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Sökning: WFRF:(Christersson Christina)

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1.
  • Pirmohamed, Munir, et al. (författare)
  • A Randomized Trial of Genotype-Guided Dosing of Warfarin
  • 2013
  • Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 369:24, s. 2294-2303
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The level of anticoagulation in response to a fixed-dose regimen of warfarin is difficult to predict during the initiation of therapy. We prospectively compared the effect of genotype-guided dosing with that of standard dosing on anticoagulation control in patients starting warfarin therapy.Methods: We conducted a multicenter, randomized, controlled trial involving patients with atrial fibrillation or venous thromboembolism. Genotyping for CYP2C9*2, CYP2C9*3, and VKORC1 (-1639GA) was performed with the use of a point-of-care test. For patients assigned to the genotype-guided group, warfarin doses were prescribed according to pharmacogenetic-based algorithms for the first 5 days. Patients in the control (standard dosing) group received a 3-day loading-dose regimen. After the initiation period, the treatment of all patients was managed according to routine clinical practice. The primary outcome measure was the percentage of time in the therapeutic range of 2.0 to 3.0 for the international normalized ratio (INR) during the first 12 weeks after warfarin initiation.Results: A total of 455 patients were recruited, with 227 randomly assigned to the genotype-guided group and 228 assigned to the control group. The mean percentage of time in the therapeutic range was 67.4% in the genotype-guided group as compared with 60.3% in the control group (adjusted difference, 7.0 percentage points; 95% confidence interval, 3.3 to 10.6; P<0.001). There were significantly fewer incidences of excessive anticoagulation (INR 4.0) in the genotype-guided group. The median time to reach a therapeutic INR was 21 days in the genotype-guided group as compared with 29 days in the control group (P<0.001).Conclusions: Pharmacogenetic-based dosing was associated with a higher percentage of time in the therapeutic INR range than was standard dosing during the initiation of warfarin therapy. 
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  • Arvidsson, Anna, 1973, et al. (författare)
  • Characterisation of structures in salivary secretion film formation. An experimental study with atomic force microscopy
  • 2004
  • Ingår i: Biofouling. - : Informa UK Limited. - 0892-7014 .- 1029-2454. ; 20:3, s. 181-8
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of the present study was to characterise the structure dynamics of pure salivary secretions retained on controlled surfaces with different surface energies in the early stage of salivary film formation. Germanium prisms prepared to have either low surface energy or medium surface energy were incubated in fresh secretions of either human parotid saliva (HPS) or human submandibular/sublingual saliva (HSMSLS) for 15, 90, and 180 min. After controlled rinsing with distilled water, the surfaces were air dried and thereafter imaged with atomic force microscopy (AFM). The amount of adsorbed material and the size of the structures detected increased with increased saliva exposure time. The film thicknesses varied from 10 to 150 nm, and both HPS and HSMSLS films contained structures with diameters varying from 40 nm to 2 microm. Some of these were clustered into special formations. The HPS films exhibited a more granular morphology than the HSMSLS films. Furthermore, branched lines were detected on the low surface energy germanium prisms incubated in saliva. The results indicate that exposure time, surface energy, and type of salivary secretion all are factors affecting the adsorption characteristics of salivary films.
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  • Baron, Tomasz, et al. (författare)
  • Changes in global longitudinal strain and left ventricular ejection fraction during the first year after myocardial infarction : results from a large consecutive cohort
  • 2018
  • Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 19:10, s. 1165-1173
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: To determine changes of global longitudinal strain (GLS) and their predictors in relation to classical echocardiographic parameters of left ventricular (LV) function, over 1 year, in consecutive patients with myocardial infarction (MI) and initially normal or impaired LV ejection fraction (EF).Methods and results: A total of 285 patients with MI prospectively included in the REBUS (RElevance of Biomarkers for future risk of thromb-oembolic events in UnSelected post-myocardial infarction patients) study underwent echocardiography within 72 h from admission and after 1 year. At baseline, 213 (74.7%) of MI patients had a normal EF (≥52% in men or ≥54% in women), but in 70.4% of them, an impaired GLS ( ≥ -18.0%) was observed. During 1-year follow-up, in patients with normal EF at baseline, GLS improved from -15.8% to - 17.4% (10.1% relative change); EF decreased from 62.5% to 59.9% (4.0% relative change); indexed end-diastolic volume, indexed end-systolic volume, and indexed stroke volume increased with 15.6%, 24.8%, and 10.0% of relative change, respectively (P < 0.001 for all the comparisons). In the whole cohort, initial impairment of LV function [by EF, wall motion score index (WMSI), or GLS], male gender, non-smoking, and treatment with beta-blockers were the independent predictors of GLS improvement. In the group with initially impaired EF, over 1 year GLS improved from -11.9% to - 14.8% (24.4% relative change) and EF from 44.6% to 52.6% (18.2% relative change) (P < 0.001 for both). Improvement in GLS significantly correlated with EF increase in the group with impaired EF (r = -0.41, P = 0.001) but not in the patients with normal EF (r = -0.14, P = ns).Conclusions: Despite diveregent evolution of GLS compared with EF and ventricular volumes, one year after MI GLS significantly improved in patients with initially both normal and impaired EF. Initial impairment of LV function (by EF, WMSI, or GLS), male gender, non-smoking, and treatment with beta-blockers were independent predictors of GLS improvement. LV remodelling was present even in patients with normal EF at baseline and during follow-up, confirming limited functional assessment by EF alone.
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  • Baron, Tomasz, et al. (författare)
  • Usefulness of traditional echocardiographic parameters in assessment of left ventricular function in patients with normal ejection fraction early after acute myocardial infarction : results from a large consecutive cohort
  • 2016
  • Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2404 .- 2047-2412. ; 17:4, s. 413-420
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: The aim of this study was to assess the frequency of left ventricular (LV) systolic function impairment using classical echocardiographic parameters and their relation to myocardial damage in patients hospitalized for acute myocardial infarction (MI) with normal LV ejection fraction (LVEF ≥52% in males or ≥54% in females).METHODS AND RESULTS: All 421 consecutive patients with MI included in the REBUS (RElevance of Biomarkers for future risk of thromboembolic events in UnSelected post-myocardial infarction patients) study underwent two-dimensional and Doppler echocardiography within 72 h after admission. A normal LVEF was present in 262 (73.8%) of the 355 patients ultimately enrolled in the study. Patients with normal LVEF more often presented with non-ST-elevation myocardial infarction and had less comorbidities when compared with those with impaired LVEF. No differences in demographic factors or relevant medications were observed. Higher value of mean annular plane systolic excursion (MAPSE), lower wall motion score index (WMSI), lower LV as well as left atrial volumes characterized patients with normal LVEF. Impaired MAPSE was present in 64.4%, WMSI >1 in 72.1%, and dilated left atrium in 33.6% of those patients. Maximal cardiac troponin concentration reflecting infarct size showed the strongest association with WMSI (β = 0.35), followed by LVEF (β = -0.29), MAPSE (β = -0.25), and indexed LV end-systolic volume (β = 0.19; P < 0.001 for all the models).CONCLUSION: In two-third of patients with MI and normal LVEF, at least one of the other markers of systolic function was outside of the normal range. WMSI reflected the size of MI better than global LV function parameters as LVEF or MAPSE.
