: 19 [6-58] versus CA: 39 [14-125], p = 0.003). SVEC burden increased post-procedurally followed by a decrease after CA whereas after AAD SVEC burden decreased and stabilized after 3 months of follow-up. Patients with low SVEC burden had low AF burden after both treatments albeit this was more pronounced after CA at 24 months of follow-up. Conclusion: AAD was superior to CA in suppressing SVEC burden after treatment of paroxysmal AF. After CA SVEC burden increased immediately post-procedural followed by a decrease whereas after AAD an early decrease was observed. Lower SVEC burden was highly associated with lower AF burden during follow-up especially after CA. (C) 2017 Elsevier B.V. All rights reserved.
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33.
  • Alhede, Christina, et al. (författare)
  • Higher burden of supraventricular ectopic complexes early after catheter ablation for atrial fibrillation is associated with increased risk of recurrent atrial fibrillation
  • 2018
  • Ingår i: Europace. - : OXFORD UNIV PRESS. - 1099-5129 .- 1532-2092. ; 20:1, s. 50-57
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims Early identification of patients who could benefit from early re-intervention after catheter ablation is highly warranted. Our aim was to investigate the association between post-procedural burden of supraventricular ectopic complexes (SVEC) and the risk of long-term atrial fibrillation (AF) recurrence. Methods and results A total of 125 patients undergoing catheter ablation for AF were included. Patients underwent 7-day Holter recordings immediately post-procedural. The number of SVEC in post-procedural Holter recordings was categorized into quartiles: 0-72, 73-212, 213-782 and amp;gt;= 783 SVEC/day. Long-term AF recurrence was defined as a combined endpoint of AF amp;gt;= 1 min during follow-up Holter recordings, cardioversion or hospitalization for AF after a 3-month blanking period and within 24 months of follow-up. High post-procedural supraventricular ectopy burden was associated with an increased risk of long-term AF recurrence in a dose-dependent manner (amp;gt;= 783 SVEC: HR 4.6 [1.9-11.5], P amp;lt; 0.001) irrespective of AF recurrence during the blanking period or other risk factors. In patients with early AF recurrence amp;lt; 90 days after catheter ablation ectopy burden was also highly predictive of long-term AF recurrence (SVEC amp;gt;= 213: HR 3.0 [1.3-6.7], P = 0.007). Correspondingly, patients with early AF recurrence but low ectopy burden remained at low risk of long-term AF recurrence after the blanking period. Conclusion Our results indicate that post-procedural ectopy burden is highly associated with long-term AF recurrence and could be a potent risk marker for selection of patients for early re-ablation. Development of future ablation risk stratification and strategies should include focus on post-procedural ectopy burden.
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34.
  • Alhede, Christina, et al. (författare)
  • The impact of supraventricular ectopic complexes in different age groups and risk of recurrent atrial fibrillation after antiarrhythmic medication or catheter ablation
  • 2018
  • Ingår i: International Journal of Cardiology. - : ELSEVIER IRELAND LTD. - 0167-5273 .- 1874-1754. ; 250, s. 122-127
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Supraventricular ectopic complexes (SVEC) are known risk factors of recurrent atrial fibrillation (AF). However, the impact of SVEC in different age groups is unknown. We aimed to investigate the risk of AF recurrence with higher SVEC burden in patients +/- 57 years, respectively, after treatment with antiarrhythmic medication (AAD) or catheter ablation (CA). Methods: In total, 260 patients with LVEF amp;gt;40% and age amp;lt;= 70 years were randomized to AAD (N = 132) or CA (N = 128) as first-line treatment for paroxysmal AF. All patients underwent 7-day Holter monitoring at baseline, and after 3, 6, 12, 18 and 24 months and were categorized according to median age +/- 57 years. We used multi-variate Cox regression analyses and we defined high SVEC burden at 3 months of follow-up as the upper 75th percentile amp;gt;195 SVEC/day. AF recurrence was defined as AF amp;gt;= 1 min, AF-related cardioversion or hospitalization. Results: Age amp;gt;57 years were significantly associated with higher AF recurrence rate after CA (58% vs 36%, p = 0.02). After CA, we observed a higher SVEC burden during follow-up in patients amp;gt;57 years which was not observed in the younger age group treatedwith CA (p = 0.006). High SVEC burden at 3 months after CA was associated with AF recurrence in older patients but not in younger patients (amp;gt;57 years: HR 3.4 [1.4-7.9], p = 0.005). We did not find any age-related differences after AAD. Conclusion: We found that younger and older patients respond differently to CA and that SVEC burden was only associated with AF recurrence in older patients. (C) 2017 Elsevier B.V. All rights reserved.
