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  • 1.
    Adlitzer, Helena
    et al.
    Regionalt cancercentrum Stockholm Gotland, Stockholm County Council, Stockholm, Sweden; Region Gotland, Visby, Sweden.
    Andershed, Birgitta
    Ersta Sköndal Högskola, Stockholm, Sweden.
    Axelsson, Bertil
    Östersunds sjukhus, Östersund, Sverige; Umeå universitet, Umeå, Sverige.
    Blomberg, Karin
    Örebro University, School of Health Sciences.
    Fridegren, Inger
    Nacka Närsjukhus, Nacka, Sverige.
    Friedrichsen, Maria
    Palliativt kompetenscentrum Östergötland, Vrinnevisjukhuset, Norrköping, Sverige; Linköpings Universitet,Linköping, Sverige.
    Fürst, Carl-Johan
    Palliativt utvecklingscentrum, Lunds universitet, Lund, sverige; Region Skåne, Kristianstad, Sverige.
    Heedman, Per-Anders
    Palliativt kompetenscentrum i Östergötland, Vrinnevisjukhuset, Norrköping, Sverige.
    Henoch, Ingela
    Sahlgrenska akademin, Göteborg, Sverige; Göteborgs universitet, Göteborg, Sverige.
    Kenne Sarenmalm, Elisabeth
    FoU Centrum, Skaraborgs sjukhus, Skövde, Sverige.
    Löfdahl, Elisabet
    Palliativa sektionen Stockholms Universitet, Stockholm, Sverige; Sahlgrenska universitetssjukhuset, Stockholm, Sverige.
    Melin-Johansson, Christina
    Mittuniversitetet, Östersund, Sverige.
    Molander, Ulla
    Sahlgrenska Universitetssjukhuset, Göteborg, Sverige.
    Persson, Hans
    Danderyds sjukhus, Stockholm, Sverige.
    Pessah-Rasmussen, Hélène
    Skånes Universitetssjukhus (SUS), Lund, Sverige.
    Rasmussen, Birgit H
    Lunds universitet, Lund, Sverige; Region Skåne, Kristianstad, Sverige.
    Schaufelberger, Maria
    Sahlgrenska universitetssjukhuset, Göteborg, Sverige.
    Seiger Cronfalk, Berit
    Ersta Sköndal Högskola, stockholm, Sverige; Karolinska Institutet, Stockholm, Sverige.
    Silk, Gerd
    Kvalitets- och utvecklingsenheten, Region Gotland, Visby, Sverige.
    Strang, Peter
    Karolinska Institutet Stockholm, Sverige; Stockholms Sjukhem, Stockholm, Sverige.
    Strömberg, Anna
    Linköpings universitetssjukhus, Linköping, Sverige.
    Tavemark, Sofia
    Örebro kommun, Örebro, Sverige.
    Ternestedt, Britt-Marie
    Ersta Sköndal Högskola, Stockholm, Sverige.
    Wennman-Larsen, Agneta
    Sophiahemmet Högskola, Stockholm, Sverige; Karolinska Institutet, Stockholm,Sverige.
    Wikström, Gerhard
    Uppsala Universitet, Uppsala, Sverige.
    Österlind, Jane
    Ersta Sköndal högskola, Stockholm, Sverige.
    Palliativ vård i livets slutskede: Nationellt vårdprogram2016Report (Other academic)
    Download full text (pdf)
    Palliativ vård i livets slutskede: Nationellt vårdprogram
  • 2.
    Agnew, Louise
    et al.
    Division of Physiotherapy, School of Health and Rehabilitation Sciences, University of Queensland, Brisbane, Australia.
    Johnston, Venerina
    Division of Physiotherapy, School of Health and Rehabilitation Sciences, University of Queensland, Brisbane, Australia.
    Ludvigsson, Maria Landen
    Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Rehab Väst, County Council of Östergötland, Motala, Sweden.
    Peterson, Gunnel
    Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Centre for Clinical Research Sörmland, Uppsala University, Uppsala, Uppsala, Sweden.
    Overmeer, Thomas
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. School of Health Care and Social Welfare, Mälardalen University, Västerås, Sweden.
    Johansson, Gun
    Institute of Environmental Medicine, Occupational and Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Peolsson, Anneli
    Division of Physiotherapy, School of Health and Rehabilitation Sciences, University of Queensland, Brisbane, Australia; Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Factors associated with work ability in patients with chronic whiplash-associated disorder grade II-III: a cross-sectional analysis2015In: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 47, no 6, p. 546-551Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the factors related to self-perceived work ability in patients with chronic whiplash-associated disorder grades II-III.

    Design: Cross-sectional analysis.

    Patients: A total of 166 working age patients with chronic whiplash-associated disorder.

    Methods: A comprehensive survey collected data on work ability (using the Work Ability Index); demographic, psychosocial, personal, work- and condition-related factors. Forward, stepwise regression modelling was used to assess the factors related to work ability.

    Results: The proportion of patients in each work ability category were as follows: poor (12.7%); moderate (39.8%); good (38.5%); excellent (9%). Seven factors explained 65% (adjusted R-2 = 0.65, p < 0.01) of the variance in work ability. In descending order of strength of association, these factors are: greater neck disability due to pain; reduced self-rated health status and health-related quality of life; increased frequency of concentration problems; poor workplace satisfaction; lower self-efficacy for performing daily tasks; and greater work-related stress.

    Conclusion: Condition-specific and psychosocial factors are associated with self-perceived work ability of individuals with chronic whiplash-associated disorder.

  • 3.
    Ahl, Rebecka
    et al.
    Örebro University, School of Medical Sciences. Department of Surgery, Division of Trauma and Acute Care Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Riddez, Louis
    Department of Surgery, Division of Trauma and Acute Care Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Mohseni, Shahin
    Department of Surgery, Division of Trauma and Acute Care Surgery, Karolinska University Hospital, Stockholm, Sweden; Department of Surgery, Division of Trauma and Acute Care Surgery, Örebro University Hospital, Örebro, Sweden; Örebro University, Örebro, Sweden.
    Digital rectal examination for initial assessment of the multi-injured patient: Can we depend on it?2016In: Annals of Medicine and Surgery, E-ISSN 2049-0801, Vol. 9, p. 77-81Article in journal (Refereed)
    Abstract [en]

    Background: Digital rectal examination (DRE) is part of the assessment of trauma patients as recommended by ATLS (R). The theory behind is to aid early diagnosis of potential lower intestinal, urethral and spinal cord injuries. Previous studies suggest that test characteristics of DRE are far from reliable. This study examines the correlation between DRE findings and diagnosis and whether DRE findings affect subsequent management.

    Materials and methods: Patients with ICD-10 codes for spinal cord, urethral and lower intestinal injuries were identified from the trauma registry at an urban university hospital between 2007 and 2011. A retrospective review of electronic medical records was carried out to analyse DRE findings and subsequent management.

    Results: 253 patients met the inclusion criteria with a mean age of 44 +/- 20 years and mean ISS of 26 +/- 16. 160 patients had detailed DRE documentation with abnormal findings in 48%. Sensitivity rate was 0.47. Correlational analysis between examination findings and diagnosis gave a kappa of 0.12. Subsequent management was not altered in any case due to DRE findings.

    Conclusion: DRE in trauma settings has low sensitivity and does not change subsequent management. Excluding or postponing this examination should therefore be considered. (C) 2016 The Author(s). Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

  • 4.
    Ahlander, Britt-Marie
    Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
    Magnetic Resonance Imaging of the Heart: Image quality, measurement accuracy and patient experience2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Non-invasive diagnostic imaging of atherosclerotic coronary artery disease (CAD) is frequently carried out with cardiovascular magnetic resonance imaging (CMR) or myocardial perfusion single photon emission computed tomography (MPS). CMR is the gold standard for the evaluation of scar after myocardial infarction and MPS the clinical gold standard for ischemia. Magnetic Resonance Imaging (MRI) is at times difficult for patients and may induce anxiety while patient experience of MPS is largely unknown.

    Aims: To evaluate image quality in CMR with respect to the sequences employed, the influence of atrial fibrillation, myocardial perfusion and the impact of patient information. Further, to study patient experience in relation to MRI with the goal of improving the care of these patients.

    Method: Four study designs have been used. In paper I, experimental cross-over, paper (II) experimental controlled clinical trial, paper (III) psychometric crosssectional study and paper (IV) prospective intervention study. A total of 475 patients ≥ 18 years with primarily cardiac problems (I-IV) except for those referred for MRI of the spine (III) were included in the four studies.

    Result: In patients (n=20) with atrial fibrillation, a single shot steady state free precession (SS-SSFP) sequence showed significantly better image quality than the standard segmented inversion recovery fast gradient echo (IR-FGRE) sequence (I). In first-pass perfusion imaging the gradient echo-echo planar imaging sequence (GREEPI) (n=30) had lower signal-to-noise and contrast–to-noise ratios than the steady state free precession sequence (SSFP) (n=30) but displayed a higher correlation with the MPS results, evaluated both qualitatively and quantitatively (II). The MRIAnxiety Questionnaire (MRI-AQ) was validated on patients, referred for MRI of either the spine (n=193) or the heart (n=54). The final instrument had 15 items divided in two factors regarding Anxiety and Relaxation. The instrument was found to have satisfactory psychometric properties (III). Patients who prior CMR viewed an information video scored significantly (lower) better in the factor Relaxation, than those who received standard information. Patients who underwent MPS scored lower on both factors, Anxiety and Relaxation. The extra video information had no effect on CMR image quality (IV).

    Conclusion: Single shot imaging in atrial fibrillation produced images with less artefact than a segmented sequence. In first-pass perfusion imaging, the sequence GRE-EPI was superior to SSFP. A questionnaire depicting anxiety during MRI showed that video information prior to imaging helped patients relax but did not result in an improvement in image quality.

    Download full text (pdf)
    Magnetic Resonance Imaging of the Heart: Image quality, measurement accuracy and patient experience
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  • 5.
    Ahmadi, Zainab
    et al.
    Lund University, Lund, Sweden.
    Sundh, Josefin
    Örebro University, School of Medical Sciences.
    Hermansson, Anna B.
    Uppsala University Hospital, Uppsala, Sweden.
    Ekström, Magnus
    Lund University, Lund, Sweden.
    Does Long-Term Oxygen Therapy 24 H/day Improve Survival Compared To 15 H/day In Hypoxemic Chronic Obstructive Pulmonary Disease?2016In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 193Article in journal (Refereed)
  • 6.
    Al Alawi, Laila
    et al.
    Institute of Public Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
    Soteriades, Elpidoforos S.
    Institute of Public Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates; Department of Environmental Health, Environmental and Occupational Medicine and Epidemiology (EOME), Harvard School of Public Health, Boston MA, USA.
    Paulo, Marilia Silva
    Institute of Public Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates; Global Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal.
    Östlundh, Linda
    National Medical Library, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
    Grivna, Michal
    Institute of Public Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
    Al Maskari, Fatima
    Institute of Public Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates; Zayed Center for Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
    Al-Rifai, Rami H.
    Institute of Public Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates; Zayed Center for Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
    Environmental assessment of cytotoxic drugs in healthcare settings: protocol for a systematic review and meta-analysis2020In: Systematic Reviews, E-ISSN 2046-4053, Vol. 9, no 1, article id 242Article, review/survey (Refereed)
    Abstract [en]

    Background: Occupational exposure to cytotoxic drugs is associated with various unfavorable health outcomes. This protocol reports a methodology for a systematic review and meta-analysis that aims to systematically review the published literature and quantify the level of environmental contamination of healthcare settings with cytotoxic drugs.

    Methods: This protocol is developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol-2015 (PRISMA-P) guidelines. Six electronic databases (PubMed, Web of Science, Scopus, Cochrane Library, CINAHL, and EMBASE) will be searched with no restrictions on publication period. Eligible studies will be identified and data will be extracted using a predefined data extraction form by at least two independent reviewers following best practice. Eligible studies should report calculated or calculable estimates on the proportion of positive samples tested for cytotoxic drugs and/or estimates on the concentration of the cytotoxic drug(s) in the tested samples. Risk of bias (RoB) will be assessed by using the RoB in Studies estimating Prevalence of Exposure to Occupational risk factors (RoB-SPEO) tool, which developed by the World Health Organization (WHO) and International Labour Organization (ILO) for environmental and occupational health systematic reviews. The random-effects model will be used to perform meta-analyses.

    Discussion: Occupational exposure to cytotoxic drugs is associated with short- and long-term adverse health outcomes. Following this protocol, the review to be carried out will be the first to fill an evidence gap on the environmental contamination of healthcare settings with cytotoxic drugs. The findings of this review will help in the understanding of the risk of occupational exposure of healthcare workers to cytotoxic drugs and facilitate the identification of priority areas for specific interventions.

    Ethics and dissemination: The systematic review methodology does not require ethics approval due to the nature of the study design. The results of the systematic review will be published in a peer-reviewed journal and will be publicly available.

    Systematic review registration: PROSPERO, dated July 14, 2020

  • 7.
    Alaie, Iman
    et al.
    Department of Neuroscience, Child and Adolescent Psychiatry, Uppsala University, Uppsala, Sweden.
    Philipson, Anna
    Örebro University, School of Health Sciences. University Health Care Research Centre.
    Ssegonja, Richard
    Department of Public Health and Caring Sciences, Child Health and Parenting (CHAP), Uppsala University, Uppsala, Sweden.
    Hagberg, Lars
    Örebro University, School of Health Sciences. Örebro University Hospital. University Health Care Research Centre.
    Feldman, Inna
    Department of Public Health and Caring Sciences, Child Health and Parenting (CHAP), Uppsala University, Uppsala, Sweden.
    Sampaio, Filipa
    Department of Public Health and Caring Sciences, Child Health and Parenting (CHAP), Uppsala University, Uppsala, Sweden.
    Möller, Margareta
    Örebro University, School of Health Sciences. University Health Care Research Centre.
    Arinell, Hans
    Department of Neuroscience, Child and Adolescent Psychiatry, Uppsala University, Uppsala, Sweden; Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden.
    Ramklint, Mia
    Department of Neuroscience, Child and Adolescent Psychiatry, Uppsala University, Uppsala, Sweden; Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden.
    Päären, Aivar
    Department of Neuroscience, Child and Adolescent Psychiatry, Uppsala University, Uppsala, Sweden.
    von Knorring, Lars
    Department of Neuroscience, Psychiatry, Uppsala University, Uppsala, Sweden.
    Olsson, Gunilla
    Department of Neuroscience, Child and Adolescent Psychiatry, Uppsala University, Uppsala, Sweden.
    von Knorring, Anne-Liis
    Department of Neuroscience, Child and Adolescent Psychiatry, Uppsala University, Uppsala, Sweden.
    Bohman, Hannes
    Department of Neuroscience, Child and Adolescent Psychiatry, Uppsala University, Uppsala, Sweden.
    Jonsson, Ulf
    Department of Neuroscience, Child and Adolescent Psychiatry, Uppsala University, Uppsala, Sweden; Center of Neurodevelopmental Disorders at Karolinska Institutet (KIND), Pediatric Neuropsychiatry Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; Centre for Psychiatry Research, Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
    Uppsala Longitudinal Adolescent Depression Study (ULADS)2019In: BMJ Open, E-ISSN 2044-6055, Vol. 9, no 3, article id e024939Article in journal (Refereed)
    Abstract [en]

    Purpose: To present the Uppsala Longitudinal Adolescent Depression Study, initiated in Uppsala, Sweden, in the early 1990s. The initial aim of this epidemiological investigation was to study the prevalence, characteristics and correlates of adolescent depression, and has subsequently expanded to include a broad range of social, economic and health-related long-term outcomes and cost-of-illness analyses.

    Participants: The source population was first-year students (aged 16-17) in upper-secondary schools in Uppsala during 1991-1992, of which 2300 (93%) were screened for depression. Adolescents with positive screening and sex/age-matched peers were invited to a comprehensive assessment. A total of 631 adolescents (78% females) completed this assessment, and 409 subsequently completed a 15year follow-up assessment. At both occasions, extensive information was collected on mental disorders, personality and psychosocial situation. Detailed social, economic and health-related data from 1993 onwards have recently been obtained from the Swedish national registries for 576 of the original participants and an age-matched reference population (N=200 000).

    Findings to date: The adolescent lifetime prevalence of a major depressive episode was estimated to be 11.4%. Recurrence in young adulthood was reported by the majority, with a particularly poor prognosis for those with a persistent depressive disorder or multiple somatic symptoms. Adolescent depression was also associated with an increased risk of other adversities in adulthood, including additional mental health conditions, low educational attainment and problems related to intimate relationships.

    Future plans: Longitudinal studies of adolescent depression are rare and must be responsibly managed and utilised. We therefore intend to follow the cohort continuously by means of registries. Currently, the participants are approaching mid-adulthood. At this stage, we are focusing on the overall long-term burden of adolescent depression. For this purpose, the research group has incorporated expertise in health economics. We would also welcome extended collaboration with researchers managing similar datasets.

  • 8.
    Allvin, Renée
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Clinical Skills Centre, Örebro University Hospital, Örebro, Sweden.
    Berndtzon, Magnus
    Metodikum – Skill Centre of Medical Simulation Region County Jönköping, Jönköping, Sweden.
    Carlzon, Liisa
    Simulation Centre West, Department of Research, Education and Development, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Edelbring, Samuel
    Department of Medical and Health Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden; Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Stockholm, Sweden.
    Hult, Håkan
    Institute of Medicine and Health, Medical Faculty, Linköping University, Linköping, Sweden.
    Hultin, Magnus
    Department of Surgical and Perioperative Sciences, Anaesthesiology and Intensive Care, Medical Faculty, Umeå University, Umeå, Sweden.
    Karlgren, Klas
    Department of Learning, Informatics, Management and Ethics, Karolinska Institutet, Stockholm, Sweden; Department of Research, Education and Development and Innovation, Södersjukhuset Hospital, Stockholm, Sweden.
    Masiello, Italo
    Department of Clinical Science and Education, Karolinska Institutet, Södersjukhuset Hospital, Stockholm, Sweden.
    Kallestedt, Marie-Louise Södersved
    Clinical Skills Centre, Centre for Clinical Research, Uppsala University, Västerås, Sweden.
    Tamás, Éva
    Department of Cardiovascular Diseases, Institute of Medicine and Health, Medical Faculty, University of Linköping, Linköping, Sweden.
    Confident but not theoretically grounded - experienced simulation educators' perceptions of their own professional development2017In: Advances in Medical Education and Practice, E-ISSN 1179-7258, Vol. 8, p. 99-108Article in journal (Refereed)
    Abstract [en]

    Background: Medical simulation enables the design of learning activities for competency areas (eg, communication and leadership) identified as crucial for future health care professionals. Simulation educators and medical teachers follow different career paths, and their education backgrounds and teaching contexts may be very different in a simulation setting. Although they have a key role in facilitating learning, information on the continuing professional development (pedagogical development) of simulation educators is not available in the literature.

    Objectives: To explore changes in experienced simulation educators' perceptions of their own teaching skills, practices, and understanding of teaching over time.

    Methods: A qualitative exploratory study. Fourteen experienced simulation educators participated in individual open-ended interviews focusing on their development as simulation educators. Data were analyzed using an inductive thematic analysis.

    Results: Marked educator development was discerned over time, expressed mainly in an altered way of thinking and acting. Five themes were identified: shifting focus, from following to utilizing a structure, setting goals, application of technology, and alignment with profession. Being confident in the role as an instructor seemed to constitute a foundation for the instructor's pedagogical development.

    Conclusion: Experienced simulation educators' pedagogical development was based on self-confidence in the educator role, and not on a deeper theoretical understanding of teaching and learning. This is the first clue to gain increased understanding regarding educational level and possible education needs among simulation educators, and it might generate several lines of research for further studies.