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  • Batra, Gorav, et al. (författare)
  • Oral anticoagulants, time in therapeutic range and renal function over time in real-life patients with atrial fibrillation and chronic kidney disease
  • 2022
  • Ingår i: Open heart. - : BMJ Publishing Group Ltd. - 2053-3624. ; 9:2
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: To describe the use of warfarin and direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) and chronic kidney disease (CKD), to evaluate changes in renal function over time and predictors of rapid decline, and to describe time in therapeutic range (TTR) and predictors of poor TTR among patients on warfarin.METHODS AND RESULTS: Using data from AuriculA, the Swedish oral anticoagulation registry, patients with AF on warfarin or DOAC were identified between 2013 and 2018 (N=6567). Estimated glomerular filtration rate (eGFR) was calculated and categorised into normal (≥90 mL/min/1.73 m2), mild CKD (60-89 mL/min/1.73 m2), moderate CKD (30-59 mL/min/1.73 m2), severe CKD (15-29 mL/min/1.73 m2) and end-stage CKD (<15 mL/min/1.73 m2)/dialysis. TTR was estimated using international normalised ratio (INR) measurements. Predictors of eGFR decline over time and of poor TTR were estimated using regression analysis. Between 2013 and 2018, use of DOAC increased from 9.2% to 89.3%, with a corresponding decline in warfarin. A similar trend was observed in patients with mild to moderate CKD, while DOAC over warfarin increased slower among patients with severe to end-stage CKD/dialysis. In patients treated with warfarin, the median TTR was 77.1%. Worse TTR was observed among patients with severe CKD (70.0%) and end-stage CKD/dialysis (67.5%). A gradual annual decline in eGFR was observed (-1.1 mL/min/1.73 m2), with a more rapid decline among patients with older age, female sex, diabetes mellitus and/or heart failure.CONCLUSION: In patients with AF, use of DOAC has steadily increased across different CKD stages, but not in patients with severe to end-stage CKD/dialysis despite these patients having poor INR control. Patients with AF have a gradual decline in renal function, with a more rapid decline among a subgroup of patients.
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  • Bay, Annika, 1970-, et al. (författare)
  • Symptoms during pregnancy in primiparous women with congenital heart disease.
  • 2024
  • Ingår i: Scandinavian Cardiovascular Journal. - : Taylor & Francis. - 1401-7431 .- 1651-2006. ; 58:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: As more women with congenital heart disease (CHD) are reaching childbearing age, it becomes more common for their symptoms to be evaluated during pregnancy. However, pregnancy-related symptoms are similar to those caused by heart disease. This study investigated the prevalence of factors associated with symptoms during pregnancy in women with CHD.Methods: The national birth register was searched for primiparous women with CHD who were registered in the national quality register for patients with CHD.Results: Symptoms during the third trimester were reported in 104 of 465 evaluated women. The most common symptom was palpitations followed by dyspnea. Factors associated with symptoms were tested in a univariable model; higher NYHA classification (>1) (OR 11.3, 95%CI 5.5-23.2), low physical activity (≤3 h/week) (OR 2.1 95%CI 1.3-3.6) and educational level ≤ 12 years (OR 1.9 95%CI 1.2-3.0) were associated with having symptoms. In multivariable analysis, low physical activity level (OR 2.4 95%CI 1.2-5.0) and higher NYHA class (OR 11.3 95%CI 5.0-25.6) remained associated with symptoms during pregnancy. There were no cases with new onset of impaired systemic ventricular function during pregnancy.Conclusion: Symptoms during pregnancy are common in women with CHD but are often already present before pregnancy. Because ordinary symptoms during pregnancy often overlap with symptoms of heart disease, it is important to know if symptoms were present before pregnancy and if they became worse during pregnancy. These results should be included in pre-pregnancy counselling and considered in the monitoring during pregnancy.
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  • Berglund, Elisabeth, et al. (författare)
  • High incidence of infective endocarditis in adults with congenital ventricular septal defect
  • 2016
  • Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 102:22, s. 1835-1839
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Ventricular septal defects (VSDs), if haemodynamically important, are closed whereas small shunts are left without intervention. The long-term prognosis in congenital VSD is good but patients are still at risk for long-term complications. The aim of this study was to clarify the incidence of infective endocarditis (IE) in adults with VSD. METHODS: The Swedish registry for congenital heart disease (SWEDCON) was searched for adults with VSD. 779 patients were identified, 531 with small shunts and 248 who had the VSD previously closed. The National Patient Register was then searched for hospitalisations due to IE in adults during a 10-year period. RESULTS: Sixteen (2%) patients were treated for IE, 6 men and 10 women, with a mean age of 46.3+/-12.2 years. The incidence of IE was 1.7-2.7/1000 years in patients without previous intervention, 20-30 times the risk in the general population. Thirteen had small shunts without previous intervention. There was no mortality in these 13 cases. Two patients had undergone repair of their VSD and also aortic valve replacement before the episode of endocarditis and a third patient with repaired VSD had a bicuspid aortic valve, all of these three patients needed reoperation because of their IE and one patient died. No patient with isolated and operated VSD was diagnosed with IE. CONCLUSIONS: A small unoperated VSD in adults carries a substantially increased risk of IE but is associated with a low risk of mortality.
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  • Cederlöf, Elin, et al. (författare)
  • Pregnancy Complications and Risk of Cardiovascular Disease Later in Life : A Nationwide Cohort Study
  • 2022
  • Ingår i: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 11:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The aim of this study was to investigate the associations between pregnancy complications and cardiovascular mortality and hospitalizations of cardiovascular disease (CVD) after adjustment for major confounding.Methods and Results: In a nationwide register‐based cohort study, women with singleton births between 1973 and 2014 were included from the Swedish Medical Birth Register. Outcomes of mortality and hospitalizations of CVD were collected from the Cause of Death Register and the National Inpatient Register. The cohort was followed from the date of the first delivery until death or end of follow‐up, whichever occurred first. The pregnancy complications studied were preeclampsia or eclampsia, gestational hypertension, gestational diabetes, preterm birth, small for gestational age, and stillbirth. Among the 2 134 239 women (mean age at first pregnancy, 27.0 [SD, 5.1] and mean parity 1.96 [SD, 0.9]), 19.1% (N=407 597) had 1 of the studied pregnancy complications. All pregnancy complications were associated with all‐cause and cardiovascular mortality and hospitalization for CVD (ischemic heart disease, ischemic stroke, and peripheral artery disease) after adjustment for major confounding in a Cox proportional hazard regression model. The adjusted hazard ratio for cardiovascular mortality was 1.84 (95% CI, 1.38–2.44) for preterm birth and 3.14 (95% CI, 1.81–5.44) for stillbirth.Conclusions: In this large cohort study, pregnancy complications were associated with all‐cause mortality, cardiovascular mortality, and hospitalizations for CVD, also after adjusting for confounding, including overweight, smoking, and comorbidities. The study highlights that less established pregnancy complications such as preterm birth and stillbirth are also associated with cardiovascular mortality and CVD.
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  • Cederlöf, Elin Täufer, et al. (författare)
  • Biomarkers associated with cardiovascular disease in women with spontaneous preterm birth : A case-control study.
  • 2024
  • Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - 0001-6349 .- 1600-0412.
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Women with spontaneous preterm birth have an increased risk of cardiovascular disease later in life. Studies suggest potential pathophysiological mechanisms in common, but whether these could be identified by measurement of soluble circulating protein biomarkers in women with spontaneous preterm birth is unknown. The aim of this study was to determine if protein biomarkers associated with cardiovascular disease distinguish women with spontaneous preterm birth from healthy controls, both at pregnancy and at follow up.MATERIAL AND METHODS: Study participants were identified in the population-based Uppsala biobank of pregnant women in Sweden, where plasma samples were collected in mid-pregnancy. In a first screening phase, we identified participants who subsequently experienced spontaneous preterm birth (<37 weeks) in the index pregnancy (N = 13) and controls (N = 6). In these samples, differences in protein expression were examined by comparative mass spectrometry. In a second validation phase, we invited 100 cases with previous spontaneous preterm birth in the index pregnancy and 100 controls (matched for age, body mass index, and year of delivery) from the same source population, to a follow-up visit 4-15 years after pregnancy. At follow up, we collected plasma samples and data on cardiovascular risk factors. We measured concentrations of selected biomarkers identified in the screening phase, as well as lipid profiles in samples both from pregnancy (biobank) and follow up.CLINICALTRIALS: gov registration NCT05693285.RESULTS: In the screening phase, fibrinogen, cadherin-5, complement C5, factor XII, plasma kallikrein, apolipoprotein M, and vitamin D-binding protein differed significantly at pregnancy. In the validation phase, 65 women agreed to participate (35 cases and 30 controls), with a median follow-up time of 11.8 years since pregnancy. The concentration of fibrinogen (p = 0.02) and triglycerides (p = 0.03) were slightly higher in cases compared with matched controls at follow up.CONCLUSIONS: Compared with women without preterm birth, those with spontaneous preterm birth had slightly higher concentrations of fibrinogen, both at mid-pregnancy and a decade after pregnancy. Additionally, we found slightly higher concentration of triglycerides at follow up in women with previous spontaneous preterm birth. The relevance of this finding is uncertain but might indicate potential pathophysiological mechanisms in common between spontaneous preterm birth and cardiovascular disease.
