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1.
  • Nilsson, Bo, et al. (author)
  • C3 and C4 are strongly related to adipose tissue variables and cardiovascular risk factors
  • 2014
  • In: European Journal of Clinical Investigation. - : John Wiley & Sons. - 0014-2972 .- 1365-2362. ; 44:6, s. 587-596
  • Journal article (peer-reviewed)abstract
    • Background In several reports, C3 and C4 have been linked to diabetes and cardiovascular disease (CVD). Here, we investigate this link and the degree of C3 activation in elderly individuals. Methods In this study, C3 and C4 and the activation fragment C3a-desArg were analysed in 1016 subjects aged 70, in which blood pressure, lipid variables and fasting blood glucose were assessed. Results C3 levels were related to all the investigated classical cardiovascular risk factors and the metabolic syndrome (BMI, waist circumference, fat distribution, blood pressure, blood glucose levels, TG) except total cholesterol and LDL cholesterol in a highly significant fashion (Spearman up to 0,5; P<0.0001). C4 and C3a-desArg were associated in the same fashion but less significantly, while the ratios C4/C3 or C3a-desArg/C3 were not, indicating thatthe association was not directly related to complement activation. The levels C3 and to a lesser degree C4 and C3a-desArg were associated particularly with CRP, but also with E-selectin and ICAM-1. In addition, C3 and C4 levels were shown to decline significantly in 15 female subjects enrolled in a weight-reduction programme over 4 months. Conclusion A strong relation between C3, C4 and C3a-desArg levels, adipose tissue and risk factors of CVD was established. The data support that theadipose tissue produces complement components and generates initiators of inflammation, such as C3a and C5a, able to trigger a cyto/chemokine response, in proportion to the amount of adipose tissue. This corroborates the concept that complement contributes to the low-grade inflammation associated with obesity.
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  • Wallentin, Lars, 1943-, et al. (author)
  • Early invasive versus non-invasive treatment in patients with non-ST-elevation acute coronary syndrome (FRISC-II) : 15 year follow-up of a prospective, randomised, multicentre study
  • 2016
  • In: The Lancet. - : ELSEVIER SCIENCE INC. - 0140-6736 .- 1474-547X. ; 388:10054, s. 1903-1911
  • Journal article (peer-reviewed)abstract
    • Background The FRISC-II trial was the first randomised trial to show a reduction in death or myocardial infarction with an early invasive versus a non-invasive treatment strategy in patients with non-ST-elevation acute coronary syndrome. Here we provide a remaining lifetime perspective on the effects on all cardiovascular events during 15 years' follow-up. Methods The FRISC-II prospective, randomised, multicentre trial was done at 58 Scandinavian centres in Sweden, Denmark, and Norway. Between June 17, 1996, and Aug 28, 1998, we randomly assigned (1:1) 2457 patients with non-ST-elevation acute coronary syndrome to an early invasive treatment strategy, aiming for revascularisation within 7 days, or a non-invasive strategy, with invasive procedures at recurrent symptoms or severe exercise-induced ischaemia. Plasma for biomarker analyses was obtained at randomisation. For long-term outcomes, we linked data with national health-care registers. The primary endpoint was a composite of death or myocardial infarction. Outcomes were compared as the average postponement of the next event, including recurrent events, calculated as the area between mean cumulative count-of-events curves. Analyses were done by intention to treat. Findings At a minimum of 15 years' follow-up on Dec 31, 2014, data for survival status and death were available for 2421 (99%) of the initially recruited 2457 patients, and for other events after 2 years for 2182 (89%) patients. During follow-up, the invasive strategy postponed death or next myocardial infarction by a mean of 549 days (95% CI 204-888; p= 0.0020) compared with the non-invasive strategy. This effect was larger in non-smokers (mean gain 809 days, 95% CI 402-1175; p(interaction) = 0.0182), patients with elevated troponin T (778 days, 357-1165; p (interaction) = 0.0241), and patients with high concentrations of growth differentiation factor-15 (1356 days, 507-1650; p (interaction) = 0.0210). The difference was mainly driven by postponement of new myocardial infarction, whereas the early difference in mortality alone was not sustained over time. The invasive strategy led to a mean of 1128 days (95% CI 830-1366) postponement of death or next readmission to hospital for ischaemic heart disease, which was consistent in all subgroups (p< 0.0001). Interpretation During 15 years of follow-up, an early invasive treatment strategy postponed the occurrence of death or next myocardial infarction by an average of 18 months, and the next readmission to hospital for ischaemic heart disease by 37 months, compared with a non-invasive strategy in patients with non-ST-elevation acute coronary syndrome. This remaining lifetime perspective supports that an early invasive treatment strategy should be the preferred option in most patients with non-ST-elevation acute coronary syndrome.
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  • Lindhagen, Lars, et al. (author)
  • Level-adjusted funnel plots based on predicted marginal expectations : an application to prophylactic antibiotics in gallstone surgery
  • 2014
  • In: Statistics in Medicine. - : Wiley. - 0277-6715 .- 1097-0258. ; 33:21, s. 3655-3675
  • Journal article (peer-reviewed)abstract
    • Funnel plots are widely used to visualize grouped data, for example, in institutional comparison. This paper extends the concept to a multi-level setting, displaying one level at a time, adjusted for the other levels, as well as for covariates at all levels. These level-adjusted funnel plots are based on a Markov chain Monte Carlo fit of a random effects model, translating the estimated model parameters to predicted marginal expectations. Working within the estimation framework, we accommodate outlying institutions using heavy-tailed random effects distributions. We also develop computer-efficient methods to compute predicted probabilities in the case of dichotomous outcome data and various random effect distributions. We apply the method to a data set on prophylactic antibiotics in gallstone surgery.
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4.
  • Simonsson, Moa, et al. (author)
  • Temporal trends in bleeding events in acute myocardial infarction : insights from the SWEDEHEART registry
  • 2020
  • In: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 41:7, s. 833-843
  • Journal article (peer-reviewed)abstract
    • AIMS: To describe the time trends of in-hospital and out-of-hospital bleeding parallel to the development of new treatments and ischaemic outcomes over the last 20 years in a nationwide myocardial infarction (MI) population.METHODS AND RESULTS: Patients with acute MI (n = 371 431) enrolled in the SWEDEHEART registry from 1995 until May 2018 were selected and evaluated for in-hospital bleeding and out-of-hospital bleeding events at 1 year. In-hospital bleeding increased from 0.5% to a peak at 2% 2005/2006 and thereafter slightly decreased to a new plateau around 1.3% by the end of the study period. Out-of-hospital bleeding increased in a stepwise fashion from 2.5% to 3.5 % in the middle of the study period and to 4.8% at the end of the study period. The increase in both in-hospital and out-of-hospital bleeding was parallel to increasing use of invasive strategy and adjunctive antithrombotic treatment, dual antiplatelet therapy (DAPT), and potent DAPT, while the decrease in in-hospital bleeding from 2007 to 2010 was parallel to implementation of bleeding avoidance strategies. In-hospital re-infarction decreased from 2.8% to 0.6% and out-of-hospital MI decreased from 12.6% to 7.1%. The composite out-of-hospital MI, cardiovascular death, and stroke decreased in a similar fashion from 18.4% to 9.1%.CONCLUSION: During the last 20 years, the introduction of invasive and more intense antithrombotic treatment has been associated with an increase in bleeding events but concomitant there has been a substantial greater reduction of ischaemic events including improved survival.
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  • Szummer, Karolina, et al. (author)
  • Improved outcomes in patients with ST-elevation myocardial infarction during the last 20 years are related to implementation of evidence-based treatments : experiences from the SWEDEHEART registry 1995-2014
  • 2017
  • In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 38:41, s. 3056-3065
  • Journal article (peer-reviewed)abstract
    • Aims Impact of changes of treatments on outcomes in ST-elevation myocardial infarction (STEMI) patients in real-life health care has not been documented. Methods and results All STEMI cases (n=105.674) registered in the nation-wide SWEDEHEART registry between 1995 and 2014 were included and followed for fatal and non-fatal outcomes for up to 20 years. Most changes in treatment and outcomes occurred from 1994 to 2008. Evidence-based treatments increased: reperfusion from 66.2 to 81.7%; primary percutaneous coronary intervention: 4.5 to 78.0%; dual antiplatelet therapy from 0 to 89.6%; statin: 14.1 to 93.6%; beta-blocker: 78.2 to 91.0%, and angiotensin-converting-enzyme/angiotensin-2-receptor inhibitors: 40.8 to 85.2% (P-value for-trend<0.001 for all). One-year mortality decreased from 22.1 to 14.1%. Standardized incidence ratio compared with the general population decreased from 5.54 to 3.74 (P<0.001). Cardiovascular (CV) death decreased from 20.1 to 11.1%, myocardial infarction (MI) from 11.5 to 5.8%; stroke from 2.9 to 2.1%; heart failure from 7.1 to 6.2%. After standardization for differences in demography and baseline characteristics, the change of 1-year CV-death or MI corresponded to a linear trend of 0.915 (95% confidence interval: 0.906-0.923) per 2-year period which no longer was significant, 0.997 (0.984-1.009), after adjustment for changes in treatment. The changes in treatment and outcomes were most pronounced from 1994 to 2008. Conclusion Gradual implementation of new and established evidence-based treatments in STEMI patients during the last 20 years has been associated with prolonged survival and lower risk of recurrent ischaemic events, although a plateauing is seen since around 2008.
