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  • 1.
    Jansson , Agneta
    Linköping University, Department of Clinical and Experimental Medicine, Oncology . Linköping University, Faculty of Health Sciences.
    17Beta-hydroxysteroid dehydrogenase enzymes and breast cancer2009In: JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, ISSN 0960-0760 , Vol. 114, no 1-2, 64-67 p.Article in journal (Refereed)
    Abstract [en]

    Sex steroids play an important role in the development and differentiation in several tissues. Biologically active hormones that are locally converted in endocrine organs in the tissue where they exert their effects without release into extracellular space is a field of endocrinology that has been called intracrinology. In pre-menopausal women the ovary is the main source of estrogens, but in post-menopausal women the estrogen production as main site of synthesis moves to peripheral tissues and almost all of the sex steroids are synthesised from precursors of adrenal origin. In breast cancer 60-80% of the tumors express high levels of oestrogen receptor (ER) alpha which gives estrogen a proliferative effect. Breast tumors tend to have a higher intratumoral estrogen concentration than normal breast tissue and plasma, and in situ synthesis and the metabolism of estrogens is believed to be of great importance for the development and progression of the disease. The activity of estrogen metabolizing enzymes in breast are mainly aromatase, estrone sulfatases and 17HSD enzymes. 17HSD1 and 17HSD2 are the family members known to be of main importance in breast cancer. High expression of 17HSD1 has been associated to poor prognosis in breast cancer and late relapse among patients with ER-positive tumors. One of the mechanisms behind high 17HSD1 expression is gene amplification. Low or absent expression of 17HSD2 is associated to decreased survival in ER-positive breast cancer. 17HSD14 is one of the latest discovered 17HSD enzymes, transfection of 17HSD14 in human breast cancer cells significantly decreased the levels of estradiol in the culture medium. Low expression of 17HSD14 mRNA expression in breast cancer was correlated to decreased survival.

    The understanding of intratumoral synthesis of sex steroids in breast cancer is crucial to understand the disease both in pre- and post-menopausal women. Further studies are desirable to state the direct role of these enzymes in breast cancer and which patients that may benefit from new therapeutic strategies targeting 17HSD enzymes. The new inhibitors targeting 17HSD1 have shown promising results in preclinical studies to have clinical potential in the future.

  • 2.
    Lundberg, Peter
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Department of Biochemistry, University of Sydney, Australia.
    Dudman, Nicholas P.
    Department of Cardiovascular Medicine, Prince Henry Hospital, University of New South Wales, Australia.
    Kuchel, Philip W.
    Department of Biochemistry, University of Sydney, Australia.
    Wilcken, David E. L.
    Present address: Department of Physical Chemistry, University of Umeå, Umeå, Sweden.
    1H NMR determination of urinary betaine in patients with premature vascular disease and mild homocysteinemia1995In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 41, no 2, 275-283 p.Article in journal (Refereed)
    Abstract [en]

    Urinary N,N,N-trimethylglycine (betaine) and N,N-dimethylglycine (DMG) have been identified and quantified for clinical purposes by proton nuclear magnetic resonance (1H NMR) measurement in previous studies. We have assessed these procedures by using both one-dimensional (1-D) and 2-D NMR spectroscopy, together with pH titration of urinary extracts to help assign 1H NMR spectral peaks. The betaine calibration curve linearity was excellent (r = 0.997, P = 0.0001) over the concentration range 0.2-1.2 mmol/L, and CVs for replicate betaine analyses ranged from 7% (n = 10) at the lowest concentration to 1% (n = 9) at the highest. The detection limit for betaine was < 15 mumol/L. Urinary DMG concentrations were substantially lower than those of betaine. Urinary betaine and DMG concentrations measured by 1H NMR spectroscopy from 13 patients with premature vascular disease and 17 normal controls provided clinically pertinent data. We conclude that 1H NMR provides unique advantages as a research tool for determination of urinary betaine and DMG concentrations.

  • 3.
    Jaarsma, Tiny
    et al.
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Arts and Sciences.
    Steinke, Elaine
    Wichita State University, KS, USA .
    20 Things You Didnt Know About Sex and Heart Disease2014In: Journal of Cardiovascular Nursing, ISSN 0889-4655, E-ISSN 1550-5049, Vol. 29, no 3, 207-208 p.Article in journal (Other academic)
  • 4.
    Hallert, Eva
    et al.
    Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Rehabilitation Center. Linköping University, Department of Medical and Health Sciences, Health Technology Assessment and Health Economics.
    Husberg, Magnus
    Linköping University, Department of Medical and Health Sciences, Health Technology Assessment and Health Economics. Linköping University, Faculty of Health Sciences.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    28-joint count disease activity score at 3 months after diagnosis of early rheumatoid arthritis is strongly associated with direct and indirect costs over the following 4 years: the Swedish TIRA project2011In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 50, no 7, 1259-1267 p.Article in journal (Refereed)
    Abstract [en]

    Methods. Three-hundred and twenty patients with early (1 year) RA were assessed at regular intervals. Clinical and laboratory data were collected and patients reported health-care utilization and number of days lost from work. At 3-month follow-up, patients were divided into two groups according to disease activity, using DAS-28 with a cut-off level at 3.2. Direct and indirect costs and EuroQol-5D over the following 4 years were compared between the groups. Multivariate regression models were used to control for possible covariates. Results. Three months after diagnosis, a DAS-28 level of epsilon 3.2 was associated with high direct and indirect costs over the following 4 years. Patients with DAS-28 epsilon 3.2 at 3-month follow-up had more visits to physician, physiotherapist, occupational therapist and nurse, higher drug costs, more days in hospital and more extensive surgery compared with patients with 3-month DAS-28 less than 3.2. Number of days lost from work due to sick leave and permanent work disability was also higher in this group. The effect of disease activity on health-related quality of life was highly significant. In regression models, DAS-28 at 3-month follow-up was significantly associated with costs over the following years. Conclusions. Three months after diagnosis, DAS-28 is an important prognostic marker regarding health-care utilization and costs. Achieving remission or low disease activity 3 months after diagnosis is likely to decrease morbidity, increase quality of life and save costs for the patient and for society over the following years.

  • 5.
    Forsgren, Mikael
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Bengtsson, Ann
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Sören, Birgitta
    Linköping University, Department of Medical and Health Sciences, Physiotherapy. Linköping University, Faculty of Health Sciences.
    Brandejsky, Vaclav
    Depts Clinical Research and Radiology, University Bern, Bern, Switzerland.
    Lund, Eva
    Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    31P MRS as a Potential Biomarker for Fibromyalgia2012In: Proceedings of the 20th Annaal Meeting & Exhibition, 5-11 May, Melbourne, Australia, 2012, 1493-1493 p.Conference paper (Refereed)
    Abstract [en]

    Major clinical symptoms in fibromyalgia (FM) are muscle pain, stiffness and fatigue. Studies have shown reduced voluntary strength and exercise capacity, lower endurance and more muscular pain even at low workload. An impaired muscle energy metabolism has therefore been proposed as a result of the disease. An earlier study using magnetic resonance spectroscopy (MRS) showed that at maximal dynamic and static contractions the concentration of inorganic phosphate was lower in FM [1]. A decrease in ATP, ADP and PCr and an increase in AMP and creatine was found in FM biopsies [2]. The purpose of this study was to non-invasively analyze the quantitative content of  phosphagens in the resting muscle in FM in comparison to healthy controls using 31P MRS of the quadriceps muscle.

