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  • 201.
    Clavarino, Giovanna
    et al.
    Ctr Hosp Univ Grenoble Alpes, France; Univ Grenoble Alpes, France.
    Gauthier, Arnaud
    Ctr Hosp Univ Grenoble Alpes, France.
    Hellmark, Thomas
    Lund Univ, Sweden.
    Carron, Pierre-Louis
    Ctr Hosp Univ Grenoble Alpes, France.
    Giovannini, Diane
    Ctr Hosp Univ Grenoble Alpes, France.
    Colliard, Sophie
    Ctr Hosp Univ Grenoble Alpes, France.
    Dragon-Durey, Marie-Agnes
    Hop Europeen Georges Pompidou, France.
    Segelmark, Mårten
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology.
    Cesbron, Jean-Yves
    Ctr Hosp Univ Grenoble Alpes, France; Univ Grenoble Alpes, France.
    Dumestre-Perard, Chantal
    Ctr Hosp Univ Grenoble Alpes, France; Univ Grenoble Alpes, France.
    Letter: Routinely used immunoassays do not detect circulating anti-GBM antibodies against native NC1 hexamer and EA epitope of the 3 chain of type IV collagen in EUROPEAN JOURNAL OF IMMUNOLOGY, vol 48, issue 6, pp 1082-10842018In: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 48, no 6, p. 1082-1084Article in journal (Other academic)
    Abstract [en]

    n/a

  • 202.
    Collet, Jean-Philippe
    et al.
    Sorbonne Université Paris 6, ACTION Study Group, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France.
    Kerneis, Mathieu
    Sorbonne Université Paris 6, ACTION Study Group, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France.
    Lattuca, Benoit
    Department of Cardiology, CHU Caremeau, Université de Montpellier, ACTION Study Group, Nimes, France.
    Yan, Yan
    Sorbonne Université Paris 6, ACTION Study Group, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France.
    Cayla, Guillaume
    Department of Cardiology, CHU Caremeau, Université de Montpellier, ACTION Study Group, Nimes, France.
    Silvain, Johanne
    Sorbonne Université Paris 6, ACTION Study Group, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France.
    Lapostolle, Frédéric
    SAMU 93 Hôpital Avicenne, Bobigny, France.
    Ecollan, Patrick
    Service Médical d’Urgence, Brigade de Sapeurs-Pompiers de Paris, Paris, France.
    Diallo, Abdourahmane
    ACTION Study Group, Unité de Recherche Clinique, Hôpital Lariboisière, Paris, France.
    Vicaut, Eric
    ACTION Study Group, Unité de Recherche Clinique, Hôpital Lariboisière, Paris, France.
    Hamm, Christian W
    Kerckhoff Klinik, Bad Nauheim, Universitätsklinikum Gießen, Giessen, Germany.
    Van 't Hof, Arnoud W
    Department of Cardiology, Isala Clinics, Zwolle, the Netherlands.
    Montalescot, Gilles
    Sorbonne Université Paris 6, ACTION Study Group, Hôpital Pitié-Salpêtrière (AP-HP), Paris, France.
    ATLANTIC Investigators, (Contributor)
    Impact of age on the effect of pre-hospital P2Y12 receptor inhibition in primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: the ATLANTIC-Elderly analysis2018In: EuroIntervention, ISSN 1774-024X, E-ISSN 1969-6213, Vol. 14, no 7, p. 789-797, article id EIJ-D-18-00182Article in journal (Refereed)
    Abstract [en]

    AIMS: The aim of the study was to examine the main results of the ATLANTIC trial in patients with ST-elevation myocardial infarction (STEMI), randomised to pre- versus in-hospital ticagrelor, according to age.

    METHODS AND RESULTS: Patients were evaluated by age class (<75 vs. ≥75 years) for demographics, prior cardiovascular history, risk factors, management, and outcomes. Elderly patients (≥75 years; 304/1,862) were more likely to be women, diabetic, lean, with a prior history of myocardial infarction and CABG, and with comorbidities (p<0.01 for all). Elderly patients presented more frequently with acute heart failure and less frequently had thromboaspiration, a stent implanted (p<0.01) and an aggressive antithrombotic regimen. Elderly patients had lower rates of pre- and post-PCI ≥70% ST-segment elevation resolution (43.9% vs. 51.6%; p=0.035), of pre- and post-PCI TIMI 3 flow (17.1% vs. 27.5%, p=0.0002), and a higher rate of the composite of death/MI/stroke/urgent revascularisation (9.9% vs. 2.9%; OR 3.67, 95% CI [2.27; 5.93], p<0.0001) and mortality (8.5% vs. 1.5%; OR 6.45, 95% CI [2.75; 15.11], p<0.0001). There was a non-significant trend towards more frequent major bleedings among elderly patients (TIMI major 2.3% vs. 1.1%; OR 2.13, 95% CI [0.88; 5.18], p=0.095). There was no significant interaction between time of ticagrelor administration (pre-hospital versus in-lab) and class of age for all outcomes.

    CONCLUSIONS: Elderly patients, who represented one sixth of the patients randomised in the ATLANTIC trial, had less successful mechanical reperfusion and a sixfold increase in mortality at 30 days, probably due to comorbidities and possible undertreatment. The effect of early ticagrelor was consistent irrespective of age.

  • 203.
    Cortez, Daniel
    et al.
    Lund University, Sweden; Penn State Milton S Hershey Medical Centre, PA 17033 USA.
    Svensson, Anneli
    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.
    Carlson, Jonas
    Lund University, Sweden.
    Graw, Sharon
    University of Colorado Denver AMC, CO USA.
    Sharma, Nandita
    Penn State Milton S Hershey Medical Centre, PA 17033 USA.
    Brun, Francesca
    University of Colorado Denver AMC, CO USA; Osped Riuniti, Italy; University of Trieste, Italy.
    Spezzacatene, Anita
    University of Colorado Denver AMC, CO USA; Osped Riuniti, Italy; University of Trieste, Italy.
    Mestroni, Luisa
    University of Colorado Denver AMC, CO USA; Osped Riuniti, Italy; University of Trieste, Italy.
    Platonov, Pyotr G.
    Lund University, Sweden; Skåne University Hospital, Sweden.
    Right precordial-directed electrocardiographical markers identify arrhythmogenic right ventricular cardiomyopathy in the absence of conventional depolarization or repolarization abnormalities2017In: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 17, article id 261Article in journal (Refereed)
    Abstract [en]

    Background: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) carries a risk of sudden death. We aimed to assess whether vectorcardiographic (VCG) parameters directed toward the right heart and a measured angle of the S-wave would help differentiate ARVD/C with otherwise normal electrocardiograms from controls. Methods: Task Force 2010 definite ARVD/C criteria were met for all patients. Those who did not fulfill Task Force depolarization or repolarization criteria (-ECG) were compared with age and gender-matched control subjects. Electrocardiogram measures of a 3-dimentional spatial QRS-T angle, a right-precordial-directed orthogonal QRS-T (RPD) angle, a root mean square of the right sided depolarizing forces (RtRMS-QRS), QRS duration (QRSd) and the corrected QT interval (QTc), and a measured angle including the upslope and downslope of the S-wave (S-wave angle) were assessed. Results: Definite ARVD/C was present in 155 patients by 2010 Task Force criteria (41.7 +/- 17.6 years, 65.2% male). -ECG ARVD/C patients (66 patients) were compared to 66 control patients (41.7 +/- 17.6 years, 65.2% male). All parameters tested except the QRSd and QTc significantly differentiated -ECG ARVD/C from control patients (p amp;lt; 0.004 to p amp;lt; 0.001). The RPD angle and RtRMS-QRS best differentiated the groups. Combined, the 2 novel criteria gave 81.8% sensitivity, 90.9% specificity and odds ratio of 45.0 (95% confidence interval 15.8 to 128.2). Conclusion: ARVD/C disease process may lead to development of subtle ECG abnormalities that can be distinguishable using right-sided VCG or measured angle markers better than the spatial QRS-T angle, the QRSd or QTc, in the absence of Taskforce ECG criteria.

