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  • 1.
    Adlitzer, Helena
    et al.
    Regionalt cancercentrum Stockholm Gotland.
    Andershed, Birgitta
    Ersta Sköndal Högskola.
    Axelsson, Bertil
    Östersunds sjukhus; Umeå universitet.
    Blomberg, Karin
    Örebro University, School of Health Sciences.
    Fridegren, Inger
    Nacka Närsjukhus.
    Friedrichsen, Maria
    Palliativt kompetenscentrum Östergötland, Vrinnevisjukhuset; Linköpings Universitet .
    Fürst, Carl-Johan
    Palliativt utvecklingscentrum, Lunds universitet och Region Skåne.
    Heedman, Per-Anders
    Palliativt kompetenscentrum i Östergötland.
    Henoch, Ingela
    Sahlgrenska akademin; Göteborgs universitet.
    Kenne Sarenmalm, Elisabeth
    FoU Centrum, Skaraborgs sjukhus, Skövde.
    Löfdahl, Elisabet
    Palliativa sektionen SU/Sahlgrenska universitetssjukhuset.
    Melin-Johansson, Christina
    Mittuniversitetet.
    Molander, Ulla
    Sahlgrenska Universitetssjukhuset, Göteborg.
    Persson, Hans
    Danderyds sjukhus.
    Pessah-Rasmussen, Hélène
    Skånes Universitetssjukhus (SUS).
    Rasmussen, Birgit H
    Lunds universitet och Region Skåne.
    Schaufelberger, Maria
    Sahlgrenska universitetssjukhuset.
    Seiger Cronfalk, Berit
    Ersta Sköndal Högskola; Karolinska Institutet.
    Silk, Gerd
    Kvalitets- och utvecklingsenheten Region Gotland.
    Strang, Peter
    Karolinska Institutet och Stockholms Sjukhem, Stockholm.
    Strömberg, Anna
    Linköpings universitetssjukhus.
    Tavemark, Sofia
    Örebro kommun.
    Ternestedt, Britt-Marie
    Ersta Sköndal Högskola, Stockholm.
    Wennman-Larsen, Agneta
    Sophiahemmet Högskola; Karolinska Institutet.
    Wikström, Gerhard
    Uppsala Universitet.
    Österlind, Jane
    Ersta Sköndal högskola.
    Palliativ vård i livets slutskede: Nationellt vårdprogram2016Report (Other academic)
  • 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, 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.
    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)
  • 5.
    Allvin, Renée
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Clinical Skills Centre.
    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, ISSN 1179-7258, 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.

  • 6.
    Almroth, Henrik
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Andersson, Torbjorn
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. 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, Stokcholm, 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.

  • 7.
    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
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    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)
    Available from: 2016-06-08 Created: 2016-06-08 Last updated: 2018-07-13Bibliographically 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: 2018-01-11Bibliographically 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: 2018-01-11Bibliographically approved
  • 8.
    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)
  • 9.
    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)
  • 10.
    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
    Show others...
    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: 2018-05-22Bibliographically 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)
    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: 2018-06-19Bibliographically 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: 2018-03-26Bibliographically 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, ISSN 1932-6203, 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: 2018-03-26Bibliographically approved
  • 11.
    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)
  • 12.
    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, ISSN 1472-6793, 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, 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: 2018-04-26Bibliographically 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: 2018-05-15Bibliographically 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: 2018-05-27Bibliographically 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: 2018-07-16Bibliographically 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: 2018-04-26Bibliographically approved
  • 13.
    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 (Baltimore, Md.), 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.

  • 14.
    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.

  • 15.
    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.

  • 16.
    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.

  • 17.
    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: 2018-06-07Bibliographically 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: 2017-12-04Bibliographically 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: 2018-07-19Bibliographically 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
    Show others...
    (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: 2018-01-13Bibliographically approved
  • 18.
    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
    Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro.
    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)
  • 19.
    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, ISSN 1932-6203, 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.

  • 20.
    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, 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 ...

  • 21.
    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.

  • 22.
    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)
    Note

    Funding Agency:

    Örebro Heart Foundation

    Research Committee of Örebro University Hospital

    Available from: 2015-02-04 Created: 2015-02-03 Last updated: 2018-06-15Bibliographically 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
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    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: 2018-07-16Bibliographically 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, 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: 2018-04-09Bibliographically 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: 2018-05-02Bibliographically approved
  • 23.
    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, Örebro University, Örebro, Sweden.
    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.

  • 24.
    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: 2018-05-22Bibliographically 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, ISSN 1932-6203, 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)
    Note

    Funding Agencies:

    Nyckelfonden (Örebro, Sweden)

    Research committee of Örebro County Council

    Available from: 2016-05-27 Created: 2016-05-16 Last updated: 2018-07-10Bibliographically 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
    Show others...
    (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: 2018-01-13Bibliographically 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: 2018-01-13Bibliographically approved
  • 25.
    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
    Clinical Epidemiology and Biostatistics, 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)
  • 26.
    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)
    Available from: 2017-03-16 Created: 2017-03-16 Last updated: 2018-05-28Bibliographically 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: 2018-06-19Bibliographically 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: 2018-07-01Bibliographically 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)000369603800016 ()26856224 (PubMedID)
    Note

    Funding Agencies:

    Medtronic

    Vascular solutions

    Terumo

    Biosensors 

    Biotronik

    Available from: 2016-03-07 Created: 2016-03-04 Last updated: 2018-07-10Bibliographically 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
    Show others...
    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: 2018-03-02Bibliographically 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
    Show others...
    (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: 2018-03-02Bibliographically approved
  • 27.
    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)
  • 28.
    Chang, Zheng
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, England.
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Långström, Niklas
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Fazel, Seena
    Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, England.
    Association Between Prescription of Major Psychotropic Medications and Violent Reoffending After Prison Release2016In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 316, no 17, p. 1798-1807Article in journal (Refereed)
    Abstract [en]

    Importance: Individuals released from prison have high rates of violent reoffending, and there is uncertainty about whether pharmacological treatments reduce reoffending risk.

    Objective: To investigate the associations between major classes of psychotropic medications and violent reoffending.

    Design, Setting, and Participants: This cohort study included all released prisoners in Sweden from July 1, 2005, to December 31, 2010, through linkage of population-based registers. Rates of violent reoffending during medicated periods were compared with rates during nonmedicated periods using within-individual analyses. Follow-up ended December 31, 2013.

    Exposures: Periods with or without dispensed prescription of psychotropic medications (antipsychotics, antidepressants, psychostimulants, drugs used in addictive disorders, and antiepileptic drugs) after prison release. Prison-based psychological treatments were investigated as a secondary exposure.

    Main Outcomes and Measures: Violent crime after release from prison.