  • 6.
    Fredriksson, Alexandru G
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization, CMIV.
    Zajac, Jakub
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization, CMIV.
    Eriksson, Jonatan
    Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Physiology.
    Dyverfeldt, Petter
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Clinical Physiology UHL. Linköping University, Center for Medical Image Science and Visualization, CMIV.
    Bolger, Ann F
    University of California San Francisco.
    Ebbers, Tino
    Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Clinical Physiology UHL. Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics.
    Carlhäll, Carljohan
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Clinical Physiology UHL. Linköping University, Center for Medical Image Science and Visualization, CMIV.
    4-D blood flow in the human right ventricle2011In: American Journal of Physiology. Heart and Circulatory Physiology, ISSN 0363-6135, E-ISSN 1522-1539, Vol. 301, no 6, H2344-H2350 p.Article in journal (Refereed)
    Abstract [en]

    Right ventricular (RV) function is a powerful prognostic indicator in many forms of heart disease, but its assessment remains challenging and inexact. RV dysfunction may alter the normal patterns of RV blood flow, but those patterns have been incompletely characterized. We hypothesized that, based on anatomic differences, the proportions and energetics of RV flow components would differ from those identified in the left ventricle (LV) and that the portion of the RV inflow passing directly to outflow (Direct Flow) would be prepared for effective systolic ejection as a result of preserved kinetic energy (KE) compared with other RV flow components. Three-dimensional, time-resolved phase-contrast velocity, and balanced steady-state free-precession morphological data were acquired in 10 healthy subjects using MRI. A previously validated method was used to separate the RV and LV end-diastolic volumes into four flow components and measure their volume and KE over the cardiac cycle. The RV Direct Flow: 1) followed a smoothly curving route that did not extend into the apical region of the ventricle; 2) had a larger volume and possessed a larger presystolic KE (0.4 +/- 0.3 mJ) than the other flow components (P andlt; 0.001 and P andlt; 0.01, respectively); and 3) represented a larger part of the end-diastolic blood volume compared with the LV Direct Flow (P andlt; 0.01). These findings suggest that diastolic flow patterns distinct to the normal RV create favorable conditions for ensuing systolic ejection of the Direct Flow component. These flow-specific aspects of RV diastolic-systolic coupling provide novel perspectives on RV physiology and may add to the understanding of RV pathophysiology.

  • 7.
    Fredriksson, Alexandru Grigorescu
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Örebrö University Hospital, Örebro, Sweden.
    Svalbring, Emil
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Eriksson, Jonatan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Dyverfeldt, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Faculty of Science & Engineering. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Carlhäll, Carl-Johan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences.
    4D flow MRI can detect subtle right ventricular dysfunction in primary left ventricular disease.2016In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 43, no 3, 558-565 p.Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To investigate whether 4D flow magnetic resonance imaging (MRI) can detect subtle right ventricular (RV) dysfunction in primary left ventricular (LV) disease.

    MATERIALS AND METHODS: 4D flow and morphological 3T MRI data were acquired in 22 patients with mild ischemic heart disease who were stratified into two groups based on LV end-diastolic volume index (EDVI): lower-LVEDVI and higher-LVEDVI, as well as in 11 healthy controls. The RV volume was segmented at end-diastole (ED) and end-systole (ES). Pathlines were emitted from the ED volume and traced forwards and backwards in time to ES. The blood volume was separated into flow components. The Direct Flow (DF) component was defined as RV inflow passing directly to outflow. The kinetic energy (KE) of the DF component was calculated. Echocardiographic conventional RV indices were also assessed.

    RESULTS: The higher-LVEDVI group had larger LVEDVI and lower LV ejection fraction (98 ± 32 ml/m(2) ; 48 ± 13%) compared to the healthy (67 ± 12, P = 0.002; 64 ± 7, P < 0.001) and lower-LVEDI groups (62 ± 10; 68 ± 7, both P < 0.001). The RV 4D flow-specific measures "DF/EDV volume-ratio" and "DF/EDV KE-ratio at ED" were lower in the higher-LVEDVI group (38 ± 5%; 52 ± 6%) compared to the healthy (44 ± 6; 65 ± 7, P = 0.018 and P < 0.001) and lower-LVEDVI groups (44 ± 6; 64 ± 7, P = 0.011 and P < 0.001). There was no difference in any of the conventional MRI and echocardiographic RV indices between the three groups.

    CONCLUSION: We found that in primary LV disease mild impairment of RV function can be detected by 4D flow-specific measures, but not by the conventional MRI and echocardiographic indices. J. Magn. Reson. Imaging 2015.

  • 8.
    Casas Garcia, Belén
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Lantz, Jonas
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Dyverfeldt, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Faculty of Science & Engineering. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    4D Flow MRI-Based Pressure Loss Estimation in Stenotic Flows: Evaluation Using Numerical Simulations2016In: Magnetic Resonance in Medicine, ISSN 0740-3194, E-ISSN 1522-2594, Vol. 75, no 4, 1808-1821 p.Article in journal (Refereed)
    Abstract [en]

    Purpose: To assess how 4D flow MRI-based pressure and energy loss estimates correspond to net transstenotic pressure gradients (TPG(net)) and their dependence on spatial resolution. Methods: Numerical velocity data of stenotic flow were obtained from computational fluid dynamics (CFD) simulations in geometries with varying stenosis degrees, poststenotic diameters and flow rates. MRI measurements were simulated at different spatial resolutions. The simplified and extended Bernoulli equations, Pressure-Poisson equation (PPE), and integration of turbulent kinetic energy (TKE) and viscous dissipation were compared against the true TPG(net). Results: The simplified Bernoulli equation overestimated the true TPG(net) (8.74 +/- 0.67 versus 6.76 +/- 0.54 mmHg). The extended Bernoulli equation performed better (6.57 +/- 0.53 mmHg), although errors remained at low TPG(net). TPG(net) estimations using the PPE were always close to zero. Total TKE and viscous dissipation correlated strongly with TPG(net) for each geometry (r(2) &gt; 0.93) and moderately considering all geometries (r(2) = 0.756 and r(2) = 0.776, respectively). TKE estimates were accurate and minorly impacted by resolution. Viscous dissipation was overall underestimated and resolution dependent. Conclusion: Several parameters overestimate or are not linearly related to TPG(net) and/or depend on spatial resolution. Considering idealized axisymmetric geometries and in absence of noise, TPG(net) was best estimated using the extended Bernoulli equation. (C) 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance.