  • 204.
    Cortez, Daniel
    et al.
    Lund Univ, Sweden; Penn State Milton S Hershey Med Ctr, PA USA; Univ Minnesota, MN USA.
    Svensson, Anneli
    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.
    Carlson, Jonas
    Lund Univ, Sweden.
    Graw, Sharon
    Univ Colorado Denver, CO USA; Univ Colorado Denver, CO USA.
    Sharma, Nandita
    Penn State Milton S Hershey Med Ctr, PA USA.
    Brun, Francesca
    Univ Colorado Denver, CO USA; Univ Colorado Denver, CO USA; Osped Riuniti, Italy; Univ Trieste, Italy.
    Spezzacatene, Anita
    Univ Colorado Denver, CO USA; Univ Colorado Denver, CO USA; Osped Riuniti, Italy; Univ Trieste, Italy.
    Mestroni, Luisa
    Univ Colorado Denver, CO USA; Univ Colorado Denver, CO USA; Osped Riuniti, Italy; Univ Trieste, Italy.
    Platonov, Pyotr G.
    Lund Univ, Sweden; Osped Riuniti, Italy; Univ Trieste, Italy; Skane Univ Hosp, Sweden.
    The S-wave angle identifies arrhythmogenic right ventricular cardiomyopathy in patients with electrocardiographically concealed disease phenotype2018In: Journal of Electrocardiology, ISSN 0022-0736, E-ISSN 1532-8430, Vol. 51, no 6, p. 1003-1008Article in journal (Refereed)
    Abstract [en]

    Background: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) carries risk of sudden death. We hypothesize that the S-wave angle differentiates ARVD/C with otherwise normal electrocardiograms from controls. Materials and methods: All patients met Task Force 2010 definite ARVD/C criteria. ARVD/C patients without Task Force depolarization/repolarization criteria (-ECG) were compared to controls. Electrocardiogram measures of QRS duration, corrected QT interval, and measured angle between the upslope and downslope of the S-wave in V2, were assessed. Results: Definite ARVD/C was present in 155 patients (42.7 +/- 17.3 years, 68.4%male). -ECG ARVD/C patients (66 patients) were compared to 66 control patients (41.8 +/- 17.6 years, 65.2%male). Only the S-wave angle differentiated -ECG ARVD/C patients from controls (amp;lt;0.001) with AU the ROC curve of 0.77 (95%Cl 0.53 to 0.71) and odds ratio of 28.3 (95%Cl 6.4 to 125.5). Conclusion: ARVD/C may lead to development of subtle ECG abnormalities distinguishable using the S-wave angle prior to development of 2010 Taskforce ECG criteria. (C) 2018 Elsevier Inc. All rights reserved.

  • 205.
    Cosedis Nielsen, Jens
    et al.
    Aarhus University Hospital, Denmark.
    Johannessen, Arne
    Gentofte University Hospital, Copenhagen, Denmark .
    Raatikainen, Pekka
    Heart Center Co. Tampere University Hospital, Tampere, Finland .
    Hindricks, Gerhard
    Leipzig University Hospital, Leipzig, Germany .
    Walfridsson, Håkan
    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.
    Pehrson, Steen Michael
    Department of Cardiology, The Heart Center, Rigshospitalet, Copenhagen, Denmark .
    Englund, Anders
    Department of Medicine, University Hospital, Örebro, Sweden .
    Hartikainen, Juha
    Kuopio University Hospital, Kuopio, Finland .
    Spange Mortensen, Leif
    UNI-C, Danish Information Technology Centre for Education and Research, Aarhus, Denmark .
    Steen Hansen, Peter
    MANTRA-PAF Investigators. UNI-C, Danish Information Technology Centre for Education and Research, Aarhus, Denmark .
    Long-term efficacy of catheter ablation as first-line therapy for paroxysmal atrial fibrillation: 5-year outcome in a randomised clinical trial2017In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 103, no 5, p. 370-378Article in journal (Refereed)
    Abstract [en]

    Objective The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial compared radiofrequency catheter ablation (RFA) with antiarrhythmic drug therapy (AAD) as first-line treatment for paroxysmal atrial fibrillation (AF). Endpoint of ablation was elimination of electrical activity inside pulmonary veins. We present the results of the 5-year follow-up.

    Methods This pre-specified 5-year follow-up included assessment of any AF and symptomatic AF burden by one 7-day Holter recording and quality of life (QoL) assessment, using SF-36 questionnaire physical and mental component scores. Analysis was intention-to-treat. Imputation was used to compensate for missing Holter data.

    Results 245 of 294 patients (83%) randomised to RFA (n=125) or AAD (n=120) attended the 5-year follow-up, 227 with Holter recording. Use of class I or III AAD was more frequent in AAD group (N=61 vs 13, p<0.001). More patients in the RFA group were free from AF (126/146 (86%) vs 105/148 (71%), p=0.001, relative risk (RR) 0.82; 95% CI 0.73 to 0.93) and symptomatic AF (137/146 (94%) vs 126/148 (85%), p=0.015, χ2 test, RR 0.91; 95% CI 0.84 to 0.98) in 7-day Holter recording. AF burden was significantly lower in the RFA group (any AF: p=0.003; symptomatic AF: p=0.02). QoL scores did not differ between randomisation groups. QoL scores remained improved from baseline (both components p<0.001), and did not differ from 2-year scores.

    Conclusions At 5 years, the occurrence and burden of any AF and symptomatic AF were significantly lower in the RFA group than in the AAD group. Improved QoL scores observed after 2 years persisted after 5 years without between-group differences.

  • 206.
    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.

  • 207.
    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.

  • 208.
    Crisci, Elisa
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ellegård, Rada
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nyström, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Rondahl, Elin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Serrander, Lena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Bergström, Tomas
    University of Gothenburg, Gothenburg, Sweden.
    Sjöwall, Christopher
    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 Rheumatology.
    Eriksson, Kristina
    University of Gothenburg, Gothenburg, Sweden.
    Larsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Complement opsonization promotes HSV-2 infection of human dendritic cells2016In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 90, no 10, p. 4939-4950Article in journal (Refereed)
    Abstract [en]

    Herpes virus type 2 (HSV2) is one of the most common sexually transmitted infections globally with a very high prevalence in many countries. During HSV2 infection viral particles become coated with complement proteins and antibodies, both existent in the genital fluids, which could influence the activation of the immune responses. In genital mucosa, the primary target cells for HSV2 infection are epithelial cells, but resident immune cells such as dendritic cells (DCs) are also infected. The DCs are the activators of the ensuing immune responses directed against HSV2, and the aim of this study was to examine the effects opsonization of HSV2, either with complement alone or with complement and antibodies, had on the infection of immature DCs and their ability to mount inflammatory and antiviral responses. Complement opsonization of HSV2 enhanced both the direct infection of immature DCs and their production of new infectious viral particles. The enhanced infection required activation of the complement cascade and functional complement receptor 3. Furthermore, HSV2 infection of DCs required endocytosis of viral particles and their delivery into an acid endosomal compartment. The presence of complement in combination with HSV1 or HSV2 specific antibodies more or less abolished the HSV2 infection of DCs.Our results clearly demonstrate the importance of studying HSV2 infection under conditions that ensue in vivo, i.e. when the virions are covered in complement fragments and complement fragments and antibodies, as this will shape the infection and the subsequent immune response and needs to be further elucidated.