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  • Szummer, Karolina, et al. (author)
  • Relations between implementation of new treatments and improved outcomes in patients with non-ST-elevation myocardial infarction during the last 20 years : experiences from SWEDEHEART registry 1995 to 2014
  • 2018
  • In: European Heart Journal. - : OXFORD UNIV PRESS. - 0195-668X .- 1522-9645. ; 39:42, s. 3766-3776
  • Journal article (peer-reviewed)abstract
    • Aims We assessed the changes in short- and long-term outcomes and their relation to implementation of new evidence- based treatments in all patients with non-ST-elevation myocardial infarction (NSTEMI) in Sweden over 20 years. Methods and results Cases with NSTEMI (n = 205 693) between 1995 and 2014 were included from the nationwide Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry. During 20 years in-hospital invasive procedures increased from 1.9% to 73.2%, percutaneous coronary intervention or coronary artery bypass grafting 6.5% to 58.1%, dual antiplatelet medication 0% to 72.7%, statins 13.3% to 85.6%, and angiotensin-converting enzyme inhibitors/angiotensin II receptor blocker 36.8% to 75.5%. The standardized 1-year mortality ratio compared with a control population decreased from 5.53 [95% confidence interval (CI) 5.30-5.75] to 3.03 (95% CI 2.89-3.19). If patients admitted the first 2 years were modelled to receive the same invasive treatments as the last 2 years the expected mortality/ myocardial infarction (MI) rate would be reduced from 33.0% to 25.0%. After adjusting for differences in baseline characteristics, the change of 1-year cardiovascular death/MI corresponded to a linearly decreasing odds ratio trend of 0.930 (95% CI 0.926-0.935) per 2-year period. This trend was substantially attenuated [0.970 (95% CI 0.964-0.975)] after adjusting for changes in coronary interventions, and almost eliminated [0.988 (95% CI 0.982-0.994)] after also adjusting for changes in discharge medications. Conclusion In NSTEMI patients during the last 20 years, there has been a substantial improvement in long-term survival and re- duction in the risk of new cardiovascular events. These improvements seem mainly explained by the gradual uptake and widespread use of in-hospital coronary interventions and evidence-based long-term medications.
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  • Batra, Gorav, et al. (author)
  • Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are associated with improved outcome but do not prevent new-onset atrial fibrillation after acute myocardial infarction
  • 2017
  • In: Journal of the American Heart Association. - 2047-9980. ; 6:3
  • Journal article (peer-reviewed)abstract
    • Background Treatment with renin‐angiotensin system (RAS) inhibitors might restrain the structural/electrical remodeling associated with atrial fibrillation (AF). Limited evidence exists regarding the potential benefits of RAS inhibition post‐acute myocardial infarction (AMI) in patients with AF. This study sought to assess the association between RAS inhibition and all‐cause mortality and new‐onset AF in patients with/without congestive heart failure (CHF) post‐AMI.Methods and Results Patients hospitalized for AMI between 2006 and 2012 were identified in Swedish registries. Patients were stratified in 4 subgroups; patients with CHF and AF (n=11 489); patients with CHF without AF (n=31 676); patients with AF without CHF (n=10 066); and patients without both CHF and AF (n=59 417). Patients exposed to RAS inhibition were compared to nontreated. Three‐year risk of all‐cause mortality and new‐onset AF was assessed using adjusted Cox regression analyses. At discharge, 83 291 (73.9%) patients received RAS inhibition. RAS inhibition was associated with lower 3‐year risk of all‐cause mortality in CHF patients with AF, adjusted hazard ratio (HR) with 95% CI 0.75 (0.70–0.81), CHF patients without AF, HR 0.65 (0.60–0.69), AF patients without CHF, HR 0.82 (0.75–0.90), and in patients without CHF and AF, HR 0.76 (0.72–0.81), respectively. RAS inhibition was not associated with lower 3‐year risk of new‐onset AF in patients without AF but with/without CHF; HR 0.96 (0.84–1.10) and 1.12 (1.02–1.22), respectively.Conclusions RAS inhibition post‐AMI was associated with lower risk of all‐cause mortality. In patients with/without CHF, RAS inhibition was not associated with lower incidence of new‐onset AF.
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  • Batra, Gorav, et al. (author)
  • Atrial fibrillation in patients undergoing coronary artery surgery is associated with adverse outcome
  • 2019
  • In: Upsala Journal of Medical Sciences. - : Taylor & Francis. - 0300-9734 .- 2000-1967. ; :1, s. 70-77
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The aim was to determine the association between atrial fibrillation (AF) and outcome in patients undergoing coronary artery bypass grafting (CABG).METHODS: All patients undergoing CABG between January 2010 and June 2013 were identified in the Swedish Heart Surgery Registry. Outcomes studied were all-cause mortality, cardiovascular mortality, myocardial infarction, congestive heart failure, ischemic stroke, and recurrent AF. Patients with history of AF prior to surgery (preoperative AF) and patients without history of AF but with AF episodes post-surgery (postoperative AF) were compared to patients with no AF using adjusted Cox regression models.RESULTS: Among 9,107 identified patients, 8.1% (n = 737) had preoperative AF, and 25.1% (n = 2,290) had postoperative AF. Median follow-up was 2.2 years. Compared to no AF, preoperative AF was associated with higher risk of all-cause mortality, adjusted hazard ratio with 95% confidence interval (HR) 1.76 (1.33-2.33); cardiovascular mortality, HR 2.43 (1.68-3.50); and congestive heart failure, HR 2.21 (1.72-2.84). Postoperative AF was associated with risk of all-cause mortality, HR 1.27 (1.01-1.60); cardiovascular mortality, HR 1.52 (1.10-2.11); congestive heart failure, HR 1.47 (1.18-1.83); and recurrent AF, HR 4.38 (2.46-7.78). No significant association was observed between pre- or postoperative AF and risk for myocardial infarction and ischemic stroke.CONCLUSIONS: Approximately 1 in 3 patients undergoing CABG had pre- or postoperative AF. Patients with pre- or postoperative AF were at higher risk of all-cause mortality, cardiovascular mortality, and congestive heart failure, but not of myocardial infarction or ischemic stroke. Postoperative AF was associated with higher risk of recurrent AF.
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  • Brännström, Kristoffer, et al. (author)
  • A Generic Method for Design of Oligomer-Specific Antibodies
  • 2014
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:3, s. e90857-
  • Journal article (peer-reviewed)abstract
    • Antibodies that preferentially and specifically target pathological oligomeric protein and peptide assemblies, as opposed to their monomeric and amyloid counterparts, provide therapeutic and diagnostic opportunities for protein misfolding diseases. Unfortunately, the molecular properties associated with oligomer-specific antibodies are not well understood, and this limits targeted design and development. We present here a generic method that enables the design and optimisation of oligomer-specific antibodies. The method takes a two-step approach where discrimination between oligomers and fibrils is first accomplished through identification of cryptic epitopes exclusively buried within the structure of the fibrillar form. The second step discriminates between monomers and oligomers based on differences in avidity. We show here that a simple divalent mode of interaction, as within e. g. the IgG isotype, can increase the binding strength of the antibody up to 1500 times compared to its monovalent counterpart. We expose how the ability to bind oligomers is affected by the monovalent affinity and the turnover rate of the binding and, importantly, also how oligomer specificity is only valid within a specific concentration range. We provide an example of the method by creating and characterising a spectrum of different monoclonal antibodies against both the A beta peptide and alpha-synuclein that are associated with Alzheimer's and Parkinson's diseases, respectively. The approach is however generic, does not require identification of oligomer-specific architectures, and is, in essence, applicable to all polypeptides that form oligomeric and fibrillar assemblies.