  • 9.
    Broström, Anders
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Nursing Science.
    Johansson, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Albers, Jan
    City Hospital Ryhov.
    Wiberg, Jan
    City Hospital Ryhov.
    Svanborg, Eva
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Neurophysiology . Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurophysiology UHL.
    Fridlund, Bengt
    Vaxjö University.
    6-month CPAP-treatment in a young male patient with severe obstructive sleep apnoea syndrome - A case study from the couples perspective2008In: European Journal of Cardiovascular Nursing, ISSN 1474-5151, Vol. 7, no 2, 103-112 p.Article in journal (Refereed)
    Abstract [en]

    Background: Obstructive sleep apnoea syndrome (OSAS) is independently associated with an increased risk for hypertension and cardiovascular disease. Continuous positive airway pressure (CPAP) can reduce mortality and morbidity, but low compliance rates are seen. Aim: To explore and describe the experiences of CPAP-treatment in a young male patient with severe OSAS during a 6-month period from the couples perspective.

    Methods and the case: A single case study with a phenomenographic approach was employed. Diagnostic procedures of OSAS and initiation of treatment with Auto-CPAP, humidifier and a nasal mask were performed during 4 visits. Conceptions were collected at 4 different occasions during the 6-month period (before, and 2 weeks, 3 months, and 6 months after treatment initiation) by means of interviews with a 33-year old male patient and his female partner.

    Findings: Totally 17 different structural aspects were found to fluctuate during the 6-month period in relation to; influence of stressors, social reactions and adaptation to increase compliance.

    Conclusion: An increased knowledge about the influence of stressors, the social reactions, and the adaptation can help healthcare personnel to identify and better understand concerns of other patients and spouses during different time phases of the initial 6-month period of CPAP-treatment.

  • 10.
    Almer, Sven
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences.
    Hjortswang, Henrik
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Linköping University, Faculty of Health Sciences.
    Hindorf , U
    Lund University.
    6-Thioguanine therapy in Crohns disease-Observational data in Swedish patients2009In: Digestive and Liver Disease, ISSN 1590-8658, Vol. 41, no 3, 194-200 p.Article in journal (Refereed)
    Abstract [en]

    Background and aims: Adverse events (AE) leading to discontinuation or dose-reduction of thiopurine therapy (TP) occur in 9-28% of patients with inflammatory bowel disease. 6-Thioguanine (6-TG) has been proposed as an alternative treatment in patients intolerant for azathioprine (AZA), but some concerns have been raised about drug safety.

    Methods: We evaluated in a prospective manner the tolerance and efficacy of 6-TG in 23 Crohns disease (CD) patients (13 men, median age 41 (19-65) years) with prior intolerance (n = 18) or resistance (It = 5) to AZA and/or 6-mercaptopurine (6-MP). In addition, eight patients had tried mycophenolate mofetil. Seventeen patients (74%) had undergone intestinal resection, often several times.

    Results: Patients were treated with a median daily dose of 40 mg 6-TG (range 20-60) for 259 (15-2272) days. Seven of 13 patients (54%) with active disease went into remission after 8 (4-26) weeks. Sixteen patients (70%) experienced AE that lead to discontinuation (n=10) after 85 (15-451) days or dose reduction (n=6) after 78 (10-853) days. Ten of 18 patients (56%) with prior TP-intolerance discontinued 6-TG treatment due to AE compared to none of five patients with TP-resistance (p=0.046). Of 13 patients that tolerated 6-TG, eight discontinued the drug due to therapeutic failure (n=5) or safety concerns (n=3). Eight patients (35%) continued treatment beyond 12 months. There was no significant difference in maximum thioguanine nucleotide levels between patients with AE leading to discontinuation/dose reduction and patients without AE, 652 (99-2488) vs. 551 (392-1574) pmol/8 x 10(8) RBC; p=0.80.

    Conclusions: In this cohort of CD patients with severe disease failing traditional thiopurine treatment, a small fraction (22%) had long-term benefit of 6-TG-treatment. 6-TG therapy seems to offer a limited therapeutic gain for patients intolerant to both AZA and 6-MP and other treatment options should be considered.

  • 11. de Boer, NKH
    et al.
    Reinisch, W
    Teml, A
    van Bodegraven, AA
    Schwab, M
    Lukas, M
    Ochsenkuhn, T
    Petritsch, W
    Knoflach, P
    Almer, Sven
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology . Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    van der Merwe, SW
    Herrlinger, KR
    Seiderer, J
    Vogelsang, H
    Mulder, CJJ
    6-thioguanine treatment in inflammatory bowel disease: A critical appraisal by a European 6-TG working party2006In: Digestion, ISSN 0012-2823, Vol. 73, no 1, 25-31 p.Article in journal (Refereed)
    Abstract [en]

    Recently, the suggestion to use 6-thioguanine (6-TG) as an alternative thiopurine in patients with inflammatory bowel disease (IBD) has been discarded due to reports about possible (hepato) toxicity. During meetings arranged in Vienna and Prague in 2004, European experts applying 6-TG further on in IBD patients presented data on safety and efficacy of 6-TG. After thorough evaluation of its risk-benefit ratio, the group consented that 6-TG may still be considered as a rescue drug in stringently defined indications in IBD, albeit restricted to a clinical research setting. As a potential indication for administering 6-TG, we delineated the requirement for maintenance therapy as well as intolerance and/or resistance to aminosalicylates, azathioprine, 6-mercaptopurine, methotrexate and infliximab. Furthermore, indications are preferred in which surgery is thought to be inappropriate. The standard 6-TG dosage should not exceed 25 mg daily. Routine laboratory controls are mandatory in short intervals. Liver biopsies should be performed after 6-12 months, three years and then three-yearly accompanied by gastroduodenoscopy, to monitor for potential hepatotoxicity, including nodular regenerative hyperplasia (NRH) and veno-occlusive disease (VOD). Treatment with 6-TG must be discontinued in case of overt or histologically proven hepatotoxicity. Copyright (c) 2006 S. Karger AG, Basel.

  • 12.
    Li, Wei
    et al.
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Johnson, Henrik
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Yuan, Xi-Ming
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    7beta-hydroxycholesterol induces natural killer cell death via oxidative lysosomal destabilization2009In: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 43, no 11, 1072-1079 p.Article in journal (Refereed)
    Abstract [en]

    Peripheral natural killer (NK) cells are reduced in patients with coronary artery disease and highly susceptible to apoptosis induced by oxidized lipids including 7beta-hydroxycholesterol (7betaOH) in vitro. The present study aimed to further explore the mechanisms behind 7betaOH-mediated cytotoxicity to human NK cells. Human NK cells were purified and treated with 7betaOH in different concentrations and times. Cell death, lysosomal and mitochondrial permeabilization and reactive oxygen species (ROS) production were then analysed. The 7betaOH induced time and dose dependent apoptosis and necrosis in human NK cells, which was preceded by loss of lysosomal integrity and enhanced ROS production. At later time points, the mitochondrial membrane permeability in 7betaOH-treated cells was significantly increased. The findings indicate that 7betaOH induces human NK cell death through early lysosomal permeabilization and consequent oxidative stress. The data further suggest that 7betaOH may induce immune disturbances in clinical settings such as atherosclerosis.