  • 9.
    Almroth, Henrik
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Andersson, Tommy
    Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Fengsrud, Espen
    Örebro University, School of Health Sciences. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Friberg, Leif
    Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Linde, P.
    Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Rosenqvist, Mårten
    Stockholm South Hospital, Karolinska Institutet, Stockholm, Sweden.
    Englund, A.
    Stockholm South Hospital, Karolinska Institutet, Stockholm, Sweden.
    The safety of flecainide treatment of atrial fibrillation: long-term incidence of sudden cardiac death and proarrhythmic events2011In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 270, no 3, p. 281-290Article in journal (Refereed)
    Abstract [en]

    Objective:To assess the safety of long-term treatment with flecainide in patients with atrial fibrillation (AF), particularly with regard to sudden cardiac death (SCD) andproarrhythmic events.

    Design: Retrospective,observational cohort study.Setting.Single-centre study at Örebro University Hospital, Sweden.

    Setting: Single-centre study at Orebro University Hospital, Sweden.

    Subjects: A total of 112 patients with paroxysmal (51%) or persistent (49%) AF (mean age 60 ± 11 years) were included after identifying all patients with AF who initiated oral flecainide treatment (mean dose 203 ± 43 mg per day) between 1998 and 2006. Standard exclusion⁄inclusion criteria for flecainide were used,andflecainidetreatmentwasusually combined withanatrioventricular-blocking agent (89%).

    Main outcome measure: Death was classified as sudden or nonsudden according to standard definitions. Proarrhythmia was defined as cardiac syncope or lifethreatening arrhythmia.

    Results: Eight deaths were reported during a mean follow- up of 3.4 ± .4 years. Compared to the general population, the standardized mortality ratios were 1.57 (95% confidence interval (CI) 0.68–3.09) for allcause mortality and 4.16 (95% CI 1.53–9.06) for death from cardiovascular disease. Three deaths were classified as SCDs. Proarrhythmic events occurred in six patients (two each with wide QRS tachycardia, 1 : 1 conducted atrial flutter and syncope during exercise).

    Conclusion: We found an increased incidence of SCD or proarrhythmic events in this real-world study of flecainide used for the treatment of AF. The findings suggest that further investigation into the safety of flecainide for the treatment of patients with AF is warranted.

  • 10.
    Amcoff, Karin
    Örebro University, School of Medical Sciences.
    Serological and faecal biomarkers in inflammatory bowel disease2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis, are relapsing and remitting disorders characterised by chronic inflammation at various sites in the gastrointestinal tract, resulting in diarrhoea and abdominal pain. Neither the aetiology nor the pathophysiology is yet fully understood, and there is currently no cure.

    The overall aim of this thesis was to add a piece of the puzzle to understanding the complex pathogenesis of IBD; to determine the role of genetic and environmental factors in the development of antibodies in IBD - which could provide insight to the aetiology of the diseases; and to find sensitive and specific faecal biomarkers to predict future flare in the diseases.

    By conducting twin-studies, we found that some serological antibodies associated with Crohn's disease seemed to be genetically predisposed (anti-OmpC and anti-I2). Genetic predisposition do not play a predominant role in the generation of other antibodies, such as ASCA, anti-CBir1 or the autoantibody most commonly found in ulcerative colitis; pANCA. Exposure to environmental factors during childhood are suggested to be of importance in the development of ASCA and anti-CBir1 in CD. Active smoking seemed to have a protective effect against development of pANCA.

    Faecal calprotectin is a known marker for intestinal inflammation. In our third study, three faecal calprotectin assays were compared, which revealed overall poor agreement. This implies that standardisation of the method is highly needed.

    In our final study, we measured faecal eosinophil derived neurotoxin (EDN) and eosinophil cationic protein (ECP) in patients with IBD every third month over a two-year period. The results revealed that the risk of relapse in UC can be predicted by measuring EDN consecutively.

    List of papers
    1. Concordance in Anti-OmpC and Anti-I2 Indicate the Influence of Genetic Predisposition: Results of a European Study of Twins with Crohn's Disease
    Open this publication in new window or tab >>Concordance in Anti-OmpC and Anti-I2 Indicate the Influence of Genetic Predisposition: Results of a European Study of Twins with Crohn's Disease
    Show others...
    2016 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 10, no 6, p. 695-702Article in journal (Refereed) Published
    Abstract [en]

    Background and Aims: An adaptive immunological response to microbial antigens has been observed in Crohn's disease (CD). Intriguingly, this serological response precedes the diagnosis in some patients and has also been observed in healthy relatives. We aimed to determine whether genetic factors are implicated in this response in a CD twin cohort.

    Methods: In total, 82 twin pairs (Leuven n = 13, Maastricht n = 8, Örebro n = 61) took part: 81 pairs with CD (concordant monozygotic n = 16, discordant monozygotic n = 22, concordant dizygotic n = 3, discordant dizygotic n = 40) and 1 monozygotic pair with both CD and ulcerative colitis. Serology for Pseudomonas fluorescens-related protein (anti-I2), Escherichia coli outer membrane porin C (anti-OmpC), CBir1flagellin (anti-CBir1) and antibodies to oligomannan (anti-Saccharomyces cerevisiae antibody [ASCA]) was determined by standardized enzyme-linked immunoassay.

    Results: All markers were more often present in CD twins than in their healthy twin siblings. Using the intraclass correlation coefficient (ICC), agreements in concentrations of anti-OmpC and anti-I2 were observed in discordant monozygotic but not in discordant dizygotic twin pairs with CD (anti-OmpC, ICC 0.80 and -0.02, respectively) and (anti-I2, ICC 0.56 and 0.05, respectively). In contrast, no agreements were found in anti-CBir, immunoglobulin (Ig) G ASCA and ASCA IgA.

    Conclusions: We show that anti-I2 and anti-CBir1 statuses have specificity for CD and confirm previous reported specificities for anti-OmpC and ASCA. Based on quantitative analyses and observed ICCs, genetics seems to predispose to the anti-OmpC and anti-I2 response but less to ASCA and anti-CBir1 responses.

    Place, publisher, year, edition, pages
    Oxford, United Kingdom: Oxford University Press, 2016
    Keywords
    Crohn’s disease, serology, genetics
    National Category
    Gastroenterology and Hepatology
    Identifiers
    urn:nbn:se:oru:diva-50589 (URN)10.1093/ecco-jcc/jjw021 (DOI)000377920100010 ()26818662 (PubMedID)2-s2.0-84985034452 (Scopus ID)
    Available from: 2016-06-08 Created: 2016-06-08 Last updated: 2023-12-08Bibliographically approved
    2. Environmental and genetic factors in the development of perinuclear-antineutrophil cytoplasmic antibody (pANCA) positive ulcerative colitis: a European twin study
    Open this publication in new window or tab >>Environmental and genetic factors in the development of perinuclear-antineutrophil cytoplasmic antibody (pANCA) positive ulcerative colitis: a European twin study
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    (English)Manuscript (preprint) (Other academic)
    National Category
    General Practice
    Identifiers
    urn:nbn:se:oru:diva-64027 (URN)
    Available from: 2018-01-11 Created: 2018-01-11 Last updated: 2018-01-11Bibliographically approved
    3. Clinical implications of assay specific differences in f-calprotectin when monitoring inflammatory bowel disease activity over time
    Open this publication in new window or tab >>Clinical implications of assay specific differences in f-calprotectin when monitoring inflammatory bowel disease activity over time
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    2017 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 3, p. 344-350Article in journal (Refereed) Published
    Abstract [en]

    Objective: With several faecal calprotectin (FC) assays on the market, it has been difficult to define a uniform threshold for discriminating between remission and active disease in patients with inflammatory bowel disease (IBD). We aimed to compare the results of different FC-assays in IBD patients, followed over time.

    Material and methods: IBD patients provided faecal samples and reported clinical activity every third month prospectively over a two year period. FC was measured with two ELISA - (Bühlmann and Immunodiagnostik) and one automated fluoroimmunoassay (Phadia).

    Results: In total, 13 patients provided 91 faecal samples. The median (IQR) concentration of FC was higher at active disease than at remission for all assays: Bühlmann 845 (1061-226) μg/g versus 62 (224-39) μg/g, Phadia 369 (975-122) μg/g versus 11 (52-11) μg/g, and Immundiagnostik 135 (302-69) μg/g versus 8 (56-4) μg/g. The Bühlmann assay produced the largest absolute difference but the corresponding relative difference seemed to be more pronounced when analysed by the Phadia - (ratio of means 8.5; 95% CI 3.3-21.9) or the Immundiagnostik assay (ratio of means 7.4; 95% CI 3.1-17.6) than by the Bühlmann assay (ratio of means 5.3; 95% CI 2.7-10.6). Consequently, the specificity for discriminating active disease from remission varied between assays (34-75%) when the cut-off 50 μg/g was used, whereas the differences in sensitivity were less pronounced.

    Conclusions: Cross-comparisons revealed overall poor agreement between the assays as well as differences in the dynamics of FC. These findings suggest that standardisation of the method is needed to implement FC as a disease monitoring tool at large-scale.

    Place, publisher, year, edition, pages
    Oxon, United Kingdom: Taylor & Francis, 2017
    Keywords
    Biomarker, Crohn's disease, faecal calprotectin, inflammatory bowel, disease, ulcerative colitis
    National Category
    Gastroenterology and Hepatology
    Identifiers
    urn:nbn:se:oru:diva-53665 (URN)10.1080/00365521.2016.1256424 (DOI)000392488800015 ()27881032 (PubMedID)2-s2.0-84996799488 (Scopus ID)
    Funder
    Swedish Research Council, 521-2011-2764
    Note

    Funding Agencies:

    Örebro University Hospital Research Foundation OLL-333321

    Uppsala-Örebro Regional Research Foundation RFR-314671

    Available from: 2016-11-28 Created: 2016-11-28 Last updated: 2018-11-29Bibliographically approved
    4. Prognostic significance of eosinophile granule proteins in inflammatory bowel disease
    Open this publication in new window or tab >>Prognostic significance of eosinophile granule proteins in inflammatory bowel disease
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    (English)Manuscript (preprint) (Other academic)
    National Category
    General Practice
    Identifiers
    urn:nbn:se:oru:diva-64028 (URN)
    Available from: 2018-01-11 Created: 2018-01-11 Last updated: 2021-12-01Bibliographically approved
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  • 11.
    Amcoff, Karin
    et al.
    Örebro University, School of Medical Sciences.
    Bergenmalm, Daniel
    University Hospital Maastricht, Maastricht, The Netherlands.
    Pierik, Marie J.
    University Hospital Maastricht, Maastricht, The Netherlands.
    Colombel, Jean-Frederic
    University Hospital Gasthuisberg, Leuven, Belgium.
    Vermeire, Severine
    Karolinska Institute, Stockholm, Sweden.
    Bodin, Lennart
    Icahn School of Medicine at Mount Sinai, New York, NY, USA.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences.
    Environmental and genetic factors in the development of perinuclear-antineutrophil cytoplasmic antibody (pANCA) positive ulcerative colitis: a European twin studyManuscript (preprint) (Other academic)
  • 12.
    Amcoff, Karin
    et al.
    Örebro University, School of Medical Sciences.
    Cao, Yang
    Örebro University, School of Medical Sciences. Karolinska Institutet, Stockholm, Sweden.
    Zhulina, Yaroslava
    Örebro University, School of Medical Sciences.
    Lampinen, Maria
    Uppsala University, Uppsala, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences.
    Carlson, Marie
    Uppsala University, Uppsala, Sweden.
    Prognostic significance of eosinophile granule proteins in inflammatory bowel diseaseManuscript (preprint) (Other academic)
  • 13.
    Andersson, Anneli
    Örebro University, School of Medical Sciences.
    How is ADHD associated with comorbidities and health related outcomes?: The role of familial factors and ADHD during pregnancy2021Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder characterized by impaired attention and hyperactivity/impulsivity. ADHD is associated with several comorbidities and health-related outcomes. However, it is uncertain whether ADHD is more strongly associated with certain disorder domains, and whether ADHD-related comorbidities and health-related outcomes is important to consider during pregnancy. 

    Aims: To expand the knowledge regarding the genetic overlap between ADHD and other psychiatric disorder symptoms, and to increase the awareness and understanding related to ADHD in women, with a focus on adverse health behaviors, mental health problems, and pregnancy outcomes. 

    Methods: The present thesis includes one systematic review and metaanalysis (Study I), and three studies based on population-based register data from Sweden (Study II, III, and IV), and Norway (Study II).

    Results: Individuals with ADHD have an increased liability to meet criteria for externalizing, internalizing and neurodevelopmental disordersymptoms, and these co-occurrences are partly due to shared genetic risks. Further, ADHD is an important risk factor to consider before, during and after pregnancy, as ADHD increases the risk of smoking during pregnancy, mental health problems postpartum, and adverse pregnancy outcomes.

    Conclusions: The genetic overlaps between ADHD and other psychiatric disorder symptoms were similar across disorder dimensions. Further, results demonstrated that ADHD is an important risk factor to consider in women surrounding pregnancy. These findings point towards the importance of recognizing that women diagnosed with ADHD need to be prioritized and allowed more attention and support by the healthcare system, specifically during their fertile years. 

    List of papers
    1. Research Review: The strength of the genetic overlap between ADHD and other psychiatric symptoms - a systematic review and meta-analysis
    Open this publication in new window or tab >>Research Review: The strength of the genetic overlap between ADHD and other psychiatric symptoms - a systematic review and meta-analysis
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    2020 (English)In: Journal of Child Psychology and Psychiatry, ISSN 0021-9630, E-ISSN 1469-7610, Vol. 61, no 11, p. 1173-1183Article, review/survey (Refereed) Published
    Abstract [en]

    Background: Attention-deficit/hyperactivity disorder (ADHD) frequently co-occurs with other psychiatric disorders. Twin studies have established that these co-occurrences are in part due to shared genetic risks. However, the strength of these genetic overlaps and the potential heterogeneity accounted for by type of psychiatric symptoms, age, and methods of assessment remain unclear. We conducted a systematic review to fill this gap.

    Methods: We searched PubMed, PsycINFO, Embase, and Web of Science until March 07, 2019. Genetic correlations (r(g)) were used as effect size measures.

    Results: A total of 31 independent studies fulfilled the inclusion criteria. The pooled estimates showed that the associations between ADHD and other psychiatric symptoms were partly explained by shared genetic factors, with a pooled genetic correlation of 0.50, 95% confidence interval: 0.46-0.60. The genetic correlations (r(g)) between ADHD and externalizing (r(g) = .49 [0.37-0.61]), internalizing (r(g) = .50 [0.39-0.69]), and neurodevelopmental (r(g) = .56 [0.47-0.66]) symptoms were similar in magnitude. The genetic correlations in childhood and adulthood werer(g) = .53 (0.43-0.63) andr(g) = .51 (0.44-0.56), respectively. For methods of assessment, the genetic correlations were also similar in strength, self-reportsr(g) = .52 (0.47-0.58), other informantsr(g) = .55 (0.41-0.69), and combined ratersr(g) = .50 (0.33-0.65).

    Conclusions: These findings indicate that the co-occurrence of externalizing, internalizing, and neurodevelopmental disorder symptoms in individuals with ADHD symptoms in part is due to a shared genetic risk.

    Place, publisher, year, edition, pages
    Blackwell Publishing, 2020
    Keywords
    ADHD, externalizing, genetic, internalizing, neurodevelopmental, overlap, twins
    National Category
    Psychiatry
    Identifiers
    urn:nbn:se:oru:diva-80610 (URN)10.1111/jcpp.13233 (DOI)000562305600001 ()32157695 (PubMedID)2-s2.0-85081327389 (Scopus ID)
    Funder
    Swedish Research Council, 2018-01041 2018-02599The Swedish Brain Foundation, FO2018-0273
    Available from: 2020-03-13 Created: 2020-03-13 Last updated: 2023-08-28Bibliographically approved
    2. Attention-deficit/hyperactivity disorder and smoking habits in pregnant women
    Open this publication in new window or tab >>Attention-deficit/hyperactivity disorder and smoking habits in pregnant women
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    2020 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 15, no 6, article id e0234561Article in journal (Refereed) Published
    Abstract [en]

    Background: Attention-deficit/hyperactivity disorder (ADHD) has been associated with an increased risk of tobacco smoking, and more difficulties with smoking cessation compared to non-ADHD individuals. Women with ADHD may therefore show elevated rates of smoking during pregnancy.

    Aims: To examine the association between ADHD and smoking habits among pregnant women in Sweden and Norway.

    Methods: Women pregnant for the first time were identified in Sweden (n = 622,037), and Norway (n = 293,383), of which 1.2% (n = 7,444), and 1.7% (n = 4,951) were defined as having ADHD, respectively. Data on smoking habits were collected early and late in pregnancy.

    Results: In Sweden, ADHD was associated with an increased risk of smoking early in pregnancy, adjusted risk ratio (adjRR) 2.69 (95% confidence interval, 2.58-2.81), and late in pregnancy, adjRR 2.95 (2.80-3.10). Similar findings were observed in the Norwegian data, early in pregnancy, adjRR 2.31 (2.21-2.40), and late in pregnancy, adjRR 2.56 (2.42-2.70). Women with ADHD were more likely to continue smoking during pregnancy, compared to women without ADHD, both in Sweden adjRR 1.13 (1.10-1.17), and in Norway, adjRR 1.16 (1.12-1.20). Having a sibling diagnosed with ADHD was associated with an increased risk of smoking early and late in pregnancy, in both Sweden and Norway.

    Conclusions: Women with ADHD are considerably more likely to smoke early and late in (their first) pregnancy and are less likely to stop smoking between the two time points. Smoking, early and late in pregnancy, co-aggregates in families with ADHD. Smoking prevention and intervention programs should be targeted towards women with ADHD, specifically during their childbearing years, to ensure better mother and child outcomes.