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  • Carrero, Juan Jesus, et al. (author)
  • Warfarin, Kidney Dysfunction, and Outcomes Following Acute Myocardial Infarction in Patients With Atrial Fibrillation
  • 2014
  • In: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 311:9, s. 919-928
  • Journal article (peer-reviewed)abstract
    • IMPORTANCE Conflicting evidence exists regarding the association between warfarin treatment, death, and ischemic stroke incidence in patients with advanced chronic kidney disease (CKD) and atrial fibrillation. OBJECTIVE To study outcomes associated with warfarin treatment in relation to kidney function among patients with established cardiovascular disease and atrial fibrillation. DESIGN, SETTING, AND PARTICIPANTS Observational, prospective, multicenter cohort study from the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry (2003-2010), which includes all Swedish hospitals that provide care for acute cardiac diseases. Participants included consecutive survivors of an acute myocardial infarction (MI) with atrial fibrillation and known serum creatinine (N = 24 317), including 21.8% who were prescribed warfarin at discharge. Chronic kidney disease stages were classified according to estimated glomerular filtration rate (eGFR). MAIN OUTCOMES AND MEASURES (1) Composite end point analysis of death, readmission due to MI, or ischemic stroke; (2) bleeding (composite of readmission due to hemorrhagic stroke, gastrointestinal bleeding, bleeding causing anemia, and others); or (3) the aggregate of these 2 outcomes within 1 year from discharge date. RESULTS A total of 5292 patients (21.8%) were treated with warfarin at discharge, and 51.7% had manifest CKD (eGFR <60 mL/min/1.73 m(2) [eGFR(<60)]). Compared with no warfarin use, warfarin was associated with a lower risk of the first composite outcome (n = 9002 events) in each CKD stratum for event rates per 100 person-years: eGFR(>60) event rate, 28.0 for warfarin vs 36.1 for no warfarin; adjusted hazard ratio (HR), 0.73 (95% CI, 0.65 to 0.81); eGFR(>30-60): event rate, 48.5 for warfarin vs 63.8 for no warfarin; HR, 0.73 (95% CI, 0.66 to 0.80); eGFR(>15-30): event rate, 84.3 for warfarin vs 110.1 for no warfarin; HR, 0.84 (95% CI, 0.70-1.02); eGFR(<= 15): event rate, 83.2 for warfarin vs 128.3 for no warfarin; HR, 0.57 (95% CI, 0.37-0.86). The risk of bleeding (n = 1202 events) was not significantly higher in patients treated with warfarin in any CKD stratum for event rates per 100 person-years: eGFR(>60) event rate, 5.0 for warfarin vs 4.8 for no warfarin; HR, 1.10 (95% CI, 0.86-1.41); eGFR(>30-60) event rate, 6.8 forwarfarin vs 6.3 for no warfarin; HR, 1.04 (95% CI, 0.81-1.33); eGFR(>15-30) event rate, 9.3 forwarfarin vs 10.4 for nowarfarin; HR, 0.82 (95% CI, 0.48-1.39); eGFR(<= 15) event rate, 9.1 forwarfarin vs 13.5 for nowarfarin; HR, 0.52 (95% CI, 0.16-1.65). Warfarin use in each CKD stratum was associated with lower hazards of the aggregate outcome (n = 9592 events) for event rates per 100 person-years: eGFR(>60) event rate, 32.1 for warfarin vs 40.0 for no warfarin; HR, 0.76 (95% CI, 0.69-0.84); eGFR(>30-60) event rate, 53.6 forwarfarin vs 69.0 for nowarfarin; HR, 0.75 (95% CI, 0.68-0.82); eGFR(>15-30) event rate, 90.2 forwarfarin vs 117.7 for nowarfarin; HR, 0.82 (95% CI, 0.68-0.99); eGFR(<= 15) event rate, 86.2 forwarfarin vs 138.2 for nowarfarin; HR, 0.55 (95% CI, 0.37-0.83). CONCLUSIONS AND RELEVANCE Warfarin treatment was associated with a lower 1-year risk for the composite outcome of death, MI, and ischemic stroke without a higher risk of bleeding in consecutive acute MI patients with atrial fibrillation. This association was not related to the severity of concurrent CKD.
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  • Cars, Thomas, et al. (author)
  • A framework for monitoring of new drugs in Sweden
  • 2019
  • In: Upsala Journal of Medical Sciences. - : TAYLOR & FRANCIS LTD. - 0300-9734 .- 2000-1967. ; 124:1, s. 46-50
  • Journal article (peer-reviewed)abstract
    • In order to monitor the net public health benefit of new drugs, especially in the light of recent stepwise approval approaches, there is a need to optimize real-time post-marketing evaluation of new drugs using data collected in routine care. Sweden, with its unique possibilities for observational research, can provide these data. We herein propose a framework for continuous monitoring of the effectiveness, safety, and cost-effectiveness of new drugs, using prospectively determined protocols designed in collaboration between all relevant stakeholders. We believe that this framework can be a useful tool for healthcare authorities and reimbursement agencies in the introduction of new drugs.
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  • Cars, Thomas, et al. (author)
  • Effectiveness of Drugs in Routine Care : A Model for Sequential Monitoring of New Medicines Using Dronedarone as Example
  • 2018
  • In: Clinical Pharmacology and Therapeutics. - : WILEY. - 0009-9236 .- 1532-6535. ; 103:3, s. 493-501
  • Journal article (peer-reviewed)abstract
    • Although there is no doubt about the scientific value of randomized controlled clinical trials, they are usually conducted in selected populations different fromthose treated in clinical practice. Therefore, it is important to optimize real-time post-marketing evaluation of the effectiveness, safety, and cost of new drugs. Using electronic health records and administrative health databases froma well-defined region with universal access to healthcare, we have built a framework for real-time sequential monitoring of the effectiveness of newly marketed drugs in routine care. We chose the antiarrhythmic agent dronedarone as the study drug and flecainide as the comparator drug for illustration of the model. We demonstrate that this model produces consistent results with increasing precision over time as data accumulates in the clinical systems. We believe that use of this model at the introduction of new drugs can provide complementary evidence, especially in settings of adaptive licensing of new drugs.
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  • Christersson, Christina, et al. (author)
  • Comparison of warfarin versus antiplatelet therapy after surgical bioprosthetic aortic valve replacement
  • 2020
  • In: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 106:11, s. 838-844
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: To compare effectiveness of warfarin and antiplatelet exposure regarding both thrombotic and bleeding events, following surgical aortic valve replacement with a biological prosthesis(bioSAVR).METHODS: The study included all patients in Sweden undergoing a bioSAVR during 2008-2014 who were alive at discharge from the index hospital stay. Exposure was analysed and defined as postdischarge dispension of any antithrombotic pharmaceutical, updated at each following dispensions and categorised as single antiplatelet (SAPT), warfarin, warfarin combined with SAPT, dual antiplatelet (DAPT) or no antithrombotic treatment. Exposure to SAPT was used as comparator. Outcome events were all-cause mortality, ischaemic stroke, haemorrhagic stroke, any thromboembolism and major bleedings. We continuously updated adjustments for comorbidities with any indication for antithrombotic treatment by Cox regression analysis.RESULTS: We identified 9539 patients with bioSAVR (36.8% women) at median age of 73 years with a mean follow-up of 3.13 years. As compared with SAPT, warfarin alone was associated with a lower incidence of ischaemic stroke (HR 0.49, 95% CI 0.35 to 0.70) and any thromboembolism (HR 0.75, 95% CI 0.60 to 0.94) but with no difference in mortality (HR 0.94, 95% CI 0.78 to 1.13). The incidence of haemorrhagic stroke (HR 1.94, 95% CI 1.07 to 3.51) and major bleeding (HR 1.67, 95% CI 1.30 to 2.15) was higher during warfarin exposure. As compared with SAPT, DAPT was not associated with any difference in ischaemic stroke or any thromboembolism. Risk-benefit analyses demonstrated that 2.7 (95% CI 1.0 to 11.9) of the ischaemic stroke cases could potentially be avoided per every haemorrhagic stroke caused by warfarin exposure instead of SAPT during the first year.CONCLUSION: In patients discharged after bioSAVR, warfarin exposure as compared with SAPT exposure was associated with lower long-term risk of ischaemic stroke and thromboembolic events, and with a higher incidence of bleeding events but with similar mortality.
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  • Christersson, Christina, et al. (author)
  • Haemorrhagic stroke and major bleeding after intervention with biological aortic valve prosthesis : risk factors and antithrombotic treatment
  • 2020
  • In: European Heart Journal, Supplement. - : OXFORD UNIV PRESS. - 1520-765X .- 1554-2815. ; 22:C, s. C26-C33
  • Journal article (peer-reviewed)abstract
    • The majority of patients with severe aortic stenosis are recommended intervention with a surgical biological prosthesis (bioSAVR) or a transcatheter aortic valve intervention (TAVI). The antithrombotic strategies after aortic valve intervention vary and include drugs targeting both platelets and the coagulation cascade. Long-term exposure and changes of antithrombotic treatment influence the risk of both bleeding and thromboembolic events. The aim was to describe an unselected sample of patients who have experienced haemorrhagic stroke and other major bleeding events after biological aortic prosthesis, their antithrombotic treatment and changes of treatments in relation to the bleeding event. All patients performing an bioSAVR or a TAVI 2008-2014 were identified in the SWEDEHEART registry and included in the study (n =10 711). The outcome events were haemorrhagic stroke and other major bleeding event. Information of drug exposure was collected from the dispensed drug registry. The incidence rate of any bleeding event was 2.85/100 patient-years the first year after aortic valve intervention. Heart failure and atrial fibrillation were present more often in patients with a first haemorrhagic stroke or other major bleeding event compared to without. The proportion of exposure to warfarin was 28.7% vs. 21.3% in patients with and without a haemorrhagic stroke. Comparable figures were 31.2% vs. 19.0% in patients with and without other major bleeding event. During 1 month prior a haemorrhagic stroke or other major bleeding event 39.4% and 38.0%, respectively, of the patients not previously exposed to antithrombotic treatment started warfarin or single antiplatelet therapy. Major bleeding events are not uncommon after aortic valve intervention with a biological prosthesis. Evaluation of comorbidities and previous bleeding might improve risk stratification for bleeding in these elderly patients. The pattern of change of antithrombotic treatment was similar in the groups with and without a bleeding event and in most patients the antithrombotic regime was unchanged the month before an event.