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  • Christersson, Cecilia, et al. (författare)
  • A predictive model for alternative admission to dental education.
  • 2015
  • Ingår i: European Journal of Dental Education. - : Wiley. - 1396-5883 .- 1600-0579. ; 19:4, s. 251-258
  • Tidskriftsartikel (refereegranskat)abstract
    • To compare academic progress and performance of students admitted through two admission systems and to analyse the predictive power of different components in an alternative admission.
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  • Christersson, Christina, et al. (författare)
  • Comparison of warfarin versus antiplatelet therapy after surgical bioprosthetic aortic valve replacement
  • 2020
  • Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 106:11, s. 838-844
  • Tidskriftsartikel (refereegranskat)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. (författare)
  • D-dimer and risk of thromboembolic and bleeding events in patients with atrial fibrillation : observations from the ARISTOTLE trial
  • 2014
  • Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 12:9, s. 1401-1412
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundD-dimer is related to adverse outcomes in arterial and venous thromboembolic diseases. ObjectivesTo evaluate the predictive value of D-dimer level for stroke, other cardiovascular events, and bleeds, in patients with atrial fibrillation (AF) treated with oral anticoagulation with apixaban or warfarin; and to evaluate the relationship between the D-dimer levels at baseline and the treatment effect of apixaban vs. warfarin. MethodsIn the ARISTOTLE trial, 18201 patients with AF were randomized to apixaban or warfarin. D-dimer was analyzed in 14878 patients at randomization. The cohort was separated into two groups; not receiving vitaminK antagonist (VKA) treatment and receiving VKA treatment at randomization. ResultsHigher D-dimer levels were associated with increased frequencies of stroke or systemic embolism (hazard ratio [HR][Q4 vs. Q1]1.72, 95% confidence interval [CI]1.14-2.59, P=0.003), death (HR[Q4 vs. Q1]4.04, 95%CI3.06-5.33) and major bleeding (HR[Q4 vs. Q1]2.47, 95%CI1.77-3.45, P<0.0001) in the no-VKA group. Similar results were obtained in the on-VKA group. Adding D-dimer level to the CHADS(2) score improved the C-index from 0.646 to 0.655 for stroke or systemic embolism, and from 0.598 to 0.662 for death, in the no-VKA group. D-dimer level improved the HAS-BLED score for prediction of major bleeds, with an increase in the C-index from 0.610 to 0.641. There were no significant interactions between efficacy and safety of study treatment and D-dimer level. ConclusionIn anticoagulated patients with AF, the level of D-dimer is related to the risk of stroke, death, and bleeding, and adds to the predictive value of clinical risk scores. The benefits of apixaban were consistent, regardless of the baseline D-dimer level.
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  • Christersson, Christina, et al. (författare)
  • Early decrease in coagulation activity after myocardial infarction is associated with lower risk of new ischemic events : Observations from the ESTEEM trial
  • 2007
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 28:6, s. 692-698
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: Patients with a recent myocardial infarction have an increased risk of recurrent ischaemic events. In the ESTEEM trial, the oral direct thrombin inhibitor ximelagatran reduced the risk of new ischaemic events when compared with placebo in aspirin treated post myocardial infarction patients. Ximelagatran persistently reduced markers of coagulation activity, i.e. prothrombin fragment 1 + 2 (F1 + 2) and D-dimer levels. The aim of this substudy was to evaluate the levels of these markers and activated thromboplastin time (APTT) in relation to new ischaemic events or bleeding. METHODS AND RESULTS: In the substudy, 518 out of 1883 patients were included and within 14 days after a myocardial infarction randomized to ximelagatran or placebo for 6 months. The clinical endpoints death, myocardial infarction, severe recurrent ischaemia, ischaemic stroke, and bleeding were evaluated. The levels of F1 + 2, D-dimer, and APTT were analysed at randomization and in serial samples during the study. Ximelagatran treatment appeared to have a larger treatment effect in patients with F1 + 2 and D-dimer levels above the median at randomization with a reduction of ischaemic events from 18 to 9% (P = 0.03) for F1 + 2 and from 20 to 9% for D-dimer (P = 0.009). A reduction of D-dimer levels was found in 60% of the patients 1 week after randomization and these patients had less ischaemic events when compared with patients with unchanged or increased levels (P = 0.03) regardless of treatment. F1 + 2 and D-dimer levels were unrelated to bleeding risk. In the ximelagatran group, increased APTT was not related to ischaemic events but associated with a raised risk of bleeding. CONCLUSION: A reduction of initially high coagulation activity, as measured by the D-dimer level, in patients with recent myocardial infarction identifies patients with a decreased risk of new ischaemic events, regardless whether the reduction occurs spontaneously or is induced by pharmacological means. Patients with higher initial coagulation activity seemed to benefit most from long-term treatment with ximelagatran.
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  • Christersson, Christina, et al. (författare)
  • Effect of apixaban compared with warfarin on coagulation markers in atrial fibrillation.
  • 2019
  • Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 105:3, s. 235-242
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Compare the effect of apixaban and warfarin on coagulation and primary haemostasis biomarkers in atrial fibrillation (AF).METHODS: The biomarker substudy from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial included 4850 patients with AF randomised to treatment with apixaban or warfarin. Sixty per cent of patients used vitamin K antagonist (VKA) within 7 days before randomisation. Prothrombin fragment 1+2 (F1+2), D-dimer, soluble CD40 ligand (sCD40L) and von Willebrand factor (vWF) antigen were analysed at randomisation and after 2 months of study treatment.RESULTS: In patients not on VKA treatment at randomisation, F1+2 and D-dimer levels were decreased by 25% and 23%, respectively, with apixaban, and by 59% and 38%, respectively, with warfarin (p<0.0001 for treatment differences for both). In patients on VKA at randomisation, F1+2 and D-dimer levels increased by 41% and 10%, respectively, with apixaban and decreased by 37% and 11%, respectively, with warfarin (p<0.0001 for treatment differences for both). sCD40L levels were slightly increased at 2 months, regardless of VKA or randomised treatment. Apixaban and warfarin also both reduced vWF antigen regardless of VKA treatment. The efficacy (stroke) and safety (bleeding) of apixaban compared with warfarin was similar irrespectively of biomarker levels at 2 months.CONCLUSIONS: Treatment with apixaban compared with warfarin for stroke prevention in patients with AF was associated with less reduction in thrombin generation and fibrin turnover. This effect of apixaban could contribute to the clinical results where apixaban was superior to warfarin both in stroke prevention and in reducing bleeding risk.TRIAL REGISTRATION NUMBER: NCT00412984.
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  • Christersson, Christina, et al. (författare)
  • Evaluation of microparticles in whole blood by multicolour flow cytometry assay
  • 2013
  • Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 73:3, s. 229-239
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveTo develop and evaluate a multicolour flow cytometry method for analysis of microparticles (MPs) in fresh whole blood without any centrifugation steps or freezing/thawing procedure. Materials and methodsFlow cytometry was performed using a FC500 MPL cytometer. The compensation in the protocol was performed based on the platelet population. Polystyrene microspheres 0.50–1.27 μm were used for size position, and the MP gate was set as particles 0.5–1.0 μm. Whole blood was incubated with annexin V and antibodies to tissue factor (TF), platelets (CD41 and CD62P), monocyte (CD14) and endothelial cells (CD144). For comparison, MPs from platelet free supernatant was used. The TF activity was evaluated by Calibrated Automated Thrombogram. ResultsAnnexin V was used to distinguish true events from background noise. For standardization, each analysis included 10,000 events in the gate of platelets. There were 622(462–1001) MPannV+/10,000 platelets and of these, 66 (49–82)/10,000 platelets expressed TF. After correction for the individual platelet counts, the amount of circulating MPannV+ was 17.1 (12.1–24.9) × 109/L in whole blood, and of these, 10% (6–12%) expressed TF. The majority of the MPs expressed CD41, and 5.6% (2.2–6.9%) of these co-expressed TF. The amount of CD41 + MPannV+ tended to correlate to the TF activity in whole blood. There was no correlation between the MPannV+ in whole blood and MPs derived from platelet free supernatant. Patients with pulmonary arterial hypertension and stable coronary artery disease had increased concentrations of CD41 + MPannV+ in whole blood.ConclusionThis multicolour flow cytometry assay in whole blood mimics the in vivo situation by avoiding several procedure steps interfering with the MP count. By standardized quantification of MPs a reference interval of MPs can be created.
