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  • 201.
    Cowper, Patricia A.
    et al.
    Duke University, NC USA.
    Pan, Wenqin
    Duke University, NC USA.
    Anstrom, Kevin J.
    Duke University, NC USA.
    Kaul, Padma
    University of Alberta, Canada.
    Wallentin, Lars
    Uppsala University, Sweden.
    Davidson-Ray, Linda
    Duke University, NC USA.
    Lundborg, Elisabet
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Janzon, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Levin, Lars-Åke
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Cannon, Christopher P.
    Brigham and Womens Hospital, MA 02115 USA.
    Harrington, Robert A.
    Stanford University, CA 94305 USA.
    Mark, Daniel B.
    Duke University, NC USA.
    Economic Analysis of Ticagrelor Therapy From a US Perspective2015In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 65, no 5, p. 465-476Article in journal (Refereed)
    Abstract [en]

    BACKGROUND Based on results of the PLATO (Platelet Inhibition and Patient Outcomes) trial comparing ticagrelor with clopidogrel therapy, the U.S. Food and Drug Administration approved ticagrelor in 2011 for reducing thrombotic cardiovascular events in patients with acute coronary syndrome (ACS) with the proviso that it be taken with low-dose aspirin. OBJECTIVES This study sought to assess the cost and cost effectiveness of ticagrelor therapy relative to clopidogrel in treating ACS patients from the perspective of the U.S. health care system. METHODS We estimated within-trial resource use and costs using U.S. low-dose aspirin patients in PLATO (n = 547). Quality-adjusted life expectancy was estimated using the total PLATO population (n = 18,624), combined with baseline risk and long-term survival data from an external ACS patient cohort. Study drugs were valued at current costs. Cost effectiveness was assessed, as was the sensitivity of results to sampling and methodological uncertainties. RESULTS One year of ticagrelor therapy, relative to that of generic clopidogrel, cost $29,665/quality-adjusted life-year gained, with 99% of bootstrap estimates falling under a $100,000 willingness-to-pay threshold. Results were robust to extensive sensitivity analyses, including variations in clopidogrel cost, exclusion of costs in extended years of life, and a recalibrated estimate of survival reflecting a lower underlying mortality risk in the United States. CONCLUSIONS For PLATO-eligible ACS patients, a U.S. perspective comparison of the current standard of dual antiplatelet therapy of aspirin with clopidogrel versus aspirin plus ticagrelor showed that the ticagrelor regimen increased life expectancy at an incremental cost well within accepted benchmarks of good value for money. (C) 2015 by the American College of Cardiology Foundation.

  • 202.
    Crespo-Leiro, Maria G.
    et al.
    Complexo Hospital University of A Coruna, Spain.
    Anker, Stefan D.
    University of Medical Centre Gottingen UMG, Germany.
    Maggioni, Aldo P.
    European Soc Cardiol, France; ANMCO Research Centre, Italy.
    Coats, Andrew J.
    Monash University, Australia.
    Filippatos, Gerasimos
    Athens University Hospital Attikon, Greece.
    Ruschitzka, Frank
    University of Heart Centre Zurich, Switzerland.
    Ferrari, Roberto
    University Hospital Ferrara, Italy; Maria Cecilia Hospital, Italy.
    Francesco Piepoli, Massimo
    AUSL Piacenza, Italy.
    Delgado Jimenez, Juan F.
    University Hospital 12 Octubre, Spain.
    Metra, Marco
    University of Brescia, Italy.
    Fonseca, Candida
    University of Nova Lisboa, Portugal.
    Hradec, Jaromir
    Charles University of Prague, Czech Republic.
    Amir, Offer
    Bar Ilan University, Israel.
    Logeart, Damien
    University of Paris Diderot, France.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Merkely, Bela
    Semmelweis University, Hungary.
    Drozdz, Jaroslaw
    Medical University of Lodz, Poland.
    Goncalvesova, Eva
    National Cardiovasc Institute, Slovakia.
    Hassanein, Mahmoud
    University of Alexandria, Egypt.
    Chioncel, Ovidiu
    University of Medicina Carol Davila, Romania.
    Lainscak, Mitja
    Gen Hospital Celje, Slovenia.
    Seferovic, Petar M.
    University of Belgrade, Serbia.
    Tousoulis, Dimitris
    University of Athens, Greece.
    Kavoliuniene, Ausra
    Lithuanian University of Health Science, Lithuania.
    Fruhwald, Friedrich
    Medical University, Austria.
    Fazlibegovic, Emir
    Clin Hospital Mostar, Bosnia and Herceg.
    Temizhan, Ahmet
    Turkey Yuksek Ihtisas Hospital, Turkey.
    Gatzov, Plamen
    University Hospital Lozenets, Bulgaria.
    Erglis, Andrejs
    Pauls Stradins Clin University Hospital, Latvia.
    Laroche, Cecile
    European Soc Cardiol, France.
    Mebazaa, Alexandre
    University of Paris Diderot, France.
    European Society of Cardiology Heart Failure Long-Term Registry (ESC-HF-LT): 1-year follow-up outcomes and differences across regions2016In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 18, no 6, p. 613-625Article in journal (Refereed)
    Abstract [en]

    AimsThe European Society of Cardiology Heart Failure Long-Term Registry (ESC-HF-LT-R) was set up with the aim of describing the clinical epidemiology and the 1-year outcomes of patients with heart failure (HF) with the added intention of comparing differences between participating countries. Methods and resultsThe ESC-HF-LT-R is a prospective, observational registry contributed to by 211 cardiology centres in 21 European and/or Mediterranean countries, all being member countries of the ESC. Between May 2011 and April 2013 it collected data on 12440 patients, 40.5% of them hospitalized with acute HF (AHF) and 59.5% outpatients with chronic HF (CHF). The all-cause 1-year mortality rate was 23.6% for AHF and 6.4% for CHF. The combined endpoint of mortality or HF hospitalization within 1year had a rate of 36% for AHF and 14.5% for CHF. All-cause mortality rates in the different regions ranged from 21.6% to 36.5% in patients with AHF, and from 6.9% to 15.6% in those with CHF. These differences in mortality between regions are thought reflect differences in the characteristics and/or management of these patients. ConclusionThe ESC-HF-LT-R shows that 1-year all-cause mortality of patients with AHF is still high while the mortality of CHF is lower. This registry provides the opportunity to evaluate the management and outcomes of patients with HF and identify areas for improvement.

  • 203.
    Daferera, Niki
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Hjortswang, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Ignatova, Simone
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Munch, Andreas
    Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Single-centre experience with anti-tumour necrosis factor treatment in budesonide-refractory microscopic colitis patients2019In: United European Gastroenterology journal, ISSN 2050-6406, E-ISSN 2050-6414, article id UNSP 2050640619871750Article in journal (Refereed)
    Abstract [en]

    Background: Microscopic colitis is an inflammatory bowel disease that causes chronic, watery diarrhoea. Microscopic colitis is usually effectively treated with budesonide, but some patients are refractory. Data on alternative treatments are sparse. Aims: The purpose of this study was to retrospectively evaluate outcome of microscopic colitis patients receiving anti-tumour necrosis factor therapy at our centre. Methods:Treatment results, including side effects, for all microscopic colitis patients receiving anti-tumour necrosis factor therapy were registered at week 12 and at end of follow-up. Clinical remission was defined as a mean of Results: The study cohort comprised 18 patients; mean age at diagnosis was 47 years (range 19-77). Ten and eight patients, respectively, received adalimumab and infliximab as first-line anti-tumour necrosis factor; seven patients received second-line anti-tumour necrosis factor due to non-response, loss of response or side effects. At week 12, 9/18 patients had achieved remission, 6/18 were responders and 3/18 were non-responders. Of the nine remission patients, 3/18 (16%) had long-lasting clinical remission post-induction therapy alone. Five patients (28%) (one first-line, four second-line anti-tumour necrosis factor) were in remission and one patient (6%) responded to maintenance treatment; follow-up was mean 22 (range 4-60) months. Six patients (33%) had minor, reversible side effects. Conclusions: Over half of budesonide-refractory microscopic colitis patients can achieve clinical remission or response on anti-tumour necrosis factor agents. Prospective studies are mandatory to evaluate the efficacy and safety of anti-tumour necrosis factor treatments in budesonide-refractory microscopic colitis.

  • 204.
    Dahl Jensen, Lasse
    et al.
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Cao, Ziquan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Nakamura, Masaki
    Karolinska Institute, Sweden .
    Yang, Yunlong
    Karolinska Institute, Sweden .
    Brautigam, Lars
    Karolinska Institute, Sweden .
    Andersson, Patrik
    Karolinska Institute, Sweden .
    Zhang, Yin
    Karolinska Institute, Sweden .
    Wahlberg, Eric
    Linköping University, Department of Medical and Health Sciences, Vascular surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Hosaka, Kayoko
    Karolinska Institute, Sweden .
    Cao, Yihai
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.
    Opposing Effects of Circadian Clock Genes Bmal1 and Period2 in Regulation of VEGF-Dependent Angiogenesis in Developing Zebrafish2012In: Cell Reports, ISSN 2211-1247, Vol. 2, no 2, p. 231-241Article in journal (Refereed)
    Abstract [en]

    Molecular mechanisms underlying circadian-regulated physiological processes remain largely unknown. Here, we show that disruption of the circadian clock by both constant exposure to light and genetic manipulation of key genes in zebrafish led to impaired developmental angiogenesis. A bmal1-specific morpholino inhibited developmental angiogenesis in zebrafish embryos without causing obvious nonvascular phenotypes. Conversely, a period2 morpholino accelerated angiogenic vessel growth, suggesting that Bmal1 and Period2 display opposing angiogenic effects. Using a promoter-reporter system consisting of various deleted vegf-promoter mutants, we show that Bmal1 directly binds to and activates the vegf promoter via E-boxes. Additionally, we provide evidence that knockdown of Bmal1 leads to impaired Notch-inhibition-induced vascular sprouting. These results shed mechanistic insight on the role of the circadian clock in regulation of developmental angiogenesis, and our findings may be reasonably extended to other types of physiological or pathological angiogenesis.

  • 205.
    Dahlén, Elsa M
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland.
    Bjarnegård, Niclas
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Nyström, Fredrik H.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland.
    Sagittal abdominal diameter is a more independent measure compared with waist circumference to predict arterial stiffness in subjects with type 2 diabetes - a prospective observational cohort study2013In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 12Article in journal (Refereed)
    Abstract [en]

    Background

    Anthropometric measurements are useful in clinical practice since they are non-invasive and cheap. Previous studies suggest that sagittal abdominal diameter (SAD) may be a better measure of visceral fat depots. The aim of this study was to prospectively explore and compare how laboratory and anthropometric risk markers predicted subclinical organ damage in 255 patients, with type 2 diabetes, after four years.

    Methods

    Baseline investigations were performed in 2006 and were repeated at follow-up in 2010. Carotid intima-media thickness (IMT) was evaluated by ultrasonography and aortic pulse wave velocity (PWV) was measured with applanation tonometry over the carotid and femoral arteries at baseline and at follow-up in a cohort of subjects with type 2 diabetes aged 55–65 years old.

    Results

    There were significant correlations between apolipoprotein B (apoB) (r = 0.144, p = 0.03), C - reactive protein (CRP) (r = 0.172, p = 0.009) at baseline and IMT measured at follow-up. After adjustment for sex, age, treatment with statins and Hba1c, the associations remained statistically significant. HbA1c, total cholesterol or LDL-cholesterol did not correlate to IMT at follow-up. Baseline body mass index (BMI) (r = 0.130, p = 0.049), waist circumference (WC) (r = 0.147, p = 0.027) and sagittal Abdominal Diameter (SAD) (r = 0.184, p = 0.007) correlated to PWV at follow-up. Challenged with sex, SBP and HbA1c, the association between SAD, not WC nor BMI, and PWV remained statistically significant (p = 0.036). In a stepwise linear regression, entering both SAD and WC, the association between SAD and PWV was stronger than the association between WC and PWV.

    Conclusions

    We conclude that apoB and CRP, but not LDL-cholesterol predicted subclinical atherosclerosis. Furthermore, SAD was more independent in predicting arterial stiffness over time, compared with WC, in middle-aged men and women with type 2 diabetes.