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  • Christersson, Christina, et al. (author)
  • Screening for Biomarkers Associated with Left Ventricular Function During Follow-up After Acute Coronary Syndrome
  • 2023
  • In: Journal of Cardiovascular Translational Research. - : Springer Nature. - 1937-5387 .- 1937-5395. ; 16:1, s. 244-254
  • Journal article (peer-reviewed)abstract
    • A proportion of patients with the acute coronary syndrome (ACS) will suffer progressive remodeling of the left ventricular (LV). The aim was to screen for important biomarkers from a large-scale protein profiling in 420 ACS patients and define biomarkers associated with reduced LV function early and 1 year after the ACS. Transferrin receptor protein 1 and NT-proBNP were associated with LV function early and after 1 year, whereas osteopontin and soluble ST2 were associated with LV function in the early phase and, tissue-type plasminogen activator after 1 year. Fatty-acid-binding protein and galectin 3 were related to worse GLS but not to LVEF 1 year after the ACS. Proteins involved in remodeling and iron transport in cardiomyocytes were related to worse LV function after ACS. Biomarkers for energy metabolism and fibrosis were exclusively related to worse LV function by GLS. Studies on the functions of these proteins might add knowledge to the biological processes involved in heart failure in long term after ACS.
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  • de Dios, Eddie, 1987, et al. (author)
  • Comparison of the patient-derived modified Japanese Orthopaedic Association scale and the European myelopathy score
  • 2024
  • In: European Spine Journal. - : SPRINGER. - 0940-6719 .- 1432-0932. ; 33:3, s. 1205-1212
  • Journal article (peer-reviewed)abstract
    • Purpose: To compare the patient-derived modified Japanese Orthopaedic Association (P-mJOA) scale with the European myelopathy score (EMS) for the assessment of patients with degenerative cervical myelopathy (DCM). Methods: In this register-based cohort study with prospectively collected data, included patients were surgically treated for DCM and had reported both P-mJOA and EMS scores at baseline, 1-year follow-up, and/or 2-year follow-up to the Swedish Spine Register. P-mJOA and EMS scores were defined as severe (P-mJOA 0–11 and EMS 5–8), moderate (P-mJOA 12–14 and EMS 9–12), or mild (P-mJOA 15–18 and EMS 13–18). P-mJOA and EMS mean scores were compared, and agreement was evaluated with Spearman’s rank correlation coefficient (ρ), the intraclass correlation coefficient (ICC), and kappa (κ) statistics. Results: Included patients (n = 714, mean age 63.2years, 42.2% female) completed 937 pairs of the P-mJOA and the EMS. The mean P-mJOA and EMS scores were 13.9 ± 3.0 and 14.5 ± 2.7, respectively (mean difference –0.61 [95% CI –0.72 to –0.51; p < 0.001]). Spearman’s ρ was 0.84 (p < 0.001), and intra-rater agreement measured with ICC was 0.83 (p < 0.001). Agreement of severity level measured with unweighted and weighted κ was fair (κ = 0.22 [p < 0.001]; κ = 0.34 [p < 0.001], respectively). Severity levels were significantly higher using the P-mJOA (p < 0.001). Conclusion: The P-mJOA and the EMS had similar mean scores, and intra-rater agreement was high, whereas severity levels only demonstrated fair agreement. The EMS has a lower sensitivity for detecting severe myelopathy but shows an increasing agreement with the P-mJOA for milder disease severity. A larger interval to define severe myelopathy with the EMS is recommended.
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23.
  • de Dios, Eddie, 1987, et al. (author)
  • Improvement rates, adverse events and predictors of clinical outcome following surgery for degenerative cervical myelopathy
  • 2022
  • In: European Spine Journal. - : Springer Science and Business Media LLC. - 0940-6719 .- 1432-0932. ; 31:12, s. 3433-3442
  • Journal article (peer-reviewed)abstract
    • Purpose: To investigate improvement rates, adverse events and predictors of clinical outcome after laminectomy alone (LAM) or laminectomy with instrumented fusion (LAM + F) for degenerative cervical myelopathy (DCM). Methods: This is a post hoc analysis of a previously published DCM cohort. Improvement rates for European myelopathy score (EMS) and Neck Disability Index (NDI) at 2- and 5-year follow-ups and adverse events are presented descriptively for available cases. Predictor endpoints were EMS and NDI scores at follow-ups, surgeon- and patient-reported complications, and reoperation-free interval. For predictors, univariate and multivariable models were fitted to imputed data. Results: Mean age of patients (LAM n = 412; LAM + F n = 305) was 68years, and 37.4% were women. LAM + F patients had more severe spondylolisthesis and less severe kyphosis at baseline, more surgeon-reported complications, more patient-reported complications, and more reoperations (p ≤ 0.05). After imputation, the overall EMS improvement rate was 43.8% at 2years and 36.3% at 5years. At follow-ups, worse EMS scores were independent predictors of worse EMS outcomes and older age and worse NDI scores were independent predictors of worse NDI outcomes. LAM + F was associated with more surgeon-reported complications (ratio 1.81; 95% CI 1.17–2.80; p = 0.008). More operated levels were associated with more patient-reported complications (ratio 1.12; 95% CI 1.02–1.22; p = 0.012) and a shorter reoperation-free interval (hazard ratio 1.30; 95% CI 1.08–1.58; p = 0.046). Conclusions: These findings suggest that surgical intervention at an earlier myelopathy stage might be beneficial and that less invasive procedures are preferable in this patient population.
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24.
  • de Dios, Eddie, et al. (author)
  • Laminectomy alone versus laminectomy with fusion for degenerative cervical myelopathy : a long-term study of a national cohort
  • 2022
  • In: European spine journal. - : Springer Science and Business Media LLC. - 0940-6719 .- 1432-0932. ; 31:2, s. 334-345
  • Journal article (peer-reviewed)abstract
    • PURPOSE: To compare patient-reported 5-year clinical outcomes between laminectomy alone versus laminectomy with instrumented fusion in patients with degenerative cervical myelopathy in a population-based cohort.METHODS: All patients in the national Swedish Spine Register (Swespine) from January 2006 until March 2019, with degenerative cervical myelopathy, were assessed. Multiple imputation and propensity score matching based on clinicodemographic and radiographic parameters were used to compare patients treated with laminectomy alone with patients treated with laminectomy plus posterior-lateral instrumented fusion. The primary outcome measure was the European Myelopathy Score, a validated patient-reported outcome measure. The scale ranges from 5 to 18, with lower scores reflecting more severe myelopathy.RESULTS: Among 967 eligible patients, 717 (74%) patients were included. Laminectomy alone was performed on 412 patients (mean age 68 years; 149 women [36%]), whereas instrumented fusion was added for 305 patients (mean age 68 years; 119 women [39%]). After imputation, the propensity for smoking, worse myelopathy scores, spondylolisthesis, and kyphosis was slightly higher in the fusion group. After imputation and propensity score matching, there were on average 212 pairs patients with a 5-year follow-up in each group. There were no important differences in patient-reported clinical outcomes between the methods after 5 years. Due to longer hospitalization times and implant-related costs, the mean cost increase per instrumented patient was approximately $4700 US.CONCLUSIONS: Instrumented fusions generated higher costs and were not associated with superior long-term clinical outcomes. These findings are based on a national cohort and can thus be regarded as generalizable.
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25.
  • de Dios, Eddie, 1987, et al. (author)
  • MRI-based measurements of spondylolisthesis and kyphosis in degenerative cervical myelopathy.
  • 2023
  • In: BMC medical imaging. - : BioMed Central (BMC). - 1471-2342. ; 23:1
  • Journal article (peer-reviewed)abstract
    • To provide normative data and to determine accuracy and reliability of preoperative measurements of spondylolisthesis and kyphosis on supine static magnetic resonance imaging (MRI) of patients with degenerative cervical myelopathy.T2-weighted midsagittal images of the cervical spine were in 100 cases reviewed twice by one junior observer, with an interval of 3 months, and once by a senior observer. The spondylolisthesis slip (SSlip, mm) and the modified K-line interval (mK-line INT, mm) were assessed for accuracy with the standard error of measurement (SEm) and the minimum detectable change (MDC). Intraobserver and interobserver reliability levels were determined using the intraclass correlation coefficient (ICC).The SEm was 0.5mm (95% CI 0.4-0.6) for spondylolisthesis and 0.6mm (95% CI 0.5-0.7) for kyphosis. The MDC, i.e., the smallest difference between two examinations that can be detected with statistical certainty, was 1.5mm (95% CI 1.2-1.8) for spondylolisthesis and 1.6mm (95% CI 1.3-1.8) for kyphosis. The highest reliability levels were seen between the second observation of the junior examiner and the senior observer (ICC=0.80 [95% CI 0.70-0.87] and ICC=0.96 [95% CI 0.94-0.98] for SSlip and mK-line INT, respectively).This study provides normative values of alignment measurements of spondylolisthesis and kyphosis in DCM patients. It further shows the importance of taking measurement errors into account when defining cut-off values for cervical deformity parameters and their potential clinical application in surgical decision-making.
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26.
  • Edfors, R., et al. (author)
  • Use of proteomics to identify biomarkers associated with chronic kidney disease and long-term outcomes in patients with myocardial infarction
  • 2020
  • In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 288:5, s. 581-592
  • Journal article (peer-reviewed)abstract
    • Background Patients with chronic kidney disease (CKD) have poor outcomes following myocardial infarction (MI). We performed an untargeted examination of 175 biomarkers to identify those with the strongest association with CKD and to examine the association of those biomarkers with long-term outcomes. Methods A total of 175 different biomarkers from MI patients enrolled in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry were analysed either by a multiple reaction monitoring mass spectrometry assay or by a multiplex assay (proximity extension assay). Random forests statistical models were used to assess the predictor importance of biomarkers, CKD and outcomes. Results A total of 1098 MI patients with a median estimated glomerular filtration rate of 85 mL min(-1)/1.73 m(2)were followed for a median of 3.2 years. The random forests analyses, without and with adjustment for differences in demography, comorbidities and severity of disease, identified six biomarkers (adrenomedullin, TNF receptor-1, adipocyte fatty acid-binding protein-4, TNF-related apoptosis-inducing ligand receptor 2, growth differentiation factor-15 and TNF receptor-2) to be strongly associated with CKD. All six biomarkers were also amongst the 15 strongest predictors for death, and four of them were amongst the strongest predictors of subsequent MI and heart failure hospitalization. Conclusion In patients with MI, a proteomic approach could identify six biomarkers that best predicted CKD. These biomarkers were also amongst the most important predictors of long-term outcomes. Thus, these biomarkers indicate underlying mechanisms that may contribute to the poor prognosis seen in patients with MI and CKD.