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  • Christersson, Christina, et al. (författare)
  • Haemorrhagic stroke and major bleeding after intervention with biological aortic valve prosthesis : risk factors and antithrombotic treatment
  • 2020
  • Ingår i: European Heart Journal, Supplement. - : OXFORD UNIV PRESS. - 1520-765X .- 1554-2815. ; 22:C, s. C26-C33
  • Tidskriftsartikel (refereegranskat)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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25.
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26.
  • Christersson, Christina, et al. (författare)
  • Long-term treatment with ximelagatran, an oral direct thrombin inhibitor, persistently reduces the coagulation activity after a myocardial infarction
  • 2005
  • Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 3:10, s. 2245-53
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: In the ESTEEM study, patients with a recent myocardial infarction were treated with aspirin and randomized to one of four doses (24-60 mg b.i.d) of the oral direct thrombin inhibitor ximelagatran or placebo for 6 months. Ximelagatran and aspirin reduced the risk of recurrent ischemic events compared with aspirin alone. In the present substudy we evaluated the different doses of ximelagatran on pharmacokinetics as measured by plasma concentration of the active compound melagatran and activated partial thromboplastin time (APTT) and pharmacodynamics as related by markers for coagulation activity, prothrombin fragment 1 + 2 (F1 + 2) and D-dimer. METHODS AND RESULTS: Plasma samples from 518 patients were collected before, during and after the treatment period. There was a linear dose-concentration relation at peak and trough and a linear relation between concentration and APTT (P < 0.001). F1 + 2 and D-dimer were decreased by 25% and 52% at 1 week (P < 0.001) in the ximelagatran groups compared with the placebo group and the reductions were maintained during the 6 months treatment. There were no differences detected in F1 + 2 or D-dimer levels between the different ximelagatran dosages. There was no correlation between the melagatran concentration and the change in F1 + 2 and D-dimer levels. After cessation of ximelagatran F1 + 2 and D-dimer levels returned to the initial levels. CONCLUSION: The dose of ximelagatran and APTT are linearly related to the plasma concentration of melagatran. Ximelagatran induces a sustained and stable reduction of thrombin generation and fibrin turnover without any relation to dose above 24 mg b.i.d. These properties indicate that long-term treatment with a low dose of ximelagatran may provide valuable depression of coagulation activity in aspirin treated post myocardial infarction patients.
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27.
  • Christersson, Christina, et al. (författare)
  • Microparticles during long-term follow-up after acute myocardial infarction : Association to atherosclerotic burden and risk of cardiovascular events
  • 2017
  • Ingår i: Thrombosis and Haemostasis. - : SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN. - 0340-6245 .- 2567-689X. ; 117:8, s. 1571-1581
  • Tidskriftsartikel (refereegranskat)abstract
    • Microparticles (MPs) are formed from platelets (PMPs), endothelial cells (EMPs) and monocytes (MMPs), and in acute myocardial infarction (MI), there is an increase of MPs in the culprit artery. In this study MPs were evaluated in whole blood in 105 patients with MI at five time-points during a two-year follow-up (FU). Patients with non-ST elevated MI had higher concentrations of CD41+MPs compared to ST elevated MI patients (p=0.024). The concentrations of PMPs in whole blood increased during the time period (p<0.001), but no significant change over time was found for EMPs and MMPs. CD62P+MP counts were higher in MI patients with diabetes (p=0.020), and patients with hypertension had increased levels of CD14+MPs (p=0.004). The amount of CD62P+TF+MPs increased significantly during FU (p<0.001). Patients with atherosclerosis in three arterial beds, i.e. coronary, carotid and peripheral arteries, had lower concentrations of CD62P+TF+MPs (p=0.035) and CD144+TF+MPs (p=0.004) compared to patients with atherosclerosis in one or two arterial beds. Higher concentrations of CD62P+MPs early after MI were associated with an increased risk of cardiovascular events during FU, hazard ratio 3.32 (95 %C11.20-9.31). Only small variations in PMP, EMP and MMP concentrations were found during long-term FU after MI and their levels seem to reflect the underlying cardiovascular disease rather than the acute MI. PMPs expressing P-selectin might be a promising biomarker for predicting future cardiovascular events, but further studies are needed to confirm these results.
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28.
  • Christersson, Christina (författare)
  • NOAK vid klaffsjukdom : bara i särskilda fall
  • 2018
  • Ingår i: Läkartidningen. - : Läkartidningen Förlag. - 0023-7205 .- 1652-7518. ; 115
  • Tidskriftsartikel (refereegranskat)abstract
    • NOAK ska inte användas vid måttlig–markerad mitralisstenos eller vid mekanisk klaffprotes.Vid förmaksflimmer och lindrig–måttlig aortaklaff­sjukdom eller degenerativ mitralisinsufficiens kan NOAK väljas som strokeprofylax.Vid förmaksflimmer och biologisk klaffprotes saknas tillräckligt stora studier. De aktuella riktlinjerna gör bedömningen att behandling med NOAK kan övervägas om det gått mer än 3 månader sedan öppen kirurgi med biologisk klaffprotes, med undantag för reumatisk mitralisstenos.NOAK är inte studerade som antitrombotisk behandling efter öppen kirurgi med biologisk klaffprotes, där annan indikation för antikoagulantia saknas. Motsvarande studier efter TAVI pågår.
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29.
  • Christersson, Christina, et al. (författare)
  • Oral anticoagulant treatment after bioprosthetic valvular intervention or valvuloplasty in patients with atrial fibrillation : A SWEDEHEART study
  • 2022
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:1
  • Tidskriftsartikel (refereegranskat)abstract
    • AimsTo describe the prevalence of atrial fibrillation (AF), use of oral anticoagulants (OAC) and change in antithrombotic treatment patterns during follow-up after valve intervention with a biological prosthesis or valvuloplasty.Methods and resultsAll patients with history of AF or new-onset AF discharged alive after valvular intervention (biological prosthesis or valvuloplasty) between 2010–2016 in Sweden were included (n = 7,362). Information about comorbidities was collected from national patient registers. Exposure to OAC was based on pharmacy dispensation data. In total 4,800 (65.2%) patients had a history of AF, and 2,562 (34.8%) patients developed new-onset AF, with 999 (39.0%) developing new-onset AF within 3 months after intervention. The proportion of patients with biological valve prosthesis was higher in patients with new-onset AF compared to history of AF (p<0.001). CHA2DS2-VASc score ≥2 was observed in 83.1% and 75.5% patients with history of AF and new-onset AF, respectively. Warfarin was more frequently dispensed than NOAC at discharge in patients with history of AF (43.9% vs 7.3%), and in patients with new-onset AF (36.6% vs 17.1%). Almost half of the AF population was not dispensed on any OAC at discharge (48.8% in patients with history of AF and 46.3% in patients with new-onset AF).ConclusionIn this real world study of patients with AF and recent valvular intervention, risk of new-onset AF after valvular intervention is high emphasizing need for frequent rhythm monitoring after intervention. A considerable undertreatment with OAC was observed despite being indicated for the majority of the patients. Warfarin was the OAC most frequently dispensed.
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30.