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35.
  • Andersson, Emelie, et al. (författare)
  • Costs of diabetes complications : hospital-based care and absence from work for 392,200 people with type 2 diabetes and matched control participants in Sweden
  • 2020
  • Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 63:12, s. 2582-2594
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS/HYPOTHESIS: The risk of complications and medical consequences of type 2 diabetes are well known. Hospital costs have been identified as a key driver of total costs in studies of the economic burden of type 2 diabetes. Less evidence has been generated on the impact of individual diabetic complications on the overall societal burden. The objective of this study was to analyse costs of hospital-based healthcare (inpatient and outpatient care) and work absence related to individual macrovascular and microvascular complications of type 2 diabetes in Sweden in 2016.METHODS: Data for 2016 were retrieved from a Swedish national retrospective observational database cross-linking individual-level data for 1997-2016. The database contained information from population-based health, social insurance and socioeconomic registers for 392,200 people with type 2 diabetes and matched control participants (5:1). Presence of type 2 diabetes and of diabetes complications were derived using all years, 1997-2016. Costs of hospital-based care and of absence from work due to diabetes complications were estimated for the year 2016. Regression analysis was used for comparison with control participants to attribute absence from work to individual complications, and to account for joint presence of complications.RESULTS: Use of hospital care for complications was higher in type 2 diabetes compared with control participants in 2016: 26% vs 12% had ≥1 hospital contact; there were 86,104 vs 24,608 outpatient visits per 100,000 people; and there were 9894 vs 2546 inpatient admissions per 100,000 people (all p < 0.001). The corresponding total costs of hospital-based care for complications were €919 vs €232 per person (p < 0.001), and 74.7% of costs were then directly attributed to diabetes (€687 per person). Regression analyses distributed the costs of days absent from work across diabetes complications per se, basic type 2 diabetes effect and unattributed causes. Diabetes complications amounted to €1317 per person in 2016, accounting for possible complex interactions (25% of total costs of days absent). Key drivers of costs were the macrovascular complications angina pectoris, heart failure and stroke; and the microvascular complications eye diseases, including retinopathy, kidney disease and neuropathy. Early mortality in working ages cost an additional €579 per person and medications used in risk-factor treatment amounted to €418 per person.CONCLUSIONS/INTERPRETATION: The economic burden of complications in type 2 diabetes is substantial. Costs of absence from work in this study were found to be greater than of hospital-based care, highlighting the need for considering treatment consequences in a societal perspective in research and policy. Graphical abstract.
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36.
  • Armstrong, David A., et al. (författare)
  • Standard electrode potentials involving radicals in aqueous solution : inorganic radicals (IUPAC Technical Report)
  • 2015
  • Ingår i: Pure and Applied Chemistry. - : Walter de Gruyter. - 0033-4545 .- 1365-3075. ; 87:11-12, s. 1139-1150
  • Tidskriftsartikel (refereegranskat)abstract
    • Recommendations are made for standard potentials involving select inorganic radicals in aqueous solution at 25 degrees C. These recommendations are based on a critical and thorough literature review and also by performing derivations from various literature reports. The recommended data are summarized in tables of standard potentials, Gibbs energies of formation, radical pK(a)'s, and hemicolligation equilibrium constants. In all cases, current best estimates of the uncertainties are provided. An extensive set of Data Sheets is appended that provide original literature references, summarize the experimental results, and describe the decisions and procedures leading to each of the recommendations.
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37.