    Place, publisher, year, edition, pages
    Public Library of Science, 2020
    National Category
    Psychiatry
    Identifiers
    urn:nbn:se:oru:diva-84849 (URN)10.1371/journal.pone.0234561 (DOI)000543273200037 ()32555596 (PubMedID)2-s2.0-85086693580 (Scopus ID)
    Funder
    Swedish Research Council, 2018-02599 2018-02119 2018-01041The Swedish Brain Foundation, FO2018-0273EU, Horizon 2020, 728018
    Note

    Funding Agencies:

    Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM)  340-2013-5867

    Stiftelsen Kristian Gerhard Jebsen  SKGJ-MED-02

    Western Norway Regional Health Authorities (Helse Vest)  

    University of Bergen  

    Norwegian research network for ADHD  

    European Union's Horizon 2020 research and innovation programme  667302

    Dr. Nils Henrichsen og hustru Anna Henrichsens legat  

    Available from: 2020-08-17 Created: 2020-08-17 Last updated: 2021-06-14Bibliographically approved
    3. Depression and Anxiety Disorders During the Postpartum Period – in Women Diagnosed with ADHD
    Open this publication in new window or tab >>Depression and Anxiety Disorders During the Postpartum Period – in Women Diagnosed with ADHD
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    (English)Manuscript (preprint) (Other academic)
    National Category
    General Practice
    Identifiers
    urn:nbn:se:oru:diva-91752 (URN)
    Available from: 2021-05-10 Created: 2021-05-10 Last updated: 2021-05-17Bibliographically approved
    4. Adverse Pregnancy Outcomes in Women Diagnosed with ADHD: A Population-Based Register Study
    Open this publication in new window or tab >>Adverse Pregnancy Outcomes in Women Diagnosed with ADHD: A Population-Based Register Study
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    (English)Manuscript (preprint) (Other academic)
    National Category
    General Practice
    Identifiers
    urn:nbn:se:oru:diva-91754 (URN)
    Available from: 2021-05-10 Created: 2021-05-10 Last updated: 2021-05-17Bibliographically approved
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    How is ADHD associated with comorbidities and health related outcomes?: The role of familial factors and ADHD during pregnancy
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  • 14.
    Andersson, Anneli
    et al.
    Örebro University, School of Medical Sciences.
    Garcia-Argibay, Miguel
    Örebro University, School of Medical Sciences.
    Oskarsson, Sofi
    Örebro University, School of Law, Psychology and Social Work.
    Tuvblad, Catherine
    Örebro University, School of Law, Psychology and Social Work. Department of Psychology, University of Southern California, United States.
    Ghirardi, Laura
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden .
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden.
    Adverse Pregnancy Outcomes in Women Diagnosed with ADHD: A Population-Based Register StudyManuscript (preprint) (Other academic)
  • 15.
    Andersson, Anneli
    et al.
    Örebro University, School of Medical Sciences.
    Garcia-Argibay, Miguel
    Örebro University, School of Medical Sciences.
    Viktorin, Alexander
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden .
    Ghirardi, Laura
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden .
    Butwicka, Agnieszka
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden; Department of Child Psychiatry, Medical University of Warsaw, Warsaw, Poland .
    Skoglund, Charlotte
    Department of clinical neuroscience, Karolinska Institutet, Stockholm, Sweden; Department of Neuroscience, Uppsala University, Uppsala Sweden.
    D’onofrio, Brian M.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden; The Department of Psychological and Brain Sciences at Indiana University, Bloomington, Indiana.
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden.
    Tuvblad, Catherine
    Örebro University, School of Law, Psychology and Social Work. Department of Psychology, University of Southern California, United States.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden.
    Depression and Anxiety Disorders During the Postpartum Period – in Women Diagnosed with ADHDManuscript (preprint) (Other academic)
  • 16.
    Andersson, Tommy
    Örebro University, School of Medical Sciences.
    Atrial fibrillation and cause of death, sex differences in mortality, and anticoagulation treatment in low-risk patients2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Atrial fibrillation (AF) is the most common arrhythmia but information on cause of death in patients with AF is sparse, and whether individuals at low risk of cerebral infarction (CVL) should receive antico-agulant medication is controversial. Studies of sex differences with respect to mortality risk have shown conflicting results.

    Methods: Data were obtained from Swedish National Registers. In Study I, there were 272 186 AF patients and matched controls and in Studies II and III, 9519 AF patients and no other diagnosis and matched controls. Study IV compared treatment with warfarin to no treatment in 48 433 patients with AF. Hazard ratio (HR) was calculated with 95% confidence intervals and outcome rates as number per 1000 person-years.

    Results: Ischemic heart disease (IHD) was the most common underlying cause of death and was present in 40.2% of AF patients at a HR of 1.7 (1.4-2.1). CVL/stroke was a cause of death in 13.1%, HR 2.7 (1.8-4.0). Among underlying and contributing causes of death, the most common diagnoses were IHD in 43.5%, HR 1.7 (1.4-2.0) and heart failure in 33.1%, HR 2.9 (2.2-3.7). The HRs for mortality in females with AF in age categories ≤65, 65-74, and 75-85 were 2.15, 1.72, and 1.44, and for males 1.76, 1.36, and 1.24. The rates of mortality in females with AF in age categories 55-64, 65-74, and 75-85 were 6.2, 20.7, and 57.3, and for males 8.5, 27.3, and 64.5. In patients 65-74 years, females with a CHA2DS2-VASc score of 2, and males with a score of 1 receiving warfarin treatment showed a significantly reduced risk of cerebral infarc-tion/stroke, HR 0.46 (0.25-0.83) for females and for males, HR 0.39 (0.21-0.73).

    Conclusions: Most common causes of death in AF patients were CVL/stroke, heart failure, and IHD. HR of mortality in patients with AF was higher in females than in males but absolute risk was higher in males with AF compared to females with AF. Anticoagulant therapy was benefi-cial in patients ≥65 years, regardless of the CHA2DS2-VASc score.

    List of papers
    1. All-cause mortality in 272 186 patients hospitalized with incident atrial fibrillation 1995-2008: a Swedish nationwide long-term case-control study
    Open this publication in new window or tab >>All-cause mortality in 272 186 patients hospitalized with incident atrial fibrillation 1995-2008: a Swedish nationwide long-term case-control study
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    2013 (English)In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no 14, p. 1061-1067Article in journal (Refereed) Published
    Abstract [en]

    Aims To evaluate long-term all-cause risk of mortality in women and men hospitalized for the first time with atrial fibrillation (AF) compared with matched controls. Methods and results A total of 272 186 patients (44% women) <= 85 years at the time of hospitalization with incidental AF 1995-2008 and 544 344 matched controls free of in-hospital diagnosis of AF were identified. Patients were followed via record linkage of the Swedish National Patient Registry and the Cause of Death Registry. Using Cox regression models, the long-term relative all-cause mortality risk, adjusted for concomitant diseases, in women vs. controls was 2.15, 1.72, and 1.44 (P < 0.001) in the age categories <= 65, 65-74, and 75-85 years, respectively. The corresponding figures for men were 1.76, 1.36, and 1.24 (P < 0.001). Among concomitant diseases, neoplasm, chronic renal failure, and chronic obstructive pulmonary disease contributed most to the increased all-cause mortality vs. controls. In patients with AF as the primary diagnosis, the relative risk of mortality was 1.63, 1.46, and 1.28 (P < 0.001) in women and 1.45, 1.17, and 1.10 (P < 0.001) in men. Conclusion Atrial fibrillation was an independent risk factor of all-cause mortality in patients with incident AF. The concomitant diseases that contributed most were found outside the thromboembolic risk scores. The highest relative risk of mortality was seen in women and in the youngest patients compared with controls, and the differences between genders in each age category were statistically significant.

    Keywords
    Atrial fibrillation, Mortality, Gender, Age, Long term
    National Category
    Cardiac and Cardiovascular Systems
    Research subject
    Cardiology
    Identifiers
    urn:nbn:se:oru:diva-38709 (URN)10.1093/eurheartj/ehs469 (DOI)000317424300014 ()23321349 (PubMedID)2-s2.0-84876218799 (Scopus ID)
    Note

    Funding agencies ar:

    AstraZeneca R&D, Mölndal, Sweden

    Örebro Heart Foundation Research and

    Committee of Örebro University Hospital

    Available from: 2014-11-18 Created: 2014-11-18 Last updated: 2024-01-16Bibliographically approved
    2. Gender-related differences in risk of cardiovascular morbidity and all-cause mortality in patients hospitalized with incident atrial fibrillation without concomitant diseases: A nationwide cohort study of 9519 patients
    Open this publication in new window or tab >>Gender-related differences in risk of cardiovascular morbidity and all-cause mortality in patients hospitalized with incident atrial fibrillation without concomitant diseases: A nationwide cohort study of 9519 patients
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    2014 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 177, no 1, p. 91-99Article in journal (Refereed) Published
    Abstract [en]

    Background: Previous studies of patients with "lone" and "idiopathic" atrial fibrillation (AF) have provided conflicting evidence concerning the development, management and prognosis of this condition.

    Methods: In this nation-wide, retrospective, cohort study, we studied patients diagnosed with incidental AF recorded in national Swedish registries between 1995 and 2008. Controls were matched for age, sex and calendar year of the diagnosis of AF in patients. All subjects were free of any in-hospital diagnosis from 1987 and until patients were diagnosed with AF and also free of any diagnosis within one year from the time of inclusion. Follow-up continued until 2009. We identified 9519 patients (31% women) and 12,468 matched controls.

    Results: Relative risks (RR) versus controls for stroke or transient ischemic attack (TIA) in women were 19.6, 4.4, 3.4 and 2.5 in the age categories <55, 55-64, 65-74 and 75-85, years respectively. Corresponding figures for men were 3.4, 2.5, 1.7 and 1.9. RR for heart failure were 6.6, 6.6, 6.3 and 3.8 in women and 7.8, 4.6, 4.9 and 2.9 in men. All RR were statistically significant with p < 0.01. RR for myocardial infarction and all-cause mortality were statistically significantly increased only in the two oldest age categories in women and 65-74 years in men.

    Conclusions: Patients with AF and no co-morbidities at inclusion had at least a doubled risk of stroke or TIA and a tripled risk of heart failure, through all age categories, as compared to controls. Women were at higher RR of stroke or TIA than men. (C) 2014 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-SA license (http://creativecommons.org/licenses/by-nc-sa/3.0/).

    Place, publisher, year, edition, pages
    Elsevier, 2014
    Keywords
    Atrial fibrillation, Cardiovascular morbidity, Mortality, Cohort, Nationwide
    National Category
    Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:oru:diva-56310 (URN)10.1016/j.ijcard.2014.09.092 (DOI)000343895000046 ()25499348 (PubMedID)2-s2.0-84909974321 (Scopus ID)
    Note

    Funding Agencies:

    AstraZeneca RD Mölndal

    Örebro Heart Foundation

    Research Committee of Örebro University Hospital OLL 2012-265231

    Available from: 2017-03-14 Created: 2017-03-14 Last updated: 2024-01-16Bibliographically approved
    3. Patients without comorbidities at the time of diagnosis of atrial fibrillation: causes of death during long-term follow-up compared to matched controls
    Open this publication in new window or tab >>Patients without comorbidities at the time of diagnosis of atrial fibrillation: causes of death during long-term follow-up compared to matched controls
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    2017 (English)In: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 40, no 11, p. 1076-1082Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Little is known about the long-term, cause-specific mortality risk in patients without comorbidities at the time of diagnosis of atrial fibrillation (AF).

    METHODS: From a nation-wide registry of patients hospitalized with incident AF between 1995 and 2008 we identified 9 519 patients with a first diagnosed AF and no comorbidities at the time of AF diagnosis. They were matched with 12 468 controls. The follow-up continued until December 2008. Causes of death were classified according to the ICD-10 codes.

    RESULTS: During follow-up, 11.1% of patients with AF and 8.3% of controls died. Cardiovascular diseases were the most common causes of death and the only diagnoses which showed significantly higher relative risk in patients with AF than controls (HR 2.0, 95% CI 1.8-2.3), and the relative risk was significantly higher in women than in men. Stroke was a more common cause among patients with AF, 13.1% versus 9.7% (HR 2.7, 95% CI 1.8-4.0), while cerebral hemorrhage was more common among controls, 4.7% versus 10.2% (HR 0.9, 95% CI 0.6-1.5). The time from AF diagnosis to death was 6.0 ± 3.1 years.

    CONCLUSIONS: In patients with incident AF and no known comorbidities at the time of AF diagnosis, only cardiovascular diseases were more often causes of death as compared to controls. Women carried a significantly higher relative risk than men.

    Place, publisher, year, edition, pages
    John Wiley & Sons, 2017
    Keywords
    atrial fibrillation, cause of death, idiopathic, morbidity, mortality
    National Category
    Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:oru:diva-61704 (URN)10.1002/clc.22776 (DOI)000417744800020 ()28841233 (PubMedID)2-s2.0-85028540727 (Scopus ID)
    Funder
    AstraZeneca
    Note

    Funding Agency:

    Örebro Heart Foundation 

    Research Committee of Örebro University Hospital, Sweden 

    Available from: 2017-11-13 Created: 2017-11-13 Last updated: 2024-01-16Bibliographically approved
    4. Patients with atrial fibrillation and outcomes of cerebral infarction in those with treatment of warfarin versus no warfarin with references to CHA(2)DS(2)-VASc score, age and sex: A Swedish nationwide observational study with 48 433 patients
    Open this publication in new window or tab >>Patients with atrial fibrillation and outcomes of cerebral infarction in those with treatment of warfarin versus no warfarin with references to CHA(2)DS(2)-VASc score, age and sex: A Swedish nationwide observational study with 48 433 patients
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    2017 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 12, no 5, article id e0176846Article in journal (Refereed) Published
    Abstract [en]

    Aims: There is controversy in the guidelines as to whether patients with atrial fibrillation and a low risk of stroke should be treated with anticoagulation, especially those with a CHA(2)DS(2)-VASc score of 1 point.

    Methods: In a retrospective, nationwide cohort study, we used the Swedish National Patient Registry, the National Prescribed Drugs Registry, the Swedish Registry of Education and the Population and Housing Census Registry. 48 433 patients were identified between 1 January 2006 and 31 December 2008 with incident atrial fibrillation who were divided in age categories, sex and a CHA(2)DS(2)-VASc score of 0, 1, 2 and >= 3 and they were included in a time-varying analysis of warfarin treatment versus no treatment. The primary end-point was cerebral infarction and stroke, and patients were followed until 31 December 2009.

    Results: Patients with 1 point from the CHA(2)DS(2)-VASc score showed the following adjusted hazard ratios (HR) with a 95% confidence interval: men 65-74 years 0.46 (0.25-0.83), men < 65 years 1.11 (0.56-2.23) and women < 65 years 2.13 (0.94-4.82), where HR < 1 indicates protection with warfarin. In patients < 65 years and 2 points, HR in men was 0.35 (0.18-0.69) and in women 1.84 (0.86-3.94) while, in women with at least 3 points, HR was 0.31 (0.16-0.59). In patients 65-74 years and 2 points, HR in men was 0.37 (0.23-0.59) and in women 0.39 ( 0.21-0.73). Categories including age >= 65 years or >= 3 points showed a statistically significant protection from warfarin.

    Conclusions: Our results support that treatment with anticoagulation may be considered in all patients with an incident atrial fibrillation diagnosis and an age of 65 years and older, i.e. also when the CHA(2)DS(2)-VASc score is 1.

    Place, publisher, year, edition, pages
    Public Library of Science, 2017
    National Category
    Cardiac and Cardiovascular Systems
    Research subject
    Cardiology
    Identifiers
    urn:nbn:se:oru:diva-57914 (URN)10.1371/journal.pone.0176846 (DOI)000400648500084 ()28472091 (PubMedID)2-s2.0-85019090489 (Scopus ID)
    Note

    Funding Agencies:

    Research Committee of Örebro University  0LL 2012-265231 

    AstraZeneca RD Mölndal  

    Örebro Heart Foundation 

    Available from: 2017-06-08 Created: 2017-06-08 Last updated: 2024-01-16Bibliographically approved
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    Atrial fibrillation and cause of death, sex differences in mortality, and anticoagulation treatment in low-risk patients
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  • 17.
    Appelros, Peter
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Neurology, Örebro University Hospital, Örebro, Sweden.
    Terent, Andreas
    Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Thrombolysis in acute stroke2015In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 385, no 9976, p. 1394-1394Article in journal (Refereed)
  • 18.
    Arinell, Karin
    Örebro University, School of Medical Sciences.
    Immobilization as a risk factor for arterial and venous thrombosis2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Aim: Immobilization and a sedentary lifestyle are correlated with an elevated risk of both arterial and venous thrombosis. The goal of this research was to investigate whether markers associated with cardiovascular disease risk are altered during long term immobilization in a human model and in the brown bear, which survives annual cycles of long-term immobilization.

    Methods: In study populations assigned to 20-60 days of strict head-down-tilt bed rest 24h a day, we analysed blood levels of the emerging cardiovascular disease marker cystatin C, soluble markers of in vivo platelet activation P-selectin and PDGF-BB, and platelet aggregation. Blood samples were taken from free-ranging brown bears in summer and again during hibernation for analysis of lipid profile and platelet aggregation. Histological examination was performed on the left anterior descending coronary artery and aortic arches of bears harvested during the hunting season.

    Results: During prolonged bed rest in humans, levels of cystatin C and platelet aggregation remained unchanged, but we observed a significant decrease in platelet activation markers. Brown bear plasma lipids were elevated during hibernation compared with the active state and cholesterol levels were generally considerably higher than normal human values. The arterial specimens showed no signs of atherosclerosis. Platelet aggregation was halved during hibernation compared to the active state.

    Conclusions: Long-term immobilization has effects on several cardiovascular risk factors in both humans and bears. Increased knowledge and understanding of the protective mechanisms that allows the brown bear to survive repeated periods of immobilization could contribute to new strategies for prevention and treatment of cardiovascular disease in humans.

    List of papers
    1. Effect of prolonged standardized bed rest on cystatin C and other markers of cardiovascular risk
    Open this publication in new window or tab >>Effect of prolonged standardized bed rest on cystatin C and other markers of cardiovascular risk
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    2011 (English)In: BMC Physiology, E-ISSN 1472-6793, Vol. 11, article id 17Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Sedentary lifestyle is associated with coronary artery disease but even shorter periods of physical inactivity may increase cardiovascular risk. Cystatin C is independently associated with cardiovascular disease and our objective was to investigate the relation between this novel biomarker and standardized bed rest. Research of immobilization physiology in humans is challenging because good biological models are in short supply. From the Women International Space simulation for Exploration study (WISE) we studied markers of atherosclerosis and kidney function, including cystatin C, in a standardized bed rest study on healthy volunteers. Fifteen healthy female volunteers participated in a 20-day ambulatory control period followed by 60 days of bed rest in head-down tilt position (-6°) 24 h a day, finalized by 20 days of recovery. The subjects were randomized into two groups during bed rest: a control group (n = 8) that remained physically inactive and an exercise group (n = 7) that participated in both supine resistance and aerobic exercise training.

    RESULTS: Compared to baseline values there was a statistically significant increase in cystatin C in both groups after bed rest (P < 0.001). Glomerular filtration rate (GFR), calculated by both cystatin C and Cockcroft-Gault equation, decreased after bed rest while there were no differences in creatinine or creatine kinase levels. CRP did not change during bed rest in the exercise group, but there was an increase of CRP in the control group during recovery compared to both the baseline and the bed rest periods. The apo-B/apo-Ai ratio increased during bed rest and decreased again in the recovery period. Subjects experienced a small but statistically significant reduction in weight during bed rest and compared to baseline weights remained lower at day 8 of recovery.

    CONCLUSION: During and following prolonged standardized bed rest the concentrations of several clinically relevant cardiovascular risk markers change.

    Place, publisher, year, edition, pages
    BioMed Central (BMC), 2011
    National Category
    Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:oru:diva-66787 (URN)10.1186/1472-6793-11-17 (DOI)22152087 (PubMedID)2-s2.0-83055192077 (Scopus ID)
    Available from: 2018-04-26 Created: 2018-04-26 Last updated: 2024-01-16Bibliographically approved
    2. Brown Bears (Ursus arctos) Seem Resistant to Atherosclerosis Despite Highly Elevated Plasma Lipids during Hibernation and Active State
    Open this publication in new window or tab >>Brown Bears (Ursus arctos) Seem Resistant to Atherosclerosis Despite Highly Elevated Plasma Lipids during Hibernation and Active State
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    2012 (English)In: Clinical and Translational Science, ISSN 1752-8054, E-ISSN 1752-8062, Vol. 5, no 3, p. 269-272Article in journal (Refereed) Published
    Abstract [en]

    Hibernation is an extreme physiological challenge for the brown bear (Ursus arctos) in which metabolism is based mainly on lipids. The study objective was to compare plasma lipids in hibernating and active free-ranging brown bears and relate them to arterial histopathology. Blood was drawn from seven immobilized free-ranging brown bears (three females, 23 years old) during hibernation in February and from the same bears while active in June and analyzed by enzymatic and automated hematology methods within 48 hours of sampling. Left anterior descending coronary arteries and aortic arches from 12 bears (six females, 1.512 years old) killed in hunting were examined by histopathology. Total plasma cholesterol decreased from hibernation to the active period (11.08 +/- 1.04 mmol/L vs. 7.89 +/- 1.96 mmol/L, P= 0.0028) as did triglyceride (3.16 +/- 0.62 mmol/L vs. 1.44 +/- 0.27 mmol/L, P= 0.00012) and LDL cholesterol (4.30 +/- 0.71 mmol/L vs. 2.02 +/- 1.03 mmol/L, P= 0.0075), whereas HDL cholesterol was unchanged. No atherosclerosis, fatty streaks, foam cell infiltration, or inflammation were seen in any arterial samples. Brown bears tolerate elevated cholesterol levels, obesity, physical inactivity, and circulatory slow flow during hibernation without signs of -atherosclerosis. This species might serve as a reverse translational model for atherosclerosis resistance.