  • Christersson, Christina, 1966- (författare)
  • Regulation of Tissue Factor and Coagulation Activity : Translation Studies with Focus on Platelet-Monocyte Aggregates and Patients with Acute Coronary Syndrome
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Myocardial infarction (MI) is often caused by a disruption of an atherosclerotic plaque with activation of coagulation, platelets and inflammation. The aims were; to investigate whether the oral direct thrombin inhibitor, ximelagatran affected markers for coagulation, platelet and inflammation in a patient cohort with recent MI and if the coagulation markers could identify patients with increased risk of new ischemic events; to evaluate some of the mechanisms involved in formation of platelet-monocyte aggregates (PMAs). In a biomarker substudy patients with recent MI were randomized to 24-60 mg of ximelagatran or placebo for six months. There was a persistent dose-independent reduction of coagulation markers (F1+2, D-dimer) by ximelagatran treatment. 60 % reduced their D-dimer levels after one week and that group had less ischemic events during treatment. There was an early increase of the platelet activation marker and ximelagatran in higher doses attenuated these increased levels. Both in vivo and in vitro the direct thrombin inhibitor diminished procoagulant activity and tissue factor (TF) presenting microparticles. In contrast, the inflammatory markers increased after six months of ximelagatran treatment. The PMA-levels were elevated for long-term after MI. In vitro thrombin inhibition diminished formation of PMAs. Formation of PMAs in stimulated whole blood was P-selectin dependent and induced TF expression through phosphorylation of the Src-family member Lyn in monocytes. Addition of an oral direct thrombin inhibitor reduces coagulation and platelet activation markers for long-term after a MI together with reduced procoagulant activity which may contribute to the clinical benefit of the drug. Early reduction of D-dimer levels seems to be suitable to identify patients with reduced risk of new ischemic events independent of antithrombotic treatment. Circulating PMAs persist after a MI connecting coagulation to inflammation. Within these aggregates P-selectin induces TF, the main initiator of coagulation, partly through phosphorylation of Lyn.
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31.
  • Christersson, Christina, et al. (författare)
  • Screening for Biomarkers Associated with Left Ventricular Function During Follow-up After Acute Coronary Syndrome
  • 2023
  • Ingår i: Journal of Cardiovascular Translational Research. - : Springer Nature. - 1937-5387 .- 1937-5395. ; 16:1, s. 244-254
  • Tidskriftsartikel (refereegranskat)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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32.
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33.
  • Christersson, Christina, et al. (författare)
  • The composition and daily variation of microparticles in whole blood in stable coronary artery disease
  • 2016
  • Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 76:1
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: The knowledge of circadian variation of microparticles (MPs) in stable coronary artery disease (SCAD) is limited. The aim of this study was to evaluate the daily variation of platelet-, endothelial- and monocyte-derived MPs in whole blood and their tissue factor expression (TF) in SCAD and whether these MPs were related to other endothelial and coagulation markers.MATERIALS AND METHODS: Serial blood samples from patients with SCAD were collected during one day. Flow cytometry was used to evaluate the amount of large MPs 0.5-1.0 μm, positive for annexin, and their expression of CD41, CD62P, CD144, CD14 and TF. The lag time and endogenous thrombin potential (ETP) was calculated by Calibrated Automated Thrombogram and soluble (s)P-selectin, sTF and vWF by ELISA.RESULTS: The majority of MPs in whole blood consisted of CD41 + MPs with no significant daily variation. In contrast, the concentration of CD62P + MPs described a daily variation with the lowest concentrations found in the evening (p = 0.031). CD62P + and CD144 + MPs had the highest expression of TF, 52.6% and 42.9%, respectively, and correlated to the endothelial activity evaluated by vWF. There was a circadian rhythm of lag time (p < 0.001) and ETP (p = 0.001). The CD62P+, CD14 + and CD144 + MPs correlated to the lag time.CONCLUSION: The different subsets of platelet-, endothelial- and monocyte-derived MPs do not present the same circadian variation and they differ in TF expression in SCAD. The MPs from activated platelets, endothelial cells and monocytes exist in low concentrations in whole blood but are related to the endothelial and coagulation activity found in SCAD.
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34.
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35.
  • Christersson, Christina, et al. (författare)
  • The Influence of Direct Thrombin Inhibitors on the Formation of Platelet-leukocyte Aggregates and Tissue Factor Expression
  • 2010
  • Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 126:4, s. E327-E333
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: High concentrations of platelet-monocyte aggregates (PMAs) have been found in patients with myocardial infarction (MI). Oral direct thrombin inhibitors (DTIs) are under evaluation as long-term antithrombotic treatment. The aim was to evaluate whether DTIs affect the formation of platelet-leukocyte aggregates, TF expression and procoagulant microparticles (MPs). Material and Methods: DTIs were added to an experimental whole blood model before platelet activation with thrombin or ADP. The concentrations of PMAs, platelet-granulocyte aggregates (PGAs), the amount of platelets bound per leukocyte and MPs were investigated by flow cytometry. TF mRNA and activity were recorded in all settings. TF activity was evaluated in a MI population treated with or without an oral DTI. Results: In vitro, thrombin and ADP increased the formation of PMAs and PGAs as well as TF mRNA expression. DTIs reduced the amount platelets bound to monocytes (p = 0.02) and to granulocytes (p = 0.001) upon thrombin stimulation together with a reduction of TF mRNA. In contrast, the ADP-induced formation of PMAs, PGAs and TF mRNA was not affected by the DTIs. Both thrombin and ADP stimulation increased the amount of TF-expressing MPs, which was effectively inhibited by the DTIs (p = 0.02-0.002). In the MI population, the DTI reduced the TF activity (p<0.001). Conclusion: DTIs modulate the formation of PMAs, PGAs and the TF production therein. Together with a reduction of procoagulant MPs, these results may contribute to the clinical benefit found of oral DTIs. Targeting different mechanisms in platelet and coagulation activation may be of importance due to the lack of effect of DTIs on ADP-induced platelet-leukocyte aggregates and TF production.
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36.
  • Christersson, Christina, et al. (författare)
  • The utility of coagulation activity for prediction of risk of mortality and cardiovascular events in guideline-treated myocardial infarction patients
  • 2017
  • Ingår i: Upsala Journal of Medical Sciences. - : Taylor & Francis. - 0300-9734 .- 2000-1967. ; 122:4, s. 224-233
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Despite improved treatment of myocardial infarction (MI), real-world patients still suffer substantial risk for subsequent cardiovascular events. Little is known about coagulation activity shortly after MI and whether coagulation activity markers may identify patients at increased risk despite contemporary treatment.OBJECTIVE: To evaluate D-dimer concentration and thrombin generation potential shortly after discharge after MI and evaluate if these markers could predict the risk of future cardiovascular and bleeding events.METHODS: Unselected MI patients (n = 421) were included in the observational REBUS study (NCT01102933) and followed for two years. D-dimer concentrations, thrombin peak, and endogenous thrombin potential (ETP) were analyzed at inclusion (3-5 days after MI) and at early follow-up (after 2-3 weeks).RESULTS: Seventy-five patients (17.8%) experienced the composite endpoint (all-cause death, MI, congestive heart failure, or all-cause stroke), and 31 patients (7.4%) experienced a clinically relevant bleeding event. D-dimer concentrations at early follow-up were associated with the composite endpoint (HR [per SD increase] 1.51 [95% CI 1.22-1.87]) and with clinically relevant bleeding (HR [per SD increase] 1.80 [95% CI 1.32-2.44]). Thrombin generation potential was not significantly associated with either the composite endpoint or with clinically relevant bleeding. Higher thrombin peak and ETP at early follow-up were both inversely associated with stroke (HR [per SD increase] 0.50 [95% CI 0.30-0.81] and 0.43 [95% CI 0.22-0.83], respectively).CONCLUSION: In unselected MI patients treated according to contemporary guidelines, D-dimer measurements may identify patients at increased risk of new cardiovascular and bleeding events. The inverse association of thrombin generation potential and risk of stroke has to be further investigated.
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37.