  • 13.
    Li, Wei
    et al.
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Johnson, Henrik
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Yuan, Xi-Ming
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    7ß-hydroxycholesterol induces natural killer cell death via oxidative lysosomal destabilization2009In: Free radical research, ISSN 1071-5762, Vol. 43, no 11, 1072-1079 p.Article in journal (Refereed)
    Abstract [en]

    Peripheral natural killer (NK) cells are reduced in patients with coronary artery disease and highly susceptible to apoptosis induced by oxidized lipids including 7beta-hydroxycholesterol (7betaOH) in vitro. The present study aimed to further explore the mechanisms behind 7betaOH-mediated cytotoxicity to human NK cells. Human NK cells were purified and treated with 7betaOH in different concentrations and times. Cell death, lysosomal and mitochondrial permeabilization and reactive oxygen species (ROS) production were then analysed. The 7betaOH induced time and dose dependent apoptosis and necrosis in human NK cells, which was preceded by loss of lysosomal integrity and enhanced ROS production. At later time points, the mitochondrial membrane permeability in 7betaOH-treated cells was significantly increased. The findings indicate that 7betaOH induces human NK cell death through early lysosomal permeabilization and consequent oxidative stress. The data further suggest that 7betaOH may induce immune disturbances in clinical settings such as atherosclerosis.

  • 14. Kälkner, Karl Mikael
    et al.
    Westlin, Jan-Erik
    Strang, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Palliative mediicin. Östergötlands Läns Landsting, ViN, LAH Linnea.
    89Strontium in the management of painful sceletal metastases2000In: Anticancer Research, ISSN 0250-7005, Vol. 20, no 2 B, 1109-1114 p.Article in journal (Refereed)
    Abstract [en]

    Purpose: To make a review of the literature of 89strontium-chloride and a retrospective study of time to palliative intended external irradiation number of portals and overall-survival after 89strontium-chloride therapy. Results: In total 93 patients were treated 116 times with 89strontium. The patients with prostatic carcinoma received 91% of all 89strontium therapies. Median over-all survival was 10 months after injection. In those cases when 89strontium was given before palliative radiotherapy, the average of total number of local fields was significantly lower (1.1 versus 4.1) compared to those cases where local fields preceded 89strontium therapy. However, time to 89new external irradiation after 89strontium injection was equal between these groups (3.8 versus 2.9 months). Conclusion:A review of literature conclude that 89strontium is effective for the reduction of pain originating from osteoblastic metastases. It also reduce the need for external radiotherapy and therefore is cost-effective. However, 89strontium is more effective in an early phase of the metastatic disease and preferably as an adjuvance to external radiotherapy.

  • 15.
    Wedajo, W.
    et al.
    Armauer Hansen Research InstituteAddis Ababa, Ethiopia; Department of Biology, Jimma UniversityJimma, Ethiopia.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Department of Infectious Diseases and Microbiology, Kalmar County HospitalKalmar, Sweden.
    Bedru, A.
    Armauer Hansen Research InstituteAddis Ababa, Ethiopia.
    Kiros, T.
    Armauer Hansen Research InstituteAddis Ababa, Ethiopia.
    Hailu, E.
    Armauer Hansen Research Institute Addis Ababa, Ethiopia.
    Mebrahtu, T.
    Armauer Hansen Research Institute Addis Ababa, Ethiopia.
    Yamuah, L.
    Armauer Hansen Research Institute Addis Ababa, Ethiopia.
    Angeby, K.
    Department of Clinical Microbiology MTC, Karolinska Hospital, Karolinska University HospitalStockholm, Sweden.
    Werngren, J.
    Department of Preparedness, Unit of Highly Pathogenic Microorganisms, Swedish Institute for Communicable Disease Control (SMI)Solna, Sweden.
    Onyebujoh, P.
    World Health Organization, Regional Office for Africa, Inter-country Support Team for East0/Southern AfricaHarare, Zimbabwe.
    Dagne, K.
    Addis Ababa University, Faculty of Life SciencesAddis Ababa, Ethiopia.
    Aseffa, A.
    Armauer Hansen Research Institute Addis Ababa, Ethiopia.
    A 24-well plate assay for simultaneous testing of first and second line drugs against Mycobacterium tuberculosis in a high endemic setting2014In: BMC Research Notes, ISSN 1756-0500, Vol. 7, no 1, 512- p.Article in journal (Refereed)
    Abstract [en]

    Background: Early detection of drug resistance is one of the priorities of tuberculosis (TB) control programs as drug resistance is increasing. New molecular assays are only accessible for a minority of the second line drugs and their availability in high endemic settings is also hampered by high cost and logistic challenges. Therefore, we evaluated a previously developed method for drug susceptibility testing (DST) including both first- and second line anti-TB drugs for use in high endemic areas. Results: Baseline mycobacterial isolates from 78 consecutive pulmonary TB patients from Addis Ababa, Ethiopia who were culture positive for Mycobacterium tuberculosis at the end of a two-month directly observed treatment short course (DOTS) were included. The isolates were simultaneously tested for isoniazid, rifampicin, ethambutol, streptomycin, amikacin, kanamycin, capreomycin, ofloxacin, moxifloxacin, ethionamide and para-aminosalicylic acid susceptibility using the indirect proportion method adopted for 24-well agar plates containing Middlebrook 7H10 medium. Applying the 24-well plate assay, 43 (55.1%) isolates were resistant to one or more of the first line drugs tested (isoniazid, rifampicin and ethambutol). MDR-TB was identified in 20.5% of this selected group and there was a perfect correlation for rifampicin resistance with the results from the genotype MTBDRplus assay. All isolates were susceptible to aminoglycosides and fluoroquinolones in agreement with the genotype MTBDRsl assay. The only tested second line drug associated to resistance was ethionamide (14.1% resistant). The method was reproducible with stable results for internal controls (one multi-drug resistant (MDR) and one pan-susceptible strain (H37Rv) and DST results could be reported at two weeks. Conclusions: The 24-well plate method for simultaneous DST for first- and second line drugs was found to be reproducible and correlated well to molecular drug susceptibility tests. It is likely to be useful in high-endemic areas for surveillance as well as for the detection of second line drug resistance in targeted groups such as in those who fail empirical MDR treatment.