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27.
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28.
  • Eggers, Kai M., 1962-, et al. (author)
  • Predicting outcome in acute myocardial infarction : an analysis investigating 175 circulating biomarkers
  • 2021
  • In: European Heart Journal. - : Oxford University Press. - 2048-8726 .- 2048-8734. ; 10:7, s. 806-812
  • Journal article (peer-reviewed)abstract
    • Aims There is a paucity of studies comprehensively comparing the prognostic value of larger arrays of biomarkers indicative of different pathobiological axes in acute myocardial infarction (MI).Methods and results In this explorative investigation, we simultaneously analysed 175 circulating biomarkers reflecting different inflammatory traits, coagulation activity, endothelial dysfunction, atherogenesis, myocardial dysfunction and damage, apoptosis, kidney function, glucose-, and lipid metabolism. Measurements were performed in samples from 1099 MI patients (SWEDEHEART registry) applying two newer multimarker panels [Proximity Extension Assay (Olink Bioscience), Multiple Reaction Monitoring mass spectrometry]. The prognostic value of biomarkers regarding all-cause mortality, recurrent MI, and heart failure hospitalizations (median follow-up <= 6.6years) was studied using Lasso analysis, a penalized logistic regression model that considers all biomarkers simultaneously while minimizing the risk for spurious findings. Tumour necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2), ovarian cancer-related tumour marker CA 125 (CA-125), and fibroblast growth factor 23 (FGF-23) consistently predicted all-cause mortality in crude and age/sex-adjusted analyses. Growth-differentiation factor 15 (GDF-15) was strongly predictive in the crude model. TRAIL-R2 and B-type natriuretic peptide (BNP) consistently predicted heart failure hospitalizations. No biomarker predicted recurrent MI. The prognostic value of all biomarkers was abrogated following additional adjustment for clinical variables owing to our rigorous statistical approach.Conclusion Apart from biomarkers with established prognostic value (i.e. BNP and to some extent GDF-15), several 'novel' biomarkers (i.e. TRAIL-R2, CA-125, FGF-23) emerged as risk predictors in patients with MI. Our data warrant further investigation regarding the utility of these biomarkers for clinical decision-making in acute MI.
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29.
  • Eggers, Kai M., 1962-, et al. (author)
  • Sex-differences in circulating biomarkers during acute myocardial infarction : An analysis from the SWEDEHEART registry
  • 2021
  • In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:4 April
  • Journal article (peer-reviewed)abstract
    • Background Sex-differences in the pathobiology of myocardial infarction are well established but incompletely understood. Improved knowledge on this topic may help clinicians to improve management of men and women with myocardial infarction. Methods In this registry-based cohort study (SWEDEHEART), we analyzed 175 circulating biomarkers reflecting various pathobiological axes in 856 men and 243 women admitted to Swedish coronary care units because of myocardial infarction. Two multimarker panels were applied (Proximity Extension Assay [Olink Bioscience], Multiple Reaction Monitoring mass spectrometry). Lasso analysis (penalized logistic regression), multiple testing-corrected Mann- Whitney tests and Cox regressions were used to assess sex-differences in the concentrations of these biomarkers and their implications on all-cause mortality and major adverse events (median follow-up up to 6.6 years). Results Biomarkers provided a very high discrimination between both sexes, when considered simultaneously (c-statistics 0.972). Compared to women, men had higher concentrations of six biomarkers with the most pronounced differences seen for those reflecting atherogenesis, myocardial necrosis and metabolism. Women had higher concentrations of 14 biomarkers with the most pronounced differences seen for those reflecting activation of the reninangiotensin- aldosterone axis, inflammation and for adipokines. There were no major variations between sexes in the associations of these biomarkers with outcome. Conclusions Severable sex-differences exist in the expression of biomarkers in patients with myocardial infarction. While these differences had no impact on outcome, our data suggest the presence of various sex-related pathways involved in the development of coronary atherosclerosis, the progression to plaque rupture and acute myocardial damage, with a greater heterogeneity in women.
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30.
  • Elmqvist, Erik, et al. (author)
  • No Benefit with Preservation of Midline Structures in Decompression for Lumbar Spinal Stenosis Results From the National Swedish Spine Registry 2-Year Post-Op
  • 2022
  • In: Spine. - : Ovid Technologies (Wolters Kluwer Health). - 0362-2436 .- 1528-1159. ; 47:7, s. 531-538
  • Journal article (peer-reviewed)abstract
    • Study Design. Observational cohort study. Objective. The aim of this study was to investigate whether preservation of the midline structures is associated with a better clinical outcome compared to classic central decompression for lumbar spinal stenosis (LSS). Summary of Background Data. The classic surgical procedure for LSS is a central, facet joint sparing decompressive laminectomy (LE). Alternative approaches have been developed to preserve the midline structures. The effect of the alternative techniques compared to LE remains unclear. Methods. All patients >50 years of age who underwent decompression surgery for LSS without concomitant fusion in the National Swedish Spine Registry (Swespine) from December 31, 2015 until October 6, 2017 were included in this study based on surgeon-reported data and patient questionnaires before and 2 years postoperatively. Propensity score matching was used to compare decompression with preservation of midline structures with patients who underwent LE. The primary outcome was the Oswestry Disability Index (ODI) and secondary outcomes were the Numeric Rating Scale (NRS) for leg and back pain, EuroQol-5 Dimensions (EQ-5D), Global Assessment (GA), patient satisfaction and rate of subsequent surgery. Results. Some 3339 patients completed a 2-year follow-up. Of these, 2974 (89%) had decompression with LE and 365 underwent midline preserving surgery. Baseline scores were comparable between the groups. Mean ODI improvement at follow-up was 16.6 (SD = 20.0) in the LE group and 16.9 (SD = 20.2) in the midline preserving surgery group. In the propensity score-matched analysis the difference in improved ODI was 0.53 (95% confidence interval, CI -1.71 to 2.76; P = 0.64). The proportion of patients who showed a decreased ODI score of at least our defined minimal clinically important difference (=8) was 68.3% after LE and 67.0% after preserving the midline structures (P = 0.73). No significant differences were found in the improvement of NRS for leg and back pain, EQ-5D, GA or patient satisfaction. The rate of subsequent surgery was 5.5% after LE and 4.9% after midline preserving surgery without a significant difference in the propensity score-matched analysis (hazard ratio, HR 0.87; 95% CI 0.49-1.54; P = 0.64). Conclusion. In this study on decompression techniques for LSS, there was no benefit in preserving the midline structures compared to LE 2 years after decompression. The conclusion is that the surgeon is free to choose the surgical method that is thought most suitable for the patient and the condition with which the patient presents.
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31.
  • Evans, Marie, et al. (author)
  • Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Myocardial Infarction Patients With Renal Dysfunction
  • 2016
  • In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 67:14, s. 1687-1697
  • Journal article (peer-reviewed)abstract
    • BACKGROUND There is no consensus whether angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) should be used for secondary prevention in all or in only high-risk patients after an acute myocardial infarction (AMI).OBJECTIVES This study sought to investigate whether ACEI/ARB treatment after AMI is associated with better outcomes across different risk profiles, including the entire spectrum of estimated glomerular filtration rates.METHODS This study evaluated discharge and continuous follow-up data on ACEI/ARB use among AMI survivors (2006 to 2009) included in a large Swedish registry. The association between ACEI/ARB treatment and outcomes (mortality, myocardial infarction, stroke, and acute kidney injury [AKI]) was studied using Cox proportional hazards models (intention-to-treat and as treated).RESULTS In total, 45,697 patients (71%) were treated with ACEI/ARB. The 3-year mortality was 19.8% (17.4% of ACEI/ARB users and 25.4% of nonusers). In adjusted analysis, significantly better survival was observed for patients treated with ACEI/ARB (3-year hazard ratio: 0.80; 95% confidence interval: 0.77 to 0.83). The survival benefit was consistent through all kidney function strata, including dialysis patients. Overall, those treated with ACEI/ARB also had lower 3-year risk for myocardial infarction (hazard ratio: 0.91; 95% confidence interval: 0.87 to 0.95), whereas treatment had no significant effect on stroke risk. The crude risk for AKI was in general low (2.5% and 2.0% for treated and nontreated, respectively) and similar across estimated glomerular filtration rate categories but was significantly higher with ACEI/ARB treatment. However, the composite outcome of AKI and mortality favored ACEI/ARB treatment.CONCLUSIONS Treatment with ACEI/ARB after AMI was associated with improved long-term survival, regardless of underlying renal function, and was accompanied by low rates of adverse renal events.
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32.