  • Christersson, Christina, et al. (författare)
  • Tissue factor and IL8 production by P-selectin-dependent platelet-monocyte aggregates in whole blood involves phosphorylation of Lyn and is inhibited by IL10
  • 2008
  • Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 6:6, s. 986-994
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: P-selectin and CD40L expressed by activated platelets induce tissue factor (TF) and inflammatory cytokines in monocytes, but little is known of the cellular signaling pathways involved. The anti-inflammatory cytokine IL10 reduces atherosclerotic plaque formation. OBJECTIVES: To evaluate the importance of P-selectin upon platelet-monocyte aggregate (PMA) formation in thrombin receptor activator peptide (TRAP) stimulated whole blood, the P-selectin-P-selectin glycoprotein ligand (PSGL)-1-induced cellular signaling pathway, and the effects of IL10 on these functions. METHODS: TF, IL8, and monocyte chemotactic protein-1 (MCP-1) production, PMAs and phosphorylation of Lyn were analyzed in whole blood, purified monocytes, and vitamin D(3)-differentiated U-937 cells stimulated with TRAP or P-selectin with or without IL10. Anti-P-selectin or anti-CD40L antibodies (Abs), Src-kinases inhibitors, SU6656 or PP2, were added in some experiments. RESULTS: TRAP and P-selectin increased TF, IL8, and MCP-1 mRNA in whole blood and purified monocytes. Anti-P-selectin Ab reduced TRAP-induced PMA formation by 80 +/- 2% (P = 0.001) and production of TF (P = 0.04) and IL8 (P = 0.01). IL10 and SU6656 had no effect on PMA formation, although both significantly reduced TF (P = 0.002 and P = 0.02) and IL8 (P = 0.009 and P = 0.001) mRNA upon TRAP and P-selectin stimulation. Induced Lyn phosphorylation in monocytes was diminished by SU6656 (P = 0.02), anti-P-selectin Ab (P = 0.02), and IL10 (P = 0.03) upon TRAP or P-selectin stimulation. These results were confirmed in the vitamin D(3)-differentiated U-937 cells. CONCLUSIONS: The formation of PMAs in whole blood was P-selectin-dependent in the long term. P-selectin-PSGL-1-induced TF and IL8 expression through Lyn phosphorylation, and part of the inhibitory effect of IL10 depends on reduced phosphorylation.
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38.
  • Christersson, Christina, et al. (författare)
  • Treatment with an Oral Direct Thrombin Inhibitor Decreases Platelet Activity but Increases Markers of Inflammation in Patients with Myocardial Infarction.
  • 2011
  • Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 270:3, s. 215-223
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Thrombin has a role not only in the coagulation process but also in inflammatory responses. Oral direct thrombin inhibitors (DTIs) are currently being evaluated in patients with thromboembolic diseases. Objectives:  To investigate whether an oral DTI affects markers for platelet and inflammatory activity after myocardial infarction (MI). Methods:  A total of 518 patients with MI were randomly assigned to ximelagatran treatment (four different dose groups) in combination with aspirin, or aspirin alone for 6 months. The levels of soluble (s) P-selectin, soluble tissue factor, C-reactive protein (CRP), interleukin (IL)-10 and IL-18 were analysed in serial blood samples.Results: sP-selectin concentration increased after 1 week and persisted at an elevated level for 6 months in all study groups (p<0.001). In the two highest ximelagatran dose groups, there was a reduced increase in sP-selectin compared to treatment with lower doses of ximelagatran and aspirin alone (p=0.01 and p=0.002, respectively). IL-18 levels did not change in the aspirin alone treatment group. By contrast, there was an elevation in IL-18 level in the lower and higher ximelagatran dose groups after 6 months (p=0.006 and p<0.001, respectively). Ximelagatran increased IL-10 levels (p=0.002) and reduced the decrease in CRP levels after 6 months compared to treatment with aspirin alone (p=0.002).Conclusion: A persistent elevation of platelet activity is found in patients with a recent MI after the cessation of acute antithrombotic treatment, and the addition of an oral DTI at higher doses decreases the activity. By contrast, long-term treatment with a DTI increases the levels of several markers of inflammation. Further studies with prolonged exposure of oral DTIs are needed for evaluation of the effect on inflammatory processes and to determine whether these agents influence clinical outcomes.
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39.
  • Daelman, Bo, et al. (författare)
  • Frailty and cognitive function in middle-aged and older adults with congenital heart disease
  • 2024
  • Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 83:12, s. 1149-1159
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Life expectancy of patients with congenital heart disease (CHD) has increased rapidly, resulting in a growing and aging population. Recent studies have shown that older people with CHD have higher morbidity, health care use, and mortality. To maintain longevity and quality of life, understanding their evolving medical and psychosocial challenges is essential.Objectives: The authors describe the frailty and cognitive profile of middle-aged and older adults with CHD to identify predictor variables and to explore the relationship with hospital admissions and outpatient visits.Methods: Using a cross-sectional, multicentric design, we included 814 patients aged ≥40 years from 11 countries. Frailty phenotype was determined using the Fried method. Cognitive function was assessed by the Montreal Cognitive Assessment.Results: In this sample, 52.3% of patients were assessed as robust, 41.9% as prefrail, and 5.8% as frail; 38.8% had cognitive dysfunction. Multinomial regression showed that frailty was associated with older age, female sex, higher physiologic class, and comorbidities. Counterintuitively, patients with mild heart defects were more likely than those with complex lesions to be prefrail. Patients from middle-income countries displayed more prefrailty than those from higher-income countries. Logistic regression demonstrated that cognitive dysfunction was related to older age, comorbidities, and lower country-level income.Conclusions: Approximately one-half of included patients were (pre-)frail, and more than one-third experienced cognitive impairment. Frailty and cognitive dysfunction were identified in patients with mild CHD, indicating that these concerns extend beyond severe CHD. Assessing frailty and cognition routinely could offer valuable insights into this aging population.
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40.
  • Dimberg, Axel, et al. (författare)
  • Higher Preoperative Plasma Thrombin Potential in Patients Undergoing Surgery for Aortic Stenosis Compared to Surgery for Stable Coronary Artery Disease
  • 2018
  • Ingår i: Clinical and applied thrombosis/hemostasis. - : SAGE PUBLICATIONS INC. - 1076-0296 .- 1938-2723. ; 24:8, s. 1282-1290
  • Tidskriftsartikel (refereegranskat)abstract
    • Aortic stenosis (AS) and coronary artery disease (CAD) influence the coagulation system, potentially affecting hemostasis during cardiac surgery. Our aim was to evaluate 2 preoperative global hemostasis assays, plasma thrombin potential and thromboelastometry, in patients with severe aortic valve stenosis compared to patients with CAD. A secondary aim was to test whether the assays were associated with postoperative bleeding. Calibrated automated thrombogram (CAT) in platelet-poor plasma and rotational thromboelastometry (ROTEM) in whole blood were analyzed in patients scheduled for elective surgery due to severe AS (n = 103) and stable CAD (n = 68). Patients with AS displayed higher plasma thrombin potential, both thrombin peak with median 252 nmol/L (interquartile range 187-319) and endogenous thrombin potential (ETP) with median 1552 nmol/L/min (interquartile range 1340-1838), when compared to patients with CAD where thrombin peak was median 174 nmol/L (interquartile range 147-229) and ETP median 1247 nmol/L/min (interquartile range 1034-1448; both P < .001). Differences persisted after adjustment for age, gender, comorbidity, and antithrombotic treatment. Differences observed in thromboelastometry between the groups did not persist after adjustment for baseline characteristics. Bleeding amount showed no relationship with plasma thrombin potential but weakly to thromboelastometry (R-2 = .064, P = .001). Patients with AS exhibited preoperatively increased plasma thrombin potential compared to patients with CAD. Plasma thrombin potential was not predictive for postoperative bleeding in patients scheduled for elective surgery.
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41.