  • 16.
    Ziemssen, Tjalf
    et al.
    Klinikum Carl Gustav Carus, Germany.
    Bajenaru, Ovidiu A.
    Carol Davila University of Medical and Pharm, Romania.
    Carra, Adriana
    Hospital Britanico Buenos Aires, Argentina.
    de Klippel, Nina
    Virga Jessaziekenhuis, Belgium.
    de Sa, Joao C.
    Hospital Santa Mari, Belgium.
    Edland, Astrid
    Central Hospital Buskerud, Norway.
    Frederiksen, Jette L.
    University of Copenhagen, Denmark.
    Heinzlef, Olivier
    Hop Tenon, France.
    Karageorgiou, Klimentini E.
    Gen Hospital Athens, Greece.
    Lander Delgado, Rafael H.
    Landtblom, Anne-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Department of Medical Specialist in Motala.
    Macias Islas, Miguel A.
    Central University of Guadalajara, Mexico.
    Tubridy, Niall
    Dublin City University, Ireland.
    Gilgun-Sherki, Yossi
    Teva Pharmaceut Ind Ltd, Israel.
    A 2-year observational study of patients with relapsing-remitting multiple sclerosis converting to glatiramer acetate from other disease-modifying therapies: the COPTIMIZE trial2014In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 261, no 11, 2101-2111 p.Article in journal (Refereed)
    Abstract [en]

    Studies suggest that patients with relapsing-remitting multiple sclerosis (RRMS) who do not benefit from other disease-modifying treatments (DMTs) may benefit from converting to glatiramer acetate (GA). COPTIMIZE was a 24-month observational study designed to assess the disease course of patients converting to GA 20 mg daily from another DMT. Eligible patients had converted to GA and had received prior DMT for 3-6 months, depending on the reasons for conversion. Patients were assessed at baseline and at 6, 12, 18, and 24 months. In total, 672 patients from 148 centers worldwide were included in the analysis. Change of therapy to GA was prompted primarily by lack of efficacy (53.6 %) or intolerable adverse events (AEs; 44.8 %). Over a 24-month period, 72.7 % of patients were relapse free. Mean annual relapse rate decreased from 0.86 [95 % confidence interval (CI) 0.81-0.91] before the change to 0.32 (95 % CI 0.26-0.40; p less than 0.0001) at last observation, while the progression of disability was halted, as the Kurtzke Expanded Disability Status Scale (EDSS) scores remained stable. Patients improved significantly (p less than 0.05) on measures of fatigue, quality of life, depression, and cognition; mobility scores remained stable. The results indicate that changing RRMS patients to GA is associated with positive treatment outcomes.

  • 17.
    Braian, Clara
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Svensson, Mattias
    Karolinska Institute, Sweden.
    Brighenti, Susanna
    Karolinska Institute, Sweden.
    Lerm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Parasa, Venkata R.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Institute, Sweden.
    A 3D Human Lung Tissue Model for Functional Studies on Mycobacterium tuberculosis Infection2015In: Journal of Visualized Experiments, ISSN 1940-087X, E-ISSN 1940-087X, no 104, 1-9 p., e53084Article in journal (Refereed)
    Abstract [en]

    Tuberculosis (TB) still holds a major threat to the health of people worldwide, and there is a need for cost-efficient but reliable models to help us understand the disease mechanisms and advance the discoveries of new treatment options. In vitro cell cultures of monolayers or co-cultures lack the three-dimensional (3D) environment and tissue responses. Herein, we describe an innovative in vitro model of a human lung tissue, which holds promise to be an effective tool for studying the complex events that occur during infection with Mycobacterium tuberculosis (M. tuberculosis). The 3D tissue model consists of tissue-specific epithelial cells and fibroblasts, which are cultured in a matrix of collagen on top of a porous membrane. Upon air exposure, the epithelial cells stratify and secrete mucus at the apical side. By introducing human primary macrophages infected with M. tuberculosis to the tissue model, we have shown that immune cells migrate into the infected-tissue and form early stages of TB granuloma. These structures recapitulate the distinct feature of human TB, the granuloma, which is fundamentally different or not commonly observed in widely used experimental animal models. This organotypic culture method enables the 3D visualization and robust quantitative analysis that provides pivotal information on spatial and temporal features of host cell-pathogen interactions. Taken together, the lung tissue model provides a physiologically relevant tissue micro-environment for studies on TB. Thus, the lung tissue model has potential implications for both basic mechanistic and applied studies. Importantly, the model allows addition or manipulation of individual cell types, which thereby widens its use for modelling a variety of infectious diseases that affect the lungs.

  • 18.
    Olsson, Anders
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, MKC - Medicin och kirurgicentrum, EMK-endokrin.
    Eriksson, M
    Johnson, O
    Kjellström, T
    Lanke, J
    Lytken Larsen, M
    Pedersen, T
    Tikkanen, MJ
    Wiklund, O
    A 52-week, multicenter, randomized, parallel-group, double-blind, double-dummy study to assess the efficacy of atorvastatin and simvastatin in reaching low-density lipoprotein cholesterol and triglyceride targets: The Treat-to-Target (3T) Study2003In: Clinical Therapeutics, ISSN 0149-2918, Vol. 25, no 1, 119-138 p.Article in journal (Refereed)
    Abstract [en]

    Background: Guidelines for the prevention of coronary heart disease call for low-density lipoprotein cholesterol (LDL-C) reduction as the primary target of treatment and reduction of triglycerides (TG) as an additional target. Objective: The purpose of this study was to investigate the ability of atorvastatin and simvastatin to reduce LDL-C and TG concentrations and to meet 3 target lipid levels: LDL-C =2.6 mmol/L, TG =1.5 mmol/L, and both LDL-C =2.6 mmol/L and TG =1.5 mmol/L. Methods: The Treat-to-Target (3T) Study was a 52-week, multicenter, randomized, parallel-group study. Using the double-blind, double-dummy technique, adult patients aged 35 to 75 years with cardiovascular disease and dyslipidemia, defined as LDL-C concentration =4.0 mmol/L (=155 mg/dL), were randomized in a 1:1 ratio to receive once-daily oral treatment with 20 mg atorvastatin or 20 mg simvastatin. Fasting (12-hour) blood samples for the estimation of lipid levels and clinical laboratory values were collected after 4, 8, 12, 26, and 52 weeks. The dose was doubled after 12 weeks if the target National Cholesterol Education Program level of LDL-C (=2.6 mmol/L [100 mg/dL]) was not reached at 8 weeks. Results: The intent-to-treat analysis included 552 patients (418 men, 134 women) randomized to receive atorvastatin and 535 (404 men, 131 women) randomized to receive simvastatin. The number of patients enrolled in the study allowed the evaluation of the drugs' effects on YG. Patient demographic characteristics were similar for the 2 treatment groups, and there were no differences in baseline lipid values. Compared with simvastatin, atorvastatin produced significantly greater reductions in LDL-C (8 weeks: -46% vs -40%, P < 0.001, 52 weeks: -49% vs -44%, P < 0.001) and in YG (8 weeks: -23% vs -14%, P < 0.001, 52 weeks: -24% vs -16%, P < 0.001). Compared with simvastatin-treated patients, a significantly greater number of atorvastatin-treated patients reached the LDL-C target after 8 weeks (45% vs 24%, P < 0.001). Fewer atorvastatin patients needed to have their dose doubled, nevertheless more atorvastatin patients reached the LDL-C target after 52 weeks (61% vs 41%, P < 0.001). Both statins were well tolerated. Muscular symptoms occurred in 12 patients (2.2%) in the atorvastatin group and in 13 patients (2.4%) in the simvastatin group. Conclusions: Atorvastatin 20 or 40 mg/d for up to 1 year of treatment was significantly more effective than simvastatin 20 or 40 mg/d m reducing LDL-C and YG levels and at achieving recommended lipid targets in this selected patient population with cardiovascular disease and dyslipidemia. Both statins were well tolerated.