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33.
  • Freyschuss, B., et al. (author)
  • Real-World Effectiveness of Anti-Resorptive Treatment in Patients With Incident Fragility Fractures—The STORM Cohort—A Swedish Retrospective Observational Study
  • 2022
  • In: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 37:4, s. 649-659
  • Journal article (peer-reviewed)abstract
    • Results from real-world evidence (RWE) from the largest healthcare region in Sweden show low uptake of antiresorptive (AR) treatment, but beneficial effect in those receiving treatment, especially for the composite outcome of hip fracture or death. For RWE studies, Sweden is unique, with virtually complete coverage of electronic medical records (EMRs) and both regional and national registries, in a universal publicly funded healthcare system. To our knowledge, there is no previous RWE study evaluating the efficacy of AR treatment compared to no AR treatment after fragility fracture, including data on parenteral treatments administered in hospital settings. The Stockholm Real World Management (STORM) study cohort was established in the healthcare region of Stockholm to retrospectively assess the effectiveness of AR treatment after first fragility fracture using the regional EMR system for both hospital and primary care. Between 2012 and 2018, we identified 69,577 fragility fracture episodes among 59,078 patients, men and women, 50 years and older. Of those, 21,141 patients met inclusion and exclusion criteria (eligible cohort). From these, the final matched study cohort comprised 9840 fragility fractures (cases receiving AR treatment [n=1640] and controls not receiving AR treatment [n=8200]). Propensity scores were estimated using logistic regression models with AR treatment as outcome and confounders as independent variables followed by analysis using Cox proportional hazard models. Real world evidence from Sweden's largest healthcare region, comprising a quarter of the Swedish population, show that only 10% of patients receive AR treatment within 1 year after a fragility fracture. Factors associated with not receiving treatment include having a diagnosis of cardiovascular disease. In those treated, AR have positive effects particularly on the composite of fracture and death (any fracture/death and hip fracture/death) in individuals matched for all major confounders. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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34.
  • Gedeborg, Rolf, et al. (author)
  • Androgen deprivation therapy, comorbidity, cancer stage and mortality from COVID-19 in men with prostate cancer
  • 2022
  • In: Scandinavian journal of urology. - : Taylor & Francis. - 2168-1805 .- 2168-1813. ; 56:2, s. 104-111
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Androgens facilitate entrance of the severe acute respiratory syndrome coronavirus 2 into respiratory epithelial cells, and male sex is associated with a higher risk of death from corona virus disease (COVID-19). Androgen deprivation therapy (ADT) could possibly improve COVID-19 outcomes.METHODS: In a case-control study nested in the Prostate Cancer data Base Sweden (PCBaSe) RAPID 2019, we evaluated the association between ADT and COVID-19 as registered cause of death in men with prostate cancer. Each case was matched to 50 controls by region. We used conditional logistic regression to adjust for confounders and also evaluated potential impact of residual confounding.RESULTS: We identified 474 men who died from COVID-19 in March-December 2020. In crude analyses, ADT exposure was associated with an increased risk of COVID-19 death (odds ratio [OR] 5.05, 95% CI: 4.18-6.10); however, the OR was substantially attenuated after adjustment for age, comorbidity, prostate cancer characteristics at diagnosis, recent healthcare use, and indicators of advanced cancer (adjusted OR 1.25, 95% CI: 0.95-1.65). If adjustment has accounted for at least 85% of confounding, then the true effect could be no more than a 5% reduction of the odds for COVID-19 death.CONCLUSIONS: The increased mortality from COVID-19 in men with prostate cancer treated with ADT was mainly related to high age, comorbidity, and more advanced prostate cancer. There was no evidence to support the hypothesis that ADT is associated with improved COVID-19 outcomes.
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35.
  • Grip, Olivia, et al. (author)
  • Open versus endovascular revascularization in the treatment of acute lower limb ischaemia
  • 2018
  • In: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 105:12, s. 1598-1606
  • Journal article (peer-reviewed)abstract
    • Background: Consensus is lacking regarding intervention for patients with acute lower limb ischaemia (ALI). The aim was to study amputation-free survival in patients treated for ALI by either primary open or endovascular revascularization.Methods: The Swedish Vascular Registry (Swedvasc) was combined with the Population Registry and National Patient Registry to determine follow-up on mortality and amputation rates. Revascularization techniques were compared by propensity score matching 1:1.Results: Of 9736 patients who underwent open surgery and 6493 who had endovascular treatment between 1994 and 2014, 3365 remained in each group after propensity score matching. Results are from the matched cohort only. Mean age of the patients was 74⋅7 years; 47⋅5 per cent were women and mean follow-up was 4⋅3 years. At 30-day follow-up, the endovascular group had better patency (83⋅0 versus 78⋅6 per cent; P < 0⋅001). Amputation rates were similar at 30 days (7⋅0 per cent in the endovascular group versus 8⋅2 per cent in the open group; P = 0⋅113) and at 1 year (13⋅8 versus 14⋅8 per cent; P = 0⋅320). The mortality rate was lower after endovascular treatment, at 30 days (6⋅7 versus 11⋅1 per cent; P < 0⋅001) and after 1 year (20⋅2 versus 28⋅6 per cent; P < 0⋅001). Accordingly, endovascular treatment had better amputation-free survival at 30 days (87⋅5 versus 82⋅1 per cent; P < 0⋅001) and 1 year (69⋅9 versus 61⋅1 per cent; P < 0⋅001). The number needed to treat to prevent one death within the rst year was 12 with an endovascular compared with an open approach. Five years after surgery, endovascular treatment still had improved survival (HR 0⋅78, 99 per cent c.i. 0⋅70 to 0⋅86) but the difference between the treatment groups occurred mainly in the rst year.Conclusion: Primary endovascular treatment for ALI appeared to reduce mortality compared with open surgery, without any difference in the risk of amputation.
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36.
  • Hambraeus, Kristina, 1970-, et al. (author)
  • Target-Attainment Rates of Low-Density Lipoprotein Cholesterol Using Lipid-Lowering Drugs One Year After Acute Myocardial Infarction in Sweden
  • 2014
  • In: American Journal of Cardiology. - : Elsevier BV. - 1879-1913 .- 0002-9149. ; 113:1, s. 17-22
  • Journal article (peer-reviewed)abstract
    • The objective of this prospective cohort study was to describe real-life use of lipid-lowering drugs and low-density lipoprotein cholesterol (LDL-C) target-attainment rates 1 year after acute myocardial infarction (AMI). LDL-C was recorded at hospital admission for AMI and at follow-up at 2 and 12 months after AMI in 17,236 patients in the Swedish heart registry, SWEDEHEART, from 2004 through 2009. Lipid-lowering treatments were identified using the Swedish Prescribed Drug Register. More than 90% of patients received statins after ANT. Simvastatin <= 40 mg was used by 80% of patients at discharge and at 2 months and 68% at 1 year after AMI. Intensive statin therapy (LDL-C-lowering capacity >40%) was prescribed for 8.4%, 11.9%, and 12.2% at these time points, and combinations of statin/ezetimibe for 1.1%, 2.8%, and 5.0%, respectively. The LDL-C target of <2.5 mmol/L (97 mg/dl) was achieved in 74.5% of patients at 2 months and 72.3% at 12 months after AMI. Treatment was intensified for only 21.3% of patients with LDL-C above target at 2 months. In multivariate analysis, higher LDL-C levels at admission and at 2 months correlated to increased risk for under treatment at 12 months after AMI. In conclusion, statin treatment after AMI in Sweden has become standard, but titration to reach recommended LDL-C levels is still suboptimal. Strategies to further improve implementation of guidelines are needed. (C) 2014 Elsevier Inc. All rights reserved.
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37.
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38.
  • Hjort, Marcus, et al. (author)
  • Differences in biomarker concentrations and predictions of long-term outcome in patients with ST-elevation and non-ST-elevation myocardial infarction
  • 2021
  • In: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 42, s. 1268-1268
  • Journal article (peer-reviewed)abstract
    • Background: Differences in biomarkers reflective of pathobiology and prognosis between ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) are incompletely understood and may offer insights for tailoring of treatment. Methods: This registry-based study included 538 STEMI and 544 NSTEMI patients admitted 2008–2014. Blood samples were collected day 1–3 after admission and 175 biomarkers were analyzed using Proximity Extension Assay and Multiple Reaction Monitoring mass spectrometry. Adjusted Lasso analysis (penalized logistic regression model) was used to select biomarkers that discriminated STEMI from NSTEMI patients. Biomarkers identified by the Lasso analysis were then evaluated in adjusted Cox regressions for associations with death or major adverse cardiovascular events. Results: Biomarkers strongly discriminated STEMI and NSTEMI when considered simultaneously in adjusted Lasso analysis (c-statistic 0.764). Eleven biomarkers independently discriminated STEMI and NSTEMI; seven showing higher concentrations in STEMI: myoglobin, N-terminal pro-B-type natriuretic peptide, serum amyloid A-1 and A-2 protein, ST2 protein, interleukin-6 and chitinase-3-like protein 1; and four showing higher concentrations in NSTEMI: fibroblast growth factor 23, membrane-bound aminopeptidase P, tumor necrosis factor-related activation-induced cytokine and apolipoprotein C-I. During up to 6.6 years of prognostic follow-up, none of these biomarkers exhibited different associations with adverse outcome between STEMI and NSTEMI. Conclusions: In the acute setting, biomarkers indicated greater myocardial dysfunction and inflammation in STEMI, whereas they displayed a more diverse pathophysiologic pattern in NSTEMI patients. These biomarkers were similarly prognostic in STEMI and NSTEMI patients. The results do not support treating STEMI and NSTEMI patients differently based on the concentrations of these biomarkers.