  • Arvin, Erik, et al. (författare)
  • Water Education ved DTU : en e-læringplatform i Moodle til individualiseret kompetenceopbygning i samfundets vandsektor
  • 2010
  • Ingår i: Læring og Medier. - : Det Kgl. Bibliotek/Royal Danish Library. - 1903-248X. ; :6, s. 1-15
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • Omstruktureringen af kommunerne i forbindelse med amternes nedlæggelse og privatiseringen af det danske samfunds vand- og spildevandsforsyning har givet store omvæltninger og nye udfordringer for mange personalegrupper. I vandbranchen er der derfor i dag et stort behov for individualiseret kompetenceopbygning inden for hele vandets kredsløb, afstrømmet regnvand, overfladevand, grundvand, vandforsyning, spildevandstransport og -rensning samt vandkvalitet og vandhygiejne.At behovet for efter- og videreuddannelse er stort beror på et skøn baseret på samtaler med fagpersoner i branchen. Desværre foreligger der ikke konkrete behovsopgørelser, og det er også uklart, hvor stor betalingsviljen til kompetenceudvikling er hos virksomhederne og kommunerne.Der er i dag det samme behov for et kompetenceløft på universitetsområdet, fordi der er sket en markant internationalisering, hvorved mange udenlandske studerende følger engelsksprogede masterprogrammer. På Danmarks Tekniske Universitet (DTU) foregår alle masterkurser på engelsk, og ca. halvdelen af de studerende på DTU Miljø's (Institut for Vand og Miljøteknologi) masterkurser er udenlandske gæstestuderende. Det er i dag en væsentlig opgave/problem at sikre, at disse studerende har de nødvendige faglige forudsætninger, når de starter på de planlagte kurser. Ellers sænkes undervisningsniveauet markant, og ressourceforbruget af hjælpelærere øges. Så også her er der brug for tilbud om individualiseret kompetenceopbygning.Men også over for de danske studerende er der behov for markante ændringer i undervisningsmetoderne. Der er en klar tendens til, at mange studerende bruger lærebøgerne som referenceværker. En voksende andel af de studerende sidder ikke mere og læser lærebøgerne igennem som i "gamle dage". E-læring kan være et middel til at give effektiv læring til disse mange studerende, der fra barnsben er tilvænnet IT-verdenen.I fremtiden vil der blive mere utraditionelle undervisningsbehov. Nogle større virksomheder vil i fremtiden skulle satse mere på salg af integrerede løsninger, f.eks. vand- og spildevandsløsninger for hele byområder. Dette kræver, at der er kompetente personer hos bygherrerne til at drive de fremtidige komplekse systemer. Her kan tilbud om uddannelse af bygherrens personale indgå som en konkurrenceparameter i virksomhedernes tilbud. Og netop her vil et fleksibelt e-læringssystem kunne få stor betydning.Målsætningen for udvikling af e-læringssystemet Water Education ved DTU er at opfylde ovennævnte undervisningsbehov. Projektet er i en udviklingsfase, hvorfor de praktiske erfaringer om udvikling af e-læringsmodulerne og brugernes vurderinger af fordele og ulemper er begrænsede. IT- og Telestyrelsen har medfinansieret projektet og deltaget aktivt i følgegruppemøder.
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38.
  • Astrup, Arne, et al. (författare)
  • The role of reducing intakes of saturated fat in the prevention of cardiovascular disease : where does the evidence stand in 2010?