  • 19. Amin, AI
    et al.
    Hallböök, Olof
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Surgery. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Lee, AJ
    Sexton, R
    Moran, BJ
    Heald, RJ
    A 5-cm colonic J pouch colo-anal reconstruction following anterior resection for low rectal cancer results in acceptable evacuation and continence in the long term2003In: Colorectal Disease, ISSN 1462-8910, Vol. 5, no 1, 33-37 p.Article in journal (Refereed)
    Abstract [en]

    Background. Optimal treatment for low rectal cancer is total mesorectal excision, with most patients suitable for low colo-rectal or colo-anal anastomosis. A colon pouch has early functional benefits, although long-term function, especially evacuation, might mitigate against its routine use. The aim of this study was to assess evacuation and continence in patients with a colon pouch, and to examine the impact of possible risk factors. Methods. In 1998, all 102 surviving patients with a colon pouch, whose stoma had been closed for more than one year, were sent a postal questionnaire. A composite incontinence score was calculated from questions on urgency, use of a pad, incontinence of gas, liquid or faeces, and a composite evacuation score from questions on medication taken to evacuate, straining, the need and number of times returned to evacuate. Results. The response rate was 90% (50 M, 42 F), with a median age of 68 years (IQR 60-78) and median follow-up of 2.6 years (IQR 1.7-3.9). The anastomosis was 3 cm or less from the anus in 45/92 (49%), and incontinence scores were worse in this group (P = 0.001). There were significantly higher incontinence scores in females (P = 0.014). Age, preoperative radiotherapy, part of colon used for anastomosis, post-operative leak and length of follow-up had no demonstrable effect on either score. Conclusion. Gender and anastomotic height were the only variables which influenced incontinence. Ninety percent of patients reported that their bowel function did not affect their overall wellbeing, and none would have preferred to have a stoma.

  • 20.
    Lindström, Tom
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Biology. Linköping University, The Institute of Technology.
    Grear, Daniel A.
    Colorado State University, USA .
    Buhnerkempe, Michael
    Colorado State University, USA .
    Webb, Colleen T.
    Colorado State University, USA .
    Miller, Ryan S.
    US Anim and Plant Health Inspect Serv, CO USA .
    Portacci, Katie
    US Anim and Plant Health Inspect Serv, CO USA .
    Wennergren, Uno
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Biology. Linköping University, The Institute of Technology.
    A Bayesian Approach for Modeling Cattle Movements in the United States: Scaling up a Partially Observed Network2013In: PLoS ONE, ISSN 1932-6203, Vol. 8, no 1Article in journal (Refereed)
    Abstract [en]

    Networks are rarely completely observed and prediction of unobserved edges is an important problem, especially in disease spread modeling where networks are used to represent the pattern of contacts. We focus on a partially observed cattle movement network in the U.S. and present a method for scaling up to a full network based on Bayesian inference, with the aim of informing epidemic disease spread models in the United States. The observed network is a 10% state stratified sample of Interstate Certificates of Veterinary Inspection that are required for interstate movement; describing approximately 20,000 movements from 47 of the contiguous states, with origins and destinations aggregated at the county level. We address how to scale up the 10% sample and predict unobserved intrastate movements based on observed movement distances. Edge prediction based on a distance kernel is not straightforward because the probability of movement does not always decline monotonically with distance due to underlying industry infrastructure. Hence, we propose a spatially explicit model where the probability of movement depends on distance, number of premises per county and historical imports of animals. Our model performs well in recapturing overall metrics of the observed network at the node level (U.S. counties), including degree centrality and betweenness; and performs better compared to randomized networks. Kernel generated movement networks also recapture observed global network metrics, including network size, transitivity, reciprocity, and assortativity better than randomized networks. In addition, predicted movements are similar to observed when aggregated at the state level (a broader geographic level relevant for policy) and are concentrated around states where key infrastructures, such as feedlots, are common. We conclude that the method generally performs well in predicting both coarse geographical patterns and network structure and is a promising method to generate full networks that incorporate the uncertainty of sampled and unobserved contacts.

  • 21.
    Lindström, Tom
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Theoretical Biology. Linköping University, Faculty of Science & Engineering. Colorado State University, CO 80523 USA; US National Institute Heatlh, MD USA; University of Exeter, England.
    Tildesley, Michael
    US National Institute Heatlh, MD USA; University of Nottingham, England.
    Webb, Colleen
    Colorado State University, CO 80523 USA; US National Institute Heatlh, MD USA.
    A Bayesian Ensemble Approach for Epidemiological Projections2015In: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 11, no 4, e1004187- p.Article in journal (Refereed)
    Abstract [en]

    Mathematical models are powerful tools for epidemiology and can be used to compare control actions. However, different models and model parameterizations may provide different prediction of outcomes. In other fields of research, ensemble modeling has been used to combine multiple projections. We explore the possibility of applying such methods to epidemiology by adapting Bayesian techniques developed for climate forecasting. We exemplify the implementation with single model ensembles based on different parameterizations of the Warwick model run for the 2001 United Kingdom foot and mouth disease outbreak and compare the efficacy of different control actions. This allows us to investigate the effect that discrepancy among projections based on different modeling assumptions has on the ensemble prediction. A sensitivity analysis showed that the choice of prior can have a pronounced effect on the posterior estimates of quantities of interest, in particular for ensembles with large discrepancy among projections. However, by using a hierarchical extension of the method we show that prior sensitivity can be circumvented. We further extend the method to include a priori beliefs about different modeling assumptions and demonstrate that the effect of this can have different consequences depending on the discrepancy among projections. We propose that the method is a promising analytical tool for ensemble modeling of disease outbreaks.