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39.
  • Hjort, Marcus, et al. (author)
  • Increased Inflammatory Activity in Patients 3 Months after Myocardial Infarction with Nonobstructive Coronary Arteries
  • 2019
  • In: Clinical Chemistry. - : AMER ASSOC CLINICAL CHEMISTRY. - 0009-9147 .- 1530-8561. ; 65:8, s. 1023-1030
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Around 5%-10% of patients with myocardial infarction (MI) present with nonobstructive coronary arteries (MINOCA). We aimed to assess pathophysiological mechanisms in MINOCA by extensively evaluating cardiovascular biomarkers in the stable phase after an event, comparing MINOCA patients with cardiovascular healthy controls and MI patients with obstructive coronary artery disease (MI-CAD).METHODS: Ninety-one biomarkers were measured with a proximity extension assay 3 months after MI in 97 MINOCA patients, 97 age-and sex-matched MI-CAD patients, and 98 controls. Lasso analyses (penalized logistic regression models) and adjusted multiple linear regression models were used for statistical analyses.RESULTS: In the Lasso analysis (MINOCA vs MI-CAD), 8 biomarkers provided discriminatory value: P-selectin glycoprotein ligand 1, C-X-C motif chemokine 1, TNF-related activation-induced cytokine, and pappalysin-1 (PAPPA) with increasing probabilities of MINOCA, and tissue-type plasminogen activator, B-type natriuretic peptide, myeloperoxidase, and interleukin-1 receptor antagonist protein with increasing probabilities of MI-CAD. Comparing MINOCA vs controls, 7 biomarkers provided discriminatory value: N-terminal pro-B-type natriuretic peptide, renin, NF-kappa-B essential modulator, PAPPA, interleukin-6, and soluble urokinase plasminogen activator surface receptor with increasing probabilities of MINOCA, and agouti-related protein with increasing probabilities of controls. Adjusted multiple linear regression analyses showed that group affiliation was associated with the concentrations of 7 of the 8 biomarkers in the comparison MINOCA vs MI-CAD and 5 of the 7 biomarkers in MINOCA vs controls.CONCLUSIONS: Three months after the MI, the biomarker concentrations indicated greater inflammatory activity in MINOCA patients than in both MI-CAD patients and healthy controls, and a varying degree of myocardial dysfunction among the 3 cohorts. 
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40.
  • Ishak, Divan, et al. (author)
  • Association of beta-blockers beyond 1 year after myocardial infarction and cardiovascular outcomes
  • 2023
  • In: Heart. - : BMJ Publishing Group Ltd. - 1355-6037 .- 1468-201X. ; 109:15, s. 1159-1165
  • Journal article (peer-reviewed)abstract
    • Objective Beta-blockers (BB) are an established treatment following myocardial infarction (MI). However, there is uncertainty as to whether BB beyond the first year of MI have a role in patients without heart failure or left ventricular systolic dysfunction (LVSD).Methods A nationwide cohort study was conducted including 43 618 patients with MI between 2005 and 2016 in the Swedish register for coronary heart disease. Follow-up started 1 year after hospitalisation (index date). Patients with heart failure or LVSD up until the index date were excluded. Patients were allocated into two groups according to BB treatment. Primary outcome was a composite of all-cause mortality, MI, unscheduled revascularisation and hospitalisation for heart failure. Outcomes were analysed using Cox and Fine-Grey regression models after inverse propensity score weighting.Results Overall, 34 253 (78.5%) patients received BB and 9365 (21.5%) did not at the index date 1 year following MI. The median age was 64 years and 25.5% were female. In the intention-to-treat analysis, the unadjusted rate of primary outcome was lower among patients who received versus not received BB (3.8 vs 4.9 events/100 person-years) (HR 0.76; 95% CI 0.73 to 1.04). Following inverse propensity score weighting and multivariable adjustment, the risk of the primary outcome was not different according to BB treatment (HR 0.99; 95% CI 0.93 to 1.04). Similar findings were observed when censoring for BB discontinuation or treatment switch during follow-up.Conclusion Evidence from this nationwide cohort study suggests that BB treatment beyond 1 year of MI for patients without heart failure or LVSD was not associated with improved cardiovascular outcomes.
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41.
  • Jaafar, Gona, et al. (author)
  • Disparities in the regional, hospital and individual levels of antibiotic use in gallstone surgery in Sweden
  • 2017
  • In: BMC Surgery. - : Springer Science and Business Media LLC. - 1471-2482. ; 17
  • Journal article (peer-reviewed)abstract
    • Background: Antimicrobial resistance may be promoted by divergent routines and lack of conformity in antibiotic treatment, especially regarding the practice of antibiotic prophylaxis. The aim of the present study was to assess differences in gallstone surgery regarding antibiotic use in Sweden.Methods: The study was based on data from the Swedish Register for Gallstone Surgery and ERCP (GallRiks) 2005-2015. Funnel plots were used to test impact of grouping factors, including, hospital and surgeon and to identify units that deviated from the rest of the population.Results: After adjusting for cofounders including age, gender, ASA classification, indication for surgery, operation time, gallbladder perforation and emergency status, there were 0/21 (0%) at the regional level, 18/76 (24%) at the hospital level and 128/1038 (12%) at the surgeon level outside the 99.9% confidence interval (CI). The estimated median odds ratios were 1.13 (95% CI 1.00-1.31) at the regional level, 1.93 (95% CI 1.70-2.19) at the hospital level and 2.38 (95% CI 2.26-2.50) at the surgeon level.Conclusion: There are significant differences between hospitals and surgeons, but little or no differences between regions. These deviations confirm the lack of standardization in regards to prescription of antibiotic prophylaxis and the need more uniform routines regarding antibiotic usage. Randomized controlled trials and large population-based studies are necessary to assess assessing the effectiveness and safety of antibiotic prophylaxis in gallstone surgery.
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42.
  • Jönelid, Birgitta, et al. (author)
  • Biochemical biomarkers associated with peripheral artery disease contribute to prediction of outcome during long-term follow up after myocardial infarction
  • Other publication (other academic/artistic)abstract
    • AbstractBackground: Few studies have investigated biomarkers and their association to cardiovascular (CV) outcomes in patients with myocardial infarction (MI) and peripheral artery disease (PAD). Tumor necrosis factor receptor 1(TNFR-1), tumor necrosis factor receptor 2(TNFR-2) and growth differentiation factor 15 (GDF-15) are inflammatory biomarkers found to predict PAD.Aim:  To evaluate whether pathological ankle brachial index (ABI) and the group of biomarkers TNFR-1, TNFR-2 and GDF-15 analyzed early after a MI, were associated with all-cause mortality and the risk of new cardiovascular events during long-term follow up. Method: 388 patients with MI included in the REBUS (Relevance of Biomarkers for future risk of Thromboembolic Events in Unselected Post-myocardial Infarction Patients) study were examined with ABI to diagnose PAD (defined as an ABI score <0.9 or > 1.4 on at least one side). TNFR-1, -2 and GDF-15 was measured using the Proseek Multiplex CVD III ⁹⁶˟⁹⁶ proximity extension assay (www.olink.com/products/cvd-i and iii-panel).  The composite results for these 3 biomarkers were dichotomized into two groups (i.e high and low values) We evaluated pathological ABI and the group with higher biomarkers values with the association to long-term outcome, and if the group of biomarkers for inflammation could further improve prediction of recurrence of cardiovascular events (mortality, new acute coronary syndrome (ACS) and the composite of mortality, new ACS, stroke/TIA and PAD) after an MI.  Results:  The mean follow-up time was 5.5 years. After adjustment for established CV risk factors, pathological ABI was associated with a higher risk of new ACS, HR 1.97, 95 % CI 1.12-3.49, p = 0.019, and the composite endpoint; HR 1.97, 95 % CI 1.29-3.01, p=0.002, compared to patients with normal ABI. The group with the higher biomarker value was associated with a higher risk for all-cause mortality; HR 1.84, 95 % CI 1.00-3.38, p=0.049 and the composite endpoint; HR 1.62, 95 % CI 1.03-2.53, p=0.035. In the ROC analyses pathological ABI added to established CV risk factors improved the AUC for a new ACS from 0.753 (95% C.I. 0.684-0.822, p<0.001) to 0.763 (95% C.I. 0.697-0.830, p<0.001). When the group with higher biomarker values was added to  established CV risk factors  AUC for all-cause mortality increased from 0.789 (95% C-I. 0.729-0.849, p<0.001) to 0.805 (95% C.I. 0.746-0.863, p<0.001).Conclusion: Despite a high proportion of revascularization and guideline-recommended secondary medical treatment, both pathological ABI and the group with higher values of the inflammatory biomarkers (TNFR-1, TNFR-2, GDF-15) predictive for PAD were associated with the risk of new CV events and mortality in patients with a recent MI. The group of inflammatory biomarkers provide additional information to established risk factors in prediction of CV outcome in this cohort with recent MI.
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43.