  • 206.
    Dahlén, Elsa M
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Clinchy, Birgitta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Nyström, Fredrik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, West County Primary Health Care.
    Abdominal Obesity and low grade Systemic Inflammation as Markers for Subclinical Organ Damage in type 2 diabetes2014In: Diabetes & Metabolism, ISSN 1262-3636, E-ISSN 1878-1780, Vol. 40, no 1, p. 76-81Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to explore associations between abdominal obesity, inflammatory markers, and subclinical organ damage in 740 patients with type 2 diabetes. Waist circumference (WC) and sagittal abdominal diameter (SAD) was measured. Blood samples were analyzed for; C-reactive protein (CRP), interleukin (IL) -1β and IL-6. Carotid intimamedia thickness (IMT) was evaluated by ultrasonography. Aortic pulse wave velocity (PWV) was measured with applanation tonometry.

    Abdominal obesity were significantly correlated with; IL-6, CRP (both p= <0.001, WC and SAD, respectively), IMT (WC p=0.012, SAD p=0.003) and PWV (p<0.001, for WC and SAD, respectively). In multiple linear regressions with IMT as dependent variable and age, sex, statins, systolic blood pressure (SBP), Body Mass Index (BMI), CRP and HbA1c, as independent variables, SAD (p=0.047) but not WC, remained associated with IMT. In stepwise linear regression, entering both SAD and WC, the association between SAD and PWV was stronger than the association between WC and PWV.

    We conclude that SAD and WC are feasible measures of obesity that provides information on inflammation, atherosclerosis and arterial stiffness in type 2 diabetes. However, SAD was slightly more robustly associated to subclinical organ damage, compared with WC.

  • 207.
    Dahlén, Elsa M
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Lindström, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Grodzinsky, Ewa
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Nyström, Fredrik
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland.
    Carotid intima-media thickness and apolipoprotein B/apolipoprotein A-I ratio in middle-aged patients with Type 2 diabetes2009In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 26, no 4, p. 384-390Article in journal (Refereed)
    Abstract [en]

    Aims To explore the association between carotid intima-media thickness (IMT) and the apolipoprotein B (apoB)/apolipoprotein A-I (apoA-I) ratio compared with conventional lipids in middle-aged patients with Type 2 diabetes.

    Methods We analysed data from 247 patients with Type 2 diabetes, aged 55–66 years, in the Cardiovascular Risk factors in Patients with Diabetes—a Prospective study in Primary care (CARDIPP-1) study. Primary care nurses measured blood pressure and anthropometric characteristics. Blood samples were taken for laboratory analyses. The carotid IMT was determined by ultrasonography at the University Hospital in Linköping and at the County Hospital Ryhov, Jönköping, Sweden.

    Results The ApoB/apoA-I ratio (r = 0.207, P = 0.001), apoB (r = 0.166, P = 0.009) and non-high-density lipoprotein cholesterol (non-HDL-c) (r = 0.129, P = 0.046) correlated with IMT. Conventional lipids, high-sensitivity C-reactive protein (hsCRP), glycated haemoglobin (HbA1c) and systolic blood pressure were not significantly correlated to IMT. A stepwise logistic regression analysis was conducted with IMT as the dependent variable and the apoB/apoA-I ratio, HbA1c, hsCRP, low-density lipoprotein cholesterol (LDL-c), total cholesterol, non-HDL-c and treatment with statins as independent variables. Following adjustment for age and gender, only the apoB/apoA-I ratio remained significantly associated with IMT (odds ratio 4.3, 95% confidence intervals 1.7–10.8, P = 0.002).

    Conclusions We conclude that there was a significant association between the apoB/apoA-I ratio and IMT in middle-aged patients with Type 2 diabetes. The association was independent of conventional lipids, hsCRP, glycaemic control and use of statins.

  • 208.
    Dalin, Frida
    et al.
    Karolinska Institutet, Stockholm, Sweden, Uppsala University, Uppsala, Sweden.
    Nordling Eriksson, Gabriel
    Karolinska Institutet, Stockholm, Sweden.
    Dahlqvist, Per
    Umeå University, Umeå, Sweden.
    Hallgren, Åsa
    Karolinska Institutet, Stockholm, Sweden.
    Wahlberg, Jeanette
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Region Östergötland, Heart and Medicine Center, Department of Endocrinology. Linköping University, Faculty of Medicine and Health Sciences.
    Ekwall, Olov
    The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Söderberg, Stefan
    Umeå University, Umeå, Sweden.
    Rönnelid, Johan
    The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Olcén, Per
    Örebro University, Örebro, Sweden.
    Winqvist, Ola
    Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Catrina, Sergiu-Bogdan
    Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Kriström, Berit
    Umeå University, Umeå, Sweden.
    Laudius, Maria
    Umeå University, Umeå, Sweden.
    Isaksson, Magnus
    Uppsala University, Uppsala, Sweden.
    Halldin Stenlid, Maria
    Uppsala University, Uppsala, Sweden.
    Gustafsson, Jan
    Uppsala University, Uppsala, Sweden.
    Gebre-Medhin, Gennet
    Uppsala University, Uppsala, Sweden.
    Björnsdottir, Sigridur
    Karolinska In Karolinska University Hospital, Stockholm, Sweden.
    Janson, Annika
    Karolinska Institutet, Stockholm, Sweden.
    Åkerman, Anna-Karin
    Örebro University, Örebro, Sweden.
    Åman, Jan
    Örebro University, Örebro, Sweden.
    Duchen, Karel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Bergthorsdottir, Ragnhildur
    Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Johannsson, Gudmundur
    Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Lindskog, Emma
    The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Landin-Olsson, Mona
    Skåne University Hospital, Malmö, Sweden..
    Elfving, Maria
    Lund University, Lund, Sweden..
    Waldenström, Erik
    Skåne University Hospital, Malmö, Sweden.
    Hulting, Anna-Lena
    Karolinska Institutet, Stockholm, Sweden.
    Kämpe, Olle
    Karolinska University Hospital, Stockholm, Karolinska Institutet, Stockholm, Sweden.
    Bensing, Sophie
    Karolinska University Hospital, Stockholm, Karolinska Institutet, Stockholm, Sweden.
    Clinical and immunological characteristics of Autoimmune Addison's disease: a nationwide Swedish multicenter study.2017In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 102, no 2, p. 379-389Article in journal (Refereed)
    Abstract [en]

    CONTEXT: Studies on clinical and immunological features of Autoimmune Addison's disease (AAD) are needed to understand the disease burden and increased mortality.

    OBJECTIVE: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles and cardiovascular risk factors.

    DESIGN, SETTING AND PARTICIPANTS: Cross sectional, population-based study. 660 AAD patients were included utilizing the Swedish Addison Registry (SAR) 2008-2014. When analyzing cardiovascular risk factors, 3,594 individuals from the population-based survey in Northern Sweden, MONICA (MONItoring of Trends and Determinants of CArdiovascular Disease), served as controls.

    MAIN OUTCOME MEASURE: Prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined.

    RESULTS: Sixty percent of the SAR cohort consisted of females. Mean age at diagnosis was significantly higher for females than for males (36.8 vs. 31.1 years). The proportion of 21-hydroxylase autoantibody positive patients was 83% and 62% of patients had one or more associated autoimmune diseases, more frequently coexisting in females (p<0.0001). AAD patients had lower BMI (p<0.0001) and prevalence of hypertension (p=0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of patients; with the mean dose 28.1±8.5 mg/day. The mean hydrocortisone equivalent dose normalized to body surface was 14.8±4.4 mg/m(2)/day. Higher hydrocortisone equivalent dose was associated with higher incidence of hypertension (p=0.046).

    CONCLUSIONS: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients do not have increased prevalence of overweight, hypertension, T2DM or hyperlipidemia. However, high glucocorticoid replacement doses may be a risk factor for hypertension.

  • 209.
    Danielsson Borssen, Åsa
    et al.
    Umeå University, Sweden.
    Marschall, Hanns-Ulrich
    University of Gothenburg, Sweden.
    Bergquist, Annika
    Karolinska University Hospital Huddinge, Sweden.
    Rorsman, Fredrik
    Uppsala University, Sweden.
    Weiland, Ola
    Karolinska University Hospital Huddinge, Sweden.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Nyhlin, Nils
    Örebro University, Sweden.
    Verbaan, Hans
    Lund University, Sweden.
    Nilsson, Emma
    Lund University, Sweden.
    Werner, Marten
    Umeå University, Sweden.
    Epidemiology and causes of death in a Swedish cohort of patients with autoimmune hepatitis2017In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 9, p. 1022-1028Article in journal (Refereed)
    Abstract [en]

    Background: Epidemiological studies of autoimmune hepatitis (AIH) show varying figures on prevalence and incidence, and data on the long-term prognosis are scarce.Objective To investigate the epidemiology, long-term prognosis and causes of death in a Swedish AIH cohort.Material and methods: Data collected from 634 AIH patients were matched to the Cause of Death Registry, and survival analyses were made. Prevalence and incidence were calculated for university hospitals with full coverage of cases and compared to the County of Vasterbotten in Northern Sweden.Results: AIH point prevalence was 17.3/100,000 inhabitants in 2009, and the yearly incidence 1990-2009 was 1.2/100,000 inhabitants and year. The time between diagnosis and end of follow-up, liver transplantation or death was in median 11.3 years (range 0-51.5 years). Men were diagnosed earlier (pamp;lt;.001) and died younger than women (p=.002). No gender differences were found concerning transplant-free, overall survival and liver-related death. Cirrhosis at diagnosis was linked to an inferior survival (pamp;lt;.001). Liver-related death was the most common cause of death (32.7%). The relative survival started to diverge from the general population 4 years after diagnosis but a distinct decline was not observed until after more than 10 years.Conclusions: Long-term survival was reduced in patients with AIH. No gender difference regarding prognosis was seen but men died younger, probably as a result of earlier onset of disease. Cirrhosis at diagnosis was a risk factor for poor prognosis and the overall risk of liver-related death was increased.

  • 210.
    Das, Debraj
    et al.
    University of Alberta, Canada.
    Savarese, Gianluigi
    Karolinska Institute, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Fu, Michael
    Department Med, Sweden.
    Howlett, Jonathan
    University of Calgary, Canada.
    Ezekowitz, Justin A.
    University of Alberta, Canada.
    Lund, Lars H.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Ivabradine in Heart Failure The Representativeness of SHIFT (Systolic Heart Failure Treatment With the IF Inhibitor Ivabradine Trial) in a Broad Population of Patients With Chronic Heart Failure2017In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 10, no 9, article id e004112Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The sinus node inhibitor ivabradine was approved for patients with heart failure (HF) after the ivabradine and outcomes in chronic HF (SHIFT [Systolic Heart Failure Treatment With the IF Inhibitor Ivabradine Trial]) trial. Our objective was to characterize the proportion of patients with HF eligible for ivabradine and the representativeness of the SHIFT trial enrollees compared with those in the Swedish Heart Failure Registry. METHODS AND RESULTS: We examined 26 404 patients with clinical HF from the Swedish Heart Failure Registry and divided them into SHIFT type (left ventricular ejection fraction amp;lt; 40%, New York Heart Association class II-IV, sinus rhythm, and heart rate amp;gt;= 70 beats per minute) and nonSHIFT type. Baseline characteristics and medication use were compared and change in eligibility over time was reported at 6 months and 1 year in a subset of patients. Overall, 14.2% (n= 3741) of patients were SHIFT type. These patients were more likely to be younger, men, have diabetes mellitus, ischemic heart disease, lower left ventricular ejection fraction, and more recent onset HF (amp;lt; 6 months; all, Pamp;lt; 0.001). Although 88.9% of SHIFT type and 88.5% of non-SHIFT type (P= 0.421) were receiving selected beta-blockers, only 58.8% and 67.3% (Pamp;lt; 0.001) were on amp;gt; 50% of target dose. From those patients who had repeated visits within 6 months (n= 5420) and 1 year (n= 6840), respectively, 10.2% (n= 555) and 10.6% (n= 724) of SHIFT-type patients became ineligible, 77.3% (n= 4188) and 77.3% (n= 5287) remained ineligible, and 4.6% (n= 252) and 4.9% (n= 335) of non-SHIFT-type patients became eligible for initiation of ivabradine. CONCLUSIONS: From the Swedish Heart Failure Registry, 14.2% of patients with HF were eligible for ivabradine. These patients more commonly were not receiving target beta-blocker dose. Over time, a minority of patients became ineligible and an even smaller minority became eligible.