    IMPORTANCE: During HSV2 infection viral particles should become coated with complement proteins and antibodies, both existent in the genital fluids, which could influence the activation of the immune responses. The dendritic cells are the activators of the immune responses directed against HSV2, and the aim of this study was to examine the effects of complement alone or complement and antibodies, on the HSV2 infection of dendritic cells and their ability to mount inflammatory and antiviral responses.Our results demonstrate that the presence of antibodies and complement in the genital environment can influence HSV2 infection under in vitro conditions that reflect the in vivo situation. We believe that our findings are highly relevant for the understanding of HSV2 pathogenesis.

  • 209.
    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.

  • 210.
    Daferera, Niki
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Kumar Kumawat, Ashok
    University of Örebro, Sweden.
    Hultgren-Hornquist, Elisabeth
    University of Örebro, Sweden.
    Ignatova, Simone
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Ström, Magnus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology. Linköping University, Faculty of Medicine and Health Sciences.
    Münch, Andreas
    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.
    Fecal stream diversion and mucosal cytokine levels in collagenous colitis: A case report2015In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 21, no 19, p. 6065-6071Article in journal (Refereed)
    Abstract [en]

    In this case report, we examined the levels of cytokines expressed before and during fecal stream diversion and after intestinal continuity was restored in a patient with collagenous colitis. We report the case of a 46-year-old woman with chronic, active collagenous colitis who either failed to achieve clinical remission or experienced adverse effects with the following drugs: loperamide, cholestyramine, budesonide, methotrexate and adalimumab. Due to the intractable nature of the disease and because the patient was having up to 15 watery bowel movements per day, she underwent a temporary ileostomy. Colonic biopsies were analyzed for mucosal cytokine protein levels before and during fecal stream diversion and after intestinal continuity was restored. Mucosal protein levels of interleukin (IL)-1 beta, IL-2, IL-6, IL-12, IL-17 A, IL-23, TNF, IFN-gamma, IL-4, IL-5, IL-10 and IL-13 were all higher during active disease and decreased to non-detectable or considerably lower levels during fecal stream diversion. One month after the restoration of bowel continuity, when the patient experienced a relapse of symptoms, IL-2, IL-23 and IL-21 levels were again increased. Our results indicate that fecal stream diversion in this patient suppressed the levels of all cytokines analyzed in colonic biopsies. With the recurrence of clinical symptoms and histological changes after bowel reconstruction, the levels of primarily proinflammatory cytokines increased. Our findings support the hypothesis that a luminal factor triggers the inflammation observed in collagenous colitis.

  • 211.
    Dahlen Gyllencreutz, J.
    et al.
    Skaraborg Hospital, Sweden.
    Paoli, J.
    University of Gothenburg, Sweden.
    Bjellerup, M.
    Lund University, Sweden.
    Bucharbajeva, Z.
    Umeå University, Sweden.
    Gonzalez, H.
    University of Gothenburg, Sweden.
    Nielsen, K.
    Lund University, Sweden.
    Sandberg, C.
    University of Gothenburg, Sweden.
    Synnerstad, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Linköping University, Faculty of Medicine and Health Sciences.
    Terstappen, K.
    Skaraborg Hospital, Sweden.
    Wennberg Larko, A. -M.
    University of Gothenburg, Sweden.
    Diagnostic agreement and interobserver concordance with teledermoscopy referrals2017In: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 31, no 5, p. 898-903Article in journal (Refereed)
    Abstract [en]

    BackgroundMalignant melanoma and non-melanoma skin cancers are among the fastest increasing malignancies in many countries. With the help of new tools, such as teledermoscopy referrals between primary health care and dermatology clinics, the management of these patients could be made more efficient. ObjectiveTo evaluate the diagnostic agreement and interobserver concordance achieved when assessing referrals sent through a mobile teledermoscopic referral system as compared to referrals sent via the current paper-based system without images. MethodsThe referral information from 80 teledermoscopy referrals and 77 paper referrals were evaluated by six Swedish dermatologists. They were asked to answer questions about the probable diagnosis, the priority, and a management decision. ResultsTeledermoscopy generally resulted in higher diagnostic agreement, better triaging and more malignant tumours being booked directly to surgery. The largest difference between the referral methods was seen for invasive melanomas. Referrals for benign lesions were significantly more often correctly resent to primary health care with teledermoscopy. However, referrals for cases of melanoma in situ were also incorrectly resent five times. The interobserver concordance was moderate with both methods. ConclusionBy adding clinical and dermoscopic images to referrals, the triage process for both benign and dangerous skin tumours can be improved. With teledermoscopy, patients with melanoma especially can receive treatment more swiftly.

  • 212.
    Dahlqvist, Per
    et al.
    Norrlands Universitetssjukhus, Umeå .
    Bensing, Sophie
    Karolinska universitetssjukhuset, Solna .
    Ekwall, Olov
    Drottning Silvias barn- och ungdomssjukhus, Göteborg .
    Wahlberg, Jeanette
    Linköping University, Department of Medical and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Bergthorsdottir, Ragnhildur
    Sahlgrenska sjukhuset, Göteborg .
    Hulting, Anna-Lena
    Karolinska universitetssjukhuset, Solna .
    [A national medical emergency card for adrenal insufficiency. A new warning card for better management and patient safety].2011In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, no 44, p. 2226-2227Article in journal (Other academic)
  • 213.
    Dahlström, Örjan
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Psychology. Linköping University, Faculty of Arts and Sciences. Linköping University, The Swedish Institute for Disability Research.
    Sjöwall, Christopher
    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 Rheumatology.
    The diagnostic accuracies of the 2012 SLICC criteria and the proposed EULAR/ACR criteria for systemic lupus erythematosus classification are comparable2019In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 28, no 6, p. 778-782Article in journal (Refereed)
    Abstract [en]

    In a joint effort, the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) recently proposed new criteria for the classification of systemic lupus erythematosus (SLE) with the overarching goal to identify potential participants for clinical studies. Herein, we present the first independent evaluation of these criteria in comparison with older classification grounds using an adult Scandinavian study population of confirmed SLE cases and individuals with SLE-mimicking conditions. We included 56 confirmed SLE cases meeting the 1982 ACR criteria (ACR-82) and/or the Fries diagnostic principle (antinuclear antibodies on at least one occasion plus involvement of at least two defined organ systems) and 55 controls with possible systemic autoimmune disease, including the presence of any SLE-related autoantibody. The proposed EULAR/ACR criteria showed a diagnostic sensitivity of 93% (95% confidence interval (CI), 0.83-0.98) compared with 83% (95% CI, 0.72-0.91) for the updated ACR criteria from 1997. The diagnostic accuracy of all tested classification grounds was fairly similar, achieving approximately 85%. However, the disease specificity of the EULAR/ACR criteria reached only 73% (95% CI, 0.59-0.83), which was comparable with the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria, 75% (95% CI, 0.61-0.85), but clearly lower than for ACR-82, 94% (95% CI, 0.83-0.99). In this first independent evaluation of a limited number of cases, we found comparable results with respect to diagnostic sensitivity, specificity and accuracy regarding the SLICC-12 and the proposed EULAR/ACR classification criteria. However, their specificity for SLE appeared to be lower compared with ACR-82.

  • 214.
    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.