    Place, publisher, year, edition, pages
    Wiley-Blackwell, 2012
    Keywords
    apolipoproteins, cholesterol, hibernation physiology, triglycerides
    National Category
    Other Biological Topics
    Identifiers
    urn:nbn:se:oru:diva-58327 (URN)10.1111/j.1752-8062.2011.00370.x (DOI)000305077100014 ()22686205 (PubMedID)2-s2.0-84862224614 (Scopus ID)
    Note

    Funding Agencies:

    NordForsk (an organization under the Nordic Council of Ministers)  44042

    Available from: 2017-06-27 Created: 2017-06-27 Last updated: 2024-01-16Bibliographically approved
    3. Downregulation of platelet activation markers during long-term immobilization
    Open this publication in new window or tab >>Downregulation of platelet activation markers during long-term immobilization
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    2013 (English)In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 24, no 5, p. 369-374Article in journal (Refereed) Published
    Abstract [en]

    Immobilization and sedentary lifestyle are risk factors for venous thromboembolism and cardiovascular disease, yet little is known about platelet function during long-term physical inactivity. Our aim was to investigate platelet activation markers and their coupling to standardized immobilization: platelet-derived growth factor (PDGF-BB) and P-selectin. We studied 15 healthy females participating in the Women International Space simulation for Exploration study. Following a 20-day ambulatory control period, the subjects underwent 60 days of bed rest in head-down tilt position (-6 degrees) 24 hours a day, finalized by 20 days of recovery. The subjects were randomized into two groups during bed rest: a control group (n = 8) that remained physically inactive and an exercise group (n = 7) that participated in both supine resistance and aerobic exercise training. Blood samples for the analysis of platelet activation markers were collected at baseline (5 days before bed rest), after 44 days of bed rest and 8 days into the recovery period. Compared to baseline, the levels of P-selectin and PDGF-BB decreased after bed rest (by 55%, p = 0.01 and 73%, p < 0.03, respectively) and remained decreased in the recovery period (by 76%, p < 0.001 and 78%, p < 0.02, respectively, compared to baseline). Platelet count (baseline value for the exercise group 260 000/mu l +/- 34 000 and baseline value for the control group 210 000/mu l +/- 30 000) did not change during the bed rest study (two-way repeated measurements ANOVA, p = ns). There were no statistical differences between the physically inactive and the exercise group. During long-term immobilization, a known risk factor for thrombosis, the levels of P-selectin and PDGF-BB decreased. Our findings indicate downregulation of platelet activation during immobilization.

    Place, publisher, year, edition, pages
    Taylor & Francis, 2013
    Keywords
    Platelets, P-selectin, PDGF, immobilization, thrombosis
    National Category
    Hematology Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:oru:diva-56417 (URN)10.3109/09537104.2012.715215 (DOI)000321065000005 ()22931233 (PubMedID)2-s2.0-84879764932 (Scopus ID)
    Available from: 2017-03-16 Created: 2017-03-16 Last updated: 2024-01-16Bibliographically approved
    4. Biochemical Foundations of Health and Energy Conservation in Hibernating Free-Ranging Subadult Brown Bear Ursus arctos
    Open this publication in new window or tab >>Biochemical Foundations of Health and Energy Conservation in Hibernating Free-Ranging Subadult Brown Bear Ursus arctos
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    2016 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 291, no 43, p. 22509-22523Article in journal (Refereed) Published
    Abstract [en]

    Brown bears (Ursus arctos) hibernate for 5-7 months without eating, drinking, urinating and defecating at a metabolic rate of only 25% of the summer activity rate. Nonetheless, they emerge healthy and alert in spring. We quantified the biochemical adaptations for hibernation by comparing the proteome, metabolome, and hematologic features of blood from hibernating and active free-ranging subadult brown bears with a focus on conservation of health and energy. We found that total plasma protein concentration increased during hibernation, even though the concentrations of most individual plasma proteins decreased, as did the white blood cell types. Strikingly, antimicrobial defense proteins increased in concentration. Central functions in hibernation involving the coagulation response and protease inhibition, as well as lipid transport and metabolism, were upheld by increased levels of very few key or broad-specificity proteins. The changes in coagulation factor levels matched the changes in activity measurements. A dramatic 45-fold increase in sex-hormone-binding-globulin SHBG levels during hibernation draws, for the first time, attention to its significant but unknown role in maintaining hibernation physiology. We propose that energy for the costly protein synthesis is reduced by three mechanisms, (i) dehydration, which increases protein concentration without de novo synthesis; (ii) reduced protein degradation rates due to a 6 °C reduction in body temperature, and decreased protease activity; and (iii) a marked redistribution of energy resources only increasing de novo synthesis of few key proteins. This comprehensive global data identified novel biochemical strategies for bear adaptations to the extreme condition of hibernation, and have implications for our understanding of physiology in general.

    Place, publisher, year, edition, pages
    Rockville, USA: American Society for Biochemistry and Molecular Biology, 2016
    Keywords
    Antimicrobial proteins, blood constituents, coagulation factor, complement system, hibernation physiology, metabolomics, protein turnover, proteomics, sex hormone-binding globulin (SHBG)
    National Category
    Biochemistry and Molecular Biology
    Research subject
    Biochemistry
    Identifiers
    urn:nbn:se:oru:diva-52176 (URN)10.1074/jbc.M116.742916 (DOI)000386760600013 ()27609515 (PubMedID)2-s2.0-84992343533 (Scopus ID)
    Note

    Funding Agency:

    Lundbech Foundation R126-2012-12408

    Aalborg University

    Available from: 2016-09-21 Created: 2016-09-14 Last updated: 2024-01-16Bibliographically approved
    5. Physical inactivity and platelet function in humans and brown bears: A comparative study
    Open this publication in new window or tab >>Physical inactivity and platelet function in humans and brown bears: A comparative study
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    2018 (English)In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 29, no 1, p. 87-90Article in journal (Refereed) Published
    Abstract [en]

    Physical inactivity increases the risk of thromboembolism. However, good standardized human models on inactivity are in short supply and experimental models are few.

    Our objective was to investigate how standardized bed rest affects platelet aggregation in humans and to investigate if aggregation is altered in a translational model system - the hibernating brown bear (Ursus arctos). We collected blood from (1) healthy male volunteers participating in a 21-day bed rest study in head-down tilt position (-6°) 24 h a day; (2) free-ranging brown bears captured during winter hibernation and again during active state in summer. We analyzed platelet function using multiple electrode platelet aggregometry. In total, 9 healthy male volunteers (age 31.0 ± 6.4 years) and 13 brown bears (7 females and 6 males, age 2.8 ± 0.6 years) were included. In hibernating bears adenosine diphosphate, arachidonic acid, thrombin receptor activating peptide, and collagen impedance aggregometry tests were all halved compared to summer active state. In human volunteers no statistically significant changes were found between baseline and the end of bed rest. In human male volunteers 3 weeks of bed rest did not affect platelet function. In hibernating brown bears platelet aggregation was halved compared to summer and we hypothesize that this is a protective measure to avoid formation of thrombi under periods of low blood flow.

    Place, publisher, year, edition, pages
    Taylor & Francis, 2018
    Keywords
    Thrombosis; Platelets; Platelet aggregation; Immobilization
    National Category
    Physiology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Hematology
    Identifiers
    urn:nbn:se:oru:diva-61740 (URN)10.1080/09537104.2017.1336530 (DOI)000423584700015 ()28758823 (PubMedID)2-s2.0-85026519068 (Scopus ID)
    Available from: 2017-11-01 Created: 2017-11-01 Last updated: 2024-01-16Bibliographically approved
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  • 19.
    Baliakas, Panagiotis
    et al.
    Department of Clinical Genetics, Uppsala University Hospital, Uppsala, Sweden; Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Kättström, Magdalena
    Örebro University, School of Medical Sciences. Section of Hematology.
    Rossing, Maria
    Center for Genomic Medicine, Copenhagen University Hospital, Copenhagen, Denmark.
    Amini, Rose-Marie
    Department of Immunology, Genetics and Pathology, Clinical and Experimental Pathology, Uppsala University and Uppsala University Hospital, Uppsala, Sweden.
    Refractory chronic "ITP": When platelet size matters2018In: Clinical Case Reports, E-ISSN 2050-0904, Vol. 6, no 9, p. 1779-1780Article in journal (Refereed)
    Abstract [en]

    Key Clinical Message

    Inherited conditions associated with thrombocytopenia should be included in the differential diagnosis of young patients with refractory immune thrombocytopenia (ITP), even in the absence of a positive family history. Early identification of such conditions is of vital importance in order to reach the right diagnosis and avoid unnecessary or even harmful medication.

  • 20.
    Bankole, Landry-Cyrille
    et al.
    Örebro University, School of Health Sciences. Laboratoire Interuniversitaire de Biologie de la Motricité, UJM-Saint-Etienne, Université de Lyon, Saint-Etienne, France; Unité de Myologie, Centre Hospitalier, Universitaire de Saint-Etienne, Saint-Etienne, France; Centre Référent Maladies Neuromusculaires Rares Rhône-Alpes, Saint-Etienne, France.
    Millet, Guillaume Y.
    Laboratoire Interuniversitaire de Biologie de la Motricité, UJM-Saint-Etienne, Université de Lyon, Saint-Etienne, France; Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, Calgary AB, Canada; INSERM U1042, Grenoble, France.
    Temesi, John
    Laboratoire Interuniversitaire de Biologie de la Motricité, UJM-Saint-Etienne, Université de Lyon, Saint-Etienne, France; Human Performance Laboratory, Faculty of Kinesiology, University of Calgary, Calgary AB, Canada.
    Bachasson, Damien
    INSERM U1042, Grenoble, France; Laboratoire HP2, Grenoble Alpes University, Grenoble, France.
    Ravelojaona, Marion
    Laboratoire Interuniversitaire de Biologie de la Motricité, UJM-Saint-Etienne, Université de Lyon, Saint-Etienne, France; Unité de Myologie, Centre Hospitalier, Universitaire de Saint-Etienne, Saint-Etienne, France; Centre Référent Maladies Neuromusculaires Rares Rhône-Alpes, Saint-Etienne, France.
    Wuyam, Bernard
    INSERM U1042, Grenoble, France; Laboratoire HP2, Grenoble Alpes University, Grenoble, France; Centre Référent Maladies Neuromusculaires Rares Rhône-Alpes, Saint-Etienne, France.
    Verges, Samuel
    INSERM U1042, Grenoble, France; Laboratoire HP2, Grenoble Alpes University, Grenoble, France.
    Ponsot, Elodie
    Örebro University, School of Health Sciences.
    Antoine, Jean-Christophe
    Centre Référent Maladies Neuromusculaires Rares Rhône-Alpes, Saint-Etienne, France.
    Kadi, Fawzi
    Örebro University, School of Health Sciences.
    Feasson, Leonard
    Laboratoire Interuniversitaire de Biologie de la Motricité, UJM-Saint-Etienne, Université de Lyon, Saint-Etienne, France; Unité de Myologie, Centre Hospitalier, Universitaire de Saint-Etienne, Saint-Etienne, France; Centre Référent Maladies Neuromusculaires Rares Rhône-Alpes, Saint-Etienne, France.
    Safety and efficacy of a 6-month home-based exercise program in patients with facioscapulohumeral muscular dystrophy A randomized controlled trial2016In: Medicine, ISSN 0025-7974, E-ISSN 1536-5964, Vol. 95, no 31, article id e4497Article in journal (Refereed)
    Abstract [en]

    Background: Previous randomized controlled trials investigating exercise training programs in facioscapulohumeral muscular dystrophy (FSHD) patients are scarce and of short duration only. This study assessed the safety and efficacy of a 6-month home-ased exercise training program on fitness, muscle, and motor function in FSHD patients.

    Methods: Sixteen FSHD patients were randomly assigned to training (TG) and control (CG) groups (both n=8) in a home-based exercise intervention. Training consisted of cycling 3 times weekly for 35minutes (combination of strength, high-intensity interval, and low-intensity aerobic) at home for 24 weeks. Patients in CG also performed an identical training program (CTG) after 24 weeks. The primary outcome was change in peak oxygen uptake (VO2 peak) measured every 6 weeks. The principal secondary outcomes were maximal quadriceps strength (MVC) and local quadriceps endurance every 12 weeks. Other outcome measures included maximal aerobic power (MAP) and experienced fatigue every 6 weeks, 6-minute walking distance every 12 weeks, and muscle characteristics from vastus lateralis biopsies taken pre- and postintervention.

    Results: The compliance rate was 91% in TG. Significant improvements with training were observed in the VO2 peak (+19%, P= 0.002) and MAP by week 6 and further to week 24. Muscle endurance, MVC, and 6-minute walking distance increased and experienced fatigue decreased. Muscle fiber cross-sectional area and citrate synthase activity increased by 34% (P=0.008) and 46% (P=0.003), respectively. Dystrophic pathophysiologic patterns were not exacerbated. Similar improvements were experienced by TG and CTG.

    Conclusions: A combined strength and interval cycling exercise-training program compatible with patients' daily professional and social activities leads to significant functional benefits without compromising muscle tissue.

  • 21.
    Baumgart, Juliane
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Obstetrics and Gynecology.
    Nilsson, Kerstin
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Obstetrics and Gynecology.
    Evers, Anneli Stavreus
    Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
    Kallak, Theodora Kunovac
    Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
    Poromaa, Inger Sundström
    Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
    Sexual dysfunction in women on adjuvant endocrine therapy after breast cancer2013In: Menopause: The Journal of the North American Menopause, ISSN 1072-3714, E-ISSN 1530-0374, Vol. 20, no 2, p. 162-168Article in journal (Refereed)
    Abstract [en]

    Objective: The goal of this study was to investigate sexual function in postmenopausal breast cancer patients treated with aromatase inhibitors.

    Methods: A population-based, cross-sectional study was conducted among postmenopausal breast cancer patients on adjuvant endocrine treatment and age-matched controls with and without estrogen treatment. Sexual function was assessed with a standardized questionnaire.

    Results: In all, 42.4% of aromatase inhibitor-treated breast cancer patients were dissatisfied with their sex life in general, and 50.0% reported low sexual interest; this was significantly more common than in tamoxifen-treated patients and controls (P < 0.05). Aromatase inhibitorYtreated patients reported insufficient lubrication in 73.9% and dyspareunia in 56.5% of cases, which were significantly more common than in controls, irrespective of hormonal use (P < 0.05). Tamoxifen-treated patients reported significantly more dyspareunia (31.3%; P < 0.05) but resembled controls in all other concerns.

    Conclusions: Our findings suggest that sexual dysfunction in aromatase inhibitorYtreated women is a greatly underestimated problem.

  • 22.
    Belayneh, Dereje K.
    et al.
    Int Cardiovasc Hosp, Addis Ababa, Ethiopia.
    Kellerth, Thomas
    Dept Cardiol, Örebro University Hospital, Örebro, Sweden.
    Thyrotoxic hypokalemic periodic paralysis in an African male: a case report2015In: Clinical Case Reports, E-ISSN 2050-0904, Vol. 3, no 2, p. 102-105Article in journal (Refereed)
    Abstract [en]

    Thyrotoxic hypokalemic periodic paralysis is a rare manifestation of thyrotoxicosis and is rarely reported in non-Asian populations. A 26-year-old Ethiopian male who presented with recurrent flaccid tetraparesis, hypokalemia, and hyperthyroidism is reported here. Thyroid function should be routinely checked in patients with acute or recurrent hypokalemic paralysis.

  • 23.
    Bengtsson, Torbjörn
    et al.
    Department of Medical and Health Sciences, Cardiovascular Inflammation Research Centre, Linköping University, Linköping, Sweden; Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Karlsson, H
    Department of Clinical and Experimental Medicine, Cardiovascular Inflammation Research Centre, Linköping University, Linköping, Sweden.
    Gunnarsson, P
    Department of Medical and Health Sciences, Cardiovascular Inflammation Research Centre, Linköping University, Linköping, Sweden.
    Skoglund, C
    Department of Medical and Health Sciences, Cardiovascular Inflammation Research Centre, Linköping University, Linköping, Sweden.
    Elison, C
    Department of Clinical and Experimental Medicine, Cardiovascular Inflammation Research Centre, Linköping University, Linköping, Sweden.
    Leanderson, P
    Department of Clinical and Experimental Medicine, Cardiovascular Inflammation Research Centre, Linköping University, Linköping, Sweden.
    Lindahl, M
    Department of Clinical and Experimental Medicine, Cardiovascular Inflammation Research Centre, Linköping University, Linköping, Sweden.
    The periodontal pathogen Porphyromonas gingivalis cleaves apoB-100 and increases the expression of apoM in LDL in whole blood leading to cell proliferation2008In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 263, no 5, p. 558-571Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Several studies support an association between periodontal disease and atherosclerosis with a crucial role for the pathogen Porphyromonas gingivalis. This study aims at investigating the proteolytic and oxidative activity of P. gingivalis on LDL in a whole blood system using a proteomic approach and analysing the effects of P. gingivalis-modified LDL on cell proliferation.

    METHODS: The cellular effects of P. gingivalis in human whole blood were assessed using lumi-aggregometry analysing reactive oxygen species production and aggregation. Blood was incubated for 30 min with P. gingivalis, whereafter LDL was isolated and a proteomic approach was applied to examine protein expression. LDL-oxidation was determined by analysing the formation of protein carbonyls. The effects of P. gingivalis-modified LDL on fibroblast proliferation were studied using the MTS assay.

    RESULTS: Incubation of whole blood with P. gingivalis caused an extensive aggregation and ROS production, indicating platelet and leucocyte activation. LDL prepared from bacteria-exposed blood showed an increased protein oxidation, elevated levels of apoM and formation of two apoB-100 N-terminal fragments. Porphyromonas gingivalis-modified LDL markedly increased the growth of fibroblasts. Inhibition of gingipain R suppressed the modification of LDL by P. gingivalis.

    CONCLUSIONS: The ability of P. gingivalis to change the protein expression and proliferative capacity of LDL may represent a crucial event in periodontitis-associated atherosclerosis.

  • 24.
    Bergh, Cecilia
    Örebro University, School of Medical Sciences.
    Life-course influences on occurrence and outcome for stroke and coronary heart disease2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Although typical clinical onset does not occur until adulthood, cardiovascular disease (CVD) may have a long natural history with accumulation of risks beginning in early life and continuing through childhood and into adolescence and adulthood. Therefore, it is important to adopt a life-course approach to explore accumulation of risks, as well as identifying age-defined windows of susceptibility, from early life to disease onset. This thesis examines characteristics in adolescence and adulthood linked with subsequent risk of CVD. One area is concerned with physical and psychological characteristics in adolescence, which reflects inherited and acquired elements from childhood, and their association with occurrence and outcome of subsequent stroke and coronary heart disease many years later. The second area focuses on severe infections and subsequent delayed risk of CVD. Data from several Swedish registers were used to provide information on a general population-based cohort of men. Some 284 198 males, born in Sweden from 1952 to 1956 and included in the Swedish Military Conscription Register, form the basis of the study cohort for this thesis. Our results indicate that characteristics already present in adolescence may have an important role in determining long-term cardiovascular health. Stress resilience in adolescence was associated with an increased risk of stroke and CHD, working in part through other CVD factors, in particular physical fitness. Stress resilience, unhealthy BMI and elevated blood pressure in adolescence were also associated with aspects of stroke severity among survivors of a first stroke. We demonstrated an association for severe infections (hospital admission for sepsis and pneumonia) in adulthood with subsequent delayed risk of CVD, independent of risk factors from adolescence. Persistent systemic inflammatory activity which could follow infection, and that might persist long after infections resolve, represents a possible mechanism. Interventions to protect against CVD should begin by adolescence; and there may be a period of heightened susceptibility in the years following severe infection when additional monitoring and interventions for CVD may be of value.