  • 211.
    Dasenaki, Marilena
    et al.
    Univ Athens, Greece.
    Papatzani, Maria
    Univ Athens, Greece.
    Gounari, Eleni
    Kings Coll Hosp NHS Fdn Trust, England.
    Magnisali, Paraskevi
    Univ Athens, Greece.
    Papadopoulou-Marketou, Nektaria
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology. Univ Athens, Greece.
    Kanaka-Gantenbein, Christina
    Univ Athens, Greece.
    Moutsatsou, Paraskevi
    Univ Athens, Greece.
    Thomaidis, Nikolaos S.
    Univ Athens, Greece.
    Simultaneous Determination of Free Cortisol, Cortisone and their Tetrahydrometabolites in Urine by Single Solvent Extraction and Liquid Chromatography-Tandem Mass Spectrometry2019In: Analytical Letters, ISSN 0003-2719, E-ISSN 1532-236XArticle in journal (Refereed)
    Abstract [en]

    A fast, efficient and low-cost high performance liquid chromatography-tandem mass spectrometry methodology was developed and validated for the simultaneous determination of free urinary cortisone, cortisol and their tetrahydro-metabolites. The developed method comprises a simple liquid-liquid extraction with CH2Cl2, followed by reversed-phase liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization (ESI) in positive mode. The baseline chromatographic separation of the analytes, including the stereoisomers tetrahydrocortisol (THF) and allo-THF, was achieved on a Hypersil Gold C-18 column with a mobile phase consisting of 0.05%v/v formic acid in water-acetonitrile, using a gradient elution program. The influence of the mobile phase composition and the ESI parameters on the sensitivity of the method was extensively studied. Sample preparation was also optimized, testing two techniques: solid phase extraction (SPE) and liquid-liquid extraction (LLE). Recoveries ranged from 74.7% (a-THF) to 93.5% (cortisol) and the method limits of detection (MLD) ranged from 0.34 ng mL(-1) (cortisol) to 1.37 ng mL(-1) (THF). Intra- and inter-day coefficient of variation of the assay varied from1.5% (allo-THF) to 13% (tetrahydrocortisone) and from 3.6% (allo-THF) to 14.9% (tetrahydrocortisone), respectively. The method was applied for the analysis of urine samples from 53 healthy individuals with a mean age of 13.96 years in order to estimate the concentration of the five corticosteroids and the ratio of the metabolites. Associations between urinary cortisol/cortisone and serum cortisol/cortisone values were also characterized.

  • 212.
    Daskalakis, Kosmas
    et al.
    Uppsala Univ, Sweden; Univ Athens, Greece.
    Chatzelis, Eleftherios
    Univ Athens, Greece; 251 Hellen Air Force and VA Gen Hosp, Greece.
    Tsoli, Marina
    Univ Athens, Greece.
    Papadopoulou, Nektaria
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Dimitriadis, Georgios K.
    Univ Hosp Coventry and Warwickshire NHS Trust, England.
    Tsolakis, Apostolos V
    Karolinska Inst, Sweden; Karolinska Univ Hosp Solna, Sweden; Uppsala Univ, Sweden.
    Kaltsas, Gregory
    Univ Athens, Greece.
    Endocrine paraneoplastic syndromes in patients with neuroendocrine neoplasms2019In: Endocrine (Basingstoke), ISSN 1355-008X, E-ISSN 1559-0100, Vol. 64, no 2, p. 384-392Article in journal (Refereed)
    Abstract [en]

    ObjectiveOur aim was to assess the prevalence of endocrine paraneoplastic syndromes (EPNS) in neuroendocrine neoplasms (NENs) and estimate its impact on patient outcomes.DesignThis is a retrospective analysis of 834 patients with NENs (611 gastrointestinal, 166 thoracic, 57 of unknown and various other primary origin). We included 719 consecutive NEN patients treated at EKPA-Laiko Hospital, Athens, Greece and 115 patients with lung carcinoid (LC) treated at Uppsala University Hospital, Uppsala, Sweden. EPNS diagnosis was based on standard criteria.MethodsTwenty-one patients with EPNS were detected: 16 with ectopic Cushings syndrome (ECS), one with hypercalcaemia due to parathyroid hormone-related protein (PTHrP) secretion, three with hypercalcitonaemia and one patient with dual secretion of calcitonin and beta-human chorionic gonadotropin (-HCG). All tumours were well-differentiated; 10 patients had Stage IV disease at diagnosis.ResultsThe prevalence of EPNS in the Greek cohort was 1.9%, whereas that of ECS among LC patients in both centres was 6.7%. Median overall survival (OS) for patients with EPNS was 160.7 months (95%CI, 86-235.4) and median event-free survival (EFS) was 25.9 months (95%CI, 0-57.2). Patients presenting with EPNS prior to NEN diagnosis had longer EFS compared to patients with synchronous or metachronous EPNS (log-rank P=0.013). Patients with ECS of extra-thoracic origin demonstrated shorter OS and EFS compared to patients with ECS of lung or thymic origin (log-rank P=0.001 and Pamp;lt;0.001, respectively). LC patients with and without ECS were comparable in 5-year and 10-year OS rates (66.7% and 33.3% versus 89.8% and 60.2%, respectively; 95%CI [189.6-300.4 months], log-rank P=0.94) and in median EFS, 67 versus 183 months, 95%CI [50.5-207.5], log-rank P=0.12).ConclusionEPNS are relatively rare in patients with NENs and mainly concern well-differentiated tumours of the foregut. Among patients with EPNS, LC-related ECS may not adversely affect patient outcomes when diagnosed prior to NEN and effectively been treated.

  • 213.
    Davidsson, Anette
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Georgiopoulos, Charalampos
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Dizdar (Dizdar Segrell), Nil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Granerus, Göran
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Zachrisson, Helene
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Comparison between visual assessment of dopaminergic degeneration pattern and semi-quantitative ratio calculations in patients with Parkinsons disease and Atypical Parkinsonian syndromes using DaTSCAN (R) SPECT2014In: Annals of Nuclear Medicine, ISSN 0914-7187, E-ISSN 1864-6433, Vol. 28, no 9, p. 851-859Article in journal (Refereed)
    Abstract [en]

    Objective To verify if I-123-FP-CIT, DaTSCAN (R) can differentiate early stages of Parkinsons disease (PD) as well as patients with Atypical Parkinsonian syndromes (APS) from manifest Parkinsons disease. Methods 128 consecutive patients were investigated with I-123-FP-CIT SPECT during a 4-year period. All patients were diagnosed according to the established consensus criteria for diagnosis of PD (n = 53) and APS (n = 19). Remaining patients were grouped early PD (before onset of L-DOPA medication), (n = 20), vascular PD (n = 6), and non-PD syndromes (n = 30) and SWEDD (n = 1). SPECT images were analyzed visually according to a predefined ranking scale of dopaminergic nerve cell degeneration, distinguishing a posterior-anterior degeneration pattern (egg shape) from a more global and severe degeneration pattern (burst striatum). Striatum uptake ratios were quantitatively analyzed with the 3D software, EXINI. Results In the group of APS patients, the burst striatum pattern was most frequent and found in 61 % (11/18 patients). In PD patients, the egg shape pattern was dominating, especially in early PD where it was present in 95 % (19/20 patients). The positive predictive value for the egg shape pattern to diagnose PD was 92 % in this material (APS and all PD patients) and the specificity 90 % for the burst striatum pattern to exclude APS. The uptake ratios were reduced in both PD and APS patients and closely related to the image ranking. Conclusion In this study, we found that in more than half of the patients it was possible to differentiate between PD and APS by visual interpretation only. Similar results were obtained using semi-quantitative uptake ratios. Combining visual assessment with uptake ratios did not add to the discriminating power of DaTSCAN (R) SPECT in this material.

  • 214.
    Davidsson, Anette
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Georgiopoulos, Charalampos
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Dizdar Segrell, Nil
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Granerus, Göran
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Zachrisson, Helene
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Comparison between visual assessment of dopaminergic degeneration pattern and semi-quantitative ratio calculations in patients with Parkinson's disease and Atypical Parkinsonian snydromes using DaTSCAN SPECT2014Conference paper (Other academic)
    Abstract [en]

    Background: Parkinson's disease (PD) is a degenerative disorder characterized by the progressive degeneration of dopamine-containing cells in substantia nigra, and it is the second most common neurodegenerative disorder worldwide. It can be difficult to differentiate between idiopathic PD and Atypical Parkinsonian syndromes (APS). In a high percentage of APS patients, the right diagnosis is not established even during late stages of the disease. Currently there is no specific test to verify PD, especially in the early stages of the disease.

    The aim was to verify if 123I-FP-CIT, DaTSCAN ® can differentiate early stages of Parkinson's disease as well as patients with Atypical Parkinsonian syndromes from manifest Parkinson's disease.

    Materials and methods: 121 consecutive patients were investigated with 123I-FP-CIT SPECT, during a four year period. All patients were diagnosed according to the established consensus criteria for diagnosis of Parkinson's disease (PD), (n=53), Atypical Parkinsonian syndromes (APS) (n=18). Remaining patients were grouped early PD (before onset the of L-dopa medication), (n=20), and non-PD syndromes (n=30). SPECT images were analysed visually according to a predefined ranking scale of dopaminergic degeneration, distinguishing a posterior-anterior degeneration pattern (egg shape) to a more global and severe degeneration pattern (burst striatum). Striatum ratios were quantitatively analysed with the 3D software, EXINI.

    Results: In the group of APS patients the burst striatum pattern was most frequent and found in 61% (11/18 patients). In PD patients the egg shape pattern was dominating, especially in early PD where it was present in 95% (19/20 patients). The sensitivity of burst striatum degeneration pattern was 61% (95%-CI 36-83%), specificity 90% (95%-CI 81-96%). The sensitivity of egg shape pattern was 74% (95%-CI 62-84%), specificity 90% (95%-CI 47-90%). The uptake ratios were reduced in both PD and APS patients and closely related to the image pattern. The lowest putamen/caudate ratio was found in early PD.

    Conclusion: In this study we found that in more than half of the patients it was possible to differentiate between PD and APS by visual interpretation only. Similar results were obtained using semi-quantitative uptake ratios, but combining visual assessment with uptake ratios did not add to the discriminating power of DATSCAN ® SPECT in this material

    References: Kahraman D, Eggers C, Schicha H, Timmermann L, Schmidt M. Visual assessment of dopaminergic degeneration pattern in 123I-FP-CIT SPECT differentiates patients with atypical parkinsonian syndromes and idiopathic Parkinson's disease. J Neurol. 2012;259:251-60

  • 215.
    Davidsson, Anette
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Olsson, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Gustafsson, Agnetha
    Karolinska University Hospital, Huddinge, Stockholm, Sweden.
    Influence of reconstruction algorithms on image quality in SPECT myocardial perfusion imaging2017In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 37, no 6, p. 655-662Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: We investigated if image- and diagnostic quality in SPECT MPI could be maintained despite a reduced acquisition time adding Depth Dependent Resolution Recovery (DDRR) for image reconstruction. Images were compared with filtered back projection (FBP) and iterative reconstruction using Ordered Subsets Expectation Maximization with (IRAC) and without (IRNC) attenuation correction (AC).

    MATERIALS AND METHODS: Stress- and rest imaging for 15 min was performed on 21 subjects with a dual head gamma camera (Infinia Hawkeye; GE Healthcare), ECG-gating with 8 frames/cardiac cycle and a low-dose CT-scan. A 9 min acquisition was generated using five instead of eight gated frames and was reconstructed with DDRR, with (IRACRR) and without AC (IRNCRR) as well as with FBP. Three experienced nuclear medicine specialists visually assessed anonymized images according to eight criteria on a four point scale, three related to image quality and five to diagnostic confidence. Statistical analysis was performed using Visual Grading Regression (VGR).