    Results: The cohort included 22 275 released prisoners (mean [SD] age, 38 [13] years; 91.9% male). During follow-up (median, 4.6 years; interquartile range, 3.0-6.4 years), 4031 individuals (18.1%) had 5653 violent reoffenses. The within-individual hazard ratio (HR) associated with dispensed antipsychotics was 0.58 (95% CI, 0.39-0.88), based on 100 events in 1596 person-years during medicated periods and 1044 events in 11 026 person-years during nonmedicated periods, equating to a risk difference of 39.7 (95% CI, 11.3-57.7) fewer violent reoffenses per 1000 person-years. The within-individual HR associated with dispensed psychostimulants was 0.62 (95% CI, 0.40-0.98), based on 94 events in 1648 person-years during medicated periods and 513 events in 4553 person-years during nonmedicated periods, equating to a risk difference of 42.8 (95% CI, 2.2-67.6) fewer violent reoffenses per 1000 person-years. The within-individual HR associated with dispensed drugs for addictive disorders was 0.48 (95% CI, 0.23-0.97), based on 46 events in 1168 person-years during medicated periods and 1103 events in 15 725 person-years during nonmedicated periods, equating to a risk difference of 36.4 (95% CI, 2.1-54.0) fewer violent reoffenses per 1000 person-years. In contrast, antidepressants and antiepileptics were not significantly associated with violent reoffending rates (HR = 1.09 [95% CI, 0.83-1.43] and 1.14 [95% CI, 0.79-1.65], respectively). The most common prison-based program was psychological treatments for substance abuse, associated with an HR of 0.75 (95% CI, 0.63-0.89), which equated to a risk difference of 23.2 (95% CI, 10.3-34.1) fewer violent reoffenses per 1000 person-years.

    Conclusions and Relevance: Among released prisoners in Sweden, rates of violent reoffending were lower during periods when individiduals were dispensed antipsychotics, psychostimulants, and drugs for addictive disorders, compared with periods in which they were not dispensed these medications. Further research is needed to understand the causal nature of this association.

  • 29.
    Chen, Qi
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
    Sjölander, Arvid
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
    Runeson, Bo
    Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    D'Onofrio, Brian M.
    Department of Psychological and Brain Sciences, Indiana University, Bloomington, USA.
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
    Larsson, Henrik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Drug treatment for attention-deficit/hyperactivity disorder and suicidal behaviour: register based study2014In: BMJ. British Medical Journal, E-ISSN 1756-1833, ISSN 0959-535X, Vol. 348, article id g3769Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the association between drug treatment for attention-deficit/hyperactivity disorder (ADHD) and risk of concomitant suicidal behaviour among patients with ADHD.

    Design: Register based longitudinal study using within patient design.

    Setting: Linkage of multiple national registers in Sweden.

    Participants: 37,936 patients with ADHD born between 1960 and 1996 and followed from 2006 to 2009 for treatment status by ADHD drug treatment and suicide related events (suicide attempt and completed suicide).

    Main outcome measure: Incidence rate of suicide related events during ADHD drug treatment periods compared with that during non-treatment periods.

    Results: Among 37,936 patients with ADHD, 7019 suicide related events occurred during 150,721 person years of follow-up. At the population level, drug treatment of ADHD was associated with an increased rate of suicide related events (hazard ratio 1.31, 95% confidence interval 1.19 to 1.44). However, the within patient comparison showed a reverse association between ADHD drug treatment and rate of suicide related events (0.89, 0.79 to 1.00). Among stimulant users, a reduced within patient rate of suicide related events was seen during treatment periods (0.81, 0.70 to 0.94). Among non-stimulant/mixed users, no significantly increased within patient rate of suicide related events during non-stimulant treatment periods was seen (0.96, 0.72 to 1.30).

    Conclusions: This study found no evidence for a positive association between the use of drug treatments for ADHD and the risk of concomitant suicidal behaviour among patients with ADHD. If anything, the results pointed to a potential protective effect of drugs for ADHD on suicidal behaviour, particularly for stimulant drugs. The study highlights the importance of using within patient designs to control for confounding in future pharmacoepidemiological studies.

  • 30.
    Chillón, Palma
    et al.
    Department of Physical Education and Sport, School of Sport Sciences, University of Granada, Granada, Spain.
    Ortega, Francisco B
    Department of Physical Education and Sport, School of Sport Sciences, University of Granada, Granada, Spain; Department of Biosciences and Nutrition, Unit for Preventive Nutrition, Karolinska Institutet, Sweden; Department of Physiology, School of Medicine, University of Granada, Granada, Spain.
    Ruiz, Jonatan R
    Department of Physical Education and Sport, School of Sport Sciences, University of Granada, Granada, Spain; Department of Biosciences and Nutrition, Unit for Preventive Nutrition, Karolinska Institutet, Sweden.
    Evenson, Kelly R
    Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at, Chapel Hill NC, United States; Center for Health Promotion and Disease Prevention, University of North Carolina at, Chapel Hill NC, United States.
    Labayen, Idoia
    Department of Biosciences and Nutrition, Unit for Preventive Nutrition, Karolinska Institutet, Sweden; Department of Nutrition and Food Sciences, University of the Basque Country (UPV/EHU) Vitoria-Gasteiz, Spain.
    Martínez-Vizcaino, Vicente
    Social and Health Care Research Center, University of Castilla-La Mancha, Cuenca, Spain.
    Hurtig-Wennlöf, Anita
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Veidebaum, Toomas
    National Institute for Heath Development, Centre of Behavioral and Health Sciences, Tallinn, Estonia.
    Sjöström, Michael
    Department of Biosciences and Nutrition, Unit for Preventive Nutrition, Karolinska Institutet, Sweden.
    Bicycling to school is associated with improvements in physical fitness over a 6-year follow-up period in Swedish children2012In: Preventive Medicine, ISSN 0091-7435, E-ISSN 1096-0260, Vol. 55, no 2, p. 108-112Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To examine whether modes of commuting to school at baseline and changes in commuting were related to 6-year changes in cardiorespiratory fitness in youth.

    METHODS: A total of 262 (142 girls) Swedish children (9 years at entry) were measured at baseline (1998/9) and follow-up (2004/5). Mode of commuting to school was assessed by questionnaire and fitness by a maximal bicycle test.

    RESULTS: At baseline, 34% of children used passive modes of commuting (e.g., car, motorcycle, bus, train), 54% walked, and 12% bicycled to school. Six years later the percentage of bicyclists increased 19% and the percentage of walkers decreased 19%. On average, children who bicycled to school increased their fitness 13% (p=0.03) more than those who used passive modes and 20% (p=0.002) more than those who walked. Children who used passive modes or walked at baseline and bicycled to school at 6 years later increased their fitness 14% (p=0.001) more than those who remained using passive modes or walking at follow-up.