    List of papers
    1. Stress resilience in male adolescents and subsequent stroke risk: cohort study
    Open this publication in new window or tab >>Stress resilience in male adolescents and subsequent stroke risk: cohort study
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    2014 (English)In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 85, no 12, p. 1331-1336Article in journal (Refereed) Published
    Abstract [en]

    Objective Exposure to psychosocial stress has been identified as a possible stroke risk, but the role of stress resilience which may be relevant to chronic exposure is uncertain. We investigated the association of stress resilience in adolescence with subsequent stroke risk.

    Methods Register-based cohort study. Some 237 879 males born between 1952 and 1956 were followed from 1987 to 2010 using information from Swedish registers. Cox regression estimated the association of stress resilience with stroke, after adjustment for established stroke risk factors.

    Results Some 3411 diagnoses of first stroke were identified. Lowest stress resilience (21.8%) compared with the highest (23.7%) was associated with increased stroke risk, producing unadjusted HR (with 95% CIs) of 1.54 (1.40 to 1.70). The association attenuated slightly to 1.48 (1.34 to 1.63) after adjustment for markers of socioeconomic circumstances in childhood; and after further adjustment for markers of development and disease in adolescence (blood pressure, cognitive function and pre-existing cardiovascular disease) to 1.30 (1.18 to 1.45). The greatest reduction followed further adjustment for markers of physical fitness (BMI and physical working capacity) in adolescence to 1.16 (1.04 to 1.29). The results were consistent when stroke was subdivided into fatal, ischaemic and haemorrhagic, with higher magnitude associations for fatal rather than non-fatal, and for haemorrhagic rather than ischaemic stroke.

    Conclusions Stress susceptibility and, therefore, psychosocial stress may be implicated in the aetiology of stroke. This association may be explained, in part, by poorer physical fitness. Effective prevention might focus on behaviour/lifestyle and psychosocial stress.

    Place, publisher, year, edition, pages
    BMJ Publishing Group Ltd, 2014
    Keywords
    stroke
    National Category
    Neurology Psychiatry Surgery
    Identifiers
    urn:nbn:se:oru:diva-35058 (URN)10.1136/jnnp-2013-307485 (DOI)000345276400010 ()2-s2.0-84896691316 (Scopus ID)
    Note

    Funding Agency:

    UK Economic and Social Research Council (ESRC) RES-596-28-0001 ES/J019119/1

    Stiftelsen Olle Engqvist Byggmästare 

    Örebro University 

    Available from: 2014-05-15 Created: 2014-05-15 Last updated: 2021-08-09Bibliographically approved
    2. Stress resilience and physical fitness in adolescence and risk of coronary heart disease in middle age
    Open this publication in new window or tab >>Stress resilience and physical fitness in adolescence and risk of coronary heart disease in middle age
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    2015 (English)In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 101, no 8, p. 623-629Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVE: Psychosocial stress is a suggested risk for coronary heart disease (CHD). The relationship of stress resilience in adolescence with subsequent CHD risk is underinvestigated, so our objective was to assess this and investigate the possible mediating role of physical fitness.

    METHODS: In this register-based study, 237 980 men born between 1952 and 1956 were followed from 1987 to 2010 using information from Swedish registers. Stress resilience was measured at a compulsory military conscription examination using a semistructured interview with a psychologist. Some 10 581 diagnoses of CHD were identified. Cox regression estimated the association of stress resilience with CHD, with adjustment for established cardiovascular risk factors.

    RESULTS: Low-stress resilience was associated with increased CHD risk. The association remained after adjustment for physical fitness and other potential confounding and mediating factors, with adjusted HRs (and 95% CIs) of 1.17 (1.10 to 1.25), with some evidence of mediation by physical fitness. CHD incidence rates per 1000 person-years (and 95% CIs) for low-stress, medium-stress and high-stress resilience were 2.61 (2.52 to 2.70), 1.97 (1.92 to 2.03) and 1.59 (1.53 to 1.67) respectively. Higher physical fitness was inversely associated with CHD risk; however, this was attenuated by low-stress resilience, shown by interaction testing (p<0.001).

    CONCLUSIONS: Low-stress resilience in adolescence was associated with increased risk of CHD in middle age and may diminish the benefit of physical fitness. This represents new evidence of the role of stress resilience in determining risk of CHD and its interrelationship with physical fitness.

    Place, publisher, year, edition, pages
    BMJ Publishing Group Ltd, 2015
    National Category
    Cardiac and Cardiovascular Systems
    Research subject
    Epidemiology; Cardiology
    Identifiers
    urn:nbn:se:oru:diva-43425 (URN)10.1136/heartjnl-2014-306703 (DOI)000351755300009 ()25740818 (PubMedID)2-s2.0-84927665875 (Scopus ID)
    Note

    Funding Agencies:

    UK Economic and Social Research Council (ESRC) RES-596-28-0001  ES/JO19119/1

    Stiftelsen Olle Engqvist Byggmästare, Folksam

    Örebro University

    Available from: 2015-03-06 Created: 2015-03-06 Last updated: 2021-08-09Bibliographically approved
    3. Determinants in adolescence of stroke-related hospital stay duration in men: a national cohort study
    Open this publication in new window or tab >>Determinants in adolescence of stroke-related hospital stay duration in men: a national cohort study
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    2016 (English)In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 47, no 9, p. 2416-2418Article in journal (Refereed) Published
    Abstract [en]

    Background and purpose: Physical and psychological characteristics in adolescence are associated with subsequent stroke risk. Our aim is to investigate their relevance to length of hospital stay and risk of second stroke.

    Methods: Swedish men born between 1952 and 1956 (n=237 879) were followed from 1987 to 2010 using information from population-based national registers. Stress resilience, body mass index, cognitive function, physical fitness, and blood pressure were measured at compulsory military conscription examinations in late adolescence. Joint Cox proportional hazards models estimated the associations of these characteristics with long compared with short duration of stroke-related hospital stay and with second stroke compared with first.

    Results: Some 3000 men were diagnosed with nonfatal stroke between ages 31 and 58 years. Low stress resilience, underweight, and higher systolic blood pressure (per 1-mm Hg increase) during adolescence were associated with longer hospital stay (compared with shorter) in ischemic stroke, with adjusted relative hazard ratios (and 95% confidence intervals) of 1.46 (1.08-1.89), 1.41 (1.04-1.91), and 1.01 (1.00-1.02), respectively. Elevated systolic and diastolic blood pressures during adolescence were associated with longer hospital stay in men with intracerebral hemorrhage: 1.01 (1.00-1.03) and 1.02 (1.00-1.04), respectively. Among both stroke types, obesity in adolescence conferred an increased risk of second stroke: 2.06 (1.21-3.45).

    Conclusions: Some characteristics relevant to length of stroke-related hospital stay and risk of second stroke are already present in adolescence. Early lifestyle influences are of importance not only to stroke risk by middle age but also to recurrence and use of healthcare resources among stroke survivors.

    Place, publisher, year, edition, pages
    Philadelphia, USA: Lippincott Williams & Wilkins, 2016
    Keywords
    Adolescent, blood pressure, length of stay, psychological stress, risk factors
    National Category
    Cardiac and Cardiovascular Systems Neurology
    Identifiers
    urn:nbn:se:oru:diva-51591 (URN)10.1161/STROKEAHA.116.014265 (DOI)000383559300052 ()27491740 (PubMedID)2-s2.0-84982813061 (Scopus ID)
    Note

    Funding Agencies:

    UK Economic and Social Research Council RES-596-28-0001  ES/JO19119/1

    Stiftelsen Olle Engqvist Byggmästare

    Folksam

    Örebro University

    Available from: 2016-08-08 Created: 2016-08-08 Last updated: 2021-08-09Bibliographically approved
    4. Severe infections and subsequent delayed cardiovascular disease: national cohort study
    Open this publication in new window or tab >>Severe infections and subsequent delayed cardiovascular disease: national cohort study
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    (English)Manuscript (preprint) (Other academic)
    National Category
    General Practice
    Identifiers
    urn:nbn:se:oru:diva-55808 (URN)
    Available from: 2017-02-16 Created: 2017-02-16 Last updated: 2024-01-16Bibliographically approved
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    Life-course influences on occurrence of stroke and outcome for stroke and coronary heart disease
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  • 25.
    Bergh, Cecilia
    et al.
    Örebro University, School of Medical Sciences.
    Fall, Katja
    Örebro University, School of Medical Sciences.
    Udumyan, Ruzan
    Örebro University, School of Medical Sciences.
    Sjöqvist, Hugo
    School of Medical Sciences, Örebro University, Örebro, sweden.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, UK .
    Severe infections and subsequent delayed cardiovascular disease: national cohort studyManuscript (preprint) (Other academic)
  • 26.
    Berglund, Annika
    et al.
    Karolinska Institutet Stroke Research Network at Södersjukhuset, Stockholm, Sweden; Department of Clinical Science and Education, Karolinska Institutet, Södersjukhuset, Stockholm, Sweden; Section of Neurology, Department of Internal Medicine, Södersjukhuset, Stockholm, Sweden; Karolinska Institutet, Center for Gender Medicine, Stockholm, Sweden.
    von Euler, Mia
    Karolinska Institutet Stroke Research Network at Södersjukhuset, Stockholm, Sweden; Department of Clinical Science and Education, Karolinska Institutet, Södersjukhuset, Stockholm, Sweden; Section of Neurology, Department of Internal Medicine, Södersjukhuset, Stockholm, Sweden Karolinska Institutet, Center for Gender Medicine, Stockholm, Sweden.
    Schenck-Gustafsson, Karin
    Karolinska Institutet, Center for Gender Medicine, Stockholm, Sweden; Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Castrén, Maaret
    Department of Clinical Science and Education, Karolinska Institutet, Södersjukhuset, Stockholm, Sweden.
    Bohm, Katarina
    Department of Clinical Science and Education, Karolinska Institutet, Södersjukhuset, Stockholm, Sweden; Section of Emergency Medicine, Södersjukhuset, Stockholm, Sweden.
    Identification of stroke during the emergency call: a descriptive study of callers' presentation of stroke2015In: BMJ Open, E-ISSN 2044-6055, Vol. 5, no 4, article id e007661Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To evaluate symptoms presented by the caller during emergency calls regarding stroke, and to assess if symptoms in the Face-Arm-Speech-Time Test (FAST) are related to identification of stroke.

    SETTING: Emergency calls to the Emergency Medical Communication Center (EMCC) concerning patients discharged with stroke diagnosis in a large teaching hospital in Stockholm, Sweden, in January-June 2011.

    PARTICIPANTS: The emergency calls of 179 patients who arrived at hospital by ambulance, and who were discharged with a stroke diagnosis and consented to participate were included in the study.

    OUTCOME MEASURES: Frequencies of stroke symptoms presented and a comparison of symptoms presented in calls with dispatch code stroke or other dispatch code.

    RESULTS: Of the 179 emergency calls analysed, 64% were dispatched as 'Stroke'. FAST symptoms, that is, facial or arm weakness or speech disturbances, were presented in 64% of the calls and were spontaneously revealed in 90%. Speech disturbance was the most common problem (54%) in all calls, followed by fall/lying position (38%) and altered mental status (27%). For patients with dispatch codes other than stroke, the dominating problem presented was a fall or being in a lying position (66%), followed by speech disturbance (31%) and altered mental status (25%). Stroke-specific symptoms were more common in patients dispatched as stroke. FAST symptoms were reported in 80% of patients dispatched as stroke compared with 35% in those dispatched as something else.

    CONCLUSIONS: This study implicates that fall/lying position and altered mental status could be considered as possible symptoms of stroke during an emergency call. Checking for FAST symptoms in these patients might uncover stroke symptoms. Future studies are needed to evaluate if actively asking for FAST symptoms in emergency calls presenting falls or a lying position can improve the identification of stroke.

    TRIAL REGISTRATION NUMBER: Stroke2010/703-31/2.

  • 27.
    Bergström, Ida
    et al.
    Department of Medical and Health Sciences, Division of Cardiovascular Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Department of Clinical Immunology and Transfusion Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Lundberg, Anna K.
    Department of Medical and Health Sciences, Division of Cardiovascular Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Jönsson, Simon
    Department of Medical and Health Sciences, Division of Cardiovascular Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Särndahl, Eva
    Örebro University, School of Medical Sciences. IRiSC - Inflammatory Response and Infection Susceptibility Centre.
    Ernerudh, Jan
    Department of Clinical Immunology and Transfusion Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Jonasson, Lena
    Department of Medical and Health Sciences, Division of Cardiovascular Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Annexin A1 in blood mononuclear cells from patients with coronary artery disease: Its association with inflammatory status and glucocorticoid sensitivity2017In: PLOS ONE, E-ISSN 1932-6203, Vol. 12, no 3, article id e0174177Article in journal (Refereed)
    Abstract [en]

    Annexin A1 (AnxA1) is a key player in resolution of inflammation and a mediator of glucocorticoid actions. In atherosclerotic tissue, increased expression of AnxA1 has been associated with protective plaque-stabilizing effects. Here, we investigated the expression of AnxA1 in peripheral blood mononuclear cells (PBMCs) from patients with coronary artery disease (CAD). Blood was collected from 57 patients with stable CAD (SCAD) and 41 healthy controls. We also included a minor group (n = 10) with acute coronary syndrome (ACS). AnxA1 mRNA was measured in PBMCs. Expression of AnxA1 protein (total and surface-bound) and glucocorticoid receptors (GR) were detected in PBMC subsets by flow cytometry. Also, salivary cortisol, interleukin(IL)-6 and IL-10 in plasma, and LPS-induced cytokine secretion from PBMCs, with or without dexamethasone, were assessed. AnxA1 mRNA was found to be slightly increased in PBMCs from SCAD patients compared with controls. However, protein expression of AnxA1 or GRs in PBMC subsets did not differ between SCAD patients and controls, despite SCAD patients showing a more proinflammatory cytokine profile ex vivo. Only surface expression of AnxA1 on monocytes correlated with dexamethasone-mediated suppression of cytokines. In ACS patients, a marked activation of AnxA1 was seen involving both gene expression and translocation of protein to cell surface probably reflecting a rapid glucocorticoid action modulating the acute inflammatory response in ACS. To conclude, surface expression of AnxA1 on monocytes may reflect the degree of glucocorticoid sensitivity. Speculatively, "normal" surface expression of AnxA1 indicates that anti-inflammatory capacity is impaired in SCAD patients.

  • 28.
    Bill-Axelson, Anna
    et al.
    Dept Surg Sci, Univ Uppsala Hosp, Uppsala, Sweden.
    Holmberg, Lars
    Reg Canc Ctr Uppsala Orebro, Univ Uppsala Hosp, Uppsala, Sweden; Sch Med, Div Canc Studies, Kings Coll London, London, England.
    Garmo, Hans
    Reg Canc Ctr Uppsala Orebro, Univ Uppsala Hosp, Uppsala, Sweden; Sch Med, Div Canc Studies, Kings Coll London, London , England.
    Rider, Jennifer R.
    Dept Med, Channing Lab, Brigham & Womens Hosp, Boston MA, USA; Sch Med, Harvard Univ, Boston MA, USA; Sch Publ Hlth, Dept Epidemiol, Harvard Univ, Boston MA, USA.
    Taari, Kimmo
    Cent Hosp, Dept Urol, Univ Helsinki, Helsinki, Finland.
    Busch, Christer
    Dept Immunol Genet & Pathol, Univ Uppsala Hosp, Uppsala, Sweden.
    Nordling, Stig
    Dept Pathol, Univ Helsinki, Helsinki, Finland.
    Häggman, Michael
    Dept Surg Sci, Univ Uppsala Hosp, Uppsala, Sweden.
    Andersson, Swen-Olof
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Dept Urol, Örebro University Hospital, Örebro, Sweden.
    Spångberg, Anders
    Dept Urol, Linköping, Linköping Univ Hosp, Linköping, Sweden.
    Andrén, Ove
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Dept Urol, Örebro University Hospital, Örebro, Sweden.
    Palmgren, Juni
    Dept Med Epidemiol & Biostat, Karolinska Inst, Stockholm, Sweden.
    Steineck, Gunnar
    Dept Pathol & Oncol, Div Clin Canc Epidemiol, Karolinska Inst, Stockholm, Sweden; Div Clin Canc Epidemiol, Sahlgrenska Academy, Gothenburg, Sweden.
    Adami, Hans-Olov
    Dept Med Epidemiol & Biostat, Karolinska Inst, Stockholm, Sweden; Sch Publ Hlth, Dept Epidemiol, Harvard Univ, Boston MA, USA.
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Dept Urol, Örebro University Hospital, Örebro, Sweden.
    Radical Prostatectomy or Watchful Waiting in Early Prostate Cancer2014In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 370, no 10, p. 932-942Article in journal (Refereed)
    Abstract [en]

    Background: Radical prostatectomy reduces mortality among men with localized prostate cancer; however, important questions regarding long-term benefit remain.

    Methods: Between 1989 and 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy and followed them through the end of 2012. The primary end points in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) were death from any cause, death from prostate cancer, and the risk of metastases. Secondary end points included the initiation of androgen-deprivation therapy.

    Results: During 23.2 years of follow-up, 200 of 347 men in the surgery group and 247 of the 348 men in the watchful-waiting group died. Of the deaths, 63 in the surgery group and 99 in the watchful-waiting group were due to prostate cancer; the relative risk was 0.56 (95% confidence interval [CI], 0.41 to 0.77; P=0.001), and the absolute difference was 11.0 percentage points (95% CI, 4.5 to 17.5). The number needed to treat to prevent one death was 8. One man died after surgery in the radical-prostatectomy group. Androgen-deprivation therapy was used in fewer patients who underwent prostatectomy (a difference of 25.0 percentage points; 95% CI, 17.7 to 32.3). The benefit of surgery with respect to death from prostate cancer was largest in men younger than 65 years of age (relative risk, 0.45) and in those with intermediate-risk prostate cancer (relative risk, 0.38). However, radical prostatectomy was associated with a reduced risk of metastases among older men (relative risk, 0.68; P=0.04).

    Conclusions: Extended follow-up confirmed a substantial reduction in mortality after radical prostatectomy; the number needed to treat to prevent one death continued to decrease when the treatment was modified according to age at diagnosis and tumor risk. A large proportion of long-term survivors in the watchful-waiting group have not required any palliative treatment. (Funded by the Swedish Cancer Society and others.)

    The randomized Swedish trial of prostatectomy versus watchful waiting in disease detected mainly clinically (not by PSA screening) continues to show a benefit for early prostatectomy. The number of men younger than 65 needed to treat to prevent one death is now four. The Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4), a randomized trial of radical prostatectomy versus watchful waiting in men with localized prostate cancer diagnosed before the era of prostate-specific antigen (PSA) testing, showed a survival benefit of radical prostatectomy as compared with observation at 15 years of follow-up.(1) By contrast, the Prostate Cancer Intervention versus Observation Trial (PIVOT), initiated in the early era of PSA testing, showed that radical prostatectomy did not significantly reduce prostate cancer-specific or overall mortality after 12 years.(2) PSA screening profoundly changes the clinical domain of study. Among other considerations, the substantial additional lead time ...