  • 2011
  • Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 93:4, s. 684-688
  • Tidskriftsartikel (refereegranskat)abstract
    • Current dietary recommendations advise reducing the intake of saturated fatty acids (SFAs) to reduce coronary heart disease (CHD) risk, but recent findings question the role of SFAs. This expert panel reviewed the evidence and reached the following conclusions: the evidence from epidemiologic, clinical, and mechanistic studies is consistent in finding that the risk of CHD is reduced when SFAs are replaced with polyunsaturated fatty acids (PUFAs). In populations who consume a Western diet, the replacement of 1% of energy from SFAs with PUFAs lowers LDL cholesterol and is likely to produce a reduction in CHD incidence of >= 2-3%. No clear benefit of substituting carbohydrates for SFAs has been shown, although there might be a benefit if the carbohydrate is unrefined and has a low glycemic index. Insufficient evidence exists to judge the effect on CHD risk of replacing SFAs with MUFAs. No clear association between SFA intake relative to refined carbohydrates and the risk of insulin resistance and diabetes has been shown. The effect of diet on a single biomarker is insufficient evidence to assess CHD risk. The combination of multiple biomarkers and the use of clinical end-points could help substantiate the effects on CHD. Furthermore, the effect of particular foods on CHD cannot be predicted solely by their content of total SFAs because individual SFAs may have different cardiovascular effects and major SFA food sources contain other constituents that could influence CHD risk. Research is needed to clarify the role of SFAs compared with specific forms of carbohydrates in CHD risk and to compare specific foods with appropriate alternatives.
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39.
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40.
  • Atar, Dan, et al. (författare)
  • Rationale and Design of the 'MITOCARE' Study: A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety and Efficacy of TRO40303 for the Reduction of Reperfusion Injury in Patients Undergoing Percutaneous Coronary Intervention for Acute Myocardial Infarction
  • 2012
  • Ingår i: Cardiology. - : S. Karger AG. - 1421-9751 .- 0008-6312. ; 123:4, s. 201-207
  • Tidskriftsartikel (refereegranskat)abstract
    • Treatment of acute ST-elevation myocardial infarction (STEMI) by reperfusion using percutaneous coronary intervention (PCI) or thrombolysis has provided clinical benefits; however, it also induces considerable cell death. This process is called reperfusion injury. The continuing high rates of mortality and heart failure after acute myocardial infarction (AMI) emphasize the need for improved strategies to limit reperfusion injury and improve clinical outcomes. The objective of this study is to assess safety and efficacy of TRO40303 in limiting reperfusion injury in patients treated for STEMI. TRO40303 targets the mitochondrial permeability transition pore, a promising target for the prevention of reperfusion injury. This multicenter, double-blind study will randomize patients with STEMI to TRO40303 or placebo administered just before balloon inflation or thromboaspiration during PCI. The primary outcome measure will be reduction in infarct size (assessed as plasma creatine kinase and troponin I area under the curve over 3 days). The main secondary endpoint will be infarct size normalized to the myocardium at risk (expressed by the myocardial salvage index assessed by cardiac magnetic resonance). The study is being financed under an EU-FP7 grant and conducted under the auspices of the MITOCARE research consortium, which includes experts from clinical and basic research centers, as well as commercial enterprises, throughout Europe. Results from this study will contribute to a better understanding of the complex pathophysiology underlying myocardial injury after STEMI. The present paper describes the rationale, design and the methods of the trial. Copyright (c) 2012 S. Karger AG, Basel
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41.
  • Baldvinsdóttir, Bryndís, et al. (författare)
  • Adverse events associated with microsurgial treatment for ruptured intracerebral aneurysms: a prospective nationwide study on subarachnoid haemorrhage in Sweden
  • 2023
  • Ingår i: Journal of Neurology Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 94:7, s. 575-580
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundAdverse events (AEs) or complications may arise secondary to the treatment of aneurysmal subarachnoid haemorrhage (SAH). The aim of this study was to identify AEs associated with microsurgical occlusion of ruptured aneurysms, as well as to analyse their risk factors and impact on functional outcome. MethodsPatients with aneurysmal SAH admitted to the neurosurgical centres in Sweden were prospectively registered during a 3.5-year period (2014-2018). AEs were categorised as intraoperative or postoperative. A range of variables from patient history and SAH characteristics were explored as potential risk factors for an AE. Functional outcome was assessed approximately 1 year after the bleeding using the extended Glasgow Outcome Scale. ResultsIn total, 1037 patients were treated for ruptured aneurysms, of which, 322 patients were treated with microsurgery. There were 105 surgical AEs in 97 patients (30%); 94 were intraoperative AEs in 79 patients (25%). Aneurysm rerupture occurred in 43 patients (13%), temporary occlusion of the parent artery >5 min in 26 patients (8%) and adjacent vessel injury in 25 patients (8%). High Fisher grade and brain oedema on CT were related to increased risk of AEs. At follow-up, 38% of patients had unfavourable outcome. Patients suffering AEs were more likely to have unfavourable outcome (OR 2.3, 95% CI 1.10 to 4.69). ConclusionIntraoperative AEs occurred in 25% of patients treated with microsurgery for ruptured intracerebral aneurysm in this nationwide survey. Although most operated patients had favourable outcome, AEs were associated with increased risk of unfavourable outcome.