  • 215.
    Dand, Nick
    et al.
    Kings Coll London, England.
    Mucha, Soeren
    Christian Albrechts University of Kiel, Germany.
    Tsoi, Lam C.
    University of Michigan, MI 48109 USA.
    Mahil, Satveer K.
    Kings Coll London, England.
    Stuart, Philip E.
    University of Michigan, MI USA.
    Arnold, Andreas
    University of Medical Greifswald, Germany.
    Baurecht, Hansjoerg
    University Hospital Schleswigholstein, Germany.
    David Burden, A.
    University of Glasgow, Scotland.
    Callis Duffin, Kristina
    University of Utah, UT USA.
    Chandran, Vinod
    University of Toronto, Canada; University of Health Network, Canada.
    Curtis, Charles J.
    NIHR, England; Maudsley NHS Fdn Trust, England; Kings Coll London, England; Kings Coll London, England.
    Das, Sayantan
    University of Michigan, MI 48109 USA.
    Ellinghaus, David
    Christian Albrechts University of Kiel, Germany.
    Ellinghaus, Eva
    Christian Albrechts University of Kiel, Germany.
    Enerbäck, Charlotta
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Esko, Tonu
    University of Tartu, Estonia.
    Gladman, Dafna D.
    University of Toronto, Canada; University of Health Network, Canada.
    Griffiths, Christopher E. M.
    University of Manchester, England.
    Gudjonsson, Johann E.
    University of Michigan, MI USA.
    Hoffman, Per
    University of Basel, Switzerland; University of Bonn, Germany.
    Homuth, Georg
    University of Med, Germany; Ernst Moritz Arndt University of Greifswald, Germany.
    Hueffmeier, Ulrike
    University Hospital Schleswigholstein, Germany; Friedrich Alexander University of Erlangen Nurnberg, Germany.
    Krueger, Gerald G.
    University of Utah, UT USA.
    Laudes, Matthias
    Christian Albrechts University of Kiel, Germany.
    Hyuck Lee, Sang
    NIHR, England; Maudsley NHS Fdn Trust, England; Kings Coll London, England; Kings Coll London, England.
    Lieb, Wolfgang
    Christian Albrechts University of Kiel, Germany.
    Lim, Henry W.
    Henry Ford Hospital, MI 48202 USA.
    Loehr, Sabine
    Friedrich Alexander University of Erlangen Nurnberg, Germany.
    Mrowietz, Ulrich
    Department of Dermatology, Venereology and Allergy, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
    Mueller-Nurayid, Martina
    Helmholtz Zentrum Munich, Germany.
    Noethen, Markus
    University of Bonn, Germany.
    Peters, Annette
    Helmholtz Zentrum Munich, Germany.
    Rahman, Proton
    Mem University of Newfoundland, Canada.
    Reis, Andre
    Friedrich Alexander University of Erlangen Nurnberg, Germany.
    Reynolds, Nick J.
    Newcastle University, England; Newcastle Hospital NHS Fdn Trust, England.
    Rodriguez, Elke
    University Hospital Schleswigholstein, Germany.
    Schmidt, Carsten O.
    University of Medical Greifswald, Germany.
    Spain, Sarah L.
    Kings Coll London, England.
    Strauch, Konstantin
    Helmholtz Zentrum Munich, Germany.
    Tejasvi, Trilokraj
    University of Michigan, MI USA.
    Voorhees, John J.
    University of Michigan, MI USA.
    Warren, Richard B.
    University of Manchester, England.
    Weichenthal, Michael
    University of Medical Centre Schleswig Holstein, Germany.
    Weidinger, Stephan
    University Hospital Schleswigholstein, Germany.
    Zawistowski, Matthew
    University of Michigan, MI 48109 USA.
    Nair, Rajan P.
    University of Michigan, MI USA.
    Capon, Francesca
    Kings Coll London, England.
    Smith, Catherine H.
    Kings Coll London, England.
    Trembath, Richard C.
    Kings Coll London, England.
    Abecasis, Goncalo R.
    University of Michigan, MI 48109 USA.
    Elder, James T.
    University of Michigan, MI USA; Ann Arbor Vet Hospital, MI USA.
    Franke, Andre
    Christian Albrechts University of Kiel, Germany.
    Simpson, Michael A.
    Kings Coll London, England.
    Barker, Jonathan N.
    Kings Coll London, England.
    Exome-wide association study reveals novel psoriasis susceptibility locus at TNFSF15 and rare protective alleles in genes contributing to type I IFN signalling2017In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 26, no 21, p. 4301-4313Article in journal (Refereed)
    Abstract [en]

    Psoriasis is a common inflammatory skin disorder for which multiple genetic susceptibility loci have been identified, but few resolved to specific functional variants. In this study, we sought to identify common and rare psoriasis-associated gene-centric variation. Using exome arrays we genotyped four independent cohorts, totalling 11 861 psoriasis cases and 28 610 controls, aggregating the dataset through statistical meta-analysis. Single variant analysis detected a previously unreported risk locus at TNFSF15 (rs6478108; P = 1.50 x 10(-8), OR = 1.10), and association of common protein-altering variants at 11 loci previously implicated in psoriasis susceptibility. We validate previous reports of protective low-frequency protein-altering variants within IFIH1 (encoding an innate antiviral receptor) and TYK2 (encoding a Janus kinase), in each case establishing a further series of protective rare variants (minor allele frequency amp;lt; 0.01) via gene-wide aggregation testing (IFIH1: p(burden) = 2.53 x 10(-7), OR = 0.707; TYK2: p(burden) = 6.17 x 10(-4), OR = 0.744). Both genes play significant roles in type I interferon (IFN) production and signalling. Several of the protective rare and low-frequency variants in IFIH1 and TYK2 disrupt conserved protein domains, highlighting potential mechanisms through which their effect may be exerted.

  • 216.
    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.

  • 217.
    Danielsson, Marita
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Operations management Region Östergötland, Övrig enhet.
    Nilsen, Per
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Rutberg, Hans
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Carlfjord, Siw
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    The professional culture among physicians in Sweden: potential implications for patient safety2018In: BMC Health Services Research, ISSN 1472-6963, E-ISSN 1472-6963, Vol. 18, no 1, article id 543Article in journal (Refereed)
    Abstract [en]

    Background

    Patient safety culture, i.e. a subset of an organization’s culture, has become an important focus of patient safety research. An organization’s culture consists of many cultures, underscoring the importance of studying subcultures. Professional subcultures in health care are potentially important from a patient safety point of view. Physicians have an important role to play in the effort to improve patient safety. The aim was to explore physicians’ shared values and norms of potential relevance for patient safety in Swedish health care.

    Methods

    Data were collected through group and individual interviews with 28 physicians in 16 semi-structured interviews, which were recorded and transcribed verbatim before being analysed with an inductive approach.

    Results

    Two overarching themes, “the competent physician” and “the integrated yet independent physician”, emerged from the interview data. The former theme consists of the categories Infallible and Responsible, while the latter theme consists of the categories Autonomous and Team player. The two themes and four categories express physicians’ values and norms that create expectations for the physicians’ behaviours that might have relevance for patient safety.

    Conclusions

    Physicians represent a distinct professional subculture in Swedish health care. Several aspects of physicians’ professional culture may have relevance for patient safety. Expectations of being infallible reduce their willingness to talk about errors they make, thus limiting opportunities for learning from errors. The autonomy of physicians is associated with expectations to act independently, and they use their decisional latitude to determine the extent to which they engage in patient safety. The physicians perceived that organizational barriers make it difficult to live up to expectations to assume responsibility for patient safety. Similarly, expectations to be part of multi-professional teams were deemed difficult to fulfil. It is important to recognize the implications of a multi-faceted perspective on the culture of health care organizations, including physicians’ professional culture, in efforts to improve patient safety.

  • 218.
    Danielsson, Marita
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsen, Per
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Rutberg, Hans
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Årestedt, Kristofer
    Faculty of Health and Life Sciences, Linnaeus University, Kalmar; The Research Unit, Kalmar County Hospital, Kalmar, Sweden..
    A National Study of Patient Safety Culture in Hospitals in Sweden2017In: Journal of patient safety, ISSN 1549-8417, E-ISSN 1549-8425Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Using the Hospital Survey on Patient Culture, our aim was to investigate the patient safety culture in all Swedish hospitals and to compare the culture among managers, physicians, registered nurses, and enrolled nurses and to identify factors associated with high overall patient safety.