  • 29.
    Bill-Axelson, Anna
    et al.
    Dept. Urology, Uppsala University Hospital, Uppsala, Sweden; Dept, Pathology & Oncology, Div. Clinical Cancer Epidemiology, Karolinska Institute, Stockholm, Sweden.
    Holmberg, Lars
    Regional Oncology Center, Uppsala University Hospital, Uppsala, Sweden; School of Medicine, Division of Cancer Studies, Kings College London, London, England.
    Ruutu, Mirja
    Cent Hosp, Dept Urol, Univ Helsinki, Helsinki, Finland.
    Garmo, Hans
    Reg Oncol Ctr, Univ Uppsala Hospital, Uppsala, Sweden; Sch Med, Div Canc Studies, Kings College London, London, UK.
    Stark, Jennifer R
    Deptartment of Urology, Örebro University Hospital, Örebro, Sweden; Dept Med, Channing Lab, Brigham & Womens Hospital, Boston MA, USA; Sch Med, Harvard University, Boston MA, USA.
    Busch, Christer
    Dept Pathol, Uppsala University Hospital, Uppsala, Sweden.
    Nordling, Stig
    Cent Hosp, Dept Pathol, Univ Helsinki, Helsinki, Finland.
    Häggman, Michael
    Dept Urology, Uppsala University Hospital, Uppsala, Sweden.
    Andersson, Swen-Olof
    Örebro University, School of Health and Medical Sciences. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Bratell, Stefan
    Dept Urology, Borås Hospital, Borås, Sweden.
    Spångberg, Anders
    Dept Urology, Linköping University Hospital, Linköping, Sweden.
    Palmgren, Juni
    Dept Med Epidemiol & Biostat, Karolinska Institute, Stockholm, Sweden.
    Steineck, Gunnar
    Dept, Pathology & Oncology, Div. Clinical Cancer Epidemiology, Karolinska Institute, Stockholm, Sweden; Div Clin Canc Epidemiol, Sahlgrenska Academy, Gothenburg, Sweden.
    Adami, Hans-Olov
    Dept Med Epidemiol & Biostat, Karolinska Institute, Stockholm, Sweden; School of Publ Health, Dept Epidemiology, Harvard Univ, Boston MA, USA.
    Johansson, J-E
    Örebro University, School of Health and Medical Sciences. Dept Urol, Örebro University Hospital, Örebro, Sweden; Center of Assessment Med Technology, Örebro University Hospital, Örebro, Sweden.
    Radical prostatectomy versus watchful waiting in early prostate cancer2011In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 364, no 18, p. 1708-1717Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In 2008, we reported that radical prostatectomy, as compared with watchful waiting, reduces the rate of death from prostate cancer. After an additional 3 years of follow-up, we now report estimated 15-year results.

    METHODS: From October 1989 through February 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy. Follow-up was complete through December 2009, with histopathological review of biopsy and radical-prostatectomy specimens and blinded evaluation of causes of death. Relative risks, with 95% confidence intervals, were estimated with the use of a Cox proportional-hazards model.

    RESULTS: During a median of 12.8 years, 166 of the 347 men in the radical-prostatectomy group and 201 of the 348 in the watchful-waiting group died (P=0.007). In the case of 55 men assigned to surgery and 81 men assigned to watchful waiting, death was due to prostate cancer. This yielded a cumulative incidence of death from prostate cancer at 15 years of 14.6% and 20.7%, respectively (a difference of 6.1 percentage points; 95% confidence interval [CI], 0.2 to 12.0), and a relative risk with surgery of 0.62 (95% CI, 0.44 to 0.87; P=0.01). The survival benefit was similar before and after 9 years of follow-up, was observed also among men with low-risk prostate cancer, and was confined to men younger than 65 years of age. The number needed to treat to avert one death was 15 overall and 7 for men younger than 65 years of age. Among men who underwent radical prostatectomy, those with extracapsular tumor growth had a risk of death from prostate cancer that was 7 times that of men without extracapsular tumor growth (relative risk, 6.9; 95% CI, 2.6 to 18.4).

    CONCLUSIONS: Radical prostatectomy was associated with a reduction in the rate of death from prostate cancer. Men with extracapsular tumor growth may benefit from adjuvant local or systemic treatment.

  • 30.
    Björkenheim, Anna
    Örebro University, School of Medical Sciences.
    Catheter ablation for atrial fibrillation: effects on rhythm, symptoms and health-related quality of life2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: AF ablation is an increasingly used treatment in patients with AF to improve patient-reported outcomes (PROs). Atrioventricular junction ablation (AVJA) is a palliative treatment option in therapy refractory AF that improves PROs but renders the patient pacemaker dependent.

    Aims: To evaluate rhythm control and PROs before and up to two years after AF ablation. To analyze the long-term incidence of and predictors of hospitalization for HF and all-cause mortality in patients who underwent AVJA and right ventricular pacing.

    Methods and Results: Fifty-four patients underwent AF ablation and both continuous rhythm monitoring via an implantable loop recorder (ILR) and intermittent rhythm monitoring three, six, 12 and 24 months after ablation. 76 % of patients had at least one AF recurrence, of whom 24 % were only detected by ILR. One third of symptom recordings did not show AF. The AF-specific AF6 scores, physician-assessed EHRA symptom class and both SF-36 summary scores all improved significantly from before to two years after ablation. There was a weak correlation between the change in AF6 scores and EHRA class from before to six and 12 months but not to 24 months after ablation. Responders to ablation (AF burden < 0.5 %), reached age- and sex-matched norms in all SF-36 domains, but non-responders only in social functioning and MCS. All AF6 scores showed at least moderate improvement in both responders and non-responders. Higher AF burden was independently associated with poorer PCS and AF6 scores. In 162 patients who underwent AVJA, hospitalization for HF occurred in 20 % of patients (two-year cumula-tive incidence 9.1 %) and 22 % died (two-year cumulative incidence 5.2 %) during a median follow-up of five years. QRS ≥ 120 ms and left atrial diame-ter were independent predictors of hospitalization for HF, and hypertension and previous HF of death.

    Conclusions: Continuous rhythm monitoring was superior to intermittent monitoring. The AF-specific AF6 was more sensitive to changes related to AF burden after AF ablation than both EHRA class and the SF-36. The long-term hospitalization rate for HF and all-cause mortality was low after AVJA.

    List of papers
    1. Predictors of hospitalization for heart failure and of all-cause mortality after atrioventricular nodal ablation and right ventricular pacing for atrial fibrillation
    Open this publication in new window or tab >>Predictors of hospitalization for heart failure and of all-cause mortality after atrioventricular nodal ablation and right ventricular pacing for atrial fibrillation
    Show others...
    2014 (English)In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 16, no 12, p. 1772-1778Article in journal (Refereed) Published
    Abstract [en]

    Aims: Atrioventricular junction ablation (AVJA) is a highly effective treatment in patients with therapy refractory atrial fibrillation (AF) but renders the patient pacemaker dependent. We aimed to analyse the long-term incidence of hospitalization for heart failure (HF) and all-cause mortality in patients who underwent AVJA because of AF and to determine predictors for HF and mortality.

    Methods and results: We retrospectively enrolled 162 consecutive patients, mean age 67 +/- 9 years, 48% women, who underwent AVJA because of symptomatic AF refractory to pharmacological treatment (n = 117) or unsuccessful repeated pulmonary vein isolation (n = 45). Hospitalization for HF occurred in 32 (20%) patients and 35 (22%) patients died, representing a cumulative incidence for hospitalization for HF and mortality over the first 2 years after AVJA of 9.1 and 5.2%, respectively. Hospitalization for HF occurred to the same extent in patients who failed pharmacological treatment as in patients with repeated pulmonary vein isolation (PVI), although the mortality was slightly higher in the former group. QRS prolongation >= 120 ms and left atrial diameter were independent predictors of hospitalization for HF, while hypertension and previous HF were independent predictors of death.

    Conclusion: The long-term hospitalization rate for HF and all-cause mortality was low, which implies that long-term ventricular pacing was not harmful in this patient population, including patients with unsuccessful repeated PVI.

    Place, publisher, year, edition, pages
    Oxford University Press, 2014
    Keywords
    Atrial fibrillation, Atrioventricular junction ablation, Heart failure, Hospitalization, Mortality
    National Category
    Cardiac and Cardiovascular Systems
    Research subject
    Cardiology
    Identifiers
    urn:nbn:se:oru:diva-42367 (URN)10.1093/europace/euu171 (DOI)000347104900016 ()25031234 (PubMedID)2-s2.0-84937512146 (Scopus ID)
    Note

    Funding Agency:

    Örebro Heart Foundation

    Research Committee of Örebro University Hospital

    Available from: 2015-02-04 Created: 2015-02-03 Last updated: 2024-01-02Bibliographically approved
    2. Rhythm Control and its Relation to Symptoms During the First Two Years After Radiofrequency Ablation for Atrial Fibrillation
    Open this publication in new window or tab >>Rhythm Control and its Relation to Symptoms During the First Two Years After Radiofrequency Ablation for Atrial Fibrillation
    Show others...
    2016 (English)In: Pacing and Clinical Electrophysiology, ISSN 0147-8389, E-ISSN 1540-8159, Vol. 39, no 9, p. 914-925Article in journal (Refereed) Published
    Abstract [en]

    Objective: To evaluate rhythm control up to two years after AF ablation and its relation to reported symptoms.

    Background: The implantable loop recorder (ILR) continuously records the ECG, has an automatic AF detection algorithm and a possibility for patients to activate an ECG recording during symptoms.

    Methods: Fifty-seven patients (mean age 57±9 years, 60% male, 88% paroxysmal AF) underwent AF ablation following ILR implantation. Device data were downloaded at the ablation and three, six, 12, 18 and 24 months after ablation.

    Results: Fifty-four patients completed the two-year follow-up. Thirteen (24%) patients had no AF episodes detected by ILR during follow-up. Ten of 41 patients (24%) with AF recurrence were only detected by ILR and AF recurrences were detected earlier by ILR (P<0.001). The median AF burden in patients with AF recurrence was 5.7% (IQR 0.4-14.4) and was even lower in patients with AF only detected by ILR (P = 0.001). Forty-eight % of the patients indicated symptoms via the patient activator but 33% of those recordings were not due to AF. Early AF recurrence (within 3 months) was highly associated with later AF recurrence (P<0.001). AF burden >0.5% and longest >6h before the ablation were independent predictors of AF recurrence during intermittent but not continuous monitoring.

    Conclusions: After AF ablation, the AF burden was low throughout the 24 months follow-up. Nevertheless, symptoms were commonly indicated but one third of patient activated recordings did not show AF. Continuous monitoring was superior to intermittent follow-up in detecting AF episodes and assessing the AF burden.

    Clinical trial registration: URL: http://clinicaltrials.gov. Unique Identifier: NCT00697359.

    Place, publisher, year, edition, pages
    Hoboken, USA: Wiley-Blackwell Publishing Inc., 2016
    Keywords
    Atrial fibrillation, catheter ablation, implantable loop recorder, monitoring, symptoms
    National Category
    Cardiac and Cardiovascular Systems
    Research subject
    Cardiology
    Identifiers
    urn:nbn:se:oru:diva-51530 (URN)10.1111/pace.12916 (DOI)000383572900002 ()27418324 (PubMedID)2-s2.0-84987723704 (Scopus ID)
    Note

    Funding Agencies:

    Medtronic

    Örebro heart foundation

    Research Committee of Örebro University Hospital, Örebro, Sweden

    Available from: 2016-08-04 Created: 2016-08-02 Last updated: 2024-01-02Bibliographically approved
    3. Assessment of Atrial Fibrillation–Specific Symptoms Before and 2 Years After Atrial Fibrillation Ablation: Do Patients and Physicians Differ in Their Perception of Symptom Relief?
    Open this publication in new window or tab >>Assessment of Atrial Fibrillation–Specific Symptoms Before and 2 Years After Atrial Fibrillation Ablation: Do Patients and Physicians Differ in Their Perception of Symptom Relief?
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    2017 (English)In: JACC: Clinical Electrophysiology, ISSN 2405-500X, E-ISSN 2405-5018, Vol. 3, no 10, p. 1168-1176Article in journal (Refereed) Published
    Abstract [en]

    Objectives: The aim of this study was to evaluate patient-reported and physician-assessed atrial fibrillation (AF)–related symptoms after AF ablation.

    Background: Success of AF ablation is usually defined as freedom from AF, although symptom relief is often patients’ desire.

    Methods: Symptom relief was assessed as perceived by patients using the short, validated, AF-specific symptom questionnaire AF6 and as classified by physicians using the European Heart Rhythm Association (EHRA) classification at baseline and 6, 12, and 24 months after AF ablation. Recurrence of arrhythmia was documented by continuous electrocardiographic monitoring.

    Results: In total, 54 patients completed the 24-month follow-up. All 6 items on the AF6, AF6 sum score, and EHRA class improved significantly over time. The greatest improvement was seen during the first 6 months after ablation, but AF6 scores showed continued improvement up to 12 months, in contrast to EHRA class. There was a low correlation between AF6 score and EHRA class, but the predictive ability was low. Both AF6 scores and EHRA class were significantly correlated with AF burden at all times after ablation. A change of >9 points in AF6 sum score corresponded to a meaningful reduction in symptom severity.

    Conclusion: Patient-reported and physician-assessed outcomes were both useful in assessing symptom relief after AF ablation, although patient-reported outcomes were more sensitive tools. There was also a discrepancy between patient-reported and physician-assessed outcomes after ablation. Freedom from AF and a low AF burden most often resulted in a reduction of symptoms, but symptom relief also occurred despite little effect on the arrhythmia.

    Place, publisher, year, edition, pages
    Elsevier, 2017
    Keywords
    atrial fibrillation, catheter ablation, symptoms, beta adrenergic receptor blocking agent, warfarin, ablation therapy, adult, aged, Article, cardiac patient, classification, controlled study, electrocardiography, european heart rhythm association classification, female, follow up, freedom, general condition improvement, human, major clinical study, male, multicenter study, patient-reported outcome, perception, physician, priority journal, recurrent disease
    National Category
    Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:oru:diva-66207 (URN)10.1016/j.jacep.2017.04.003 (DOI)2-s2.0-85021385993 (Scopus ID)
    Available from: 2018-03-28 Created: 2018-03-28 Last updated: 2024-02-23Bibliographically approved
    4. Patient-Reported Outcomes in Relation to Continuously Monitored Rhythm Before and During 2 Years After Atrial Fibrillation Ablation Using a Disease-Specific and a Generic Instrument
    Open this publication in new window or tab >>Patient-Reported Outcomes in Relation to Continuously Monitored Rhythm Before and During 2 Years After Atrial Fibrillation Ablation Using a Disease-Specific and a Generic Instrument
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    2018 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 5, article id e008362Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Atrial fibrillation (AF) ablation improves patient-reported outcomes, irrespective of mode of intermittent rhythm monitoring. We evaluated the use of an AF-specific and a generic patient-reported outcomes instrument during continuous rhythm monitoring 2 years after AF ablation.

    METHODS AND RESULTS: Fifty-four patients completed the generic 36-Item Short-Form Health Survey and the AF-specific AF6 questionnaires before and 6, 12, and 24 months after AF ablation. All patients underwent continuous ECG monitoring via an implantable loop recorder. The generic patient-reported outcomes scores were compared with those of a Swedish age- and sex-matched population. After ablation, both summary scores reached normative levels at 24 months, while role-physical and vitality remained lower than norms. Responders to ablation (AF burden <0.5%) reached the norms in all individual 36-Item Short-Form Health Survey domains, while nonresponders (AF burden >0.5%) reached norms only in social functioning and mental component summary. All AF6 items and the sum score showed moderate to large improvement in both responders and nonresponders, although responders showed significantly greater improvement in all items except item 1 from before to 24 months after ablation. Higher AF burden was independently associated with poorer physical component summary and AF6 sum score.

    CONCLUSIONS: The AF-specific AF6 questionnaire was more sensitive to changes related to AF burden than the generic 36-Item Short-Form Health Survey. Patients improved as documented by both instruments, but a higher AF burden after ablation was associated with poorer AF-specific patient-reported outcomes and poorer generic physical but not mental health. Our results support the use of an AF-specific instrument, alone or in combination with a generic instrument, to assess the effect of ablation.

    CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00697359.

    Place, publisher, year, edition, pages
    Wiley-Blackwell Publishing Inc., 2018
    Keywords
    Atrial fibrillation, catheter ablation, quality of life
    National Category
    Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:oru:diva-65285 (URN)10.1161/JAHA.117.008362 (DOI)000430007700018 ()29478027 (PubMedID)2-s2.0-85042700710 (Scopus ID)
    Note

    Funding Agencies:

    Örebro Heart Foundation  

    Research Committee of Örebro University Hospital, Örebro, Sweden 

    Available from: 2018-02-27 Created: 2018-02-27 Last updated: 2024-01-02Bibliographically approved
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    Catheter ablation for atrial fibrillation: effects on rhythm, symptoms and health-related quality of life
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  • 31.
    Björkman Hjalmarsson, Louise
    Örebro University, School of Medical Sciences.
    Aspects of neonatal septicaemia: prevention and complications2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Study I was part of the Extremely Preterm Infants in Sweden Study (EXPRESS), a prospective national study including all infants born <27 weeks in Sweden in 2004-2007 that survived their first year of life (n=497). Neonatal sepsis was evaluated as a risk factor for neonatal morbidities. Definite sepsis was associated with severe bronchopulmonary dysplasia and prolonged hospital stay, but not with a higher risk of retinopathy of prematurity or intraventricular haemorrhage.

    Study II was a non-randomized single-centre intervention study evaluating possible preventive effects on coagulase-negative staphylococci (CoNS) sepsis when the scrub the hub method was used. During the intervention period, the incidence of CoNS sepsis decreased from 1.5% to 0% (CI: 0.53-2.58%, p=0.06).

    Study III was an in-vitro study evaluating leakage of isopropanol (IPA) and ethanol when alcohol caps and scrub the hub were used to disinfect hubs. Alcohol leakage was measured using gas chromatography. IPA was detected in all samples from cap circuits, and mean leakage increased over time. Ethanol levels were low, and scrub the hub therefore seems safe to use.

    Study IV was a survey study evaluating reported hygiene routines from Swedish neonatal intensive care units (NICUs) included in the EXPRESS study. Routines were compared between the EXPRESS period (2004- 2007) and 2013. Improvements were seen regarding basic hygiene routines, routines for work clothing, and follow-up of compliance. Antibiotic prophylaxis decreased while fungal prophylaxis increased, but the empiric treatment of suspected late-onset sepsis (LOS) showed heterogeneity.

    Study V investigated the association between incidence in LOS in the EXPRESS cohort and the hygiene routines previously evaluated in Study IV. Strict catheter routines, blood culture routines, and non-use of antibiotic prophylaxis were associated with decreased sepsis risk.

    List of papers
    1. Sepsis as a risk factor for neonatal morbidity in extremely preterm infants
    Open this publication in new window or tab >>Sepsis as a risk factor for neonatal morbidity in extremely preterm infants
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    2015 (English)In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 104, no 11, p. 1070-1076Article in journal (Refereed) Published
    Abstract [en]

    Aim: This study evaluated sepsis as a risk factor for neonatal morbidities and investigated the association between specific pathogens and neonatal morbidities.

    Methods: This was a nationwide Swedish prospective cohort study, consisting of the 497 extremely premature children, who were born before 27weeks of gestation between 2004 and 2007 and survived their first year of life. Neonatal sepsis was evaluated as a risk factor for neonatal morbidity using multiple logistic linear regression analyses.