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42.
  • Banister, David, et al. (författare)
  • Transport Policy Scenarios for the EU : 2020 Images of the Future
  • 2000
  • Ingår i: Innovation. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • It is essential to take a longer term view if sustainable mobility is to become a reality. This paper takes a perspective to 2020 and constructs Images of the future which conform to the principles of sustainable mobility. Set at the EU level, clear environmental, regional development and efficiency targets are set, within which strategies are developed, based on different combinations of technological innovation and the decoupling of economic growth from transport growth. The external political situation is taken as given with either a move towards greater co-operation (and extension) or towards greater fragmentation (and regionalisaization) in Europe. The three Images of the future (2020) demonstrate that challenging targets for sustainable mobility can be achieved through a range of different policy actions within the transport sector and more widely. Immediate action is required and even more difficult choices will have to be made in the EU 15, if large-scale extension of the EU takes place. Improvements in vehicle technology alone will not achieve the targets. More fundamental changes have to take place in the way in which people make travel choices and in the means by which freight is transported. All of these measures must involve less travel, more efficient and cleaner travel modes.
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43.
  • Baun, Anders, et al. (författare)
  • A methodology for ranking and hazard identification of xenobiotic organic compounds in urban stormwater
  • 2006
  • Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 370:1, s. 29-38
  • Tidskriftsartikel (refereegranskat)abstract
    • The paper presents a novel methodology (RICH, Ranking and Identification of Chemical Hazards) for ranking and identification ofxenobiotic organic compounds of environmental concern in stormwater discharged to surface water. The RICHmethod is illustrated as afunnel fitted with different filters that sort out problematic and hazardous compounds based on inherent physico-chemical and biologicalproperties. The outcomes of the RICH procedure are separate lists for both water phase and solid phase associated compounds. Theselists comprise: a justified list of compounds which can be disregarded in hazard/risk assessments, a justified list of stormwater prioritypollutants which must be included in hazard/risk assessments, and a list of compounds which may be present in discharged stormwater,but cannot be evaluated due to lack of data. The procedure was applied to 233 xenobiotic organic chemicals (XOCs) of relevance forstormwater. Of these 233 compounds, 121 compounds were found to be priority pollutants with regard to solids phases (i.e. suspendedsolids, soil, or sediments) when stormwater is discharged to surface water and 56 compounds were found to be priority pollutants withregard to the water phase. For 11% of the potential stormwater priority pollutants the screening procedure could not be carried out due tolack of data on basic physico-chemical properties and/or data on bioaccumulation, resistance to biodegradation, and ecotoxicity. Thetiered approach applied in the RICH procedure and the focus on the phases relevant for monitoring or risk assessment in the aquaticenvironment refines the list of “compounds of concern” when compared to the outcome of existing classification schemes. In this paperthe RICH procedure is focused on effects in the aquatic environment exemplified with xenobiotic organic compounds (XOCs) found inurban stormwater, but it may be transferred to other environmental compartments and problems. Thus, the RICH procedure can be usedas a stand-alone tool for selection of potential priority pollutants or it can be integrated in larger priority setting frameworks.
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44.
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45.
  • Bernigaud, Virgile, et al. (författare)
  • Electron capture-induced dissociation of AK dipeptide dications : Influence of ion velocity, crown-ether complexation and collision gas
  • 2008
  • Ingår i: International Journal of Mass Spectrometry. - : Elsevier BV. - 1387-3806 .- 1873-2798. ; 276:2-3, s. 77-81
  • Tidskriftsartikel (refereegranskat)abstract
    • The fragmentation of doubly protonated AK dipeptide ions has been investigated after collisional electron transfer. Electron capture leads to three dominant channels, H loss, NH3 loss, and N–Cα bond breakage to give either c+ or z+ fragment ions. The relative importance of these channels has been explored as a function of ion velocity, the degree of complexation with crown ether, and collision gas. Our results indicate that H loss and NH3 loss are competing channels whereas the probability of N–Cα bond breakage is more or less constant.