  • Diogo Löfgren, Christina, et al. (författare)
  • A systematic review of methods to diagnose oral dryness and salivary gland function
  • 2012
  • Ingår i: BMC Oral Health. - : BioMed Central. - 1472-6831. ; 12:29
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The most advocated clinical method for diagnosing salivary dysfunction is to quantitate unstimulated and stimulated whole saliva (sialometry). Since there is an expected and wide variation in salivary flow rates among individuals, the assessment of dysfunction can be difficult. The aim of this systematic review is to evaluate the quality of the evidence for the efficacy of diagnostic methods used to identify oral dryness. Methods A literature search, with specific indexing terms and a hand search, was conducted for publications that described a method to diagnose oral dryness. The electronic databases of PubMed, Cochrane Library, and Web of Science were used as data sources. Four reviewers selected publications on the basis of predetermined inclusion and exclusion criteria. Data were extracted from the selected publications using a protocol. Original studies were interpreted with the aid of Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Results The database searches resulted in 224 titles and abstracts. Of these abstracts, 80 publications were judged to meet the inclusion criteria and read in full. A total of 18 original studies were judged relevant and interpreted for this review. In all studies, the results of the test method were compared to those of a reference method. Based on the interpretation (with the aid of the QUADAS tool) it can be reported that the patient selection criteria were not clearly described and the test or reference methods were not described in sufficient detail for it to be reproduced. None of the included studies reported information on uninterpretable/intermediate results nor data on observer or instrument variation. Seven of the studies presented their results as a percentage of correct diagnoses. Conclusions The evidence for the efficacy of clinical methods to assess oral dryness is sparse and it can be stated that improved standards for the reporting of diagnostic accuracy are needed in order to assure the methodological quality of studies. There is need for effective diagnostic criteria and functional tests in order to detect those individuals with oral dryness who may require oral treatment, such as alleviation of discomfort and/or prevention of diseases.
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42.
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43.
  • Diogo Löfgren, Christina, et al. (författare)
  • Screening for Oral Dryness in Relation to Salivary Flow Rate Addresses the Need for Functional Tests of Saliva
  • 2010
  • Ingår i: Oral health & preventive dentistry. - : Quintessence. - 1757-9996 .- 1602-1622. ; 8:3, s. 243-252
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: The aim of the present study was to assess the occurrence of reported subjective oral dryness in relation to objective sialometric values in a randomly selected group and a dental care-seeking group. Materials and Methods: A questionnaire assessing subjective oral dryness was sent out to a randomly selected sample of 200 individuals. The dental care-seeking group was recruited from among patients attending the Department of Oral Diagnostics, Malmo University. A total of 200 patients were asked to participate in the present study. In total, 312 individuals (78%) completed the survey and 157 individuals agreed to participate in the complementary clinical examination that included measures of salivary flow rate. Results: The reported subjective oral dryness was 20% and 28.6% for the randomly selected group and the dental care-seeking group, respectively. No statistically significant differences were found between the two study populations with regard to percentage of reported subjective oral dryness, and stimulated and unstimulated salivary flow rates (P > 0.05). In the dental care-seeking group, individuals reporting subjective oral dryness presented 'a small degree of abrasion in the dentine in the incisor region' to a greater extent (P < 0.05). No statistically significant association between subjective oral dryness and unstimulated and stimulated salivary flow rates was found in either of the studied populations (P > 0.05). Individuals identified with subjective or objective oral dryness presented to a greater extent a history of oral rehabilitation compared to individuals who showed no indication of oral dryness. Conclusions: No association between sialometric measures and subjective report of oral dryness was found in the present study.
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44.
  • Diogo Löfgren, Christina, et al. (författare)
  • The Challenge of Measuring Viscoelastic Properties of Human Whole Saliva to Fit Clinical Purpose
  • 2015
  • Ingår i: International Journal of Oral and Dental Health. - : ClinMed International. - 2469-5734. ; 1:4
  • Tidskriftsartikel (refereegranskat)abstract
    • To understand the protective functions of saliva secreted from different glands in the masticatory process, it is of interest to study its viscoelastic properties. Characterization of saliva samples are not that easily performed in a clinical setting, since most of the experimental techniques and instruments available are developed for research purposes. The aim of this study was to characterize how the viscoelastic properties of saliva can be measured and monitored using two laboratory instruments. Unstimulated whole saliva from 11 healthy volunteers was characterized using two instruments, an ARES-G2 rheometer and a Bohlin Oscillating Cup Rheometer. Measurements performed on unstimulated human whole saliva showed that the ARES rheometer will in linear viscoelastic conditions of the sample give absolute viscoelastic numbers of undisturbed saliva whilst the BOCR can be used to give an indication of gel strength, gel formation, and gel stability in viscoelastic samples being sheared in their non-linear viscoelastic region by introducing a Saliva Gel Strength Index, SGSI. Both methods clearly illustrate the presence of viscoelastic properties in saliva.
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45.
  • Doehner, Wolfram, et al. (författare)
  • Interaction of heart failure and stroke : A clinical consensus statement of the ESC Council on Stroke, the Heart Failure Association (HFA) and the ESC Working Group on Thrombosis
  • 2023
  • Ingår i: European Journal of Heart Failure. - : John Wiley & Sons. - 1388-9842 .- 1879-0844. ; 25:12, s. 2107-2129
  • Tidskriftsartikel (refereegranskat)abstract
    • Heart failure (HF) is a major disease in our society that often presents with multiple comorbidities with mutual interaction and aggravation. The comorbidity of HF and stroke is a high risk condition that requires particular attention to ensure early detection of complications, efficient diagnostic workup, close monitoring, and consequent treatment of the patient. The bi-directional interaction between the heart and the brain is inherent in the pathophysiology of HF where HF may be causal for acute cerebral injury, and - in turn - acute cerebral injury may induce or aggravate HF via imbalanced neural and neurovegetative control of cardiovascular regulation. The present document represents the consensus view of the ESC Council on Stroke, the Heart Failure Association and the ESC Working Group on Thrombosis to summarize current insights on pathophysiological interactions of the heart and the brain in the comorbidity of HF and stroke. Principal aspects of diagnostic workup, pathophysiological mechanisms, complications, clinical management in acute conditions and in long-term care of patients with the comorbidity are presented and state-of-the-art clinical management and current evidence from clinical trials is discussed. Beside the physicians perspective, also the patients values and preferences are taken into account. Interdisciplinary cooperation of cardiologists, stroke specialists, other specialists and primary care physicians is pivotal to ensure optimal treatment in acute events and in continued long-term treatment of these patients. Key consensus statements are presented in a concise overview on mechanistic insights, diagnostic workup, prevention and treatment to inform clinical acute and continued care of patients with the comorbidity of HF and stroke.
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46.
  • Edvinsson, B., et al. (författare)
  • Does persistent (patent) foramen ovale closure reduce the risk of recurrent decompression sickness in scuba divers?
  • 2021
  • Ingår i: Diving and hyperbaric medicine. - : Diving and Hyperbaric Medicine Journal. - 1833-3516 .- 2209-1491. ; 51:1, s. 63-67
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Interatrial communication is associated with an increased risk of decompression sickness (DCS) in scuba diving. It has been proposed that there would be a decreased risk of DCS after closure of the interatrial communication, i.e., persistent (patent) foramen ovale (PFO). However, the clinical evidence supporting this is limited. Methods: Medical records were reviewed to identify Swedish scuba divers with a history of DCS and catheter closure of an interatrial communication. Thereafter, phone interviews were conducted with questions regarding diving and DCS. All Swedish divers who had had catheter-based PFO-closure because of DCS were followed up, assessing post-closure diving habits and recurrent DCS. Results: Nine divers, all with a PFO, were included. Eight were diving post-closure. These divers had performed 6,835 dives (median 410, range 140-2,200) before closure, and 4,708 dives (median 413, range 11-2,000) after closure. Seven cases with mild and 10 with serious DCS symptoms were reported before the PFO closure. One diver with a small residual shunt suffered serious DCS post-closure; however, that dive was performed with a provocative diving profile. Conclusion: Divers with PFO and DCS continue to dive after PFO closure and this seems to be fairly safe. Our study suggests a conservative diving profile when there is a residual shunt after PFO closure, to prevent recurrent DCS events.
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47.