    RESULTS: Observer confidence in statements on image quality was highest for the images that were reconstructed using DDRR (P<0·01 compared to FBP). Iterative reconstruction without DDRR was not superior to FBP. Interobserver variability was significant for statements on image quality (P<0·05) but lower in the diagnostic statements on ischemia and scar. The confidence in assessing ischemia and scar was not different between the reconstruction techniques (P = n.s.).

    CONCLUSION: SPECT MPI collected in 9 min, reconstructed with DDRR and AC, produced better image quality than the standard procedure. The observers expressed the highest diagnostic confidence in the DDRR reconstruction.

  • 216.
    Davidsson, Anette
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Olsson, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Holmberg, Bengt
    Gustafsson, Agnetha
    Karolinska University.
    Left ventricle ejection fraction with gated myocardial perfusion SPECT: a comparison between a conventional scintillation detector gamma camera and cadmium-zinc-telluride dectector camera2014Conference paper (Refereed)
  • 217.
    Davidsson, Anette
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Olsson, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Norberg, Pernilla
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Myokardscintigrafi med ny hjärtkamera (D-SPECT): Hur mycket kan vi minska strålbelastningen till patienten utan att försämra diagnostisk bildkvalité?2015Conference paper (Other academic)
  • 218.
    De Backer, Ole
    et al.
    Copenhagen University Hospital, Denmark.
    Gotberg, Matthias
    Skåne University Hospital, Sweden.
    Ihlberg, Leo
    Helsinki University Hospital, Finland.
    Packer, Erik
    Haukeland Hospital, Norway.
    Savontaus, Mikko
    Turku University Hospital, Finland.
    Nielsen, Niels Erik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Jorgensen, Troels H.
    Copenhagen University Hospital, Denmark.
    Nykanen, Antti
    Helsinki University Hospital, Finland.
    Baranowski, Jacek
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Niemela, Matti
    Oulu University Hospital, Finland.
    Eskola, Markku
    Tampere University Hospital, Finland.
    Bjursten, Henrik
    Skåne University Hospital, Sweden.
    Söndergaard, Lars
    Copenhagen University Hospital, Denmark.
    Efficacy and safety of the Lotus Valve System for treatment of patients with severe aortic valve stenosis and intermediate surgical risk: Results from the Nordic Lotus-TAVR registry2016In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 219, p. 92-97Article in journal (Refereed)
    Abstract [en]

    Background: Transcatheter aortic valve replacement (TAVR) has becomean established therapeutic option for patients with symptomatic, severe aortic valve stenosis (AS) who are ineligible or at high risk for conventional valvular surgery. In Northwestern Europe, the TAVR technology is also increasingly used to treat patients with an intermediate risk profile. Methods and results: The study was designed as an independent Nordic multicenter registry of intermediate risk patients treated with the Lotus Valve System (Boston Scientific, MA, USA; N = 154). Valve Academic Research Consortium (VARC)-defined device success was obtained in 97.4%. A Lotus Valve was successfully implanted in all patients. There was no valve migration, embolization, ectopic valve deployment, or TAV-in-TAV deployment. The VARC-defined combined safety rate at 30 days was 92.2%, with a mortality rate of 1.9% and stroke rate of 3.2%. The clinical efficacy rate after 30 days was 91.6% - only one patient had moderate aortic regurgitation. When considering only those patients in the late experience group (N=79), the combined safety and clinical efficacy rates were 93.7% and 92.4%, respectively. The pacemaker implantation rate was 27.9% - this rate was 12.8% in case of a combined implantation depth amp;lt;4 mm and a device/annulus ratio amp;lt; 1.05. Conclusions: The present study demonstrates the efficacy and safety of the repositionable, retrievable Lotus Valve System in intermediate risk patients with AS. The VARC-defined device success rate was 97.4% with a 30-day patient safety and clinical efficacy rate of more than 90%. Less than moderate aortic regurgitation was obtained in 99.4% of patients. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

  • 219.
    De Basso, Rachel
    et al.
    Jonköping Hospital, Sweden .
    Astrand, Hakan
    Jonköping Hospital, Sweden .
    Ryden Ahlgren, Asa
    Lund University, Sweden .
    Sandgren, Thomas
    Capio Lundby Hospital, Sweden .
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Low wall stress in the popliteal artery: Other mechanisms responsible for the predilection of aneurysmal dilatation?2014In: Vascular Medicine, ISSN 1358-863X, E-ISSN 1477-0377, Vol. 19, no 2, p. 131-136Article in journal (Refereed)
    Abstract [en]

    The popliteal artery (PA) is, after aorta, the most common site for aneurysm formation. Why the PA is more susceptible than other peripheral muscular arteries is unknown. We hypothesized that the wall composition, which in turn affects wall properties, as well as the circumferential wall stress (WS) imposed on the arterial wall, might differ compared to other muscular arteries. The aim was to study the WS of the PA in healthy subjects with the adjacent, muscular, common femoral artery (CFA) as a comparison. Ninety-four healthy subjects were included in this study (45 males, aged 10-78 years and 49 females, aged 10-83 years). The diameter and intima-media thickness (IMT) in the PA and CFA were investigated with ultrasound. Together with blood pressure the WS was defined according to the law of Laplace adjusted for IMT. The diameter increased with age in both PA and CFA (pless than0.001), with males having a larger diameter than females (pless than0.001). IMT increased with age in both PA and CFA (pless than0.001), with higher IMT values in males only in PA (pless than0.001). The calculated WS was unchanged with age in both arteries, but lower in PA than in CFA in both sexes (pless than0.001). In conclusion, this study shows that the PA and CFA WS is maintained during aging, probably due to a compensatory remodelling response with an increase in arterial wall thickness. However, the stress imposed on the PA wall is quite low, indicating that mechanisms other than WS contribute to the process of pathological arterial dilatation in the PA.

  • 220.
    De Basso, Rachel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Hedblad, Bo
    Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.
    Carlson, Joyce
    Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.
    Persson, Margaretha
    Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.
    Östling, Gerd
    Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.
    Länne, Toste
    Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Increased carotid plaque burden in men with the Fibrillin-1 2/3 genotype2014In: Clinical and experimental pharmacology & physiology, ISSN 0305-1870, E-ISSN 1440-1681, Vol. 41, no 9, p. 637-642Article in journal (Refereed)
    Abstract [en]

    Objective: Fibrillin-1 is an important constituent of the vascular wall and earlier studies have indicated an effect of the Fibrillin-1 (FBN1) 2/3 genotype on blood pressure as well as aortic stiffness in men. The aim was to determine if the FBN1 2/3 genotype was associated with presence of carotid plaque and incident cardiovascular morbidity and mortality in middle-aged subjects.

    Material and Method: The FBN1 genotype was characterized in 5765 subjects (2424 men, 3341 women; aged 45-69 years) recruited from the Malmö Diet and Cancer Study Cardiovascular Cohort, Sweden. Plaque occurrence and intima media thickness (IMT) of the carotid artery were assessed by ultrasound. Incidence of first cardiovascular events (myocardial infarction and stroke) and cause-specific mortality was monitored during a mean of 13.2 years follow-up.

    Results: The most common FBN1 genotypes were 2/2, 2/3 and 2/4 which accounted for 92.2% (n=5317) of the subjects. There were no differences between the three genotypes regarding age, blood pressure, glucose, lipids, smoking habits, CCA diameter and IMT in men and women. Presence of plaque in the carotid artery was higher in men with genotype 2/3 as compared to the 2/2 and 2/4 genotypes, (55% vs. 46% and 50%, p=0.007). No similar difference was observed in women. No significant relationship was observed between FBN1 genotypes and incidence of CVD or all-cause mortality.

    Conclusions: The increased prevalence of plaque in the carotid artery of middle-aged men with FBN1 2/3 genotype indicates a pathological arterial wall remodeling with a more pronounced atherosclerotic burden. 

  • 221.
    De Basso, Rachel
    et al.
    Jonköping University, Sweden; Jonköping University, Sweden.
    Sandgren, Thomas
    Capio Lundby Hospital, Sweden.
    Ryden Ahlgren, Asa
    Lund University, Sweden.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Increased cardiovascular risk without generalized arterial dilating diathesis in persons who do not have abdominal aortic aneurysm but who are first-degree relatives of abdominal aortic aneurysm patients2015In: Clinical and experimental pharmacology & physiology, ISSN 0305-1870, E-ISSN 1440-1681, Vol. 42, no 6, p. 576-581Article in journal (Refereed)
    Abstract [en]

    There is a strong genetic predisposition towards abdominal aortic aneurysm (AAA), but it is unknown whether persons without AAA but with first-degree relatives who are AAA patients have a generalized dilating diathesis, defect arterial wall mechanics, or increased cardiovascular risk. The aim of the study was to investigate arterial diameters and wall mechanics at multiple arterial sites in these subjects and compare them with controls without a family history of AAA. This study included 118 first-degree relatives of patients with AAA and 66 controls (age: 40-80years). The abdominal aorta, common carotid artery, common femoral artery, and popliteal artery were investigated by echo-tracking ultrasound. The relatives had no arterial dilatation, but they did tend to have smaller diameters than controls. Relatives had a higher heart rate, diastolic blood pressure, and mean arterial pressure than controls. The distensibility coefficient and the compliance coefficient were decreased in all arteries in male relatives, adjusted for age and smoking; these coefficients were normalized after adjustment for mean arterial pressure and heart rate. Female relatives had a lower compliance coefficient in the abdominal aorta, adjusted for age and smoking. After adjustment for mean arterial pressure and heart rate, the difference disappeared. No general arterial dilatation in relatives without AAA was found, supporting the hypothesis that the dilating diathesis is linked to the aneurysmal manifestation in the abdominal aorta. Although the threat of aneurysmal dilatation and rupture seems to be lacking in these subjects, heart rate, blood pressure, and arterial wall stiffness were all increased, which may indicate a higher risk of developing cardiovascular morbidity and mortality.

  • 222.
    De Geer, Jakob
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Gjerde, Marcus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Department of Clinical Physiology in Kalmar, Linköping University, County Council of Kalmar, Kalmar, Sweden.
    Olsson, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Persson, Anders
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Large variation in blood flow between left ventricular segments, as detected by adenosine stress dynamic CT perfusion.2015In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 35, no 4, p. 291-300Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Dynamic cardiac CT perfusion (CTP) is based on repeated imaging during the first-pass contrast agent inflow. It is a relatively new method that still needs validation.

    PURPOSE: To evaluate the variation in adenosine stress dynamic CTP blood flow as compared to (99m) Tc SPECT. Secondarily, to compare manual and automatic segmentation.

    METHODS: Seventeen patients with manifest coronary artery disease were included. Nine were excluded from evaluation for various reasons. All patients were examined with dynamic stress CTP and stress/rest SPECT. CTP blood flow was compared with SPECT on a per segment basis. Results for manual and automated AHA segmentation were compared.

    RESULTS: CTP showed a positive correlation with SPECT, with correlation coefficients of 0·38 and 0·41 for manual and automatic segmentation, respectively (P<0·0001). There was no significant difference between the correlation coefficients of the manual and automated segmentation procedures (P = 0·75). The average per individual global CTP blood flow value for normal segments varied by a factor of 1·9 (manual and automatic segmentation). For the whole patient group, the CTP blood flow value in normal segments varied by a factor of 2·9/2·7 (manual/automatic segmentation). Within each patient, the average per segment blood flow in normal segments varied by a factor of 1·3-2·0/1·2-2·1 (manual/automatic segmentation).

    CONCLUSION: A positive but rather weak correlation was found between CTP and (99m) Tc SPECT. Large variations in CTP blood flow suggest that a cut-off value for stress myocardial blood flow is inadequate to detect ischaemic segments. Dynamic CTP is hampered by a limited coverage.

  • 223.
    De Geer, Jakob
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Sandstedt, Mårten
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Björkholm, Anders
    Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Alfredsson, Joakim
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Janzon, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Persson, Anders
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Software-based on-site estimation of fractional flow reserve using standard coronary CT angiography data.2016In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 57, no 10, p. 1186-1192Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The significance of a coronary stenosis can be determined by measuring the fractional flow reserve (FFR) during invasive coronary angiography. Recently, methods have been developed which claim to be able to estimate FFR using image data from standard coronary computed tomography angiography (CCTA) exams.