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46.
  • Bhatt, Deepak L., et al. (författare)
  • Rationale, design and baseline characteristics of the effect of ticagrelor on health outcomes in diabetes mellitus patients Intervention study
  • 2019
  • Ingår i: Clinical Cardiology. - : Wiley. - 0160-9289 .- 1932-8737. ; 42:5, s. 498-505
  • Tidskriftsartikel (refereegranskat)abstract
    • In the setting of prior myocardial infarction, the oral antiplatelet ticagrelor added to aspirin reduced the risk of recurrent ischemic events, especially, in those with diabetes mellitus. Patients with stable coronary disease and diabetes are also at elevated risk and might benefit from dual antiplatelet therapy. The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS, NCT01991795) is a Phase 3b randomized, double-blinded, placebo-controlled trial of ticagrelor vs placebo, on top of low dose aspirin. Patients >= 50 years with type 2 diabetes receiving anti-diabetic medications for at least 6 months with stable coronary artery disease as determined by a history of previous percutaneous coronary intervention, bypass grafting, or angiographic stenosis of >= 50% of at least one coronary artery were enrolled. Patients with known prior myocardial infarction (MI) or stroke were excluded. The primary efficacy endpoint is a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety endpoint is Thrombolysis in Myocardial Infarction major bleeding. A total of 19 220 patients worldwide have been randomized and at least 1385 adjudicated primary efficacy endpoint events are expected to be available for analysis, with an expected average follow-up of 40 months (maximum 58 months). Most of the exposure is on a 60 mg twice daily dose, as the dose was lowered from 90 mg twice daily partway into the study. The results may revise the boundaries of efficacy for dual antiplatelet therapy and whether it has a role outside acute coronary syndromes, prior myocardial infarction, or percutaneous coronary intervention.
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47.
  • Bjerkesjö, Peter, et al. (författare)
  • Utvärdering av Åtgärdsprogram för hotade arter och naturtyper (ÅGP)
  • 2022
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • IVL Svenska Miljöinstitutet har på uppdrag av Naturvårdsverket utvärderat arbetet med åtgärdsprogram för hotade arter och naturtyper (ÅGP) med fokus på hur ÅGPverksamheten fungerar när det gäller möjligheten att bidra till miljömålet ”Ett rikt växt- och djurliv”.Åtgärdsprogram för hotade arter och naturtyper (ÅGP) är en bred verksamhet där Naturvårdsverket i dagsläget ansvarar för 132 terrestra program, som spänner över alla organismgrupper och många olika naturtyper. Utöver det har Havs- och vattenmyndigheten (HaV) ansvar för 21 åtgärdsprogram och kunskapsuppbyggande program för akvatiska arter och naturtyper. Åtgärdsprogrammen genomförs till största del av länsstyrelserna som samverkar med andra verksamheter och aktörer så som markägare och regionala myndigheter i genomförandet av åtgärderna som specificerats i programmen. Utvärderingen består av en kartläggning av ÅGP-verksamheten samt djupintervjuer med länsstyrelser. Den utgår från tre huvudfrågeställningar:1. Relevans: Möter ÅGP-verksamheten identifierade behov i förhållande till miljömålet Ett rikt växt- och djurliv? 2. Sammanhang: Hur fungerar ÅGP-verksamheten i relation till andra verktyg/åtgärder? 3. Effektivitet: Uppnår ÅGP-verksamheten mål och resultat på ett effektivt sätt? Resultaten visar att ÅGP-verksamheten svarar mot identifierade behov genom att vara ett avgränsat verktyg som fokuserar på aktiva åtgärder där de behövs som mest. Detta förstärks genom att programmen genomförs lokalt av länsstyrelserna i samverkan med andra lokala aktörer, vilket bidrar till att programmen är förankrade i lokalt identifierade behov. Tillgängliga ekonomiska resurser uppfattas dock som starkt otillräckliga för att kunna möta alla identifierade behov och för att kunna arbeta med alla åtgärdsprogram.