  • Eriksson, Peter J, 1959, et al. (författare)
  • Transcatheter Intervention for Coarctation of the Aorta A Nordic Population-Based Registry With Long-Term Follow-Up
  • 2023
  • Ingår i: Jacc-Cardiovascular Interventions. - : Elsevier BV. - 1936-8798 .- 1876-7605. ; 16:4, s. 444-453
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND Coarctation of the aorta (CoA), a congenital narrowing of the proximal descending thoracic aorta, is a relatively common form of congenital heart disease. Untreated significant CoA has a major impact on morbidity and mortality. In the past 3 decades, transcatheter intervention (TCI) for CoA has evolved as an alternative to surgery.OBJECTIVES The authors report on all TCIs for CoA performed from 2000 to 2016 in 4 countries covering 25 million inhabitants, with a mean follow-up duration of 6.9 years.METHODS During the study period, 683 interventions were performed on 542 patients.RESULTS The procedural success rate was 88%, with 9% considered partly successful. Complications at the intervention site occurred in 3.5% of interventions and at the access site in 3.5%. There was no in-hospital mortality. During follow-up, TCI for CoA reduced the presence of hypertension significantly from 73% to 34%, but despite this, many patients remained hypertensive and in need of continuous antihypertensive treatment. Moreover, 8% to 9% of patients needed aortic and/or aortic valve surgery during follow-up.CONCLUSIONS TCI for CoA can be performed with a low risk for complications. Lifetime follow-up after TCI for CoA seems warranted. (J Am Coll Cardiol Intv 2023;16:444-453) & COPY; 2023 by the American College of Cardiology Foundation.
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48.
  • Erlinge, David, et al. (författare)
  • Identification of vulnerable plaques and patients by intracoronary near-infrared spectroscopy and ultrasound (PROSPECT II) : a prospective natural history study
  • 2021
  • Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 397:10278, s. 985-995
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Near-infrared spectroscopy (NIRS) and intravascular ultrasound are promising imaging modalities to identify non-obstructive plaques likely to cause coronary-related events. We aimed to assess whether combined NIRS and intravascular ultrasound can identify high-risk plaques and patients that are at risk for future major adverse cardiac events (MACEs).Methods: PROSPECT II is an investigator-sponsored, multicentre, prospective natural history study done at 14 university hospitals and two community hospitals in Denmark, Norway, and Sweden. We recruited patients of any age with recent (within past 4 weeks) myocardial infarction. After treatment of all flow-limiting coronary lesions, three-vessel imaging was done with a combined NIRS and intravascular ultrasound catheter. Untreated lesions (also known as non-culprit lesions) were identified by intravascular ultrasound and their lipid content was assessed by NIRS. The primary outcome was the covariate-adjusted rate of MACEs (the composite of cardiac death, myocardial infarction, unstable angina, or progressive angina) arising from untreated non-culprit lesions during follow-up. The relations between plaques with high lipid content, large plaque burden, and small lumen areas and patient-level and lesion-level events were determined. This trial is registered with ClinicalTrials.gov, NCT02171065.Findings: Between June 10, 2014, and Dec 20, 2017, 3629 non-culprit lesions were characterised in 898 patients (153 [17%] women, 745 [83%] men; median age 63 [IQR 55-70] years). Median follow-up was 3.7 (IQR 3.0-4.4) years. Adverse events within 4 years occurred in 112 (13.2%, 95% CI 11.0-15.6) of 898 patients, with 66 (8.0%, 95% CI 6.2-10.0) arising from 78 untreated non-culprit lesions (mean baseline angiographic diameter stenosis 46.9% [SD 15.9]). Highly lipidic lesions (851 [24%] of 3500 lesions, present in 520 [59%] of 884 patients) were an independent predictor of patient-level non-culprit lesion-related MACEs (adjusted odds ratio 2.27, 95% CI 1.25-4.13) and nonculprit lesion-specific MACEs (7.83, 4.12-14.89). Large plaque burden (787 [22%] of 3629 lesions, present in 530 [59%] of 898 patients) was also an independent predictor of non-culprit lesion-related MACEs. Lesions with both large plaque burden by intravascular ultrasound and large lipid-rich cores by NIRS had a 4-year non-culprit lesion-related MACE rate of 7.0% (95% CI 4.0-10.0). Patients in whom one or more such lesions were identified had a 4-year non-culprit lesion-related MACE rate of 13.2% (95% CI 9.4-17.6).Interpretation: Combined NIRS and intravascular ultrasound detects angiographically non-obstructive lesions with a high lipid content and large plaque burden that are at increased risk for future adverse cardiac outcomes.
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49.
  • Fritz Hansson, Astrid, et al. (författare)
  • Clinical Outcomes in Patients With Atrial Fibrillation Treated With Non-Vitamin K Oral Anticoagulants Across Varying Body Mass Index
  • 2023
  • Ingår i: Journal of the American Heart Association. - : American Heart Association. - 2047-9980. ; 12:22
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There are conflicting data on outcomes in patients with atrial fibrillation treated with non-vitamin K oral anticoagulants across varying body mass index (BMI). We investigated cardiovascular and bleeding risk in patients with atrial fibrillation with varying BMI.Methods and Results: Observational cohort study from the Swedish oral anticoagulation registry between August 2, 2011, and December 31, 2018. Primary outcomes were mortality, ischemic stroke/systemic embolism, and major bleeding. Baseline BMI (kg/m(2)) was analyzed continuously and categorized: underweight (<18.5 kg/m(2)), normal weight (18.5 to <25 kg/m(2)), preobesity (25 to <30 kg/m(2)), and obesity class I to III (30 to <35, 35 to <40, and >= 40 kg/m(2)). Adjusted Cox models and nonlinear relationships of BMI were modeled using restricted cubic splines. Non-vitamin K oral anticoagulant-treated patients with atrial fibrillation were included (n=26 047). At baseline, 602 (2.3%) were underweight, 9101 (34.9%) were normal weight, 9970 (38.3%) were preobese, 4280 (16.4%) were obese class I, 1486 (5.7%) were obese class II, and 608 (2.3%) were obese class III. Underweight and obesity class III were in adjusted continuous analysis associated with increased mortality and major bleeding, with lowest risk observed among preobese patients with BMI 28.2 and 26.2 kg/m(2), respectively. In adjusted categorical analysis, underweight was associated with increased mortality (hazard ratio [HR], 1.77 [95% CI, 1.57-1.99]) and nonsignificant higher risk of major bleeding (HR, 1.23 [95% CI, 0.95-1.58]). Similarly, obesity class III was associated with increased mortality (HR, 1.67 [95% CI, 1.40-1.99]) and major bleeding (HR, 1.68 [95% CI, 1.29-2.17]). No significant association was observed between higher BMI and ischemic stroke/systemic embolism.Conclusions: In non-vitamin K oral anticoagulant-treated patients with atrial fibrillation, there appears to be a U-shaped relationship between BMI and mortality and major bleeding.
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50.
  • Fritz Hansson, Astrid, et al. (författare)
  • Major bleeding in patients with atrial fibrillation treated with apixaban versus warfarin in combination with amiodarone : nationwide cohort study
  • 2024
  • Ingår i: Open heart. - : BMJ Publishing Group Ltd. - 2053-3624. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Amiodarone is an established treatment for atrial fibrillation (AF) but might interfere with the metabolism of apixaban or warfarin. Therefore, the aim was to investigate the occurrence of major bleeding among patients with AF treated with amiodarone in combination with apixaban or warfarin.Methods Retrospective observational study using Swedish health registers. All patients with AF in the National Patient Register and the National Dispensed Drug Register with concomitant use of amiodarone and warfarin or apixaban between 1 June 2013 and 31 December 2018 were included. Propensity score matching was performed, and matched cohorts were compared using Cox proportional HRs. The primary outcome was major bleeding resulting in hospitalisation based on International Classification of Diseases (ICD)-10 codes. Secondary outcomes included intracranial bleeding, gastrointestinal bleeding and other bleeding. Exploratory outcomes included ischaemic stroke/systemic embolism and all-cause/cardiovascular (CV) mortality.Results A total of 12 103 patients met the inclusion criteria and 8686 patients were included after propensity score matching. Rates of major bleeding were similar in the apixaban (4.3/100 patient-years) and warfarin cohort (4.5/100 patient-years) (HR: 1.03; 95% CI: 0.76 to 1.39) during median follow-up of 4.4 months. Similar findings were observed for secondary outcomes including gastrointestinal bleeding and other bleeding, and exploratory outcomes including ischaemic stroke/systemic embolism and all-cause/CV mortality.Conclusions Among patients treated with amiodarone in combination with apixaban or warfarin, major bleeding and thromboembolic events were rare and with no significant difference between the treatment groups.
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