    PURPOSE: To evaluate the accuracy of non-invasively computed fractional flow reserve (cFFR) from CCTA.

    MATERIAL AND METHODS: A total of 23 vessels in 21 patients who had undergone both CCTA and invasive angiography with FFR measurement were evaluated using a cFFR software prototype. The cFFR results were compared to the invasively obtained FFR values. Correlation was calculated using Spearman's rank correlation, and agreement using intraclass correlation coefficient (ICC). Sensitivity, specificity, accuracy, negative predictive value, and positive predictive value for significant stenosis (defined as both FFR ≤0.80 and FFR ≤0.75) were calculated.

    RESULTS: The mean cFFR value for the whole group was 0.81 and the corresponding mean invFFR value was 0.84. The cFFR sensitivity for significant stenosis (FFR ≤0.80/0.75) on a per-lesion basis was 0.83/0.80, specificity was 0.76/0.89, and accuracy 0.78/0.87. The positive predictive value was 0.56/0.67 and the negative predictive value was 0.93/0.94. The Spearman rank correlation coefficient was ρ = 0.77 (P < 0.001) and ICC = 0.73 (P < 0.001).

    CONCLUSION: This particular CCTA-based cFFR software prototype allows for a rapid, non-invasive on-site evaluation of cFFR. The results are encouraging and cFFR may in the future be of help in the triage to invasive coronary angiography.

  • 224.
    de Geer, Lina
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Oscarsson, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Variability in echocardiographic measurements of left ventricular function in septic shock patients2015In: Cardiovascular Ultrasound, ISSN 1476-7120, E-ISSN 1476-7120, Vol. 13, no 1, p. 19-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Echocardiography is increasingly used for haemodynamic evaluation and titration of therapy in intensive care, warranting reliable and reproducible measurements. The aim of this study was to evaluate the observer dependence of echocardiographic findings of left ventricular (LV) diastolic and systolic dysfunction in patients with septic shock.

    METHODS: Echocardiograms performed in 47 adult patients admitted with septic shock to a general intensive care unit (ICU) were independently evaluated by one cardiologist and one intensivist for the following signs: decreased diastolic tissue velocity of the base of the LV septum (e), increased early mitral inflow (E) to e ratio (E/e), decreased LV ejection fraction (EF) and decreased LV global longitudinal peak strain (GLPS). Diastolic dysfunction was defined as e <8.0cm/s and/or E/e [greater than or equal to]15 and systolic dysfunction as EF <50% and/or GLPS>15%. Ten randomly selected examinations were re-analysed two months later. Pearson’s r was used to test the correlation and Bland-Altman plots to assess the agreement between observers. Kappa statistics were used to test the consistency between readers and intraclass correlation coefficients (ICC) for inter- and intraobserver variability.

    RESULTS: In 44 patients (94%), image quality was sufficient for echocardiographic measurements. The agreement between observers was moderate (k=0.60 for e, k=0.50 for E/e and k=0.60 for EF) to good (k=0.71 for GLPS). Pearson’s r was 0.76 for e, 0.85 for E/e, 0.78 for EF and 0.84 for GLPS (p<0.001 for all four). The ICC between observers for e was very good (0.85; 95% confidence interval (CI) 0.73-0.92), good for E/e (0.70; 95% CI 0.45 - 0.84), very good for EF (0.87; 95% CI 0.77 - 0.93), excellent for GLPS (0.91; 95% CI 0.74 - 0.95), and very good for all measures repeated by one of the observers. On Bland-Altman analysis, the mean differences and 95% limits of agreement for e, E/e, EF and GLPS were 0.01 (0.04 - 0.07), 2.0 (14.2 - 18.1), 0.86 (16 - 14.3) and 0.04 (5.04 - 5.12), respectively.

    CONCLUSIONS: Moderate observer-related differences in assessing LV dysfunction were seen. GLPS is the least user dependent and most reproducible echocardiographic measurement of LV function in septic shock.

  • 225.
    de Geer, Lina
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Oscarsson, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Gustafsson, Mikael
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Lung ultrasound in quantifying lung water in septic shock patients2015In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 19, no 1, p. 140-Article in journal (Refereed)
    Abstract [en]

    Quantification of lung ultrasound (LUS) artifacts (B-lines) is used to assess pulmonary congestion in emergency medicine and cardiology [1,2]. We investigated B-lines in relation to extravascular lung-water index (EVLWI) from invasive transpulmonary thermodilution in septic shock patients. Our aim was to evaluate the role of LUS in an intensive care setting.

  • 226.
    de Geer, Lina
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Oscarsson Tibblin, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Walther, Sten M.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    No association with cardiac death after sepsis: A nationwide observational cohort study2019In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 63, no 3, p. 344-351Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Cardiac dysfunction is a well-known complication of sepsis, but its long-term consequences and implications for patients remain unclear. The aim of this study was to investigate cardiac outcome in sepsis by assessing causes of death up to 2 years after treatment in an Intensive Care Unit (ICU) in a nationwide register-based cohort collected from the Swedish Intensive Care Registry.

    METHODS: A cohort of 13 669 sepsis and septic shock ICU patients from 2008 to 2014 was collected together with a non-septic control group, matched regarding age, sex and severity of illness (n = 6582), and all without preceding severe cardiac disease. For a large proportion of the severe sepsis and septic shock patients (n = 7087), no matches were found. Information on causes of death up to 2 years after ICU admission was sought in the Swedish National Board of Health and Welfare's Cause of Death Registry.

    RESULTS: Intensive Care Unit mortality was nearly identical in a matched comparison of sepsis patients to controls (24% in both groups) but higher in more severely ill sepsis patients for whom no matches were found (33% vs 24%, P < 0.001). There was no association of sepsis to cardiac deaths in the first month (OR 1.03, 95%CI 0.87 to 1.20, P = 0.76) nor up to 2 years after ICU admission (OR 1.01, 95%CI 0.82 to 1.25, P = 0.94) in an adjusted between-group comparison.

    CONCLUSIONS: There was no association with an increased risk of death related to cardiac disease in patients with severe sepsis or septic shock when compared to other ICU patients with similar severity of illness.

  • 227.
    Dinis, Paulo
    et al.
    Ctr Hosp and Univ Coimbra, Portugal; Ctr Saude Mil Coimbra, Portugal.
    Teixeira, Rogerio
    Ctr Hosp and Univ Coimbra, Portugal; Univ Coimbra, Portugal.
    Dores, Helder
    Hosp Forcas Armadas, Portugal.
    Correia, Pedro
    Ctr Hosp and Univ Coimbra, Portugal; Ctr Saude Mil Coimbra, Portugal.
    Lekedal, Hanna
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Bergman, Marie
    Linköping University.
    Cachulo, Maria Carmo
    Ctr Hosp and Univ Coimbra, Portugal.
    Cardoso, Joaquim
    Ctr Saude Mil Coimbra, Portugal.
    Goncalves, Lino
    Ctr Hosp and Univ Coimbra, Portugal.
    Exercise-induced cardiac remodeling in athletes and in special forces soldiers2018In: REVISTA PORTUGUESA DE CARDIOLOGIA, ISSN 0870-2551, Vol. 37, no 3, p. 249-256Article in journal (Refereed)
    Abstract [en]

    Introduction: Exercise-induced cardiac remodeling is frequent in athletes. This adaptation is structurally manifested by an increase in cardiac dimensions and mass. Soldiers are also subject to intense physical exercise, although with different characteristics. Objective: To compare exercise-induced cardiac remodeling in competitive athletes and in soldiers on a special forces training course. Methods: We studied 17 soldiers (all male and Caucasian, mean age 21 3 years) who completed a special forces course and 17 basketball players (47.3% male, 64.7% Caucasian, mean age 21 +/- 3 years). Assessment included a transthoracic echocardiogram and analysis of myocardial mechanics. This assessment was performed at the beginning and end of the military course and the sports season, respectively. Results: Cardiac remodeling was observed in both groups. The soldiers presented a predominantly eccentric pattern, with increased left ventricular (LV) size (49.7 +/- 3.2 vs. 52.8 +/- 3.4 mm; p amp;lt; 0.01), increased LV mass (93.1 +/- 7.7 vs. 100.2 +/- 11.4 g/m2; p amp;lt; 0.01) and decreased relative wall thickness (0.40 +/- 0.1 vs. 0.36 +/- 0.1; p = 0.05). The basketball players showed a concentric pattern, with decreased LV size (52.0 +/- 4.7 vs. 50.4 +/- 4.7 mm; p = 0.05), and increased relative wall thickness (0.33 +/- 0.1 vs. 0.36 +/- 0.1; p = 0.05). Although there was no significant difference in LV myocardial strain in the groups separately, when compared there was a significant decrease (-20.2 +/- 1.6% vs. -19.4 +/- 2.1%; p = 0.03). Conclusion: Cardiac remodeling was frequent, with an eccentric pattern in soldiers and a concentric pattern in basketball players. Myocardial deformation may represent a physiological adaptation to physical exercise. (C) 2017 Sociedade Portuguesa de Cardiologia. Published by Elsevier Espana, S.L.U. All rights reserved.

  • 228.
    Dittrich, Christian
    et al.
    Kaiser Franz Josef Spital, Austria Kaiser Franz Josef Spital, Austria .
    Papai-Szekely, Zsolt
    St George Hospital Fejer County, Hungary .
    Vinolas, Nuria
    Hospital Clin Barcelona, Spain .
    Sederholm, Christer
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Hartmann, Joerg T.
    Department Internal Medical II Hematol and Medical Oncol, Germany Catholic Hospital Consortium Ostwestfalen, Germany .
    Behringer, Dirk
    Clin Hematol and Oncol, Germany .
    Kazeem, Gbenga
    Eli Lilly UK, England .
    Desaiah, Durisala
    Eli Lilly Corp Centre, IN USA .
    Leschinger, Monika I.
    Lilly Deutschland GmbH, Germany .
    von Pawel, Joachim
    Asklepios Hospital Munchen Gauting, Germany .
    A randomised phase II study of pemetrexed versus pemetrexed plus erlotinib as second-line treatment for locally advanced or metastatic non-squamous non-small cell lung cancer2014In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 50, no 9, p. 1571-1580Article in journal (Refereed)
    Abstract [en]

    Introduction: Pemetrexed and erlotinib have been approved as second-line monotherapy for locally advanced or metastatic non-small cell lung cancer (NSCLC). This multicentre, randomised, open-label, parallel phase II study assessed efficacy and safety of pemetrexed versus pemetrexed + erlotinib in patients with advanced non-squamous NSCLC. Methods: NSCLC stage III-IV patients who failed one prior platinum-based chemotherapy regimen, greater than= 1 measurable lesion by Response Evaluation Criteria in Solid Tumors, and Eastern Cooperative Oncology Group performance status less than= 2 were eligible. Patients received pemetrexed 500 mg/m(2) with vitamin B-12 and folic acid q3w alone or combined with erlotinib 150 mg daily. The primary end-point was progression-free survival (PFS). Secondary end-points were overall survival (OS), time-to-treatment failure (TTTF), response and toxicity. Results: Of 165 randomised non-squamous patients, 159 were treated (pemetrexed: 83; pemetrexed + erlotinib: 76). The median PFS (months; 95% CI) was 2.89 (1.94, 3.38) for pemetrexed versus 3.19 (2.86, 4.70) for pemetrexed + erlotinib (hazard ratio [HR] 0.63; 95% CI: (0.44, 0.90); P = 0.0047). The median OS (months; 95% CI) was 7.75 (5.29, 10.41) for pemetrexed versus 11.83 (8.18, 16.66) for pemetrexed + erlotinib (HR: 0.68; 95% CI: 0.46, 0.98; P = 0.019). The median TTTF (months: 95% CI) was 2.4 (1.74, 2.99) for pemetrexed versus 3.0 (2.23, 4.07) for pemetrexed + erlotinib (HR 0.64; 95% CI: 0.46, 0.89; P = 0.0034). One patient died in pemetrexed + erlotinib arm due to febrile neutropenia. Grades 3/4 drug-related toxicities (in greater than= 5% of patients) in pemetrexed/pemetrexed + erlotinib were febrile neutropenia (2.4%/10.5%), diarrhoea (1.2%/5.3%), rash (1.2%/9.2%); anaemia (6%/11.8%), leukopenia (9.6%/23.7%), neutropenia (9.6%/25.0%), and thrombocytopenia (4.8%/14.5%). Conclusions: Pemetrexed + erlotinib treatment significantly improved PFS, OS and TTTF in 2nd line non-squamous NSCLC and was associated with an increase in grade 3/4 toxicities compared with pemetrexed alone.