ÅGP-verksamheten fungerar som ett bra komplement till andra verktyg och åtgärder i och med att den kan fokusera på de mest hotade arterna utanför skyddade områden där andra insatser saknas. Länsstyrelserna har i många fall lyckats med att hitta synergier internt mellan ÅGP-verksamheten och, framför allt, arbetet med områdesskydd och reservatsförvaltning. Samtidigt finns det styrmedel som uppfattas motverka ÅGP-verksamheten. Här nämns miljöersättningssystemet som styr markanvändning på ett sätt som är oförenlig med behoven för många av de mest hotade arterna. Dessutom finns ett antal styrmedel som enligt länsstyrelserna inte direkt motverkar ÅGP-verksamheten, men som skulle behöva revideras för att kunna användas för artbevarande.Mål för ÅGP-verksamheten finns uppsatta på programnivå och på miljömålsnivå. Mål för hela ÅGP-verksamhetens effekter saknas och därmed saknas även uppföljningar av ÅGP-verksamhetens samlade bidrag. Bristen på ekonomiska resurser och den efterföljande tidsbristen hos länsstyrelserna ses som hinder för måluppfyllelsen på programnivå. Tidsbristen bidrar även till att länsstyrelsernas arbete blir mer ”ad hoc” och att de har svårt att planera långsiktigt strategiskt eller exempelvis hitta synergier mellan program. Organisationsformen där Naturvårdsverket och Havs- och Vattenmyndigheten administrerar, länsstyrelsen genomför och koordinerar samverkan lokalt och mellan länsstyrelserna, och SLU Artdatabanken erbjuder expertstöd uppfattas huvudsakligen som effektivt. Effektiviteten av ÅGP-verksamheten är starkt beroende av länsstyrelsernas framgång i att engagera andra aktörer i arbetet med programmen men även där försvåras arbetet av bristen på ekonomiska resurser. För effektiviteten är även kunskapsutbyte och lärande mellan länsstyrelserna centralt. En struktur där varje program har en nationell koordinator finns på plats, men rollen för de nationella koordinatorerna uppfattas av vissa som otydlig, och det finns en stor variation i nivån av kunskapsutbyte och lärande mellan de olika programmen.Utifrån utvärderingens resultat har följande rekommendationer tagits fram:Överväg att sätta upp mål för ÅGP-verksamheten som helhet och utveckla uppföljningen av verksamhetens samlade bidrag. För att uppnå detta behöver även rapporteringen från länsstyrelserna utvecklas och harmoniseras av Naturvårdsverket och Havs- och VattenmyndighetenTydliggör Havs- och Vattenmyndighetens uppdrag inom akvatiska åtgärdsprogram. I nuläget saknar Havs- och Vattenmyndigheten ett tydligt uppdrag att arbeta med åtgärdsprogrammen då detta inte specificeras i myndighetens regleringsbrev.Utred potentialen och konsekvenserna av eventuella ytterligare prioriteringar. På grund av de begränsade ekonomiska resurserna kan länsstyrelserna inte arbeta med alla program som är relevanta i deras län. Trots att Naturvårdsverket har gjort tidigare försök till prioriteringar uppfattas det svårt att kunna prioritera ner program. Därför föreslår vi en utredning för att bedöma vad en hårdare prioritering mellan arterna skulle få för konsekvenser för de hotade arterna och naturtyperna. Länsstyrelserna ska involveras i utredningen som sedan kan användas som underlag för fortsatta diskussioner om prioriteringar.Tydliggör och vidareutveckla länsstyrelsernas nationella koordinering av program för att den samlade effektiviteten inte blir lidande på grund av begränsat lärande och utbyte mellan länsstyrelserna.Integrera bevarande av hotade arter och naturtyper i andra politikområden och andra sektorsmyndigheters arbete. Resultaten visar att andra myndigheter samverkar i varierande grad med ÅGP-verksamheten och att vissa styrmedel motverkar ÅGP:s syfte. Vi rekommenderar även en fördjupad utredning om vilka styrmedel och policyer som motverkar eller inte stödjer ÅGP-verksamhetens syfte, och om vilka ändringar som kan göras.Undersök möjligheten att stärka kopplingen mellan svenska och europeiska forskningsprojekt och ÅGP-verksamheten. Naturvårdsverket och Havs- och Vattenmyndigheten har begränsade möjligheter att utlysa forskningsfinansiering och därför behövs samarbete med svenska forskningsfinansiärer.Förstärk ÅGP-verksamheten med ytterligare resurser. Vi har i utvärderingen konstaterat att de resurser som finns till att arbeta med ÅGP inte står i proportion till dels de behov som finns utifrån att nå miljömålet Ett rikt växtoch djurliv och dels de åtgärder som pekas ut i åtgärdsprogrammen. En rekommendation från utvärderingen är att regeringen förstärker resurstilldelningen för arbetet med hotade arter och naturtyper som del av en förstärkt satsning på arbetet med biologisk mångfald. 