  • 22.
    Bergkvist, Liza
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    Sandin, Linnea
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Kågedal, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Brorsson, Ann-Christin
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, Faculty of Science & Engineering.
    A beta PP processing results in greater toxicity per amount of A beta(1-42) than individually expressed and secreted A beta(1-42) in Drosophila melanogaster2016In: BIOLOGY OPEN, ISSN 2046-6390, Vol. 5, no 8, 1030-1039 p.Article in journal (Refereed)
    Abstract [en]

    The aggregation of the amyloid-beta (A beta) peptide into fibrillar deposits has long been considered the key neuropathological hallmark of Alzheimers disease (AD). A beta peptides are generated from proteolytic processing of the transmembrane A beta precursor protein (A beta PP) via sequential proteolysis through the beta-secretase activity of beta-site A beta PP-cleaving enzyme (BACE1) and by the intramembranous enzyme gamma-secretase. For over a decade, Drosophila melanogaster has been used as a model organism to study AD, and two different approaches have been developed to investigate the toxicity caused by AD-associated gene products in vivo. In one model, the A beta peptide is directly over-expressed fused to a signal peptide, allowing secretion of the peptide into the extracellular space. In the other model, human A beta PP is co-expressed with human BACE1, resulting in production of the A beta peptide through the processing of A beta PP by BACE1 and by endogenous fly gamma-secretase. Here, we performed a parallel study of flies that expressed the A beta(1-42) peptide alone or that co-expressed A beta PP and BACE1. Toxic effects (assessed by eye phenotype, longevity and locomotor assays) and levels of the A beta(1-42), A beta(1-40) and A beta(1-38) peptides were examined. Our data reveal that the toxic effect per amount of detected A beta(1-42) peptide was higher in the flies co-expressing A beta PP and BACE1 than in the A beta(1-42)-expressing flies, and that the co-existence of A beta(1-42) and A beta(1-40) in the flies co-expressing A beta PP and BACE1 could be of significant importance to the neurotoxic effect detected in these flies. Thus, the toxicity detected in these two fly models seems to have different modes of action and is highly dependent on how and where the peptide is generated rather than on the actual level of the A beta(1-42) peptide in the flies. This is important knowledge that needs to be taken into consideration when using Drosophila models to investigate disease mechanisms or therapeutic strategies in AD research.

  • 23.
    Fritschi, Sarah K.
    et al.
    German Centre Neurodegenerat Disease DZNE, Germany; University of Tubingen, Germany; University of Tubingen, Germany.
    Cintron, Amarallys
    Emory University, GA 30329 USA.
    Ye, Lan
    German Centre Neurodegenerat Disease DZNE, Germany; University of Tubingen, Germany; University of Tubingen, Germany.
    Mahler, Jasmin
    German Centre Neurodegenerat Disease DZNE, Germany; University of Tubingen, Germany; University of Tubingen, Germany.
    Buehler, Anika
    German Centre Neurodegenerat Disease DZNE, Germany; University of Tubingen, Germany.
    Baumann, Frank
    German Centre Neurodegenerat Disease DZNE, Germany; University of Tubingen, Germany.
    Neumann, Manuela
    German Centre Neurodegenerat Disease DZNE, Germany; University of Tubingen, Germany.
    Nilsson, Peter
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Hammarström, Per
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Walker, Lary C.
    Emory University, GA 30329 USA; Emory University, GA 30322 USA.
    Jucker, Mathias
    German Centre Neurodegenerat Disease DZNE, Germany; University of Tubingen, Germany .
    A beta seeds resist inactivation by formaldehyde2014In: Acta Neuropathologica, ISSN 0001-6322, E-ISSN 1432-0533, Vol. 128, no 4, 477-484 p.Article in journal (Refereed)
    Abstract [en]

    Cerebral beta-amyloidosis can be exogenously induced by the intracerebral injection of brain extracts containing aggregated beta-amyloid (A beta) into young, pre-depositing A beta precursor protein- (APP) transgenic mice. Previous work has shown that the induction involves a prion-like seeding mechanism in which the seeding agent is aggregated A beta itself. Here we report that the beta-amyloid-inducing activity of Alzheimers disease (AD) brain tissue or aged APP-transgenic mouse brain tissue is preserved, albeit with reduced efficacy, after formaldehyde fixation. Moreover, spectral analysis with amyloid conformation-sensitive luminescent conjugated oligothiophene dyes reveals that the strain-like properties of aggregated A beta are maintained in fixed tissues. The resistance of A beta seeds to inactivation and structural modification by formaldehyde underscores their remarkable durability, which in turn may contribute to their persistence and spread within the body. The present findings can be exploited to establish the relationship between the molecular structure of A beta aggregates and the variable clinical features and disease progression of AD even in archived, formalin-fixed autopsy material.

  • 24.
    Landtblom, Anne-Marie
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Lindvall, Björn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Neurology . Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Ledin, Torbjörn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
    Berlin, Gösta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    A case report of plasmapheresis treatment in a patient with paraneoplastic cerebellar degeneration and high anti-Yo antibody titers2008In: Therapeutic Apheresis and Dialysis, ISSN 1744-9979, Vol. 12, no 1, 82-85 p.Article in journal (Refereed)
    Abstract [en]

    A patient with paraneoplastic cerebellar degeneration due to anti-Purkinje cell antibodies (anti-Yo) arising from ovarian carcinoma with metastases was treated with three plasmapheresis (PP) series (a total of 22 PP treatments) over one year and was monitored by repeated otoneurological testing, balance tests and clinical investigations. Blood samples for antibody titers were checked on several occasions. Initially there was a weak clinical response and significantly improved test results regarding the caloric response, as well as a possible effect on visual suppression of the vestibulo-ocular reflex after caloric ear irrigation. After the first series of PP treatment, new metastases were found. A half year later there was a progressive course with increasing general symptoms. Serology tests showed continuously high titers of anti-Yo antibody, although somewhat lower after PP. We thus report a minor and short-lived effect of PP, possibly inhibited by the natural course of metastatic disease. © 2008 International Society for Apheresis.

  • 25.
    Lundqvist, G
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Axelson, Olav
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    Flodin, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Occupational and Environmental Medicine. Östergötlands Läns Landsting, Pain and Occupational Centre, Occupational and Environmental Medicine Centre.
    A case-control study of fatty liver disease and organic solvent exposure.  1999In: American Journal of Industrial Medicine, ISSN 0271-3586, Vol. 35, 132-136 p.Article in journal (Refereed)
  • 26.
    Bergfors, Elisabet
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Lundmark, Katarzyna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Nyström Kronander, Ulla
    Linköping University, Department of Clinical and Experimental Medicine, Allergy Centre. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Allergy Center.
    A child with a long-standing, intensely itching subcutaneous nodule on a thigh: an uncommon (?) reaction to commonly used vaccines2013In: BMJ Case Reports, ISSN 1757-790XArticle in journal (Refereed)
    Abstract [en]

    A 2-year-old girl presented with an intensely itching subcutaneous nodule on the front of a thigh. The nodule persisted for 10 months until it was excised. Subsequent investigation for malignancy and systemic disease showed no pathological findings. The diagnosis, persistent itching vaccination granuloma, was revealed by hazard almost 2 years after the onset of symptoms. Persistent itching subcutaneous nodules at the injection site for aluminium containing vaccines (mostly diphtheria-tetanus-pertussis combination vaccines for primary immunisation of infants) may appear with a long delay after the vaccination (months), cause prolonged itching (years) and are often associated with contact allergy to aluminium. The condition is poorly recognised in Health Care which may lead to prolonged symptoms and unnecessary investigations.