  • 229.
    Dong, Mei
    et al.
    Shandong University, Peoples R China .
    Yang, Xiaoyan
    Shandong University, Peoples R China .
    Lim, Sharon
    Karolinska Institute, Sweden .
    Cao, Ziquan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Honek, Jennifer
    Karolinska Institute, Sweden .
    Lu, Huixia
    Shandong University, Peoples R China .
    Zhang, Cheng
    Shandong University, Peoples R China .
    Seki, Takahiro
    Karolinska Institute, Sweden .
    Hosaka, Kayoko
    Karolinska Institute, Sweden .
    Wahlberg, Eric
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Yang, Jianmin
    Shandong University, Peoples R China .
    Zhang, Lei
    Shandong University, Peoples R China .
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Sun, Baocun
    Tianjin Medical University, Peoples R China .
    Li, Xuri
    Sun Yat Sen University, Peoples R China .
    Liu, Yizhi
    Sun Yat Sen University, Peoples R China .
    Zhang, Yun
    Shandong University, Peoples R China .
    Cao, Yihai
    Karolinska Institute, Sweden .
    Cold Exposure Promotes Atherosclerotic Plaque Growth and Instability via UCP1-Dependent Lipolysis2013In: Cell Metabolism, ISSN 1550-4131, E-ISSN 1932-7420, Vol. 18, no 1, p. 118-129Article in journal (Refereed)
    Abstract [en]

    Molecular mechanisms underlying the cold-associated high cardiovascular risk remain unknown. Here, we show that the cold-triggered food-intake-independent lipolysis significantly increased plasma levels of small low-density lipoprotein (LDL) remnants, leading to accelerated development of atherosclerotic lesions in mice. In two genetic mouse knockout models (apolipoprotein E-/- [ApoE(-/-)] and LDL receptor(-/-) [Ldlr(-/-)] mice), persistent cold exposure stimulated atherosclerotic plaque growth by increasing lipid deposition. Furthermore, marked increase of inflammatory cells and plaque-associated microvessels were detected in the cold-acclimated ApoE(-/-) and Ldlr(-/-) mice, leading to plaque instability. Deletion of uncoupling protein 1 (UCP1), a key mitochondrial protein involved in thermogenesis in brown adipose tissue (BAT), in the ApoE(-/-) strain completely protected mice from the cold-induced atherosclerotic lesions. Cold acclimation markedly reduced plasma levels of adiponectin, and systemic delivery of adiponectin protected ApoE(-/-) mice from plaque development. These findings provide mechanistic insights on low-temperature-associated cardiovascular risks.

  • 230.
    Dulai, Parambir S
    et al.
    University of California at San Diego, La Jolla, CA..
    Singh, Siddharth
    University of California at San Diego, La Jolla, CA.
    Patel, Janki
    University of California at San Diego, La Jolla, CA.
    Soni, Meera
    University of California at San Diego, La Jolla, CA.
    Prokop, Larry J
    Mayo Clinic, Rochester, Minnesota.
    Younossi, Zobair
    Department of Medicine, Inova Fairfax Hospital, Falls Church, VA.
    Sebastiani, Giada
    McGill University Health Centre, Montreal, Quebec, Canada.
    Ekstedt, Mattias
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Hagstrom, Hannes
    Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Nasr, Patrik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Stal, Per
    Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Wong, Vincent Wai-Sun
    Chinese University of Hong Kong, Hong Kong.
    Kechagias, Stergios
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Hultcrantz, Rolf
    Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Loomba, Rohit
    University of California at San Diego, La Jolla, CA.
    Increased risk of mortality by fibrosis stage in non-alcoholic fatty liver disease: Systematic Review and Meta-analysis.2017In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 65, no 5, p. 1557-1565Article, review/survey (Refereed)
    Abstract [en]

    BACKGROUND: Liver fibrosis is the most important predictor of mortality in nonalcoholic fatty liver disease (NAFLD). Quantitative risk of mortality by fibrosis stage has not been systematically evaluated. We aimed to quantify the fibrosis stage-specific risk of all-cause and liver-related mortality in NAFLD.

    METHODS: Through a systematic review and meta-analysis, we identified 5 adult NAFLD cohort studies reporting fibrosis stage specific mortality (0-4). Using fibrosis stage 0 as a reference population, fibrosis stage-specific mortality rate ratios (MRR) with 95% confidence intervals (CI), for all-cause and liver-related mortality, were estimated. The study is reported according to the PRISMA statement.

    RESULTS: 1,495 NAFLD patients with 17,452 patient years of follow-up were included. Compared to NAFLD patients with no fibrosis (stage 0), NAFLD patients with fibrosis were at an increased risk for all-cause mortality and this risk increased with increase in the stage of fibrosis: stage 1, MRR, 1.58 (95% CI 1.19-2.11); stage 2, MRR, 2.52 (95% CI 1.85-3.42); stage 3, MRR, 3.48 (95% CI 2.51-4.83), and stage 4, MRR, 6.40 (95% CI 4.11-9.95). The results were more pronounced as the risk of liver-related mortality increased exponentially with increase in the stage of fibrosis: stage 1, MRR, 1.41 (95% CI 0.17-11.95); stage 2, MRR, 9.57 (95% CI 1.67-54.93); stage 3, MRR, 16.69 (95% CI 2.92-95.36); and stage 4, MRR, 42.30 (95% CI 3.51-510.34).

    LIMITATIONS: Inability to adjust for co-morbid conditions or demographics known to impact fibrosis progression in NAFLD, and the inclusion of patients with simple steatosis and NASH without fibrosis in the reference comparison group.

    CONCLUSION: The risk of liver-related mortality increases exponentially with increase in fibrosis stage. These data have important implications in assessing utility of each stage and benefits of regression of fibrosis from one stage to another. This article is protected by copyright. All rights reserved.

  • 231.
    Dyverfeldt, Petter
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Bissell, Malenka
    University of Oxford, England.
    Barker, Alex J.
    Northwestern University, IL 60611 USA.
    Bolger, Ann F
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. University of Calif San Francisco, CA USA.
    Carlhäll, Carljohan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Francios, Christopher J.
    University of Wisconsin, WI 53706 USA.
    Frydrychowicz, Alex
    University Hospital Schleswig Holstein, Germany.
    Geiger, Julia
    University of Childrens Hospital Zurich, Switzerland.
    Giese, Daniel
    University Hospital Cologne, Germany.
    Hope, Michael D.
    University of Calif San Francisco, CA USA.
    Kilner, Philip J.
    University of London Imperial Coll Science Technology and Med, England.
    Kozerke, Sebastian
    University of Zurich, Switzerland; ETH, Switzerland.
    Myerson, Saul
    University of Oxford, England.
    Neubauer, Stefan
    University of Oxford, England.
    Wieben, Oliver
    University of Wisconsin, WI 53706 USA.
    Markl, Michael
    Northwestern University, IL 60611 USA; Northwestern University, IL 60611 USA.
    4D flow cardiovascular magnetic resonance consensus statement2015In: Journal of Cardiovascular Magnetic Resonance, ISSN 1097-6647, E-ISSN 1532-429X, Vol. 17, no 72Article, review/survey (Refereed)
    Abstract [en]

    Pulsatile blood flow through the cavities of the heart and great vessels is time-varying and multidirectional. Access to all regions, phases and directions of cardiovascular flows has formerly been limited. Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) has enabled more comprehensive access to such flows, with typical spatial resolution of 1.5x1.5x1.5 - 3x3x3 mm(3), typical temporal resolution of 30-40 ms, and acquisition times in the order of 5 to 25 min. This consensus paper is the work of physicists, physicians and biomedical engineers, active in the development and implementation of 4D Flow CMR, who have repeatedly met to share experience and ideas. The paper aims to assist understanding of acquisition and analysis methods, and their potential clinical applications with a focus on the heart and greater vessels. We describe that 4D Flow CMR can be clinically advantageous because placement of a single acquisition volume is straightforward and enables flow through any plane across it to be calculated retrospectively and with good accuracy. We also specify research and development goals that have yet to be satisfactorily achieved. Derived flow parameters, generally needing further development or validation for clinical use, include measurements of wall shear stress, pressure difference, turbulent kinetic energy, and intracardiac flow components. The dependence of measurement accuracy on acquisition parameters is considered, as are the uses of different visualization strategies for appropriate representation of time-varying multidirectional flow fields. Finally, we offer suggestions for more consistent, user-friendly implementation of 4D Flow CMR acquisition and data handling with a view to multicenter studies and more widespread adoption of the approach in routine clinical investigations.

  • 232.
    Dyverfeldt, Petter
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Comparison of Respiratory Motion Suppression Techniques for 4D Flow MRI2017In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 78, no 5, p. 1877-1882Article in journal (Refereed)
    Abstract [en]

    Purpose: The purpose of this work was to assess the impact of respiratory motion and to compare methods for suppression of respiratory motion artifacts in 4D Flow MRI. Methods: A numerical 3D aorta phantom was designed based on an aorta velocity field obtained by computational fluid mechanics. Motion-distorted 4D Flow MRI measurements were simulated and several different motion-suppression techniques were evaluated: Gating with fixed acceptance window size, gating with different window sizes in inner and outer kspace, and k-space reordering. Additionally, different spatial resolutions were simulated. Results: Respiratory motion reduced the image quality. All motion-suppression techniques improved the data quality. Flow rate errors of up to 30% without gating could be reduced to less than 2.5% with the most successful motion suppression methods. Weighted gating and gating combined with kspace reordering were advantageous compared with conventional fixed-window gating. Spatial resolutions finer than the amount of accepted motion did not lead to improved results. Conclusion: Respiratory motion affects 4D Flow MRI data. Several different motion suppression techniques exist that are capable of reducing the errors associated with respiratory motion. Spatial resolutions finer than the degree of accepted respiratory motion do not result in improved data quality. (C) 2017 International Society for Magnetic Resonance in Medicine.

  • 233.
    Dyverfeldt, Petter
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Letter by Dyverfeldt and Ebbers regarding article "Estimation of turbulent kinetic energy using 4D phase-contrast MRI: Effect of scan parameters and target vessel size"2016In: Magnetic Resonance Imaging, ISSN 0730-725X, E-ISSN 1873-5894, Vol. 34, no 8, p. 1226-1226Article in journal (Other academic)
    Abstract [en]

    n/a

  • 234.
    Dyverfeldt, Petter
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Pulse wave velocity with 4D flow MRI: Systematic differences and age-related regional vascular stiffness2014In: Magnetic Resonance Imaging, ISSN 0730-725X, E-ISSN 1873-5894, Vol. 32, no 10, p. 1266-1271Article in journal (Refereed)
    Abstract [en]

    Purpose: The objective of this study was to compare multiple methods for estimation of PWV from 4D flow MRI velocity data and to investigate if 4D flow MRI-based PWV estimation with piecewise linear regression modeling of travel-distance vs. travel time is sufficient to discern age-related regional differences in PWV. Methods: 4D flow MRI velocity data were acquired in 8 young and Solder (age: 23 +/- 2 vs. 58 +/- 2 years old) normal volunteers. Travel-time and travel-distance were measured throughout the aorta and piecewise linear regression was used to measure global PWV in the descending aorta and regional PWV in three equally sized segments between the top of the aortic arch and the renal arteries. Six different methods for extracting travel-time were compared. Results: Methods for estimation of travel-time that use information about the whole flow waveform systematically overestimate PWV when compared to methods restricted to the upslope-portion of the waveforms (p less than 0.05). In terms of regional PWV, a significant interaction was found between age and location (p less than 0.05). The age-related differences in regional PWV were greater in the proximal compared to distal descending aorta. Conclusion: Care must be taken as different classes of methods for the estimation of travel-time produce different results. 4D flow MRI-based PWV estimation with piecewise linear regression modeling of travel-distance vs. travel time can discern age-related differences in regional PWV well in line with previously reported data.