    CONCLUSIONS: Implementing initiatives that encourage bicycling to school may be a useful strategy to increase cardiorespiratory fitness of children.

  • 31.
    Danielsson-Tham, Marie-Louise
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Lura rötmånaden!1995In: SLU just nu! – Personaltidning för Sveriges lantbruksuniversitet, ISSN 1102-0954, no 5, p. 20-20Article in journal (Other (popular science, discussion, etc.))
    Abstract [sv]

    Tiden mellan den 22 juli och 23 augusti benämns i folkmun rötmånaden. Denna månad är känd för allehanda ruskigheter. Då föds kalvar med två huvuden, såren vill inte läka och mjölken surnar.

  • 32.
    Danielsson-Tham, Marie-Louise
    et al.
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala.
    Bannerman, Elisabeth
    Institut Pasteur, Paris, France.
    Bille, Jacques
    Lausanne, Switzerland.
    Ericsson, Henrik
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala.
    Jacquet, Christine
    Institut Pasteur, Paris, France.
    Loncarevic, Semir
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala.
    Rocourt, Jocelyne
    Institut Pasteur, Paris, France.
    Tham, Wilhelm
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala.
    Ursing, Jan
    Malmö Allmänna Sjukhus, Malmö, Sweden.
    The characterization of Swedish human Listeria monocygtogenes strains isolated 1958–19941995In: Proceedings of the XII International Symposium on Problems of Listeriosis, Canning Bridge: Promaco Conventions , 1995, p. 469-469Conference paper (Refereed)
  • 33.
    De Bruyne, Bernard
    et al.
    Cardiovasc Ctr Aalst, Onze Lieve Vrouw Hosp, Aalst, Belgium.
    Fearon, William F.
    Med Ctr, Stanford Univ, Stanford CA, USA.; Palo Alto Vet Affairs Hlth Care Syst, Stanford CA USA.
    Pijls, Nico H. J.
    Dept Cardiol, Catharina Hosp, Eindhoven, Netherlands; Dept Biomed Engn, Eindhoven Univ Technol, Eindhoven, Netherlands.
    Barbato, Emanuele
    Cardiovasc Ctr Aalst, Onze Lieve Vrouw Hosp, Aalst, Belgium.
    Tonino, Pim
    Dept Cardiol, Catharina Hosp, Eindhoven, Netherlands; Dept Biomed Engn, Eindhoven Univ Technol, Eindhoven, Netherlands.
    Piroth, Zsolt
    Hungarian Inst Cardiol, Budapest, Hungary.
    Jagic, Nikola
    Clin Ctr Kragujevac, Kragujeva, Serbia.
    Mobius-Winckler, Sven
    Heart Ctr Leipzig, Leipzig, Germany.
    Rioufol, Gilles
    Cardiovasc Hosp, Lyon, France.
    Witt, Nils
    Södersjukhuset, Karolinska Inst, Stockholm, Sweden.
    Kala, Petr
    Univ Hosp, Brno, Czech Republic.
    MacCarthy, Philip
    Kings Coll Hosp, London, England.
    Engstroem, Thomas
    Rigshosp, Univ Copenhagen Hosp,Copenhagen, Denmark.
    Oldroyd, Keith
    Golden Jubilee Natl Hosp, Glasgow, Scotland.
    Mavromatis, Kreton
    Atlanta Vet Affairs Med Ctr, Decatur GA USA.
    Manoharan, Ganesh
    Royal Victoria Hosp, Belfast, North Ireland.
    Verlee, Peter
    Eastern Maine Med Ctr, Bangor, Wales.
    Fröbert, Ole
    Örebro University Hospital.
    Curzen, Nick
    Southampton Univ Hosp NHS Trust, Southampton, England.
    Johnson, Jane B.
    St Jude Med, St Paul MN, USA.
    Limacher, Andreas
    Inst Social & Prevent Med, Univ Bern, Bern, Switzerland; Dept Clin Res, Clin Trials Unit, Univ Bern, Bern, Switzerland.
    Nueesch, Eveline
    Inst Social & Prevent Med, Univ Bern, Bern, Switzerland; Dept Clin Res, Clin Trials Unit, Univ Bern, Bern, Switzerland.
    Jueni, Peter
    Inst Social & Prevent Med, Univ Bern, Bern, Switzerland; Dept Clin Res, Clin Trials Unit, Univ Bern, Bern, Switzerland.
    Fractional Flow Reserve-Guided PCI for Stable Coronary Artery Disease2014In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 371, no 13, p. 1208-1217Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We hypothesized that in patients with stable coronary artery disease and stenosis, percutaneous coronary intervention (PCI) performed on the basis of the fractional flow reserve (FFR) would be superior to medical therapy.

    METHODS: In 1220 patients with stable coronary artery disease, we assessed the FFR in all stenoses that were visible on angiography. Patients who had at least one stenosis with an FFR of 0.80 or less were randomly assigned to undergo FFR-guided PCI plus medical therapy or to receive medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy alone and were included in a registry. The primary end point was a composite of death from any cause, nonfatal myocardial infarction, or urgent revascularization within 2 years.

    RESULTS: The rate of the primary end point was significantly lower in the PCI group than in the medical-therapy group (8.1% vs. 19.5%; hazard ratio, 0.39; 95% confidence interval [CI], 0.26 to 0.57; P<0.001). This reduction was driven by a lower rate of urgent revascularization in the PCI group (4.0% vs. 16.3%; hazard ratio, 0.23; 95% CI, 0.14 to 0.38; P<0.001), with no significant between-group differences in the rates of death and myocardial infarction. Urgent revascularizations that were triggered by myocardial infarction or ischemic changes on electrocardiography were less frequent in the PCI group (3.4% vs. 7.0%, P = 0.01). In a landmark analysis, the rate of death or myocardial infarction from 8 days to 2 years was lower in the PCI group than in the medical-therapy group (4.6% vs. 8.0%, P = 0.04). Among registry patients, the rate of the primary end point was 9.0% at 2 years.

    CONCLUSIONS: In patients with stable coronary artery disease, FFR-guided PCI, as compared with medical therapy alone, improved the outcome. Patients without ischemia had a favorable outcome with medical therapy alone.