    Results: We found that 326 (66%) of the infants had at least one sepsis episode and coagulase-negative staphylococci was the most common pathogen. Definite sepsis, with an odds ratio (OR) of 1.6, was associated with severe bronchopulmonary dysplasia, but not clinical sepsis (OR 1.1). Definite sepsis was also associated with a prolonged hospital stay (OR 1.6). Sepsis was not significantly associated with a higher risk of retinopathy of prematurity or intraventricular haemorrhage.

    Conclusion: Extremely preterm infants face a great risk of acquiring neonatal sepsis, with coagulase-negative staphylococci being the most common pathogen in this population. Definite sepsis seemed to be a risk factor for severe bronchopulmonary dysplasia and prolonged hospital stay, but the associations were weaker than in previous studies.

    Place, publisher, year, edition, pages
    Wiley-Blackwell, 2015
    Keywords
    Morbidity, Neonatal, Prematurity, Risk factor, Sepsis
    National Category
    Pediatrics
    Research subject
    Pediatrics
    Identifiers
    urn:nbn:se:oru:diva-46694 (URN)10.1111/apa.13104 (DOI)000363866200018 ()26118325 (PubMedID)2-s2.0-84945493792 (Scopus ID)
    Funder
    Swedish Research Council, 2006-3858
    Note

    Funding Agencies:

    Lilla Barnets Fond

    Evy and Gunnar Sandbergs Foundation

    Birgit and Håkan Ohlssons Foundation

    Available from: 2015-11-23 Created: 2015-11-23 Last updated: 2021-05-26Bibliographically approved
    2. Scrubbing the hub of intravenous catheters with an alcohol wipe for 15 sec reduced neonatal sepsis
    Open this publication in new window or tab >>Scrubbing the hub of intravenous catheters with an alcohol wipe for 15 sec reduced neonatal sepsis
    2015 (English)In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 104, no 3, p. 232-236Article in journal (Refereed) Published
    Abstract [en]

    Aim: The aim of this study was to investigate whether scrubbing the hub of intravenous catheters with an alcohol wipe for 15 sec could reduce the incidence of neonatal sepsis in a level-three neonatal intensive care unit.

    Methods: We studied the incidence of neonatal sepsis caused by coagulase-negative staphylococci (CoNS) for 16.5 months before the initiative was launched on May 15, 2012 and then for a further 8.5 months after it was introduced. The hub routine was applied to all intravenous catheters.

    Results: During the control period before the initiative was launched, there were nine cases of CoNS sepsis compared with no cases after it was introduced, resulting in a decrease in sepsis incidence from 1.5% to 0% with a risk reduction of 1.5% (0.53-2.58%) (p = 0.06). In the preterm infant population, the incidence of sepsis decreased from 3.6% to 0% (1.1-6.0%) (p = 0.11).

    Conclusion: Scrubbing the hub of intravenous catheters with an alcohol wipe for 15 sec seemed to be an efficient way of preventing sepsis caused by CoNS in newborn infants. However, the evidence for the benefits will remain weak until a large randomised trial has been completed.

    Place, publisher, year, edition, pages
    Hoboken, USA: Wiley-Blackwell, 2015
    Keywords
    Coagulase-negative staphylococci, Infection, Intravenous catheters, Neonatal sepsis, Prevention
    National Category
    Pediatrics
    Research subject
    Pediatrics
    Identifiers
    urn:nbn:se:oru:diva-43932 (URN)10.1111/apa.12866 (DOI)000350062400012 ()25399485 (PubMedID)2-s2.0-84923181512 (Scopus ID)
    Available from: 2015-03-30 Created: 2015-03-30 Last updated: 2021-05-26Bibliographically approved
    3. Leakage of isopropanol from port protectors used in neonatal intensive care
    Open this publication in new window or tab >>Leakage of isopropanol from port protectors used in neonatal intensive care
    (English)Manuscript (preprint) (Other academic)
    National Category
    General Practice
    Identifiers
    urn:nbn:se:oru:diva-69661 (URN)
    Available from: 2018-10-17 Created: 2018-10-17 Last updated: 2021-05-26Bibliographically approved
    4. Hygiene routines in the EXPRESS study: a Swedish national survey of hygiene practices in neonatal intensive care
    Open this publication in new window or tab >>Hygiene routines in the EXPRESS study: a Swedish national survey of hygiene practices in neonatal intensive care
    (English)Manuscript (preprint) (Other academic)
    National Category
    General Practice
    Identifiers
    urn:nbn:se:oru:diva-69662 (URN)
    Available from: 2018-10-17 Created: 2018-10-17 Last updated: 2021-05-26Bibliographically approved
    5. Hygiene routines in the EXPRESS study: impact of hygiene routines and antibiotic prophylaxis on neonatal sepsis incidence
    Open this publication in new window or tab >>Hygiene routines in the EXPRESS study: impact of hygiene routines and antibiotic prophylaxis on neonatal sepsis incidence
    (English)Manuscript (preprint) (Other academic)
    National Category
    General Practice
    Identifiers
    urn:nbn:se:oru:diva-69663 (URN)
    Available from: 2018-10-17 Created: 2018-10-17 Last updated: 2021-05-26Bibliographically approved
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    Aspects of neonatal septicaemia – prevention and complications
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  • 32.
    Björkman Hjalmarsson, Louise
    et al.
    Örebro University, School of Medical Sciences. Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Hagberg, Jessika
    Örebro University, School of Science and Technology. Department of Occupational and Environmental Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Schollin, Jens
    Örebro University, School of Medical Sciences.
    Ohlin, Andreas
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Pediatrics.
    Leakage of isopropanol from port protectors used in neonatal intensive careManuscript (preprint) (Other academic)
  • 33.
    Björkman Hjalmarsson, Louise
    et al.
    Örebro University, School of Medical Sciences. Department of Paediatrics, Örebro University Hospital, Örebro, Sweden.
    Ohlin, Andreas
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Paediatrics.
    Schollin, Jens
    Örebro University, School of Medical Sciences.
    Bodin, Lennart
    Örebro University, Örebro University School of Business. Intervention and Implementation Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm; Department of Statistics, Örebro University, Örebro, Sweden.
    Hygiene routines in the EXPRESS study: impact of hygiene routines and antibiotic prophylaxis on neonatal sepsis incidenceManuscript (preprint) (Other academic)
  • 34.
    Björkman Hjalmarsson, Louise
    et al.
    Örebro University, School of Medical Sciences. Department of Paediatrics, Örebro University Hospital, Örebro, Sweden.
    Schollin, Jens
    Örebro University, School of Medical Sciences.
    Bodin, Lennart
    Örebro University, Örebro University School of Business. Intervention and Implementation Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, Department of Statistics, Örebro University, Örebro, Sweden.
    Ohlin, Andreas
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Paediatrics.
    Hygiene routines in the EXPRESS study: a Swedish national survey of hygiene practices in neonatal intensive careManuscript (preprint) (Other academic)
  • 35.
    Boman, Tomas
    et al.
    Department of Social Work and Psychology, Faculty of Health and Occupational Studies, University of Gävle, Gävle, Sweden; Swedish Institute for Disability Research, Örebro University, Örebro, Sweden.
    Kjellberg, Anders
    Department of Building, Energy and Environmental Engineering, Faculty of Engineering and Sustainable Development, University of Gävle, Gävle, Sweden.
    Danermark, Berth
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Swedish Institute for Disability Research.
    Boman, Eva
    Department of Social Work and Psychology, Faculty of Health and Occupational Studies, University of Gävle, Gävle, Sweden.
    Employment opportunities for persons with different types of disability2015In: Alter;European Journal of Disability Research ;Journal Europeen de Recherche Sur le Handicap, ISSN 1875-0672, E-ISSN 1875-0680, Vol. 9, no 2, p. 116-129Article in journal (Refereed)
    Abstract [en]

    The employment status of groups with different disabilities was analysed as were potentially important moderating factors (work ability, structural and individual factors). A secondary analysis was performed on 4359 respondents with disabilities from Statistics Sweden's Labour Market Investigation. The respondents were divided into six disability groups (communicative-hearing, communicative-speech-reading, communicative-vision, psychological disability, medical disability, physical disability). Logistic regression analyses showed that the probability of being employed was highest among respondents with hearing disabilities and respondents with psychological disabilities were least likely to be employed. Being a woman (very young or old) with only primary education and with partially or very impaired work ability, reduced employment opportunities. Higher education did not increase employment opportunities for respondents with impaired workability. In summary, the type of disability is essential for employment opportunities, and differences between disability groups cannot be explained by differences in other variables. The moderating factors studied were found to be of equal importance in all groups.

  • 36.
    Bozorg, Soran Rabin
    Örebro University, School of Medical Sciences.
    Various Aspects of Gastrointestinal Disease: Examining Validity and Health Economic Outcomes2022Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Introduction: Recent years have seen significant research advances within the gastroenterological field. Some of these consist of the recognition of serrated polyps as a precursor to colorectal cancer, and the realization of the health economic burden associated with gastrointestinal diseases.

    Aim: In this thesis, we aim to validate the specificity of serrated polyps in the ESPRESSO cohort (Paper I). We also aim to estimate work loss in patients with celiac disease, including the temporal relationship of work loss before and after diagnosis (Paper II).

    Method: By using the ESPRESSO cohort, we collected data on patients with serrated polyps and patients with celiac disease. In Paper I, the specificity of serrated polyps in the ESPRESSO cohort were validated by a structured retrospective review of patient chart. In Paper II, we estimated work loss in patients with celiac disease as compared withgeneral-population comparators matched on age, sex, county of residence and year of diagnosis.

    Result: The presence of a serrated polyp was confirmed in 101 out of 106 individuals identified through the ESPRESSO cohort, yielding a positive predictive value of 95% (95% confidence interval: 89-98%). Patients with celiac disase had 42.5 lost work days as compared to 28.6 days in comparators (mean difference, 14.7; 95% confidence interval, 13.2-16.2), corresponding to a relative increase of 49%. Excess work loss in patients with celiac disease was observed even 5 years before diagnosis and remained eleveated during the years after diagnosis this loss. Notebly, the excess work loss was concentrated to a small proportion while most celiac patients did not have any work loss before or after diagnosis. 

    Conclusion: The ESPRESSO cohort has a high specificity for serrated polyps. Patients with celiac disease miss more work days than the general population even before diagnosis, and this loss persists after diagnosis.

    List of papers
    1. Validation of serrated polyps (SPs) in Swedish pathology registers
    Open this publication in new window or tab >>Validation of serrated polyps (SPs) in Swedish pathology registers
    2019 (English)In: BMC Gastroenterology, ISSN 1471-230X, E-ISSN 1471-230X, Vol. 20, no 1, article id 3Article in journal (Refereed) Published
    Abstract [en]

    Background: Little is known about the natural history of serrated polyps (SPs), partly due to the lack of large-scale epidemiologic data. In this study, we examined the validity of SP identification according to SNOMED (Systematised Nomenclature of Medicine) codes and free text from colorectal histopathology reports.

    Methods: Through the ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) study, we retrieved data on SPs from all pathology departments in Sweden in 2015-2017 by using SNOMED codes and free-text search in colorectal histopathology reports. Randomly selected individuals with a histopathology report of SPs were validated against patient charts using a structured, retrospective review.

    Results: SPs were confirmed in 101/106 individuals with a histopathology report of SPs, yielding a positive predictive value (PPV) of 95% (95%CI = 89-98%). By year of diagnosis, the PPV was 89% (95%CI = 69-97%), 96% (95%CI = 81-99%) and 97% (95%CI = 89-99%) for individuals diagnosed before 2001 (n = 19), between 2001 and 2010 (n = 26) and after 2010 (n = 61), respectively. According to search method, the PPV for individuals identified by SNOMED codes was 100% (95%CI = 93-100%), and 93% (95%CI = 86-97%) using free-text search. Recorded location (colon vs. rectum) was correct in 94% of all SP histopathology reports (95%CI = 84-98%) identified by SNOMED codes. Individuals with SPs were classified into hyperplastic polyps (n = 34; 32%), traditional serrated adenomas (n = 3; 3%), sessile serrated adenomas/polyps (SSA/Ps) (n = 70; 66%), unspecified SPs (n = 3, 3%), and false positive SPs (n = 5, 5%). For individuals identified by SNOMED codes, SSA/Ps were confirmed in 49/52 individuals, resulting in a PPV of 94% (95%CI: 84-98%). In total, 57% had >= 2 polyps (1: n = 44, 2-3: n = 33 and >= 4: n = 27). Some 46% of SPs (n = 71) originated from the proximal colon and 24% were >= 10 mm in size (n = 37). Heredity for colorectal cancer, intestinal polyposis syndromes, or both was reported in seven individuals (7%). Common comorbidities included diverticulosis (n = 45, 42%), colorectal cancer (n = 19, 18%), and inflammatory bowel disease (n = 10, 9%).

    Conclusion: Colorectal histopathology reports are a reliable data source to identify individuals with SPs.

    Place, publisher, year, edition, pages
    BMC, 2019
    Keywords
    Hyperplastic polyp, Serrated adenoma, Serrated polyp, Sessile serrated adenoma, polyp, Traditional serrated adenoma, Validation
    National Category
    Gastroenterology and Hepatology
    Identifiers
    urn:nbn:se:oru:diva-79085 (URN)10.1186/s12876-019-1134-6 (DOI)000505006900003 ()31892305 (PubMedID)2-s2.0-85077353973 (Scopus ID)
    Note

    Funding Agency:

    Karolinska Institutet and Union for International Cancer Control (Yamagiwa-Yoshida Award)  YY2/17/554363

    Available from: 2020-01-15 Created: 2020-01-15 Last updated: 2023-07-03Bibliographically approved
    2. Work loss in patients with celiac disease: A population-based longitudinal study
    Open this publication in new window or tab >>Work loss in patients with celiac disease: A population-based longitudinal study
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    2022 (English)In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 20, no 5, p. 1068-1076.e6Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Celiac disease (CD) affects around 1% of the population worldwide. Data on work disability in celiac patients remain scarce. We estimated work loss in celiac patients including its temporal relationship to diagnosis.

    METHODS: Through biopsy reports from Sweden's 28 pathology departments, we identified 16,005 working-aged patients with prevalent CD (villus atrophy) as of January 1, 2015, and 4,936 incident patients diagnosed with CD in 2008-2015. Each patient was matched to up to 5 general-population comparators. Using nationwide social insurance registers, we retrieved prospectively-recorded data on compensation for sick leave and disability leave to assess work loss in patients and comparators.

    RESULTS: In 2015, patients with prevalent CD had a mean of 42.5 lost work days as compared with 28.6 in comparators (mean difference: 14.7, 95%CI: 13.2-16.2), corresponding to a relative increase of 49%. More than half of the work loss (60.1%) in celiac patients was derived from a small subgroup (7%) while 75.4% had no work loss. Among incident patients, the annual mean difference between patients and comparators was 8.0 (5.4-10.6) lost work days 5 years before CD diagnosis, which grew to 13.7 (9.1-18.3) days 5 years after diagnosis. No difference in work loss was observed between patients with or without mucosal healing at follow-up.

    CONCLUSIONS: Celiac patients lost more work days than comparators before their diagnosis, and this loss increased after diagnosis. Identifying patients with an increased risk of work loss may serve as a target to mitigate work disability, and thereby reduce work loss, in CD.

    Place, publisher, year, edition, pages
    Elsevier, 2022
    Keywords
    Economic burden, absenteeism, cost, health economics
    National Category
    Gastroenterology and Hepatology
    Identifiers
    urn:nbn:se:oru:diva-94360 (URN)10.1016/j.cgh.2021.09.002 (DOI)000822564600014 ()34509642 (PubMedID)2-s2.0-85119898535 (Scopus ID)
    Funder
    Karolinska Institute
    Note

    Funding agency:

    Örebro University Hospital

    Available from: 2021-09-16 Created: 2021-09-16 Last updated: 2023-02-17Bibliographically approved
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  • 37.
    Cajander, Sara
    Örebro University, School of Medical Sciences.
    Dynamics of Human Leukocyte Antigen-D Related expression in bacteremic sepsis2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Monocytic human leukocyte antigen-D related (mHLA-DR) expression determined by flow cytometry has been suggested as a biomarker of sepsisinduced immunosuppression.

    In order to facilitate use of HLA-DR in clinical practice, a quantitative real-time PCR technique measuring HLA-DR at the transcription level was developed and evalutated. Levels of HLA-DR mRNA correlated to mHLADR expression and were robustly measured, with high reproducibility, during the course of infection. Dynamics of mHLA-DR expression was studied during the first weeks of bloodstream infection (BSI) and was found to be dependent on the bacterial etiology of BSI. Moreover, mHLA-DR was shown to be inversely related to markers of inflammation. In patients with unfavourable outcome, sustained high C-reactive protein level and high neutrophil count were demonstrated along with low mHLA-DR expression and low lymphocyte count. This supports the theory of sustained inflammation in sepsis-induced immunosuppression. The association between mHLA-DR and bacterial etiology may be linked to the clinical trajectory via differences in ability to cause intractable infection. Staphylococcus aureus was the dominating etiology among cases with unfavourable outcome. With focus on patients with S. aureus BSI, those with complicated S. aureus BSI were found to have lower HLA-DR mRNA expression during the first week than those with uncomplicated S. aureus BSI. If these results can be confirmed in a larger cohort, HLA-DR measurement could possibly become an additional tool for early identification of patients who require further investigation to clear infectious foci and achieve source control.

    In conclusion, PCR-based measurement of HLA-DR is a promising method for measurements of the immune state in BSI, but needs further evaluation in the intensive care unit setting to define the predictive and prognostic value for deleterious immunosuppression. The etiology of infection should be taken into consideration in future studies of translational immunology in sepsis.

    List of papers
    1. Preliminary results in quantitation of HLA-DRA by real-time PCR: a promising approach to identify immunosuppression in sepsis
    Open this publication in new window or tab >>Preliminary results in quantitation of HLA-DRA by real-time PCR: a promising approach to identify immunosuppression in sepsis
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    2013 (English)In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 17, no 5, article id R223Article in journal (Refereed) Published
    Abstract [en]

    Introduction: Reduced monocyte human leukocyte antigen (mHLA)-DR surface expression in the late phase of sepsis is postulated as a general biomarker of sepsis-induced immunosuppression and an independent predictor of nosocomial infections. However, traditional monitoring of mHLA-DR by flow cytometry has disadvantages due to specific laboratory requirements. An mRNA-based HLA-DR monitoring by polymerase chain reaction (PCR) would improve the clinical usage and facilitate conduction of large multicenter studies. In this study, we evaluated an mRNA-based HLA-DR monitoring by quantitative real-time PCR (qRT-PCR) as an alternative method to traditional flow cytometry.

    Methods: Fifty-nine patients with sepsis and blood culture growing pathogenic bacteria were studied. Blood samples were collected at day 1 or 2 after admission, for measurement of mHLA-DR by flow cytometry and mRNA expression of HLA-DRA and class II transactivator (CIITA) by qRT-PCR. Blood samples from blood donors were used as controls (n = 30).

    Results: A significant reduced expression of mHLA-DR, HLA-DRA, and CIITA was seen in septic patients compared with controls. HLA-DRA mRNA level in whole blood was highly correlated with surface expression of mHLA-DR.

    Conclusions: Patients with sepsis display a diminished expression of HLA-DR at the monocyte surface as well as in the gene expression at the mRNA level. The mRNA expression level of HLA-DRA monitored by qRT-PCR correlates highly with surface expression of HLA-DR and appears to be a possible future biomarker for evaluation of immunosuppression in sepsis.