  • 235.
    Dyverfeldt, Petter
    et al.
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Eriksson, Jonatan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Sigfridsson, Andreas
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Escobar Kvitting, John-Peder
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Carlhäll, Carljohan
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Bolger, Ann F.
    University of California San Francisco, San Francisco, California, USA.
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Extending 4D Flow Visualization to the Human Right Ventricle2009In: Proceedings of International Society for Magnetic Resonance in Medicine: 17th Scientific Meeting 2009, International Society for Magnetic Resonance in Medicine , 2009, p. 3860-3860Conference paper (Refereed)
    Abstract [en]

    The right ventricle has an important role in cardiovascular disease. However, because of the complex geometry and the sensitivity to the respiratory cycle, imaging of the right ventricle is challenging. We investigated whether 3D cine phase-contrast MRI can provide data with sufficient accuracy for visualizations of the 4D blood flow in the right ventricle. Whole-heart 4D flow measurements with optimized imaging parameters and post-processing tools were made in healthy volunteers. Pathlines emitted from the right atrium could be traced through the right ventricle to the pulmonary artery without leaving the blood pool and thereby met our criteria for sufficient accuracy.

  • 236.
    Dyverfeldt, Petter
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Sigfridsson, Andreas
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Knutsson, Hans
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, The Institute of Technology. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    A Novel MRI Framework for the Quantification of Any Moment of Arbitrary Velocity Distributions.2010In: Proc. Intl. Soc. Mag. Reson. Med. 18 (2010), ISMRM , 2010, p. 1359-1359Conference paper (Other academic)
    Abstract [en]

    Under the assumption that the intravoxel velocity distribution is symmetric about its mean, the well-known MRI phase-difference method permits an estimation of the mean velocity of a voxel. The mean velocity corresponds to the first moment of the velocity distribution. Here, a novel framework for the quantification of any moment of arbitrary spin velocity distributions is presented. Simulations on realistic velocity distributions demonstrate its application. The presented moment framework may assist in improving the understanding of existing MRI methods for the quantification of flow and motion and serve as a basis for the development of new methods.

  • 237.
    Dyverfeldt, Petter
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Sigfridsson, Andreas
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Knutsson, Hans
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Ebbers, Tino
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    MR flow imaging beyond the mean velocity: Estimation of the skew  and kurtosis of intravoxel velocity distributions2011In: ISMRM 2011, International Society for Magnetic Resonance in Medicine ( ISMRM ) , 2011Conference paper (Other academic)
  • 238.
    Eckard, Nathalie
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Janzon, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Levin, Lars-Åke
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Comment: Including Both Costs and Effects - The Challenge of Using Cost-Effectiveness Data in National-Level Policy-Making: A Response to Recent Commentaries2015In: International Journal of Health Policy and Management, ISSN 2322-5939, E-ISSN 2322-5939, Vol. 4, no 8, p. 565-566Article in journal (Other academic)
  • 239.
    Eckard, Nathalie
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Nedlund, Ann-Charlotte
    Linköping University, Department of Social and Welfare Studies, NISAL - National Institute for the Study of Ageing and Later Life. Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Janzon, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Levin, Lars-Åke
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Reaching agreement in uncertain circumstances: the practice of evidence-based policy in the case of the Swedish National Guidelines for heart diseases2017In: Evidence and Policy: A Journal of Research, Debate and Practice, ISSN 1744-2648, no 4, p. 687-707Article in journal (Refereed)
    Abstract [en]

    This paper explores the practice of evidence-based policy in a Swedish healthcare context. The study focused on how policymakers in the specific working group, the Priority-Setting Group (PSG), handled the various forms of evidence and values and their competing rationalities, when producing the Swedish National Guidelines for heart diseases that are based on both clinical and economic evidence and are established to support explicit priority-setting in healthcare. The study contributes to the theoretical and practical debate on evidence-based policy (EBP) by illustrating how the practical tensions of coming to agreement were managed, to a large extent, through deliberation and by creativity.

  • 240.
    Eckerblad, Jeanette
    et al.
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences.
    Tödt, Kristina
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences. Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Jakobsson, Per
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Unosson, Mitra
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Health Sciences.
    Skargren, Elisabeth
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Health Sciences.
    Kentsson, M.
    Ryhov Hospital, Jönköping, Sweden.
    Theander, K.
    Karlstad University, Sweden; Värmland County Council, Karlstad, Sweden.
    Symptom burden in stable COPD patients with moderate or severe airflow limitation2014In: Heart & Lung, ISSN 0147-9563, E-ISSN 1527-3288, Vol. 43, no 4, p. 351-357Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    To describe a multidimensional symptom profile in patients with stable chronic obstructive pulmonary disease (COPD) and determine whether symptom experience differed between patients with moderate or severe airflow limitations.

    BACKGROUND:

    Patients with severe airflow limitation experience numerous symptoms, but little is known regarding patients with moderate airflow limitation.

    METHODS:

    A multidimensional symptom profile (Memorial Symptom Assessment Scale) was assessed in 42 outpatients with moderate and 49 with severe airflow limitations.

    RESULTS:

    The mean number of symptoms in the total sample was 7.9 (±4.3) with no difference between patients with moderate and severe airflow limitations. The most prevalent symptoms with the highest MSAS symptom burden scores were shortness of breath, dry mouth, cough, sleep problems, and lack of energy in both groups.

    CONCLUSIONS:

    Patients with moderate or severe airflow limitations experience multiple symptoms with high severity and distress. An assessment of their multidimensional symptom profile might contribute to better symptom management.

  • 241.
    Edelbring, Samuel
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institutet.
    Karlsson, Katarina
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Meyer, Frida
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Tamás, Éva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Utvärdering av IPL-simulering på Clinicum: Simuleringsdag ”Akuta situationer” för sistaårsstudenter från sjuksköterske- och läkarprogrammen HT 20162017Report (Other academic)
    Abstract [sv]

    En gemensam simuleringsdag för sjuksköterske- och läkarstudenter har utvärderats och diskuteras här i relation till interprofessionellt lärande och simuleringsbaserat lärande.

    IPL-simuleringen kännetecknas av ett starkt studentengagemang och upplevs som mycket relevant och kliniskt autentisk. Den simuleringsbaserade satsningen är alltså fortsatt aktuell och har utvecklats till en hög nivå med relevans för lärande och klinisk förberedelse. Innehållet rör såväl kliniska som team­relaterade kunskaper och kompetenser. Simulering som undervisningsform uppskattas högt och simulerings­instruktörens bidrag till lärandet lyfts fram. Ambitionsnivån kan ytterligare höjas på några punkter. Kurskamraternas bidrag i lärandet kan ytterligare stärkas, likaså omvårdnads­innehållet i scenarierna.

    IPL-mål adresseras i aktiviteten, i synnerhet ökar teamsamverkan progressivt under dagen. Det inter­professionella lärandet kan stärkas ännu mer  genom att linjera tydligare med övriga IPL-moment samt knyta an till de uttalade IPL-curriculum-målen.

  • 242.
    Edenbrandt, Lars
    et al.
    Lund University, Sweden Sahlgrens University Hospital, Sweden EXINI Diagnost AB, Sweden .
    Hoglund, Peter
    Skåne University Hospital, Sweden .
    Frantz, Sophia
    Lund University, Sweden .
    Hasbak, Philip
    Rigshosp, Denmark .
    Johansen, Allan
    Odense University Hospital, Denmark .
    Johansson, Lena
    Sahlgrens University Hospital, Sweden .
    Kammeier, Annett
    Ruhr University of Bochum, Germany .
    Lindner, Oliver
    Ruhr University of Bochum, Germany .
    Lomsky, Milan
    Sahlgrens University Hospital, Sweden .
    Matsuo, Shinro
    Kanazawa University, Japan .
    Nakajima, Kenichi
    Kanazawa University, Japan .
    Nystrom, Karin
    EXINI Diagnost AB, Sweden .
    Olsson, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Sjostrand, Karl
    EXINI Diagnost AB, Sweden .
    Svensson, Sven-Eric
    Blekingesjukhuset, Sweden .
    Wakabayashi, Hiroshi
    Kanazawa University, Japan .
    Tragardh, Elin
    Lund University, Sweden .
    Area of ischemia assessed by physicians and software packages from myocardial perfusion scintigrams2014In: BMC Medical Imaging, ISSN 1471-2342, E-ISSN 1471-2342, Vol. 14, no 5Article in journal (Refereed)
    Abstract [en]

    Background: The European Society of Cardiology recommends that patients with greater than 10% area of ischemia should receive revascularization. We investigated inter-observer variability for the extent of ischemic defects reported by different physicians and by different software tools, and if inter-observer variability was reduced when the physicians were provided with a computerized suggestion of the defects. Methods: Twenty-five myocardial perfusion single photon emission computed tomography (SPECT) patients who were regarded as ischemic according to the final report were included. Eleven physicians in nuclear medicine delineated the extent of the ischemic defects. After at least two weeks, they delineated the defects again, and were this time provided a suggestion of the defect delineation by EXINI Heart(TM) (EXINI). Summed difference scores and ischemic extent values were obtained from four software programs. Results: The median extent values obtained from the 11 physicians varied between 8% and 34%, and between 9% and 16% for the software programs. For all 25 patients, mean extent obtained from EXINI was 17.0% (+/- standard deviation (SD) 14.6%). Mean extent for physicians was 22.6% (+/- 15.6%) for the first delineation and 19.1% (+/- 14.9%) for the evaluation where they were provided computerized suggestion. Intra-class correlation (ICC) increased from 0.56 (95% confidence interval (CI) 0.41-0.72) to 0.81 (95% CI 0.71-0.90) between the first and the second delineation, and SD between physicians were 7.8 (first) and 5.9 (second delineation). Conclusions: There was large variability in the estimated ischemic defect size obtained both from different physicians and from different software packages. When the physicians were provided with a suggested delineation, the inter-observer variability decreased significantly.

  • 243.
    Edner, Magnus
    et al.
    Karolinska Institute, Sweden.
    Benson, Lina
    Karolinska Institute, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lund, Lars H.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Association between renin-angiotensin system antagonist use and mortality in heart failure with severe renal insufficiency: a prospective propensity score-matched cohort study2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no 34, p. 2318-2326Article in journal (Refereed)
    Abstract [en]

    Aims In heart failure (HF) with reduced ejection fraction (EF), renin-angiotensin receptor (RAS) antagonists reduce mortality. However, severe renal insufficiency was an exclusion criterion in trials. We tested the hypothesis that RAS antagonists are associated with reduced mortality also in HF with severe renal insufficiency. Methods and results We studied patients with EF less than= 39% registered in the prospective Swedish Heart Failure Registry. In patients with creatinine greater than221 mu mol/L or creatinine clearance less than30 mL/min, propensity scores for RAS-antagonist use were derived from 36 variables. The association between RAS antagonist use and all-cause mortality was assessed with Cox regression in a cohort matched 1:1 based on age and propensity score. To assess consistency, we performed the same analysis as a positive control in patients without severe renal insufficiency. Between 2000 and 2013, there were 24 283 patients of which 2410 [age, mean (SD), 82 (9), 45% women] had creatinine greater than221 mu mol/L or creatinine clearance less than30 mL/min and were treated (n = 1602) or not treated (n = 808) with RAS antagonists. In the matched cohort of 602 vs. 602 patients [age 83 (8), 42% women], RAS antagonist use was associated with 55% [95% confidence interval (CI) 51-59] vs. 45% (41-49) 1-year survival, P less than 0.001, with a hazard ratio (HR) for mortality of 0.76 (95% CI 0.67-0.86, P less than 0.001). In positive control patients without severe renal insufficiency [n = 21 873; age 71 (12), 27% women], the matched HR was 0.79 (95% CI 0.72-0.86, P less than 0.001). Conclusion In HF with severe renal insufficiency, the use of RAS antagonists was associated with lower all-cause mortality. Prospective randomized trials are needed before these findings can be applied to clinical practice.