  • 34.
    De Bruyne, Bernard
    et al.
    Onze-Lieve-Vrouw Clinic, Cardiovascular Center Aalst, Aalst, Belgium .
    Fröbert, Ole
    Örebro University Hospital, Region Örebro län, Örebro, Sweden.
    Fearon, William F.
    Stanford University Medical Center, Stanford CA, USA.
    Fractional Flow Reserve-Guided PCI versus Medical Therapy in Stable Coronary Disease2012In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 367, no 11, p. 991-1001Article in journal (Refereed)
    Abstract [en]

    Background: The preferred initial treatment for patients with stable coronary artery disease is the best available medical therapy. We hypothesized that in patients with functionally significant stenoses, as determined by measurement of fractional flow reserve (FFR), percutaneous coronary intervention (PCI) plus the best available medical therapy would be superior to the best available medical therapy alone.

    Methods: In patients with stable coronary artery disease for whom PCI was being considered, we assessed all stenoses by measuring FFR. Patients in whom at least one stenosis was functionally significant (FFR, ≤0.80) were randomly assigned to FFR-guided PCI plus the best available medical therapy (PCI group) or the best available medical therapy alone (medical-therapy group). Patients in whom all stenoses had an FFR of more than 0.80 were entered into a registry and received the best available medical therapy. The primary end point was a composite of death, myocardial infarction, or urgent revascularization.

    Results: Recruitment was halted prematurely after enrollment of 1220 patients (888 who underwent randomization and 332 enrolled in the registry) because of a significant between-group difference in the percentage of patients who had a primary endpoint event: 4.3% in the PCI group and 12.7% in the medical-therapy group (hazard ratio with PCI, 0.32; 95% confidence interval [CI], 0.19 to 0.53; P<0.001). The difference was driven by a lower rate of urgent revascularization in the PCI group than in the medical-therapy group (1.6% vs. 11.1%; hazard ratio, 0.13; 95% CI, 0.06 to 0.30; P<0.001); in particular, in the PCI group, fewer urgent revascularizations were triggered by a myocardial infarction or evidence of ischemia on electrocardiography (hazard ratio, 0.13; 95% CI, 0.04 to 0.43; P<0.001). Among patients in the registry, 3.0% had a primary end-point event.

    Conclusions: In patients with stable coronary artery disease and functionally significant stenoses, FFR-guided PCI plus the best available medical therapy, as compared with the best available medical therapy alone, decreased the need for urgent revascularization. In patients without ischemia, the outcome appeared to be favorable with the best available medical therapy alone. (Funded by St. Jude Medical; ClinicalTrials.gov number, NCT01132495.)

  • 35.
    Elwin, Marie
    Örebro University, School of Medical Sciences.
    Description and measurement of sensory symptoms in autism spectrum2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Unusual responses to sensory stimuli have been reported in nearly all children with autism spectrum conditions (ASC). A few studies on adults indicate that the sensory and perceptual problems persist into adulthood. Sensory symptoms have not been included in the diagnostic criteria for ASC but in the new diagnostic manual (DSM-5, 2013) hyper- or hyporeactivity or unusual sensory interests were included in the diagnostic criteria for ASC. Sensory phenomena are mostly investigated in studies involving children and the scales used to measure sensory reactivity have been constructed on the basis of the scientific literature and parents’ reports. The experiences of adults with ASC are not well understood and have not been systematically used to develop measures.

    The overall aim of the thesis was to capture the first-hand experiences of and perspectives on sensory reactivity and translate them into a self-rating scale. To fulfil this overarching aim the personal sensory experiences of adults with ASC were investigated and the variations and range of atypical sensory phenomena explored and described in two qualitative studies (study I and II). The analyses of the firstperson descriptions enabled the development of items for a scale. These were reduced in steps and the final scale which was named the Sensory Reactivity in Autism Spectrum scale (SR-AS) comprised 32 items in four subscales: high awareness/ hyperreactivity, low awareness/hyporeactivity, strong sensory interests and sensory/motor. The SR-AS was validated using content and factor analyses. Its discriminative validity was then investigated as well as its reliability in the form of internal consistency (study III). In the final step the scale was used to identify clusters of atypical sensory functioning in adults with ASC by hierarchical cluster analysis (study IV). Three different sensory clusters were found.

    The main contribution of this thesis is its presentation of individual experience and perspectives and the creation of an clinical tool to measure atypical sensory reactivity frequently experienced by people with ASC. The ways in which the SR-AS can be used comprise assessment of individual sensory patterns for self-knowledge and awareness, to enable the development of coping strategies and to provide information on environmental adjustments required. In diagnostic processes where other criteria for ASC are fulfilled the SR-AS can be used for assessing sensory symptoms according to the DSM-5.

    List of papers
    1. Autobiographical Accounts of Sensing in Asperger Syndrome and High-Functioning Autism
    Open this publication in new window or tab >>Autobiographical Accounts of Sensing in Asperger Syndrome and High-Functioning Autism
    2012 (English)In: Archives of Psychiatric Nursing, ISSN 0883-9417, E-ISSN 1532-8228, Vol. 26, no 5, p. 420-429Article in journal (Refereed) Published
    Abstract [en]

    Sensory experiences in Asperger syndrome (AS) or high-functioning autism (HFA) were explored by qualitative content analysis of autobiographical texts by persons with AS/HFA. Predetermined categories of hyper- and hyposensitivity were applied to texts. Hypersensitivity consists of strong reactions and heightened apprehension in reaction to external stimuli, sometimes together with overfocused or unselective attention. It was common in vision, hearing, and touch. In contrast, hyposensitivity was frequent in reaction to internal and body stimuli such as interoception, proprioception, and pain. It consists of less registration, discrimination, and recognition of stimuli as well as cravings for specific stimuli. Awareness of the strong impact of sensitivity is essential for creating good environments and encounters in the context of psychiatric and other health care.

    Place, publisher, year, edition, pages
    Philadelphia, USA: Elsevier, 2012
    National Category
    General Practice
    Research subject
    Medicine
    Identifiers
    urn:nbn:se:oru:diva-49474 (URN)10.1016/j.apnu.2011.10.003 (DOI)000309437700011 ()22999038 (PubMedID)2-s2.0-84866446577 (Scopus ID)
    Available from: 2016-03-29 Created: 2016-03-24 Last updated: 2018-05-14Bibliographically approved
    2. Too much or too little: hyper- and hypo-reactivity in high-functioning autism spectrum conditions
    Open this publication in new window or tab >>Too much or too little: hyper- and hypo-reactivity in high-functioning autism spectrum conditions
    2013 (English)In: Journal of Intellectual & Developmental Disability, ISSN 1366-8250, E-ISSN 1469-9532, Vol. 38, no 3, p. 232-241Article in journal (Refereed) Published
    Abstract [en]

    Background: Sensory reactivity in people with autism spectrum conditions (ASC) has been found to differ in comparison to reactivity in people without ASC. In this study sensory experiences of high-functioning individuals with ASC were explored and described.

    Method: Interview data from 15 participants with a diagnosis of ASC were analysed by content analysis.