  •  
48.
  • Bozovic, Gracijela, et al. (författare)
  • Circulation stabilizing therapy and pulmonary high-resolution computed tomography in a porcine brain-dead model.
  • 2016
  • Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 60:1, s. 93-102
  • Tidskriftsartikel (refereegranskat)abstract
    • Currently 80% of donor lungs are not accepted for transplantation, often due to fluid overload. Our aim was to investigate if forced fluid infusion may be replaced by a new pharmacological therapy to stabilize circulation after brain death in an animal model, and to assess therapy effects on lung function and morphology trough blood gas parameters and state-of-the-art High-resolution CT (HRCT).
  •  
49.
  •  
50.
  • Christensen, Diana Hedevang, et al. (författare)
  • Type 2 diabetes classification : a data-driven cluster study of the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort
  • 2022
  • Ingår i: BMJ Open Diabetes Research and Care. - : BMJ. - 2052-4897. ; 10:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction A Swedish data-driven cluster study identified four distinct type 2 diabetes (T2D) clusters, based on age at diagnosis, body mass index (BMI), hemoglobin A1c (HbA1c) level, and homeostatic model assessment 2 (HOMA2) estimates of insulin resistance and beta-cell function. A Danish study proposed three T2D phenotypes (insulinopenic, hyperinsulinemic, and classical) based on HOMA2 measures only. We examined these two new T2D classifications using the Danish Centre for Strategic Research in Type 2 Diabetes cohort. Research design and methods In 3529 individuals, we first performed a k-means cluster analysis with a forced k-value of four to replicate the Swedish clusters: severe insulin deficient (SIDD), severe insulin resistant (SIRD), mild age-related (MARD), and mild obesity-related (MOD) diabetes. Next, we did an analysis open to alternative k-values (ie, data determined the optimal number of clusters). Finally, we compared the data-driven clusters with the three Danish phenotypes. Results Compared with the Swedish findings, the replicated Danish SIDD cluster included patients with lower mean HbA1c (86 mmol/mol vs 101 mmol/mol), and the Danish MOD cluster patients were less obese (mean BMI 32 kg/m 2 vs 36 kg/m 2). Our data-driven alternative k-value analysis suggested the optimal number of T2D clusters in our data to be three, rather than four. When comparing the four replicated Swedish clusters with the three proposed Danish phenotypes, 81%, 79%, and 69% of the SIDD, MOD, and MARD patients, respectively, fitted the classical T2D phenotype, whereas 70% of SIRD patients fitted the hyperinsulinemic phenotype. Among the three alternative data-driven clusters, 60% of patients in the most insulin-resistant cluster constituted 76% of patients with a hyperinsulinemic phenotype. Conclusion Different HOMA2-based approaches did not classify patients with T2D in a consistent manner. The T2D classes characterized by high insulin resistance/hyperinsulinemia appeared most distinct.
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