    METHODS: The study used a correlational design based on cross-sectional surveys from health care practitioners in Swedish health care (N = 23,781). We analyzed the associations between overall patient safety (outcome variable) and 12 culture dimensions and 5 background characteristics (explanatory variables). Simple logistic regression analyses were conducted to determine the bivariate association between each explanatory variable and the outcome variable. The explanatory variables were entered to determine the multivariate associations between the variables and the outcome variable.

    RESULTS: The highest rated culture dimensions were "teamwork within units" and "nonpunitive response to error," and the lowest rated dimensions were "management support for patient safety" and "staffing." The multivariate analysis showed that long professional experience (>15 years) was associated with increased probability for high overall patient safety. Compared with general wards, the probability for high overall patient safety was higher for emergency care but lower for psychiatric care. The probability for high overall patient safety was higher for both enrolled nurses and physicians compared with managers.

    CONCLUSIONS: The safety culture dimensions of the Hospital Survey on Patient Culture contributed far more to overall patient safety than the background characteristics, suggesting that these dimensions are very important in efforts to improve the overall patient safety culture.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

  • 219.
    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.

  • 220.
    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.

  • 221.
    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.

  • 222.
    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.

  • 223.
    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)
  • 224.
    Davies Forsman, Lina
    et al.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Niward, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Hu, Yi
    Fudan Univ, Peoples R China; Fudan Univ, Peoples R China.
    Zheng, Rongrong
    Xiamen City Ctr Dis Control, Peoples R China.
    Zheng, Xubin
    Fudan Univ, Peoples R China.
    Ke, Ran
    Xiamen City Ctr Dis Control, Peoples R China.
    Cai, Weiping
    Xiamen City Ctr Dis Control, Peoples R China.
    Hong, Chao
    Xiamen City Ctr Dis Control, Peoples R China.
    Li, Yang
    Fudan Univ, Peoples R China.
    Gao, Yazhou
    Fudan Univ, Peoples R China.
    Werngren, Jim
    Publ Hlth Agcy Sweden, Sweden.
    Paues, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Kuhlin, Johanna
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Simonsson, Ulrika S. H.
    Uppsala Univ, Sweden.
    Eliasson, Erik
    Karolinska Univ Hosp, Sweden.
    Alffenaar, Jan-Willem
    Univ Groningen, Netherlands.
    Mansjo, Mikael
    Publ Hlth Agcy Sweden, Sweden.
    Hoffner, Sven
    Karolinska Inst, Sweden.
    Xu, Biao
    Fudan Univ, Peoples R China.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Kalmar Cty Hosp, Sweden.
    Bruchfeld, Judith
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Plasma concentrations of second-line antituberculosis drugs in relation to minimum inhibitory concentrations in multidrug-resistant tuberculosis patients in China: a study protocol of a prospective observational cohort study2018In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 8, no 9, article id e023899Article in journal (Refereed)
    Abstract [en]

    Introduction Individualised treatment through therapeutic drug monitoring (TDM) may improve tuberculosis (TB) treatment outcomes but is not routinely implemented. Prospective clinical studies of drug exposure and minimum inhibitory concentrations (MICs) in multidrug-resistant TB (MDR-TB) are scarce. This translational study aims to characterise the area under the concentration-time curve of individual MDR-TB drugs, divided by the MIC for Mycobacterium tuberculosis isolates, to explore associations with markers of treatment progress and to develop useful strategies for clinical implementation of TDM in MDR-TB. Methods and analysis Adult patients with pulmonary MDR-TB treated in Xiamen, China, are included. Plasma samples for measure of drug exposure are obtained at 0, 1, 2, 4, 6, 8 and 10 hours after drug intake at week 2 and at 0, 4 and 6 hours during weeks 4 and 8. Sputum samples for evaluating time to culture positivity and MIC determination are collected at days 0, 2 and 7 and at weeks 2, 4, 8 and 12 after treatment initiation. Disease severity are assessed with a clinical scoring tool (TBscore II) and quality of life evaluated using EQ-5D-5L. Drug concentrations of pyrazinamide, ethambutol, levofloxacin, moxifloxacin, cycloserine, prothionamide and para-aminosalicylate are measured by liquid chromatography tandem-mass spectrometry and the levels of amikacin measured by immunoassay. Dried blood spot on filter paper, to facilitate blood sampling for analysis of drug concentrations, is also evaluated. The MICs of the drugs listed above are determined using custom-made broth microdilution plates and MYCOTB plates with Middlebrook 7H9 media. MIC determination of pyrazinamide is performed in BACTEC MGIT 960. Ethics and dissemination This study has been approved by the ethical review boards of Karolinska Institutet, Sweden and Fudan University, China. Informed written consent is given by participants. The study results will be submitted to a peer-reviewed journal. Trial registration number NCT02816931; Pre-results.

  • 225.
    Dawson, Andreas
    et al.
    Malmö University, Sweden.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    List, Thomas
    Malmö University, Sweden; Skåne University Hospital, Sweden.
    Svensson, Peter
    Aarhus University, Denmark.
    Ernberg, Malin
    Karolinska Institute, Sweden; Aarhus University Hospital, Denmark.
    Effects of Experimental Tooth Clenching on Pain and Intramuscular Release of 5-HT and Glutamate in Patients With Myofascial TMD2015In: The Clinical Journal of Pain, ISSN 0749-8047, E-ISSN 1536-5409, Vol. 31, no 8, p. 740-749Article in journal (Refereed)
    Abstract [en]

    Objectives: It has been suggested that tooth clenching may be associated with local metabolic changes, and is a risk factor for myofascial temporomandibular disorders (M-TMD). This study investigated the effects of experimental tooth clenching on the levels of 5-HT, glutamate, pyruvate, and lactate, as well as on blood flow and pain intensity, in the masseter muscles of M-TMD patients. Methods: Fifteen patients with M-TMD and 15 pain-free controls participated. Intramuscular microdialysis was performed to collect 5-HT, glutamate, pyruvate, and lactate and to assess blood flow. Two hours after the insertion of a microdialysis catheter, participants performed a 20-minute repetitive tooth clenching task (50% of maximal voluntary contraction). Pain intensity was measured throughout. Results: A significant effect of group (P less than 0.01), but not of time, was observed on 5-HT levels and blood flow. No significant effects of time or group occurred on glutamate, pyruvate, or lactate levels. Time and group had significant main effects on pain intensity (P less than 0.05 and less than 0.001). No significant correlations were identified between: (1) 5-HT, glutamate, and pain intensity; or between (2) pyruvate, lactate, and blood flow. Discussion: This experimental tooth clenching model increased jaw muscle pain levels in M-TMD patients and evoked low levels of jaw muscle pain in controls. M-TMD patients had significantly higher levels of 5-HT than controls and significantly lower blood flow. These 2 factors may facilitate the release of other algesic substances that may cause pain.

  • 226.
    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.

  • 227.
    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.

  • 228.
    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.

  • 229.
    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.
    Engvall, Jan
    Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    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.
    Strain echocardiography in septic shock - a comparison with systolic and diastolic function parameters, cardiac biomarkers and outcome2015In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 19, no 1, article id 122Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Myocardial dysfunction is a well-known complication in septic shock but its characteristics and frequency remains elusive. Here, we evaluate global longitudinal peak strain (GLPS) of the left ventricle as a diagnostic and prognostic tool in septic shock.