    Results: Seven aspects of sensory experiences were identified: Being hyper- and hypo-reactive, reacting to general overload, having strong stimuli preferences, managing attentiveness to stimuli, managing sensory/motor stimuli, and dealing with consequences of sensory reactions in daily life.

    Conclusions: The categorisation of sensory reactivity in this study can guide clinicians on how to pose questions about sensory issues to individuals with ASC. The assessment of spectrum-specific sensory experiences in high-functioning ASC and their association with other social and nonsocial features of ASC are goals for further research.

    Place, publisher, year, edition, pages
    Taylor & Francis, 2013
    Keywords
    Autism spectrum disorder, sensory reactivity, qualitative research
    National Category
    Nursing
    Research subject
    Occupational therapy; Caring sciences
    Identifiers
    urn:nbn:se:oru:diva-30899 (URN)10.3109/13668250.2013.815694 (DOI)000323729700005 ()23984882 (PubMedID)2-s2.0-84883442689 (Scopus ID)
    Available from: 2013-09-26 Created: 2013-09-20 Last updated: 2018-05-21Bibliographically approved
    3. Development and pilot validation of a sensory reactivity scale for adults with high functioning autism spectrum conditions: Sensory Reactivity in Autism Spectrum (SR-AS)
    Open this publication in new window or tab >>Development and pilot validation of a sensory reactivity scale for adults with high functioning autism spectrum conditions: Sensory Reactivity in Autism Spectrum (SR-AS)
    2016 (English)In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 70, no 2, p. 103-110Article in journal (Refereed) Published
    Abstract [en]

    Background: Unusual reactions to sensory stimuli are experienced by 90-95% of people with an autism spectrum condition (ASC). Self-reported sensory reactivity in ASC has mainly been measured with generic questionnaires developed and validated on data from the general population. Interest in sensory reactivity in ASC increased after the inclusion of hyper- and hypo-reactivity together with unusual sensory interest as diagnostic markers of ASC in the DSM-5.

    Aims: To develop and pilot validate a self-report questionnaire designed from first-hand descriptions of the target group of adults diagnosed with high functioning ASC. Psychometric properties of the questionnaire were evaluated on a sample of participants with ASC diagnoses (N = 71) and a random sample from the general population (N = 162).

    Results: The Sensory Reactivity in Autism Spectrum (SR-AS is intended to be used as a screening tool in diagnostic processes with adults and for support in adapting compensating strategies and environmental adjustments. The internal consistency was high for both the SR-AS and its subscales. The total scale Cronbach's alpha was 0.96 and the subscales alphas were 0.80. Confirmatory factor analysis (CFA) showed best fit for a four-factor model of inter-correlated factors: hyper and hypo-reactivity, strong sensory interest and a sensory/motor factor. The questionnaire discriminated well between ASC-diagnosed participants and participants from the general population.

    Conclusions: The SR-AS displayed good internal consistency and discriminatory power and promising factorial validity.

    Place, publisher, year, edition, pages
    Taylor & Francis, 2016
    Keywords
    Autism spectrum, Psychometric validation, Scale development, Sensory reactivity
    National Category
    Psychiatry
    Research subject
    Psychiatry
    Identifiers
    urn:nbn:se:oru:diva-47286 (URN)10.3109/08039488.2015.1053984 (DOI)000366184300004 ()26158770 (PubMedID)2-s2.0-84949437448 (Scopus ID)
    Note

    Funding Agencies:

    Research Committee of Örebro County Council

    Uppsala-Örebro Regional Research Council

    Available from: 2016-01-07 Created: 2016-01-04 Last updated: 2017-12-01Bibliographically approved
    4. Sensory clusters of adults with and without autism spectrum conditions
    Open this publication in new window or tab >>Sensory clusters of adults with and without autism spectrum conditions
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    General Practice
    Research subject
    Medicine
    Identifiers
    urn:nbn:se:oru:diva-49580 (URN)
    Available from: 2016-03-29 Created: 2016-03-29 Last updated: 2018-01-10Bibliographically approved
  • 36.
    Elwin, Marie
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Psychiatric Research centre, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Ek, Lena
    Department of Psychology, Stockholm University, Sweden.
    Schröder, Agneta
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Psychiatric Research centre, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Kjellin, Lars
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Psychiatric Research centre, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Autobiographical Accounts of Sensing in Asperger Syndrome and High-Functioning Autism2012In: Archives of Psychiatric Nursing, ISSN 0883-9417, E-ISSN 1532-8228, Vol. 26, no 5, p. 420-429Article in journal (Refereed)
    Abstract [en]

    Sensory experiences in Asperger syndrome (AS) or high-functioning autism (HFA) were explored by qualitative content analysis of autobiographical texts by persons with AS/HFA. Predetermined categories of hyper- and hyposensitivity were applied to texts. Hypersensitivity consists of strong reactions and heightened apprehension in reaction to external stimuli, sometimes together with overfocused or unselective attention. It was common in vision, hearing, and touch. In contrast, hyposensitivity was frequent in reaction to internal and body stimuli such as interoception, proprioception, and pain. It consists of less registration, discrimination, and recognition of stimuli as well as cravings for specific stimuli. Awareness of the strong impact of sensitivity is essential for creating good environments and encounters in the context of psychiatric and other health care.

  • 37.
    Elwin, Marie
    et al.
    Örebro University, School of Health Sciences.
    Schröder, Agneta
    Örebro University, School of Health Sciences.
    Ek, Lena
    Department of Psychology, Lund University, Lund, Sweden.
    Wallsten, Tuula
    Centre for Clinical Research, Uppsala University, the County Hospital, Västerås, Sweden.
    Kjellin, Lars
    Örebro University, School of Health Sciences.
    Sensory clusters of adults with and without autism spectrum conditionsManuscript (preprint) (Other academic)
  • 38.
    Emilsson, Louise
    et al.
    Örebro University, School of Medicine, Örebro University, Sweden. Primary Care Res Unit, Värmlands Nysäter, Värmland County Council, Sweden.
    James, Stefan
    Department of Medical Sciences, Cardiology and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Ludvigsson, Jonas F.
    Örebro University Hospital. Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Ischaemic heart disease in first-degree relatives to coeliac patients2014In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 44, no 4, p. 359-364Article in journal (Refereed)
    Abstract [en]

    Objective: Coeliac disease (CD) has been linked to an increased risk of ischaemic heart disease (IHD). We examined the risk of IHD in first-degree relatives and spouses to coeliac patients to ascertain the genetic contribution to IHD excess risk.