  • Jönelid, Birgitta, et al. (author)
  • Biomarkers in addition to clinical characteristics for prediction of peripheral artery disease in patients with recent myocardial infarction
  • Journal article (other academic/artistic)abstract
    • AbstractBackground Few studies have examined biomarkers in CAD and peripheral artery disease (PAD), their association and the ability to predict PAD.Methods: Two prospectively observational studies including unselected patients with recent myocardial infarction were used for the analyses. PAD was defined as an abnormal ankle brachial index (ABI) score (<0.9 or > 1.4) on at least one side. The proximity extension assay (PEA) technique was used to simultaneously analyze 92 biomarkers with association to cardiovascular disease in samples early after an acute MI. Random forest was used to identify the biomarkers with a higher association to PAD. The additional discriminatory accuracy of adding biomarkers to clinical characteristics were analyzed by the c-statistics.Results:  Six biomarkers were identified associated with prediction of PAD in the REBUS cohort. Three of these could be validated in the VaMIS cohort; Tumor necrosis factor receptor (TNFR-1),  Tumor necrosis factor receptor 2 (TNFR-2) and Growth Differentiation Factor 15 (GDF-15) with an increase in c-statistics; Tnfr1:0.709 (95% CI 0.640, 0.779) and 0.746 (95% CI 0.706,0.787), Tnfr2: 0.703 (95% CI 0.633, 0.773) and 0.745 (95% CI 0.704, 0.785), GDF-15: 0.710 (95% CI 0.640, 0.781) and 0.752 (95% CI 0.711, 0.792) in the REBUS and VaMIS cohort respectively. Adding a group of biomarkers to clinical characteristics further increased the c-statistics compared to a single biomarker.Conclusions: Three biomarkers out of a panel of 92; TNFR-1, TNFR-2 and GDF-15 were identified associated with PAD in MI patients and could improve prediction of PAD in addition to clinical characteristics.  
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44.
  • Jönelid, Birgitta, et al. (author)
  • Screening of biomarkers for prediction of multisite artery disease in patients with recent myocardial infarction
  • 2021
  • In: Scandinavian Journal of Clinical and Laboratory Investigation. - : Taylor & Francis. - 0036-5513 .- 1502-7686. ; 81:5, s. 353-360
  • Journal article (peer-reviewed)abstract
    • A few studies have examined biomarkers in patients with myocardial infarction (MI) and peripheral artery disease (PAD), i.e. multisite artery disease (MSAD). The aim of the study was firstly, to associate biomarkers with the occurrence of PAD/MSAD and secondly, if those can, in addition to clinical characteristics, identify MI patients with MSAD.In two prospectively observational studies including unselected patients with recent MI, PAD was defined as an abnormal ankle-brachial index (ABI) score (1.4). The proximity extension assay (PEA) technique was used, simultaneously analyzing 92 biomarkers with association to cardiovascular disease. Biomarkers were tested for univariate associations with PAD. Random forest was used to identify biomarkers with a higher association to PAD. The additional discriminatory accuracy of adding biomarkers to clinical characteristics was analyzed by the c-statistics. Nine biomarkers were identified as significantly associated with MSAD/PAD in the primary patient cohort, analyzed early after the MI. In the prediction analysis, six biomarkers were identified associated with PAD. Three of these; Tumor necrosis factor receptor (TNFR-1), Tumor necrosis factor receptor 2 (TNFR-2) and Growth Differentiation Factor 15 (GDF-15) improved c-statistics when added to clinical characteristics from 0.683 (95% CI 0.610-0.756) to 0.715 (95% CI 0.645-0.784) in the primary patient cohort with a similar result, 0.729 (95% CI 0.687-0.770) to 0.752 (95% CI 0.771-0.792) in the secondary patient cohort. Biomarkers associated with inflammatory pathways are associated with MSAD in MI patients. Three biomarkers of 92; TNFR-1, TNFR-2 and GDF-15, in this exploratory added information in the prediction of MSAD and emphasis the importance of further studies.
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45.
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46.
  • Lindhagen, Johan E., et al. (author)
  • Application of bridging-law concepts to short-fibre composites : 1. DCB test procedures for bridging law and fracture energy
  • 2000
  • In: Composites Science And Technology. - 0266-3538 .- 1879-1050. ; 60:6, s. 871-883
  • Journal article (peer-reviewed)abstract
    • This is the first paper in a series of four where notch sensitivities, fracture energies and bridging laws of short-fibre polymer composites are investigated. In the context of crack-bridging, the bridging law is an important material parameter. The bridging law can be used in combination with a stress analysis to address failure problems, for instance large-scale bridging, where linear elastic fracture mechanics is not valid. The bridging law of the material is sensitive to material composition and fibre architecture. Owing to the lack of established procedures, it is of interest to develop experimental and analytical methods for determination of the bridging law and fracture energy of short-fibre polymer composites. A method based on a large DCB specimen loaded by pure bending moments is used. Commercial GMT and SMC materials are investigated in addition to chopped-strand-mat laminates based on glass fibres of two different lengths and two thermoset matrices of different ductility. Fracture energies and bridging law data are successfully determined. All materials demonstrate softening bridging laws and this is discussed on the basis of observed mechanisms of failure and existing micromechanical models.
  •  
47.
  • Lindhagen, J. E., et al. (author)
  • Application of bridging-law concepts to short-fibre composites 4. FEM analysis of notched tensile specimens
  • 2000
  • In: Composites Science And Technology. - 0266-3538 .- 1879-1050. ; 60:16, s. 2895-2901
  • Journal article (peer-reviewed)abstract
    • This is the fourth paper in a series of four where notch sensitivities, fracture energies and bridging laws in short-fibre polymer composites are investigated. In this paper finite-element modelling (FEM) of centre-hole-notched tensile specimens is performed, with different bridging laws governing crack growth. Crack lengths, crack profiles and stress distributions are predicted. The results are compared with experimentally determined crack shapes from an earlier investigation. Only with softening bridging laws can the experimental results be matched. The predicted crack lengths are sensitive to bridging-law parameters. When bridging laws determined by the double cantilever beam (DCB) method are applied, the predicted crack lengths and profiles show good correlation with the experimental results. The results support the validity of the DCB method to determine bridging laws in short-fibre composites.
  •  
48.
  • Lindhagen, J. E., et al. (author)
  • Application of bridging-law concepts to short-fibre composites - Part 1 : DCB test procedures for bridging law and fracture energy
  • 2000
  • In: Composites Science And Technology. - 0266-3538 .- 1879-1050. ; 60:6, s. 871-883
  • Journal article (peer-reviewed)abstract
    • This is the first paper in a series of four where notch sensitivities, fracture energies and bridging laws of short-fibre polymer composites are investigated. In the context of crack-bridging, the bridging law is an important material parameter. The bridging law can be used in combination with a stress analysis to address failure problems, for instance large-scale bridging, where linear elastic fracture mechanics is not valid. The bridging law of the material is sensitive to material composition and fibre architecture. Owing to the lack of established procedures, it is of interest to develop experimental and analytical methods for determination of the bridging law and fracture energy of short-fibre polymer composites. A method based on a large DCB specimen loaded by pure bending moments is used. Commercial GMT and SMC materials are investigated in addition to chopped-strand-mat laminates based on glass fibres of two different lengths and two thermoset matrices of different ductility. Fracture energies and bridging law data are successfully determined. All materials demonstrate softening bridging laws and this is discussed on the basis of observed mechanisms of failure and existing micromechanical models.
  •  
49.
  • Lindhagen, J. E., et al. (author)
  • Application of bridging-law concepts to short-fibre composites - Part 2. Notch sensitivity
  • 2000
  • In: Composites Science And Technology. - 0266-3538 .- 1879-1050. ; 60:6, s. 885-893
  • Journal article (peer-reviewed)abstract
    • This is the second paper in a series of four where notch sensitivities, fracture energies and bridging laws are studied in short-fibre polymer composites. Estimates based on an order-of-magnitude criterion indicate that previous notch sensitivity studies on short-fibre composites are limited to small notch sizes in the ductile region. For this reason, centre-hole notch sensitivity is studied experimentally as a function of relatively large notch diameters in the range 15-60 mm. The materials have different matrices, glass-fibre content and fibre lengths. The onset of notch sensitivity is observed for all materials (glass-mat thermoplastics, sheet-moulding compounds and chopped-strand-mat laminates), although large notch sizes are required. The reasons for this are discussed as well as the influence of different material parameters. On the basis of the material bridging law and laminate Young's modulus, it was possible to rank different short-fibre composites with respect to notch sensitivity.
  •  
50.
  • Lindhagen, J. E., et al. (author)
  • Application of bridging-law concepts to short-fibre composites Part 3 : Bridging law derivation from experimental crack profiles
  • 2000
  • In: Composites Science And Technology. - 0266-3538 .- 1879-1050. ; 60:16, s. 2883-2894
  • Journal article (peer-reviewed)abstract
    • This is the third paper in a series of four where notch sensitivity, fracture energy and bridging laws are studied in short-fibre polymer composites. Here, bridging laws are derived from experimental crack-opening profiles in centre-hole notched tensile specimens. The materials studied are three types of commercial glass-mat composites with different reinforcement structures and matrices. The materials have softening bridging laws and the calculated fracture energies from bridging laws are in good agreement with values determined directly by experiment. The calculated maximum local bridging stress is found to be higher than the uniaxial tensile strength. An outline of a failure criterion for notched specimens based on the crack-bridging approach is presented.
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