    METHODS: Fifty adult patients with septic shock admitted to a general intensive care unit were included. Transthoracic echocardiography was performed on the first day, and repeated during and after ICU stay. Laboratory and clinical data and data on outcome were collected daily from admission and up to 7 days, shorter in cases of death or ICU discharge. The correlation of GLPS to left ventricular systolic and diastolic function parameters, cardiac biomarkers and clinical data were compared using Spearman's correlation test and linear regression analysis, and the ability of GLPS to predict outcome was evaluated using a logistic regression model.

    RESULTS: On the day of admission, there was a strong correlation and co-linearity of GLPS to left ventricular ejection fraction (LVEF), mitral annular motion velocity (é) and to amino-terminal pro-brain natriuretic peptide (NT-proBNP) (Spearman's ρ -0.70, -0.53 and 0.54, and R(2) 0.49, 0.20 and 0.24, respectively). In LVEF and NT-proBNP there was a significant improvement during the study period (analysis of variance (ANOVA) with repeated measures, p = 0.05 and p < 0.001, respectively), but not in GLPS, which remained unchanged over time (p = 0.10). GLPS did not correlate to the improvement in clinical characteristics over time, did not differ significantly between survivors and non-survivors (-17.4 (-20.5-(-13.7)) vs. -14.7 (-19.0 - (-10.6)), p = 0.11), and could not predict mortality.

    CONCLUSIONS: GLPS is frequently reduced in septic shock patients, alone or in combination with reduced LVEF and/or é. It correlates with LVEF, é and NT-proBNP, and remains affected over time. GLPS may provide further understanding on the character of myocardial dysfunction in septic shock.

  • 230.
    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.

  • 231.
    De Geer, Lina
    et al.
    Linköping University, Department of Medical and Health Sciences. 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. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Norrköping.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Walther, Sten M.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Cardiac mortality after severe sepsis and septic shock: A nationwide observational cohort study2015Manuscript (preprint) (Other academic)
    Abstract [en]

    Introduction: Cardiac dysfunction is a well-known complication of sepsis, but its long-term consequences remain unclear. The aim of this study was to investigate cardiac outcome after sepsis by assessing causes of death in a nationwide register-based cohort.

    Methods: A cohort of 9,520 severe sepsis and septic shock intensive care (ICU) patients without preceding severe cardiac failure and discharged alive from the ICU was collected from the Swedish Intensive Care Registry (SIR) from 2008 to 2013, together with a nonseptic control group (n = 4,577). Patients were matched according to age, sex and severity of illness. Information on cause of death after ICU discharge was sought in the Swedish National Board of Health and Welfare’s Cause of Death Registry.

    Results: After ICU discharge, 3,954 (42%) of severe sepsis or septic shock patients died. In 654 (16%) of these, cardiac failure was registered as the cause of death. The follow-up time was 17,693 person-years (median 583 days/person; maximum 5.7 years) and the median (IQR) time from ICU discharge to cardiac failure-related death 81 (17 - 379) days. With increasing severity of illness (quartiles of SAPS3), the hazard rate for cardiac failure-related death increased (hazard ratio (HR) 1.58 (95% CI 1.19 - 2.09, p <0.001) in the highest quartile compared to the lowest). In a matched comparison between severe sepsis or septic shock patients and controls, survival was similar, and the hazard rate for cardiac failurerelated death did not differ between groups (HR 0.97, 95% CI 0.88 – 1.10, p = 0.62).

    Conclusions: The risk of death with cardiac failure as the cause of death after severe sepsis or septic shock increases with severity of illness on admission. Patients with severe sepsis or septic shock are not, however, at an increased risk of death with cardiac failure as the cause of death when compared to other ICU patients with similar severity of illness.

  • 232.
    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.

  • 233.
    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.

  • 234.
    Dellgren, Linus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. inkoping, Sweden.
    Claesson, Carina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Högdahl, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Forsberg, Jon
    Not Found:Linkoping Univ, Dept Clin and Expt Med, Linkoping, Sweden; Linkoping Univ, Dept Urol, Linkoping, Sweden.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences.
    Hällgren, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Phenotypic screening for quinolone resistance in Escherichia coli2019In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 38, no 9, p. 1765-1771Article in journal (Refereed)
    Abstract [en]

    Recent studies show that rectal colonization with low-level ciprofloxacin-resistant Escherichia coli (ciprofloxacin minimal inhibitory concentration (MIC) above the epidemiological cutoff point, but below the clinical breakpoint for resistance), i.e., in the range amp;gt; 0.06-0.5 mg/L is an independent risk factor for febrile urinary tract infection after transrectal ultrasound-guided biopsy (TRUS-B) of the prostate, adding to the other risk posed by established ciprofloxacin resistance in E. coli (MIC amp;gt; 0.5 mg/L) as currently defined. We aimed to identify the quinolone that by disk diffusion best discriminates phenotypic wild-type isolates (ciprofloxacin MIC amp;lt;= 0.06 mg/L) of E. coli from isolates with acquired resistance, and to determine the resistance genotype of each isolate. The susceptibility of 108 E. coli isolates was evaluated by ciprofloxacin, levofloxacin, moxifloxacin, nalidixic acid, and pefloxacin disk diffusion and correlated to ciprofloxacin MIC (broth microdilution) using EUCAST methodology. Genotypic resistance was identified by PCR and DNA sequencing. The specificity was 100% for all quinolone disks. Sensitivity varied substantially, as follows: ciprofloxacin 59%, levofloxacin 46%, moxifloxacin 59%, nalidixic acid 97%, and pefloxacin 97%. We suggest that in situations where low-level quinolone resistance might be of importance, such as when screening for quinolone resistance in fecal samples pre-TRUS-B, a pefloxacin (S amp;gt;= 24 mm) or nalidixic acid (S amp;gt;= 19 mm) disk, or a combination of the two, should be used. In a setting where plasmid-mediated resistance is prevalent, pefloxacin might perform better than nalidixic acid.

  • 235.
    Detert, H.
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Community Medicine.
    Hedlund, S.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Anderson, Chris
    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 Dermatology and Venerology.
    Rodvall, Y.
    Karolinska Institute, Sweden.
    Festin, Karin
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Whiteman, D. C.
    University of Queensland, Australia.
    Falk, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Validation of sun exposure and protection index (SEPI) for estimation of sun habits2015In: Cancer Epidemiology, ISSN 1877-7821, E-ISSN 1877-783X, Vol. 39, no 6, p. 986-993Article in journal (Refereed)
    Abstract [en]

    Background: In both Sweden and Australia high incidence rates of skin cancer have become a major health problem. In prevention and risk communication, it is important to have reliable ways for identifying people with risky sun habits. In this study the validity and reliability of the questionnaire Sun Exposure Protection Index (SEPI), developed to assess individuals sun habits and their propensity to increase sun protection during routine, often brief, clinical encounters, has been evaluated. The aim of our study was to evaluate validity and reliability of the proposed SEPI scoring instrument, in two countries with markedly different ultraviolet radiation environments (Sweden and Australia). Method: Two subpopulations in Sweden and Australia respectively were asked to fill out the SEPI together with the previously evaluated Readiness to Alter Sun Protective Behaviour questionnaire (RASP-B) and the associated Sun-protective Behaviours Questionnaire. To test reliability, the SEPI was again filled out by the subjects one month later. Results: Comparison between SEPI and the questions in the Sun-protective Behaviours Questionnaire, analyzed with Spearmans Rho, showed good correlations regarding sun habits. Comparison between SEPI and RASP-B regarding propensity to increase sun protection showed concurrently lower SEPI mean scores for action stage, but no difference between precontemplation and contemplation stages. The SEPI test-retest analysis indicated stability over time. Internal consistency of the SEPI, assessed with Cronbachs alpha estimation showed values marginally lower than the desired &gt;0.70 coefficient value generally recommended, and was somewhat negatively affected by the question on sunscreen use, likely related to the classic "sunscreen paradox". There were some differences in the performance of the SEPI between the Swedish and Australian samples, possibly due to the influence of "available" sunlight and differing attitudes to behaviour and protection "at home" and on vacation. Conclusions: SEPI appears to be a stable instrument with an overall acceptable validity and reliability, applicable for use in populations exposed to different UVR environments, in order to evaluate individual sun exposure and protection. (C) 2015 The Authors. Published by Elsevier Ltd.