    Study design and setting: Coeliac disease was defined as having a biopsy-verified villous atrophy (Marsh grade 3) in 1969-2008 (n=29096). Coeliac patients were matched to 144522 controls. Through Swedish registers, we identified all first-degree relatives and spouses to coeliac patients and their controls, in total 87622 unique coeliac relatives and 432655 unique control relatives. Our main outcome measure was IHD defined according to relevant international classification of disease codes in the Swedish Inpatient Registry or in the Cause of Death Registry. Hazard ratios (HR) and confidence intervals (CI) were estimated through Cox regression adjusted for sex, age-group and calendar year at study entry of the relative.

    Result: During a median follow-up of 108 years, 2880 coeliac relatives and 13817 control relatives experienced IHD. First-degree relatives of coeliac patients were at increased risk of IHD (HR=105; 95% CI=100-109, P-value=004), while spouses were at no increased risk (HR=099; 95% CI=087-112). The excess risk of IHD in coeliac first-degree relatives aged 40-59years was 70/100000 person-years.

    Conclusion: First-degree relatives to coeliac patients seem to be at an increased risk of IHD but the excess risk is so small that it has little clinical relevance.

  • 39.
    Ericsson, Henrik
    et al.
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala.
    Danielsson-Tham, Marie-Louise
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala.
    Tham, Wilhelm
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala.
    Listeria monocytogenes serovar 4b strains divided into two groups using polymerase chain reaction (PCR) and restriction enzyme analysis (REA)1995In: Proceedings of the XII Interenational Symposium on Problems of Listeriosis, Canning Bridge: Promaco Conventions , 1995, p. 421-421Conference paper (Refereed)
  • 40.
    Eriksson, Carl
    Örebro University, School of Medical Sciences.
    Epidemiological and therapeutic aspects of Inflammatory Bowel Disease2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Introduction: The two main forms of inflammatory bowel disease (IBD) are Crohn’s disease and ulcerative colitis. These are chronic inflammatory disorders, mainly affecting the gastrointestinal tract.

    Aims: The overall aims of this thesis were to study the epidemiology of ulcerative colitis in Örebro, Sweden; to examine certain aspects of anaemia in IBD; and to determine the clinical effectiveness of medical treatments.

    Material and methods: Cohort studies with the sampling frame defined by the geographic boundaries of the primary catchment area of Örebro University Hospital (Papers I‒III), or by the entire IBD population in Sweden registered in the Swedish national quality registry for IBD (SWIBREG; paper IV), were performed to determine the epidemiology of ulcerative colitis, the incidence and prevalence of anaemia in IBD, and the clinical effectiveness of thiopurine drugs and vedolizumab in routine care.

    Results: A fivefold increase in the incidence and a tenfold increase in the prevalence of ulcerative colitis was observed in Örebro during the past 50 years. In parallel, the prognosis, in terms of risk for colectomy within 10 years from diagnosis, improved during the same time period. Earlier and more widespread use of thiopurine drugs may have contributed to the decrease in colectomies. Anaemia is common in IBD, particularly in Crohn’s disease. Vedolizumab, a new drug targeting leucocyte migration to the gut, appears to be well tolerated and effective in Swedish real-world IBD care.

    Conclusion: Ulcerative colitis is on the rise, and data from Örebro indicate that the number of IBD patients in Sweden already exceeds 70,000. Improved knowledge of long-term outcomes of medical therapy may have far-reaching implications for future IBD management.

    List of papers
    1. Changes in medical management and colectomy rates: a population-based cohort study on the epidemiology and natural history of ulcerative colitis in Orebro, Sweden, 1963-2010
    Open this publication in new window or tab >>Changes in medical management and colectomy rates: a population-based cohort study on the epidemiology and natural history of ulcerative colitis in Orebro, Sweden, 1963-2010
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    2017 (English)In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 46, no 8, p. 748-757Article in journal (Refereed) Published
    Abstract [en]

    Background: Whether the epidemiology of ulcerative colitis (UC) has changed during recent decades is partly unknown.

    Aim: To depict temporal trends in the epidemiology and medical treatment of UC as well as the long-term risk of progression in disease extent and colectomy, during 1963-2010.

    Methods: Patients were identified by evaluation of all medical records in the archive of the Colitis Clinic, Orebro University Hospital. Comparisons were made between three time periods, 1963-1975, 1976-1990 and 1991-2005.

    Results: The annual age-standardised incidence increased from 3.5 to 18.5 per 100 000 during the study period (P < .01). Correspondingly, the prevalence increased from 44 to 474 per 100 000 between 1965 and 2010. A higher proportion of males than females had extensive colitis at diagnosis (odds ratio: 1.55; 95% CI 1.17-2.05; P < .01). The risk for progression in disease extent was 34.5% and 18.5% at 10 years, for patients with proctitis and left-sided colitis, respectively (P < .01). The use of 5-aminosalicylates, within 10 years, rise from 79% to 92% between 1963-1975 and 1976-1990 (P < .01). Thiopurine use increased from 7% in 1976-1990 to 34% during 1991-2005 (P < .01). The colectomy rate at 10 years was 13.5% (95% CI 11.1%-15.8%), and the risk was lower among patients diagnosed in 1991-2005 compared to 1963-1975 (adjusted hazard ratio: 0.61; 95% CI 0.39-0.94; P = .02).

    Conclusion: The incidence and prevalence of UC increased over time, and the observed prevalence in 2010 is among the highest reported. In parallel, a decrease in colectomy rates was observed during the most recent decades, potentially reflecting improved medical treatment.

    Place, publisher, year, edition, pages
    Hoboken, USA: John Wiley & Sons, 2017
    National Category
    Gastroenterology and Hepatology
    Identifiers
    urn:nbn:se:oru:diva-61349 (URN)10.1111/apt.14268 (DOI)000411717800005 ()28833287 (PubMedID)2-s2.0-85029232492 (Scopus ID)
    Note

    Funding Agency:

    Swedish Government's Agreement for Medical Training and Research  OLL-549221

    Available from: 2017-10-09 Created: 2017-10-09 Last updated: 2018-07-19Bibliographically approved
    2. Incidence, prevalence, and clinical outcome of anaemia in inflammatory bowel disease: A population-based cohort study
    Open this publication in new window or tab >>Incidence, prevalence, and clinical outcome of anaemia in inflammatory bowel disease: A population-based cohort study
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    General Practice
    Identifiers
    urn:nbn:se:oru:diva-66679 (URN)
    Available from: 2018-04-19 Created: 2018-04-19 Last updated: 2018-04-19Bibliographically approved
    3. Impact of thiopurines on the natural history and surgical outcome of ulcerative colitis: a cohort study
    Open this publication in new window or tab >>Impact of thiopurines on the natural history and surgical outcome of ulcerative colitis: a cohort study
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    2018 (English)In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, article id gutjnl-2017-315521Article in journal (Refereed) Epub ahead of print
    Abstract [en]

    OBJECTIVE: Thiopurines are used as maintenance therapy in ulcerative colitis (UC), but whether these drugs influence the natural history of the disease is unknown. We aimed to assess the effect of thiopurines in terms of colectomy, hospital admission, progression in disease extent and anti-tumour necrosis factor (TNF) therapy within 10 years from initiation.