  • 244.
    Ekerstad, Niklas
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences. NU NAL Uddevalla Hosp Grp, Sweden.
    Pettersson, Staffan
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Alexander, Karen
    Duke Clin Res Inst, NC USA.
    Andersson, David
    Linköping University, Department of Management and Engineering, Economics. Linköping University, Faculty of Arts and Sciences.
    Eriksson, Sofia
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Janzon, Magnus
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Lindenberger, Marcus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Swahn, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Alfredsson, Joakim
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Frailty as an instrument for evaluation of elderly patients with non-ST-segment elevation myocardial infarction: A follow-up after more than 5 years2018In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 25, no 17, p. 1813-1821Article in journal (Refereed)
    Abstract [en]

    Background There is a growing body of evidence on the relevance of using frailty measures also in a cardiovascular context. The estimated time to death is crucial in clinical decision-making in cardiology. However, data on the importance of frailty in long-term mortality are very scarce. The aim of the study was to assess the prognostic value of frailty on mortality at long-term follow-up of more than 5 years in patients 75 years or older hospitalised for non-ST-segment elevation myocardial infarction. We hypothesised that frailty is independently associated with long-term mortality. Design This was a prospective, observational study conducted at three centres. Methods and results Frailty was assessed according to the Canadian Study of Health and Aging clinical frailty scale (CFS). Of 307 patients, 149 (48.5%) were considered frail according to the study instrument (degree 5-7 on the scale). The long-term all-cause mortality of more than 5 years (median 6.7 years) was significantly higher among frail patients (128, 85.9%) than non-frail patients (85, 53.8%), (P amp;lt; 0.001). In Cox regression analysis, frailty was independently associated with mortality from the index hospital admission to the end of follow-up (hazard ratio 2.06, 95% confidence interval 1.51-2.81; P amp;lt; 0.001) together with age (P amp;lt; 0.001), ejection fraction (P = 0.012) and Charlson comorbidity index (P = 0.018). Conclusions In elderly non-ST-segment elevation myocardial infarction patients, frailty was independently associated with all-cause mortality at long-term follow-up of more than 6 years. The combined use of frailty and comorbidity may be the ultimate risk prediction concept in the context of cardiovascular patients with complex needs.

  • 245.
    Ekerstad, Niklas
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences.
    Swahn, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Janzon, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Alfredsson, Joakim
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Löfmark, Rurik
    Stockholm Centre for Healthcare Ethics, LIME, Karolinska Institutet, Sweden .
    Lindenberger, Marcus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping. Ryhov County Hospital, Jönköping, Sweden .
    Andersson, David
    Linköping University, Department of Management and Engineering, Economics. Linköping University, Faculty of Arts and Sciences.
    Carlsson, Per
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences.
    Frailty is independently associated with 1-year mortality for elderly patients with non-ST-segment elevation myocardial infarction2014In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 21, no 10, p. 1216-1224Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: For the large population of elderly patients with cardiovascular disease, it is crucial to identify clinically relevant measures of biological age and their contribution to risk. Frailty is denoting decreased physiological reserves and increased vulnerability. We analysed the manner in which the variable frailty is associated with 1-year outcomes for elderly non-ST-segment elevation myocardial infarction (NSTEMI) patients. METHODS AND RESULTS: Patients aged 75 years or older, with diagnosed NSTEMI were included at three centres, and clinical data including judgment of frailty were collected prospectively. Frailty was defined according to the Canadian Study of Health and Aging Clinical Frailty Scale. Of 307 patients, 149 (48.5%) were considered frail. By Cox regression analyses, frailty was found to be independently associated with 1-year mortality after adjusting for cardiovascular risk and comorbid conditions (hazard ratio 4.3, 95% CI 2.4-7.8). The time to the first event was significantly shorter for frail patients than for nonfrail (34 days, 95% CI 10-58, p = 0.005). CONCLUSIONS: Frailty is strongly and independently associated with 1-year mortality. The combined use of frailty and comorbidity may constitute an important risk prediction concept in regard to cardiovascular patients with complex needs.

  • 246.
    Ekerstad, Niklas
    et al.
    Linköping University, Department of Medical and Health Sciences, Health Technology Assessment and Health Economics. Linköping University, Faculty of Health Sciences.
    Swahn, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Janzon, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Alfredsson, Joakim
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Löfmark, Rurik
    LIME, Karolinska Institutet, Stockholm, Sweden.
    Lindenberger, Marcus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Carlsson, Per
    Linköping University, Department of Medical and Health Sciences, Health Technology Assessment and Health Economics. Linköping University, Faculty of Health Sciences.
    Frailty is independently associated with short-term outcomes for elderly patients with non-st-segment elevation myocardial infarction2012Conference paper (Refereed)
  • 247.
    Ekman, Bertil
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Alstrand, N
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences. County Hospital, Kalmar .
    Bachrach-Lindström, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria C
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Wahlberg, Jeanette
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Altered Chemokine Th1/Th2 Balance in Addison's Disease: Relationship with Hydrocortisone Dosing and Quality of Life2014In: Hormone and Metabolic Research, ISSN 0018-5043, E-ISSN 1439-4286, Vol. 46, no 1, p. 48-53Article in journal (Refereed)
    Abstract [en]

    The adrenalitis found in autoimmune Addison’s disease (AAD) is considered having a Th1-driven pathogenesis. Circulating Th1- and Th2-associated chemokines responsible for the trafficking of leukocytes to inflammatory sites are markers for the Th1/Th2 balance. The aim of the study was to assess if the same daily hydrocortisone dose of 30 mg given in either 2 or 4 doses to patients with AAD could affect the Th1/Th2 balance of circulating chemokines.

    Fifteen patients (6 women) with AAD were included in this randomised, placebo controlled, double blind cross-over study. Samples for chemokines, Th1-associated (CXCL10, CXCL11) and Th2-associated (CCL17, CCL22), were drawn 5 times during a 24-h period at the end of each treatment period and analysed with Luminex. Seven control subjects did the same diurnal blood sampling once. Subjects with AAD had higher median diurnal levels of the Th1-associated chemokines than controls, CXCL10 [43 (33–56) pg/ml vs. 22 (19–34) pg/ml, p<0.01] and CXCL11 [37 (29–48) pg/ml vs. 16 (9–24) pg/ml, p<0.001], whereas no significant difference was found regarding the Th2-related chemokines. Similar chemokine levels were found when the same hydrocortisone dose of 30 mg was divided in 2 or 4 doses. Levels of CXCL11 correlated negatively with scores of SF-36 domains (high score indicate better health) of General Health (GH) and total score for Physical Component Summary (PCS), and these negative correlations were most pronounced at 04:00 h on the 2-dose regimen. Patients with AAD have a dominant Th1 chemokine profile that partially correlates to reduced quality of life.

  • 248.
    Ekman, Bertil
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Fitts, David
    ViroPharma Incorporated, Exton, Pennsylvania, USA .
    Marelli, Claudio
    ViroPharma SPRL, Maidenhead, UK .
    Murray, Robert D.
    St James’s University Hospital, Leeds, UK .
    Quinkler, Marcus
    Charité University of Medicine, Berlin, Germany .
    Zelissen, Pierre M. J.
    University Medical Center Utrecht, Netherlands .
    European Adrenal Insufficiency Registry (EU-AIR): a comparative observational study of glucocorticoid replacement therapy2014In: BMC Endocrine Disorders, ISSN 1472-6823, E-ISSN 1472-6823, Vol. 14, no 40Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Increased morbidity and mortality associated with conventional glucocorticoid replacement therapy for primary adrenal insufficiency (primary AI; estimated prevalence 93-140/million), secondary AI (estimated prevalence, 150-280/million, respectively) or congenital adrenal hyperplasia (estimated prevalence, approximately 65/million) may be due to the inability of typical glucocorticoid treatment regimens to reproduce the normal circadian profile of plasma cortisol. A once-daily modified-release formulation of hydrocortisone has been developed to provide a plasma cortisol profile that better mimics the daytime endogenous profile of cortisol. Here, we describe the protocol for the European Adrenal Insufficiency Registry (EU-AIR), an observational study to assess the long-term safety of modified-release hydrocortisone compared with conventional glucocorticoid replacement therapies in routine clinical practice (ClinicalTrials.gov identifier: NCT01661387).

    METHODS:

    Patients enrolled in EU-AIR have primary or secondary AI and are receiving either modified-release or conventional glucocorticoid replacement therapy. The primary endpoints of EU-AIR are the incidence of intercurrent illness, adrenal crisis and serious adverse events (SAEs), as well as the duration of SAEs and dose changes related to SAEs. Data relating to morbidity, mortality, adverse drug reactions, dosing and concomitant therapies will be collected. Patient diaries will record illness-related dose changes between visits. All decisions concerning medical care are made by the registry physician and patient. Enrolment is targeted at achieving 3600 patient-years of treatment (1800 patient-years per group) for the primary analysis, which is focused on determining the non-inferiority of once-daily modified-release replacement therapy compared with conventional glucocorticoid therapy.

    RESULTS:

    Recruitment began in August 2012 and, as of March 2014, 801 patients have been enrolled. Fifteen centres are participating in Germany, the UK and Sweden, with recruitment soon to be initiated in the Netherlands.

    CONCLUSIONS:

    EU-AIR will provide a unique opportunity not only to collect long-term safety data on a modified-release preparation of glucocorticoid but also to evaluate baseline data on conventional glucocorticoid replacement. Such data should help to improve the treatment of AI.

  • 249.
    Ekman, Bertil
    et al.
    Region Östergötland, Heart and Medicine Center, Department of Endocrinology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Wahlberg Topp, Jeanette
    Region Östergötland, Heart and Medicine Center, Department of Endocrinology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Landberg, Eva
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences.
    Urine oligosaccharide pattern in patients with hyperprolactinaemia2015In: Glycoconjugate Journal, ISSN 0282-0080, E-ISSN 1573-4986, Vol. 32, no 8, p. 635-641Article in journal (Refereed)
    Abstract [en]

    Free milk-type oligosaccharides are produced during pregnancy and lactation and may have an impact on several cells in the immune system. Our aim was to investigate if patients with isolated hyperprolactinaemia, not related to pregnancy, also have increased synthesis and urinary excretion of milk-type oligosaccharides and to compare the excretion pattern with that found during pregnancy. Urine samples were collected as morning sample from 18 patients with hyperprolactinaemia, 13 healthy controls with normal prolactin levels and four pregnant women. After purification, lactose and free oligosaccharides were analysed and quantified by high-performance anion-exchange chromatography with pulsed amperometric detection. The identity of peaks was confirmed by exoglycosidase treatment and comparison with oligosaccharide standards. Prolactin was measured in serum collected between 09 and 11 a.m. by a standardized immunochemical method. Patients with hyperprolactinaemia had higher urinary excretion of lactose than normoprolactinemic controls and urinary lactose correlated positively to prolactin levels (r = 0.51, p less than 0.05). Increased levels of the fucosylated oligosaccharides 2-fucosyl lactose and lacto-di-fucotetraose were found in urine from three and two patients, respectively. The acidic oligosaccharide 3-sialyl lactose was found in high amount in urine from two patients with prolactin of greater than 10,000 mU/l. However, pregnant women in their third trimester had the highest concentration of all these oligosaccharides and excretion increased during pregnancy. This study is first to show that both lactose and certain fucosylated and sialylated milk-type oligosaccharides are increased in some patients with hyperprolactinaemia. It remains to elucidate the functional importance of these findings.

  • 250.
    Ekstedt, Mattias
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Hagström, Hannes
    Unit of Gastroenterology and Hepatology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm .
    Nasr, Patrik
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Stal, Per
    Unit of Gastroenterology and Hepatology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm .
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Gastroentorology.
    Hultcrantz, Rolf
    Unit of Gastroenterology and Hepatology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm.
    Nonalcoholic Fatty Liver Disease Activity Score and Mortality: Imperfect But Not Insignificant REPLY2016In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 64, no 1, p. 310-311Article in journal (Refereed)
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