    Place, publisher, year, edition, pages
    London, United Kingdom: BioMed Central, 2013
    National Category
    Medical and Health Sciences Clinical Laboratory Medicine
    Research subject
    Medicine
    Identifiers
    urn:nbn:se:oru:diva-34293 (URN)10.1186/cc13046 (DOI)000331540900039 ()24093602 (PubMedID)2-s2.0-84884967732 (Scopus ID)
    Note

    Funding Agencies:

    Nyckelfonden (Örebro, Sweden)

    Research committee of Örebro County Council

    Available from: 2014-03-13 Created: 2014-03-13 Last updated: 2024-01-10Bibliographically approved
    2. Quantitative Real-Time Polymerase Chain Reaction Measurement of HLA-DRA Gene Expression in Whole Blood Is Highly Reproducible and Shows Changes That Reflect Dynamic Shifts in Monocyte Surface HLA-DR Expression during the Course of Sepsis
    Open this publication in new window or tab >>Quantitative Real-Time Polymerase Chain Reaction Measurement of HLA-DRA Gene Expression in Whole Blood Is Highly Reproducible and Shows Changes That Reflect Dynamic Shifts in Monocyte Surface HLA-DR Expression during the Course of Sepsis
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    2016 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 11, no 5, article id e0154690Article in journal (Refereed) Published
    Abstract [en]

    Introduction: A decrease in the expression of monocyte surface protein HLA-DR (mHLA-DR), measured by flow cytometry (FCM), has been suggested as a marker of immunosuppression and negative outcome in severe sepsis. However, FCM is not always available due to sample preparation that limits its use to laboratory operational hours. In this prospective study we evaluated dynamic changes in mHLA-DR expression during sepsis in relation to changes in HLA-DRA gene expression and Class II transactivator (CIITA), measured by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR).

    Aims: The aims of this study were: 1. to validate the robustness of qRT-PCR measurement of HLA-DRA- and CIITA-mRNA expression, in terms of reproducibility; and 2. to see if changes in expression of these genes reflect changes in mHLA-DR expression during the course of severe and non-severe bacteraemic sepsis.

    Methods and Findings: Blood samples were collected from 60 patients with bacteraemic sepsis on up to five occasions during Days 1-28 after hospital admission. We found the reproducibility of the qRT-PCR method to be high by demonstrating low threshold variations (<0.11 standard deviation (SD)) of the qRT-PCR system, low intra-assay variation of Ct-values within triplicates (≤0.15 SD) and low inter-assay variations (12%) of the calculated target gene ratios. Our results also revealed dynamic HLA-DRA expression patterns during the course of sepsis that reflected those of mHLA-DR measured by FCM. Furthermore, HLA-DRA and mHLA-DR recovery slopes in patients with non-severe sepsis differed from those in patients with severe sepsis, shown by mixed model for repeated measurements (p<0.05). However, during the first seven days of sepsis, PCR-measurements showed a higher magnitude of difference between the two sepsis groups. Mean differences (95% CI) between severe sepsis (n = 20) and non-severe sepsis (n = 40) were; on day 1-2, HLA-DRA 0.40 (0.28-0.59) p<0.001, CIITA 0.48 (0.32-0.72) p = 0.005, mHLA-DR 0.63 (0.45-1.00) p = 0.04, day 7 HLA-DRA 0.59 (0.46-0.77) p<0.001, CIITA 0.56 (0.41-0.76) p<0.001, mHLA-DR 0.81 (0.66-1.00) p = 0.28.

    Conclusion: We conclude that qRT-PCR measurement of HLA-DRA expression is robust, and that this method appears to be preferable to FCM in identifying patients with severe sepsis that may benefit from immunostimulation.

    Place, publisher, year, edition, pages
    San Francisco, USA: Public Library of Science, 2016
    National Category
    Infectious Medicine
    Identifiers
    urn:nbn:se:oru:diva-50323 (URN)10.1371/journal.pone.0154690 (DOI)000375676400061 ()27144640 (PubMedID)2-s2.0-85009996236 (Scopus ID)
    Note

    Funding Agencies:

    Nyckelfonden (Örebro, Sweden)

    Research committee of Örebro County Council

    Available from: 2016-05-27 Created: 2016-05-16 Last updated: 2024-01-10Bibliographically approved
    3. Monocytic HLA-DR expression differs between bacterial etiologies and is inversely related to C-reactive protein and neutrophil count during the course of bloodstream infection
    Open this publication in new window or tab >>Monocytic HLA-DR expression differs between bacterial etiologies and is inversely related to C-reactive protein and neutrophil count during the course of bloodstream infection
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    (English)Manuscript (preprint) (Other academic)
    National Category
    General Practice
    Identifiers
    urn:nbn:se:oru:diva-57488 (URN)
    Available from: 2017-04-25 Created: 2017-04-25 Last updated: 2024-01-10Bibliographically approved
    4. Expression of HLA-DRA and CD74 mRNA in whole blood during the course of complicated and uncomplicated Staphylococcus aureus bacteraemia
    Open this publication in new window or tab >>Expression of HLA-DRA and CD74 mRNA in whole blood during the course of complicated and uncomplicated Staphylococcus aureus bacteraemia
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    (English)Manuscript (preprint) (Other academic)
    National Category
    General Practice
    Identifiers
    urn:nbn:se:oru:diva-56198 (URN)
    Available from: 2017-03-08 Created: 2017-03-08 Last updated: 2024-01-10Bibliographically approved
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    Dynamics of Human Leukocyte Antigen-D Related expression in bacteremic sepsis
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  • 38.
    Cajander, Sara
    et al.
    Örebro University, School of Medical Sciences.
    Rasmussen, Gunlög
    Örebro University, School of Medical Sciences.
    Tina, Elisabet
    Örebro University, School of Medical Sciences.
    Magnuson, Anders
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Medical Sciences.
    Källman, Jan
    Örebro University, School of Medical Sciences.
    Strålin, Kristoffer
    Karolinska University Hospital, Stockholm, Sweden; Karolinska Institute, Stockholm, Sweden .
    Monocytic HLA-DR expression differs between bacterial etiologies and is inversely related to C-reactive protein and neutrophil count during the course of bloodstream infectionManuscript (preprint) (Other academic)
  • 39.
    Calais, Fredrik
    Örebro University, School of Medical Sciences.
    Coronary artery disease and prognosis in relation to cardiovascular risk factors, interventional techniques and systemic atherosclerosis2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Aim: To evaluate the prognosis associated with location and severity of coronary and systemic atherosclerosis in patients with coronary artery disease (CAD) in relation to risk factors and interventional techniques.

    Methods: The thesis comprised six longitudinal studies based on three patient cohorts: The Swedish Coronary Angiography and Angioplasty Registry, the Västmanland Myocardial Infarction Survey, and the Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia study, to evaluate clinical outcome relative to coronary lesion location and severity, extracoronary artery disease (ECAD), intervention techniques, and leisuretime physical inactivity (LTPI).

    Results: Stent placement in the proximal left anterior descending artery (LAD) was more often associated with restenosis than was stenting in the other coronary arteries. The use of drug-eluting stents in the LAD was associated with a lower risk of restenosis and death compared to baremetal stents. Thrombus aspiration in in the LAD during acute ST elevation myocardial infarction (MI) did not improve clinical outcome, irrespective of adjunct intervention technique. Clinical, but not subclinical, ECAD was associated with poor prognosis in patients with MI. Longitudinal extent of CAD at the time of MI was a predictor of ECAD, and coexistence of extensive CAD and ECAD was associated with particularly poor prognosis following MI. Self-reported LTPI was associated with MI and all-cause mortality independent of ECAD.

    Conclusions: Drug-eluting stents, but not thrombus aspiration, improved prognosis following percutaneous coronary intervention in the proximal LAD. Self- reported LTPI, clinical ECAD, and systemic atherosclerosis defined groups with poor prognosis after MI.

    List of papers
    1. Proximal coronary artery intervention: Stent thrombosis, restenosis and death
    Open this publication in new window or tab >>Proximal coronary artery intervention: Stent thrombosis, restenosis and death
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    2013 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 170, no 2, p. 227-232Article in journal (Refereed) Published
    Abstract [en]

    Background: Percutaneous coronary intervention (PCI) of lesions in the proximal left anterior descending coronary artery (LAD) may confer a worse prognosis compared with the proximal right coronary artery (RCA) and left circumflex coronary artery (LCX). Methods: From May 2005, to May 2011 we identified all PCIs for proximal, one-vessel coronary artery disease in the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). We evaluated restenosis, stent thrombosis (ST) and mortality in the LAD as compared to the RCA and LCX according to stent type, bare metal (BMS) or drug-eluting stents (DES). Results: 7840 single vessel proximal PCI procedures were identified. Mean follow-up time was 792 days. No differences in restenosis or ST were seen between the LAD and the RCA. The frequency of restenosis and ST was higher in the proximal LAD compared to the proximal LCX (restenosis: hazard ratio (HR) 2.28, confidence interval (CI) 1.56-3.34 p < 0.001; ST: HR 2.32, CI 1.11-4.85 p = 0.024). We found no difference in mortality related to coronary artery. In the proximal LAD, DES implantation was associated with a lower restenosis rate (HR 0.39, CI 0.27-0.55 < 0.001) and mortality (HR 0.58, CI 0.41-0.82 p = 0.002) compared with BMS. In the proximal RCA and LCX, DES use was not associated with lower frequency of clinical restenosis or mortality. Conclusions: Following proximal coronary artery intervention restenosis was more frequent in the LAD than in the LCX. Solely in the proximal LAD we found DES use to be associated with a lower risk of restenosis and death weighted against BMS. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

    Keywords
    Angioplasty, Coronary artery disease, Drug-eluting stents
    National Category
    Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:oru:diva-56452 (URN)10.1016/j.ijcard.2013.10.060 (DOI)000327889200032 ()24211065 (PubMedID)2-s2.0-84889081672 (Scopus ID)
    Available from: 2017-03-16 Created: 2017-03-16 Last updated: 2024-01-16Bibliographically approved
    2. Leisure-time physical inactivity and risk of myocardial infarction and all-cause mortality: A case-control study
    Open this publication in new window or tab >>Leisure-time physical inactivity and risk of myocardial infarction and all-cause mortality: A case-control study
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    2014 (English)In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 177, no 2, p. 599-600Article in journal (Refereed) Published
    Place, publisher, year, edition, pages
    Elsevier, 2014
    Keywords
    Exercise, Cardiovascular diseases, Myocardial infarction, Peripheral artery disease
    National Category
    Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:oru:diva-56360 (URN)10.1016/j.ijcard.2014.08.137 (DOI)000345232200087 ()25223818 (PubMedID)2-s2.0-84913582534 (Scopus ID)
    Available from: 2017-03-15 Created: 2017-03-15 Last updated: 2024-01-16Bibliographically approved
    3. ST-Elevation Myocardial Infarction, Thrombus Aspiration, and Different Invasive Strategies: A TASTE Trial Substudy
    Open this publication in new window or tab >>ST-Elevation Myocardial Infarction, Thrombus Aspiration, and Different Invasive Strategies: A TASTE Trial Substudy
    2015 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, no 6, article id e001755Article in journal (Refereed) Published
    Abstract [en]

    Background: The clinical effect of thrombus aspiration in ST-elevation myocardial infarction may depend on the type of aspiration catheter and stenting technique.

    Methods and Results: The multicenter, prospective, randomized, open-label trial Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia (TASTE) did not demonstrate a clinical benefit of thrombus aspiration compared to percutaneous coronary intervention alone. We assessed the effect of type of aspiration device, stent type, direct stenting, and postdilatation on outcomes at 1 year. There was no difference in all-cause mortality, between the 3 most frequently used aspiration catheters (Eliminate [Terumo] 5.4%, Export [Medtronic] 5.0%, Pronto [Vascular Solutions] 4.5%) in patients randomized to thrombus aspiration. There was no difference in mortality between directly stented patients randomized to thrombus aspiration compared to patients randomized to percutaneous coronary intervention only (risk ratio 1.08, 95% CI 0.70 to 1.67, P=0.73). Similarly, there was no difference in mortality between the 2 randomized groups for patients receiving drug-eluting stents (risk ratio 0.89, 95% CI 0.63 to 1.26, P=0.50) or for those treated with postdilation (risk ratio 0.72, 95% CI 0.49 to 1.07, P=0.11). Furthermore, there was no difference in rehospitalization for myocardial infarction or stent thrombosis between the randomized arms in any of the subgroups.

    Conclusions: In patients with ST-elevation myocardial infarction randomized to thrombus aspiration, the type of aspiration catheter did not affect outcome. Stent type, direct stenting, or postdilation did not affect outcome irrespective of treatment with thrombus aspiration and percutaneous coronary intervention or percutaneous coronary intervention alone.

    Keywords
    angioplasty, myocardial infarction, stenting, thrombus aspiration
    National Category
    Cardiac and Cardiovascular Systems
    Research subject
    Cardiology
    Identifiers
    urn:nbn:se:oru:diva-45542 (URN)10.1161/JAHA.114.001755 (DOI)000357025100014 ()26077585 (PubMedID)
    Funder
    Swedish Research CouncilSwedish Heart Lung Foundation, 20100178 B0010401
    Note

    Funding Agencies:

    Swedish Association of Local Authorities and Regions

    Terumo Medical Corporation

    Medtronic Solution

    Svenska Hjartförbundet

    Vascular Solution

    Available from: 2015-08-12 Created: 2015-08-12 Last updated: 2024-01-16Bibliographically approved
    4. Thrombus aspiration in patients with large anterior myocardial infarction: A Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia trial substudy
    Open this publication in new window or tab >>Thrombus aspiration in patients with large anterior myocardial infarction: A Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia trial substudy
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    2016 (English)In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 172, no 2, p. 129-134Article in journal (Refereed) Published
    Abstract [en]

    Background: The TASTE trial did not demonstrate clinical benefit of thrombus aspiration (TA). High-risk patients might benefit from TA.

    Methods: The TASTE trial was a multicenter, randomized, controlled, open-label trial obtaining end points from national registries. Patients (n = 7,244) with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) were randomly assigned 1: 1 to TA and PCI or to PCI alone. We assessed the 1-year clinical effect of TA in a subgroup with potentially large anterior STEMI: mid or proximal left anterior descending coronary artery infarct lesion, thrombolysis in myocardial infarction 0 to 2 flow, and symptom onset to PCI time = 5 hours. In this substudy, patient eligibility criteria corresponded to that of the INFUSE-AMI study.

    Results: In total, 1,826 patients fulfilled inclusion criteria. All-cause mortality at 1 year of patients randomized to TA did not differ from those randomized to PCI only (hazard ratio [HR] 1.05, 95% CI 0.74-1.49, P = .77). Rates of rehospitalization for myocardial infarction, heart failure, and stent thrombosis did not differ between groups (HR 0.87, 95% CI 0.51-1.46, P = .59; HR 1.10 95% CI 0.77-1.58, P = .58; and HR 0.75, 95% CI 0.30-1.86, P = .53, respectively). This was also the case for the combined end point of all-cause mortality and rehospitalization for myocardial infarction, heart failure, or stent thrombosis (HR 1.00, 95% CI 0.79-1.26, P = .99).

    Conclusion: In patients with STEMI and large area of myocardium at risk, TA did not affect outcome within 1 year.

    Place, publisher, year, edition, pages
    Elsevier, 2016
    National Category
    Cardiac and Cardiovascular Systems
    Research subject
    Cardiology
    Identifiers
    urn:nbn:se:oru:diva-48941 (URN)10.1016/j.ahj.2015.11.012 (DOI)000369659400016 ()26856224 (PubMedID)2-s2.0-84959295967 (Scopus ID)
    Note

    Funding Agencies:

    Medtronic

    Vascular solutions

    Terumo

    Biosensors 

    Biotronik

    Available from: 2016-03-07 Created: 2016-03-04 Last updated: 2024-01-16Bibliographically approved
    5. Prognostic impact of subclinical or manifest extracoronary artery diseases after acute myocardial infarction
    Open this publication in new window or tab >>Prognostic impact of subclinical or manifest extracoronary artery diseases after acute myocardial infarction
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    2017 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 263, p. 53-59Article in journal (Refereed) Published
    Abstract [en]

    Background and aims: In patients with coronary artery disease (CAD), clinically overt extracoronary artery diseases (ECADs), including claudication or previous strokes, are associated with poor outcomes. Subclinical ECADs detected by screening are common among such patients. We aimed to evaluate the prognostic impact of subclinical versus symptomatic ECADs in patients with acute myocardial infarction (AMI).

    Methods: In a prospective observational study, 654 consecutive patients diagnosed with AMI underwent ankle brachial index (ABI) measurements and ultrasonographic screening of the carotid arteries and abdominal aorta. Clinical ECADs were defined as prior strokes, claudication, or extracoronary artery intervention. Subclinical ECADs were defined as the absence of a clinical ECAD in combination with an ABI <= 0.9 or >1.4, carotid artery stenosis, or an abdominal aortic aneurysm.

    Results: At baseline, subclinical and clinical ECADs were prevalent in 21.6% and 14.4% of the patients, respectively. Patients with ECADs received evidence-based medication more often at admission but similar medications at discharge compared with patients without ECADs. During a median follow-up of 5.2 years, 166 patients experienced endpoints of hospitalization for AMI, heart failure, stroke, or cardiovascular death. With ECAD-free cases as reference and after adjustment for risk factors, a clinical ECAD (hazard ratio [HR] 2.10, 95% confidence interval [CI] 1.34-3.27, p = 0.001), but not a subclinical ECAD (HR 1.35, 95% CI 0.89-2.05, p = 0.164), was significantly associated with worse outcomes.

    Conclusions: Despite receiving similar evidence-based medication at discharge, patients with clinical ECAD, but not patients with a subclinical ECAD, had worse long-term prognosis than patients without an ECAD after AMI. (C) 2017 The Authors. Published by Elsevier Ireland Ltd.

    Place, publisher, year, edition, pages
    Elsevier, 2017
    Keywords
    Extracoronary artery disease, Myocardial infarction, Prognosis
    National Category
    Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:oru:diva-60724 (URN)10.1016/j.atherosclerosis.2017.05.027 (DOI)000407634000884 ()28599258 (PubMedID)2-s2.0-85020304353 (Scopus ID)
    Note

    Funding Agencies:

    Sparbanksstiftelsen Nya  552  693  0932  2297 

    County of Västmanland  

    Swedish Medical Association

    Available from: 2017-09-11 Created: 2017-09-11 Last updated: 2024-01-16Bibliographically approved
    6. Incremental prognostic value of coronary and systemic atherosclerosis aftermyocardial infarction
    Open this publication in new window or tab >>Incremental prognostic value of coronary and systemic atherosclerosis aftermyocardial infarction
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    (English)Manuscript (preprint) (Other academic)
    National Category
    General Practice Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:oru:diva-65425 (URN)
    Available from: 2018-03-02 Created: 2018-03-02 Last updated: 2024-01-16Bibliographically approved
    Download full text (pdf)
    Coronary artery disease and prognosis in relation to cardiovascular risk factors, interventional techniques and systemic atherosclerosis
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  • 40.
    Calais, Fredrik
    et al.
    Örebro University, School of Medical Sciences.
    Eriksson Östman, Maja
    Örebro University, Faculty of Health, Department of Cardiology, Sweden.
    Hedberg, Pär
    Centre for Clinical Research, Uppsala University and Department of Clinical Physiology, Västmanland County Hospital, Västerås, Sweden.
    Rosenblad, Andreas
    Centre for Clinical Research, Uppsala University Västmanland County Hospital, Västerås, Sweden.
    Leppert, Jerzy
    Centre for Clinical Research, Uppsala University Västmanland County Hospital, Västerås, Sweden.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Incremental prognostic value of coronary and systemic atherosclerosis aftermyocardial infarctionManuscript (preprint) (Other academic)
  • 41.