  • 236.
    Dettenkofer, Markus
    et al.
    University of Freiburg, Germany.
    Humphreys, Hilary
    Royal Coll Surg, Ireland; Beaumont Hospital, Ireland.
    Saenz, Henri
    European Soc Clin Microbiol and Infect Disease, Switzerland.
    Carlet, Jean
    Grp Hospital Paris St Joseph, France.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Ruef, Christian
    Hirslanden Klin, Switzerland.
    Widmer, Andreas
    University of Basel Hospital, Switzerland.
    Wolkewitz, Martin
    University of Freiburg, Germany.
    Cookson, Barry
    UCL, England.
    Key priorities in the prevention and control of healthcare-associated infection: a survey of European and other international infection prevention experts2016In: Infection. Zeitschrift für Klinik und Therapie der Infektionen, ISSN 0300-8126, E-ISSN 1439-0973, Vol. 44, no 6, p. 719-724Article in journal (Refereed)
    Abstract [en]

    Purpose Prevention and control of healthcare-associated infection (HCAI) are important within and beyond Europe. However, it is unclear which areas are considered important by HCAI prevention and control professionals. This study assesses the priorities in the prevention and control of HCAI as judged by experts in the field. Methods A survey was conducted by the European Society of Clinical Microbiology and Infectious Diseases focussing on seven topics using SurveyMonkey (R). Through a newsletter distributed by email, about 5000 individuals were targeted throughout the world in February and March 2013. Participants were asked to rate the importance of particular topics from one (low importance) to ten (extraordinary importance), and there was no restriction on giving equal importance to more than one topic. Results A total of 589 experts from 86 countries participated including 462 from Europe (response rate: 11.8 %). Physicians accounted for 60 % of participants, and 57 % had ten or more years experience in this area. Microbial epidemiology/resistance achieved the highest priority scoring with 8.9, followed by surveillance 8.2, and decolonisation/disinfection/antiseptics with 7.9. Under epidemiology/resistance, highly resistant Gram-negative bacilli scored highest (9.0-9.2). The provision of computerised healthcare information systems for the early detection of outbreaks was accorded the top priority under surveillance. The prevention of surgical site and central line infections ranked highest under the category of specific HCAI and HCAI in certain settings. Differences between regions are described. Conclusion These findings reflect the concerns of experts in HCAI prevention and control. The results from this survey should inform national and international agencies on future action and research priorities.

  • 237.
    Di Giuseppe, Daniela
    et al.
    Karolinska Inst, Sweden.
    Frisell, Thomas
    Karolinska Inst, Sweden.
    Ernestam, Sofia
    Karolinska Univ Hosp, Sweden.
    Forsblad-DElia, Helena
    Umea Univ, Sweden.
    Lindqvist, Elisabet
    Lund Univ, Sweden; Skane Univ Hosp, Sweden.
    Lindstrom, Ulf
    Gothenburg Univ, Sweden.
    Sjöwall, Christopher
    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 Rheumatology.
    Askling, Johan
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Uptake of rheumatology biosimilars in the absence of forced switching2018In: Expert Opinion on Biological Therapy, ISSN 1471-2598, E-ISSN 1744-7682, Vol. 18, no 5, p. 499-504Article in journal (Refereed)
    Abstract [en]

    Background: To describe the uptake and system-level effects of the introduction of biosimilars in a setting without forced switching.Research design and methods: We used data from the Swedish Rheumatology Quality register from start of marketing of infliximab (Remsima (R) and Inflectra (R)) and etanercept (Benepali (R)) biosimilars until 31 December 2016. We compared users of each originator-product and its biosimilar(s) by line of treatment: bDMARD-naive patients, non-medical switchers (vs. matched patients remaining on originator), and patients switching from a previous bDMARD of another type.Results: From the start of marketing 1343 patients started an infliximab biosimilar (22 months) and 2691 started etanercept (9months). Overall, the introduction of these biosimilars resulted in an increase of the total number of ongoing infliximab and etanercept treatments (originator + biosimilar) . At the end of the study period, biosimilars accounted for 31% of all infliximab treatments and 31% of all etanercept-treated patients. For each line of therapy, we noted only small differences in patient characteristics between those starting the originator product vs. its biosimilar(s).Conclusions: Introduction of biosimilars have effects beyond replacement of the originator product, in terms of an increased rate of bDMARD initiation. Selection to non-medical switching displayed no particular disease- or patient-characteristics.

  • 238.
    Dieker, Jurgen
    et al.
    Radboud University of Nijmegen, Netherlands.
    Berden, Jo H.
    Radboud University of Nijmegen, Netherlands.
    Bakker, Marinka
    Radboud University of Nijmegen, Netherlands.
    Briand, Jean-Paul
    CNRS, France.
    Muller, Sylviane
    CNRS, France.
    Voll, Reinhard
    University of Medical Centre Freiburg, Germany; University of Medical Centre Freiburg, Germany.
    Sjöwall, Christopher
    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 Rheumatology.
    Herrmann, Martin
    Friedrich Alexander University of Erlangen Nuremberg, Germany.
    Hilbrands, Luuk B.
    Radboud University of Nijmegen, Netherlands.
    van der Vlag, Johan
    Radboud University of Nijmegen, Netherlands.
    Autoantibodies against Modified Histone Peptides in SLE Patients Are Associated with Disease Activity and Lupus Nephritis2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 10, article id e0165373Article in journal (Refereed)
    Abstract [en]

    Persistent exposure of the immune system to death cell debris leads to autoantibodies against chromatin in patients with systemic lupus erythematosus (SLE). Deposition of antichromatin/ chromatin complexes can instigate inflammation in multiple organs including the kidney. Previously we identified specific cell death-associated histone modifications as targets of autoantibodies in SLE. In this study we addressed, in a large cohort of SLE patients and controls, the question whether plasma reactivities with specific histone peptides associated with serology and clinical features. Plasma from SLE patients with and without lupus nephritis, disease controls, and healthy controls, were tested in ELISA with histone H4 peptide acetylated at lysines 8, 12 and 16 (H4p(ac)), H2B peptide acetylated at lysine 12 (H2Bp(ac)), H3 peptide trimethylated at lysine 27 (H3p(me)), and their unmodified equivalents. SLE patients displayed a higher reactivity with the modified equivalent of each peptide. Reactivity with H4p(ac) showed both a high sensitivity (89%) and specificity (91%) for SLE, while H2Bp(ac) exhibited a high specificity (96%) but lower sensitivity (69%). Reactivity with H3p(me) appeared not specific for SLE. Anti-H4p(ac) and anti-H2Bp(ac) reactivity demonstrated a high correlation with disease activity. Moreover, patients reacting with multiple modified histone peptides exhibited higher SLEDAI and lower C3 levels. SLE patients with renal involvement showed higher reactivity with H2B/H2Bp(ac) and a more pronounced reactivity with the modified equivalent of H3p(me) and H2Bp(ac). In conclusion, reactivity with H4p(ac) and H2Bp(ac) is specific for SLE patients and correlates with disease activity, whereas reactivity with H2Bp(ac) is in particular associated with lupus nephritis.