    DESIGN: Patients diagnosed with UC within the Örebro University Hospital catchment area, during 1963-2010, who initiated thiopurines (n=253) were included. To overcome the risk of confounding by indication, we compared patients who stopped treatment within 12 months because of an adverse reaction (n=76) with patients who continued therapy or discontinued due to other reasons (n=177) and assessed long-term outcomes using Cox regression with adjustment for potential confounding factors.

    RESULTS: The cumulative probability of colectomy within 10 years was 19.5% in tolerant patients compared with 29.0% in intolerant (adjusted HR 0.49; 95% CI 0.21 to 0.73). The probability of hospital admission was 34.0% in tolerant versus 56.2% in intolerant patients (adjusted HR 0.36; 95% CI 0.23 to 0.56). The risk for progression in disease extent was 20.4% in tolerant patients compared with 48.8% in intolerant (adjusted HR 0.47; 95% CI 0.21 to 1.06). Within 10 years, 16.1% of tolerant and 27.5% of intolerant patients received anti-TNF therapy (adjusted HR 0.49; 95% CI 0.26 to 0.92).

    CONCLUSION: Based on the novel approach of comparing patients tolerant and intolerant to thiopurines, we reveal that thiopurines have a profound beneficial impact of the natural history and long-term colectomy rates of UC.

    Place, publisher, year, edition, pages
    BMJ Publishing Group Ltd, 2018
    Keywords
    6-mercaptopurine, azathioprine, chronic ulcerative colitis, tnf-alpha
    National Category
    Medical and Health Sciences Gastroenterology and Hepatology
    Identifiers
    urn:nbn:se:oru:diva-66417 (URN)10.1136/gutjnl-2017-315521 (DOI)29618498 (PubMedID)
    Available from: 2018-04-09 Created: 2018-04-09 Last updated: 2018-07-19Bibliographically approved
    4. Long-term effectiveness of vedolizumab in inflammatory bowel disease: a national study based on the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG)
    Open this publication in new window or tab >>Long-term effectiveness of vedolizumab in inflammatory bowel disease: a national study based on the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG)
    Show others...
    2017 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 6-7, p. 722-729Article in journal (Refereed) Published
    Abstract [en]

    Objectives: Clinical trials have demonstrated the efficacy of vedolizumab in inflammatory bowel disease (IBD). However, these findings may not reflect the clinical practice. Therefore, we aimed to describe a vedolizumab-treated patient population and assess long-term effectiveness.

    Materials and methods: Patients initiating vedolizumab between 1 June 2014 and 30 May 2015 were identified through the Swedish National Quality Registry for IBD. Prospectively collected data on treatment and disease activity were extracted. Clinical remission was defined as Patient Harvey Bradshaw index<5 in Crohn's disease (CD) and Patient Simple Clinical Colitis Activity index<3 in ulcerative colitis (UC).

    Results: Two-hundred forty-six patients (147CD, 92 UC and 7 IBD-Unclassified) were included. On study entry, 86% had failed TNF-antagonist and 48% of the CD patients had undergone1 surgical resection. After a median follow-up of 17 (IQR: 14-20) months, 142 (58%) patients remained on vedolizumab. In total, 54% of the CD- and 64% of the UC patients were in clinical remission at the end of follow-up, with the clinical activity decreasing (p<.0001 in both groups). Faecal-calprotectin decreased in CD (p<.0001) and in UC (p=.001), whereas CRP decreased in CD (p=.002) but not in UC (p=.11). Previous anti-TNF exposure (adjusted HR: 4.03; 95% CI: 0.96-16.75) and elevated CRP at baseline (adjusted HR: 2.22; 95% CI: 1.10-4.35) seemed to be associated with discontinuation because of lack of response. Female sex was associated with termination because of intolerance (adjusted HR: 2.75; 95% CI: 1.16-6.48).

    Conclusion: Vedolizumab-treated patients represent a treatment-refractory group. A long-term effect can be achieved, even beyond 1 year of treatment.

    Place, publisher, year, edition, pages
    Taylor & Francis, 2017
    Keywords
    Vedolizumab, clinical practice, inflammatory bowel disease, Crohn's disease, ulcerative colitis
    National Category
    Gastroenterology and Hepatology
    Identifiers
    urn:nbn:se:oru:diva-57787 (URN)10.1080/00365521.2017.1304987 (DOI)000399808100018 ()28362144 (PubMedID)2-s2.0-85018512957 (Scopus ID)
    Note

    Funding Agencies:

    Swedish Government  OLL-549221  OLL-526131  ALFSKANE-539811 

    Hedlund Foundation  

    Österlund Foundation  

    Available from: 2017-05-23 Created: 2017-05-23 Last updated: 2018-04-19Bibliographically approved
  • 41.
    Eriksson, Carl
    et al.
    Örebro University, School of Medical Sciences.
    Henriksson, Ida
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Brus, Ole
    Örebro University, School of Medical Sciences.
    Zhulina, Yaroslava
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Nyhlin, Nils
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Tysk, Curt
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Karolinska Institutet, Stockholm, Sweden; University College London, London, United Kingdom.
    Incidence, prevalence, and clinical outcome of anaemia in inflammatory bowel disease: A population-based cohort studyManuscript (preprint) (Other academic)
  • 42.
    Fang, Fang
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Fall, Katja
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Valdimarsdottir, Unnur
    Center of Public Health Sciences, University of Iceland, Reykjavík, Iceland.
    Suicide and Cardiovascular Death after a Cancer Diagnosis REPLY2012In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 367, no 3, p. 277-277Article in journal (Refereed)
  • 43.
    Fang, Xin
    et al.
    Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Li, Runkui
    College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, China; State Key Laboratory of Resources and Environmental Information System, Institute of Geographic Sciences and Natural Resources Research, Chinese Academy of Sciences, Beijing, China.
    Kan, Haidong
    Key Laboratory of Public Health Safety of the Ministry of Education and Key Laboratory of Health Technology Assessment of the Ministry of Health, School of Public Health, Fudan University, Shanghai, China; Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention (LAP 3 ), Fudan University, Shanghai, China.
    Bottai, Matteo
    Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Fang, Fang
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Cao, Yang
    Örebro University, School of Medical Sciences. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Clinical Epidemiology and Biostatistics, Örebro University, Örebro, Sweden.
    Bayesian model averaging method for evaluating associations between air pollution and respiratory mortality: a time-series study2016In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 6, no 8, article id e011487Article in journal (Refereed)
    Abstract [en]

    Objective: To demonstrate an application of Bayesian model averaging (BMA) with generalised additive mixed models (GAMM) and provide a novel modelling technique to assess the association between inhalable coarse particles (PM10) and respiratory mortality in time-series studies.