  • 239.
    Dionne-Odom, J. Nicholas
    et al.
    University of Alabama Birmingham, AL 35294 USA.
    Hooker, Stephanie A.
    University of Colorado, CO 80217 USA.
    Bekelman, David
    University of Colorado, CO 80220 USA.
    Ejem, Deborah
    University of Alabama Birmingham, AL 35294 USA.
    McGhan, Gwen
    University of Alabama Birmingham, AL 35294 USA.
    Kitko, Lisa
    Penn State University, PA 16802 USA.
    Strömberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Wells, Rachel
    University of Alabama Birmingham, AL 35294 USA.
    Astin, Meka
    University of Alabama Birmingham, AL 35294 USA.
    Gok Metin, Zehra
    Hacettepe University, Turkey.
    Mancarella, Gisella
    University of Alabama Birmingham, AL 35294 USA.
    Pamboukian, Salpy V.
    University of Alabama Birmingham, AL 35294 USA.
    Evangelista, Lorraine
    University of Calif Irvine, CA 92697 USA.
    Buck, Harleah G.
    University of S Florida, FL 33612 USA.
    Bakitas, Marie A.
    University of Alabama Birmingham, AL 35294 USA.
    Family caregiving for persons with heart failure at the intersection of heart failure and palliative care: a state-of-the-science review2017In: Heart Failure Reviews, ISSN 1382-4147, E-ISSN 1573-7322, Vol. 22, no 5, p. 543-557Article, review/survey (Refereed)
    Abstract [en]

    Many of the 23 million individuals with heart failure (HF) worldwide receive daily, unpaid support from a family member or friend. Although HF and palliative care practice guidelines stipulate that support be provided to family caregivers, the evidence base to guide care for this population has not been comprehensively assessed. In order to appraise the state-of-the-science of HF family caregiving and recommend areas for future research, the aims of this review were to summarize (1) how caregivers influence patients, (2) the consequences of HF for caregivers, and (3) interventions directed at HF caregivers. We reviewed all literature to December 2015 in PubMed and CINAHL using the search terms "heart failure" AND "caregiver." Inclusion criteria dictated that studies report original research of HF family caregiving. Articles focused on children or instrument development or aggregated HF with other illnesses were excluded. We identified 120 studies, representing 5700 caregivers. Research on this population indicates that (1) caregiving situations vary widely with equally wide-ranging tasks for patients to help facilitate their health behaviors, psychological health and relationships, and quality of life (QoL); (2) caregivers have numerous unmet needs that fluctuate with patients unpredictable medical status, are felt to be ignored by the formal healthcare system, and can lead to distress, burden, and reduced QoL; and (3) relatively few interventions have been developed and tested that effectively support HF family caregivers. We provide recommendations to progress the science forward in each of these areas that moves beyond descriptive work to intervention development and clinical trials testing.

  • 240.
    Dragioti, Elena
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Björk, Mathilda
    Linköping University, Department of Social and Welfare Studies, Division of Occupational Therapy. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Larsson, Britt
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    A Meta-Epidemiological Appraisal of the Effects of Interdisciplinary Multimodal Pain Therapy Dosing for Chronic Low Back Pain2019In: JOURNAL OF CLINICAL MEDICINE, ISSN 2077-0383, Vol. 8, no 6, article id 871Article in journal (Refereed)
    Abstract [en]

    Using a meta-analysis, meta-regression, and a meta-epidemiological approach, we conducted a systematic review to examine the influence of interdisciplinary multimodal pain therapy (IMPT) dosage on pain, disability, return to work, quality of life, depression, and anxiety in published randomised controlled trials (RCTs) in patients with non-specific chronic low back pain (CLBP). We considered all RCTs of IMPT from a Cochrane review and searched PubMed for additional RCTs through 30 September 2018. A subgroup random-effects meta-analysis by length, contact, and intensity of treatment was performed followed by a meta-regression analysis. Using random and fixed-effect models and a summary relative odds ratio (ROR), we compared the effect sizes (ES) from short-length, non-daily contact, and low-intensity RCTs with long-length, daily contact, and high-intensity RCTs. Heterogeneity was quantified with the I-2 metric. A total of 47 RCTs were selected. Subgroup meta-analysis showed that there were larger ES for pain and disability in RCTs with long-length, non-daily contact, and low intensity of treatment. Larger ES were also observed for quality of life in RCTs with short-length, non-daily contact, and low intensity treatment. However, these findings were not confirmed by the meta-regression analysis. Likewise, the summary RORs were not significant, indicating that the length, contact, and intensity of treatment did not have an overall effect on the investigated outcomes. For the outcomes investigated here, IMPT dosage is not generally associated with better ES, and an optimal dosage was not determined.

  • 241.
    Dragioti, Elena
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Larsson, Britt
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Bernfort, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    Levin, Lars-Åke
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Gerdle, Björn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Prevalence of different pain categories based on pain spreading on the bodies of older adults in Sweden: a descriptive-level and multilevel association with demographics, comorbidities, medications, and certain lifestyle factors (PainS65+)2016In: Journal of Pain Research, ISSN 1178-7090, E-ISSN 1178-7090, Vol. 9, p. 1131-1141Article in journal (Refereed)
    Abstract [en]

    Background and objective: There is limited knowledge about the prevalence of pain and its relation to comorbidities, medication, and certain lifestyle factors in older adults. To address this limitation, this cross-sectional study examined the spreading of pain on the body in a sample of 6611 subjects amp;gt;= 65 years old (mean age = 75.0 years; standard deviation [SD] = 7.7) living in southeastern Sweden. Methods: Sex, age, comorbidities, medication, nicotine, alcohol intake, and physical activity were analyzed in relation to the following pain categories: local pain (LP) (24.1%), regional pain medium (RP-Medium) (20.3%), regional pain heavy (RP-Heavy) (5.2%), and widespread pain (WSP) (1.7%). Results: RP-Medium, RP-Heavy, and WSP were associated more strongly with women than with men (all pamp;lt;0.01). RP-Heavy was less likely in the 80-84 and amp;gt;85 age groups compared to the 65-69 age group (both pamp;lt;0.01). Traumatic injuries, rheumatoid arthritis/osteoarthritis, and analgesics were associated with all pain categories (all pamp;lt;0.001). An association with gastrointestinal disorders was found in LP, RP-Medium, and RP-Heavy (all pamp;lt;0.01). Depressive disorders were associated with all pain categories, except for LP (all pamp;lt;0.05). Disorders of the central nervous system were associated with both RP-Heavy and WSP (all pamp;lt;0.05). Medication for peripheral vascular disorders was associated with RP-Medium (pamp;lt;0.05), and hypnotics were associated with RP-Heavy (pamp;lt;0.01). Conclusion: More than 50% of older adults suffered from different pain spread categories. Women were more likely to experience greater spreading of pain than men. A noteworthy number of common comorbidities and medications were associated with increased likelihood of pain spread from LP to RP-Medium, RP-Heavy, and WSP. Effective management plans should consider these observed associations to improve functional deficiency and decrease spreading of pain-related disability in older adults.

  • 242.
    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.

  • 243.
    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.

  • 244.
    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.

  • 245.
    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

  • 246.
    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)
  • 247.
    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.

  • 248.
    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.

  • 249.
    Edlund, Charlotta
    et al.
    Folkhälsomyndigheten, Sverige.
    Skoog, Gunilla
    Folkhälsomyndigheten, Sverige.
    Grape, Malin
    Folkhälsomyndigheten, Sverige.
    Hedin, Katarina
    FoU, Region Kronoberg, Sverige.
    Sundvall, Pär-Daniel
    FoU primärvård, Västra Götalandsregionen, Sverige.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Dags att fylla kunskapsluckor om antibiotikaanvändning i praxis2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, no 12Article in journal (Other academic)
  • 250.
    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.

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