    Design: A time-series study using regional death registry between 2009 and 2010.

    Setting: 8 districts in a large metropolitan area in Northern China.

    Participants: 9559 permanent residents of the 8 districts who died of respiratory diseases between 2009 and 2010.

    Main outcome measures: Per cent increase in daily respiratory mortality rate (MR) per interquartile range (IQR) increase of PM10 concentration and corresponding 95% confidence interval (CI) in single-pollutant and multipollutant (including NOx, CO) models.

    Results: The Bayesian model averaged GAMM (GAMM+ BMA) and the optimal GAMM of PM10, multipollutants and principal components (PCs) of multipollutants showed comparable results for the effect of PM10 on daily respiratory MR, that is, one IQR increase in PM10 concentration corresponded to 1.38% vs 1.39%, 1.81% vs 1.83% and 0.87% vs 0.88% increase, respectively, in daily respiratory MR. However, GAMM+ BMA gave slightly but noticeable wider CIs for the single-pollutant model (-1.09 to 4.28 vs -1.08 to 3.93) and the PCs-based model (-2.23 to 4.07 vs -2.03 vs 3.88). The CIs of the multiple-pollutant model from two methods are similar, that is, -1.12 to 4.85 versus -1.11 versus 4.83.

    Conclusions: The BMA method may represent a useful tool for modelling uncertainty in time-series studies when evaluating the effect of air pollution on fatal health outcomes.

  • 44.
    Fazel, Seena
    et al.
    Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.
    Zetterqvist, Johan
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Henrik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Långström, Niklas
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Antipsychotics, mood stabilisers, and risk of violent crime2014In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 384, no 9949, p. 1206-1214Article in journal (Refereed)
    Abstract [en]

    Background: Antipsychotics and mood stabilisers are prescribed widely to patients with psychiatric disorders worldwide. Despite clear evidence for their efficacy in relapse prevention and symptom relief, their effect on some adverse outcomes, including the perpetration of violent crime, is unclear. We aimed to establish the effect of antipsychotics and mood stabilisers on the rate of violent crime committed by patients with psychiatric disorders in Sweden.

    Methods: We used linked Swedish national registers to study 82,647 patients who were prescribed antipsychotics or mood stabilisers, their psychiatric diagnoses, and subsequent criminal convictions in 2006-09. We did within-individual analyses to compare the rate of violent criminality during the time that patients were prescribed these medications versus the rate for the same patients while they were not receiving the drugs to adjust for all confounders that remained constant within each participant during follow-up. The primary outcome was the occurrence of violent crime, according to Sweden's national crime register.

    Findings: In 2006-09, 40,937 men in Sweden were prescribed antipsychotics or mood stabilisers, of whom 2657 (6·5%) were convicted of a violent crime during the study period. In the same period, 41,710 women were prescribed these drugs, of whom 604 (1·4 %) had convictions for violent crime. Compared with periods when participants were not on medication, violent crime fell by 45% in patients receiving antipsychotics (hazard ratio [HR] 0·55, 95% CI 0·47-0·64) and by 24% in patients prescribed mood stabilisers (0·76, 0·62-0·93). However, we identified potentially important differences by diagnosis-mood stabilisers were associated with a reduced rate of violent crime only in patients with bipolar disorder. The rate of violence reduction for antipsychotics remained between 22% and 29% in sensitivity analyses that used different outcomes (any crime, drug-related crime, less severe crime, and violent arrest), and was stronger in patients who were prescribed higher drug doses than in those prescribed low doses. Notable reductions in violent crime were also recorded for depot medication (HR adjusted for concomitant oral medications 0·60, 95% CI 0·39-0·92).

    Interpretation: In addition to relapse prevention and psychiatric symptom relief, the benefits of antipsychotics and mood stabilisers might also include reductions in the rates of violent crime. The potential effects of these drugs on violence and crime should be taken into account when treatment options for patients with psychiatric disorders are being considered.

    Funding: The Wellcome Trust, the Swedish Prison and Probation Service, the Swedish Research Council, and the Swedish Research Council for Health, Working Life and Welfare.

  • 45.
    Fengsrud, Espen
    Örebro University, School of Medical Sciences.
    Atrial fibrillation: endoscopic ablation and postoperative studies2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Introduction: Atrial fibrillation (AF) is associated with an increased risk of stroke, heart failure and cardiovascular death. Initial treatment focuses on rhythm or rate control and anticoagulation after risk assessment. Catheter abla-tion (CA) is an option in highly symptomatic patients but is less effective in long-standing persistent AF(LSPAF). Total endoscopic ablation is an alternative, but its clinical role needs further evaluation. In patients undergoing aortocoronary bypass graft (CABG) surgery, up to 9 % present with preoperative AF. One-third experience postoperative AF, which is associated with increased hospital stay, risk of stroke and decreased long-term survival. The long-term effects on heart rhythm have not been studied.

    Methods and Results: 571 patients undergoing CABG from 1999 to 2000 were followed for six years. Postoperative AF was the strongest independent risk factor for late AF and an age-independent risk factor for late mortality. 615 pa-tients from the same cohort, including patients with preoperative AF, were fol-lowed up at 15 years. Death due to cerebral ischaemia, heart failure and sudden death were most common in the pre- and postoperative AF groups. The presence of pre- or postoperative AF was an independent risk factor for late mortality.

    In our first ten patients, total endoscopic ablation of AF using a right-sided unilateral approach was feasible and safe with acceptable results. 36 patients with symptomatic LSPAF were then randomized to total endoscopic ablation or rate control. Loop recorders were implanted in all patients. In the control group, all patients were in permanent AF for 12 months. In the ablation group, 12/15 patients (80%) were in SR without antiarrhythmic drugs at 12 months. Median freedom of AF at 3–12 months was 95%, and 8/15 (53%) had an AF burden of < 5%. Myocardial function, physical working capacity(PWC) and subjective physical and mental health improved.

    Conclusions: Postoperative AF patients have an eightfold increased risk of future AF and a doubled long-term cardiovascular mortality. Both pre- or post-operative AF in CABG patients is a major risk factor for late cardiovascular morbidity and mortality. Total endoscopic ablation of AF is feasible and safe. In patients with LSPAF, it significantly reduced AF burden at 12 months compared with controls. Myocardial function, PWC and subjective physical and mental health improved.