  • 27.
    Jung, Michaela
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Holmqvist, Annica
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Albertsson, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    A clinical study of metastasized rectal cancer treatment: assessing a multimodal approach2014In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 31, no 3, 839- p.Article in journal (Refereed)
    Abstract [en]

    Metastasized rectal cancer has long been considered incurable. During recent years, the treatment of rectal cancer patients has been improved, and nowadays, a subgroup of patients might even be cured. The aim of this study was to investigate the optimal timing of treatment in a multimodal therapy schedule in order to see whether the addition of bevacizumab (Avastin) to conventional chemotherapy was effective. The study included 39 patients with metastatic rectal cancer between 2009 and 2011, and three were excluded due to the lack of metastases or lack of follow-up information. The remaining 36 patients were divided into groups by treatment intention. The group with curative intention received mainly oxaliplatin (Eloxatin) in combination with capecitabine (Xeloda) with or without bevacizumab (Avastin) for 2 months followed by preoperative radiotherapy (RT) and surgery. Palliative patients had very different treatments depending on their needs of palliation. The median survival time for patients with curative intention was 31 months and for the palliative patients 12 months. Four of the patients (11%) with curative intention were considered cured at the end of follow-up. The response to chemotherapy after 2-month treatment is a good prognostic sign for which patients can be cured. Long-lasting palliation can be obtained with this treatment schedule. The main side effects were gastrointestinal events, including bowel perforation, neuropathy, thrombo-embolic disease and reduced general condition. All side effects are known, and the treatment is considered tolerable. We conclude that a good treatment schedule would be oxaliplatin (Eloxatin) in combination with capecitabine (Xeloda) with or without bevacizumab (Avastin) for 2 months, followed by preoperative RT and surgery.

  • 28.
    Basile, Maurizio
    et al.
    Linköping University, Department of Computer and Information Science.
    Raciti, Massimiliano Gabriele
    Linköping University, Department of Computer and Information Science.
    A Cloud-Based Execution Environment for a Pandemic Simulator2009Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The aim of this thesis is to develop a flexible distributed platform designed toexecute a disease outbreaks simulator in a fast way over many types of platformsand operating systems. The architecture is realized using the Elastic ComputeCloud (EC2) supplied by Amazon and Condor as middleware among the varioustypes of OS. The second part of the report describes the realization of a webapplication that allows users to manage easily the various part of the architecture,to launch the simulations and to view some statistics of the relative results.

  • 29.
    Deng, C
    et al.
    Univ Ottawa, Inst Heart, Div Cardiac Surg, Ottawa, ON K1Y 4W7 Canada.
    Zhang, PC
    Univ Ottawa, Inst Heart, Div Cardiac Surg, Ottawa, ON K1Y 4W7 Canada.
    Vulesevic, B
    Univ Ottawa, Inst Heart, Div Cardiac Surg, Ottawa, ON K1Y 4W7 Canada.
    Kuraitis, D
    Univ Ottawa, Inst Heart, Div Cardiac Surg, Ottawa, ON K1Y 4W7 Canada.
    Li, FF
    Univ Ottawa, Inst Eye, Ottawa, ON K1Y 4W7 Canada.
    Yang, AF
    Agr & Agri Food Canada, Ottawa, ON Canada.
    Griffith, May
    Univ Ottawa, Inst Eye, Ottawa, ON K1Y 4W7 Canada.
    Ruel, M
    Univ Ottawa, Inst Heart, Div Cardiac Surg, Ottawa, ON K1Y 4W7 Canada.
    Suuronen, EJ
    Univ Ottawa, Inst Heart, Div Cardiac Surg, Ottawa, ON K1Y 4W7 Canada.
    A Collagen-Chitosan Hydrogel for Endothelial Differentiation and Angiogenesis2010In: TISSUE ENGINEERING PART A, ISSN 1937-3341, Vol. 16, no 10, 3099-3109 p.Article in journal (Refereed)
    Abstract [en]

     Cell therapy for the treatment of cardiovascular disease has been hindered by low cell engraftment, poor survival, and inadequate phenotype and function. In this study, we added chitosan to a previously developed injectable collagen matrix, with the aim of improving its properties for cell therapy and neovascularization. Different ratios of collagen and chitosan were mixed and chemically crosslinked to produce hydrogels. Swell and degradation assays showed that chitosan improved the stability of the collagen hydrogel. In culture, endothelial cells formed significantly more vascular-like structures on collagen-chitosan than collagen-only matrix. While the differentiation of circulating progenitor cells to CD31(+) cells was equal on all matrices, vascular endothelial-cadherin expression was increased on the collagen-chitosan matrix, suggesting greater maturation of the endothelial cells. In addition, the collagen-chitosan matrix supported a significantly greater number of CD133(+) progenitor cells than the collagen-only matrix. In vivo, subcutaneously implanted collagen-chitosan matrices stimulated greater vascular growth and recruited more von Willebrand factor (vWF(+)) and CXCR4(+) endothelial/angiogenic cells than the collagen-only matrix. These results indicate that the addition of chitosan can improve the physical properties of collagen matrices, and enhance their ability to support endothelial cells and angiogenesis for use in cardiovascular tissue engineering applications.

  • 30.
    Elwing, B
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, Division of Preventive and Social Medicine and Public Health Science.
    Kullberg, C
    Kucinskiene, Z
    Björegren, M
    Abaravicius, A
    Kristenson, Margareta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of health and environment.
    A comparative study of food intake between Lithuanian and Swedish middle-aged men: The LiVicordia study2001In: Scandinavian Journal of Nutrition/Næringsforskning, ISSN 1102-6480, Vol. 45, no 3, 126-130 p.Article in journal (Other (popular science, discussion, etc.))
    Abstract [en]

    Background: In 1994, the mortality in coronary heart disease was four times higher among Lithuanian middle-aged men than among Swedish men. Over the period 1993-1995, the LiVicordia study investigated possible causes for this difference. We have earlier reported lower serum levels of cholesterol and higher susceptibility of low-density lipoprotein cholesterol for oxidation among Lithuanian men. Objective: In this part of the study, the aim was to compare mean estimates of food intake. Design: Cross-sectional study of random samples of 50-year-old men from each of the cities of Link÷ping, Sweden and Vilnius, Lithuania (n=150). The volunteers were interviewed about their food intake with the 24-hour recall method. Results: We found no differences in total energy intake, but Vilnius men had a higher energy intake from fat. Vilnius men consumed more fat from meat and less vegetable fat, while fat intake from dairy products was almost the same. Also, Vilnius men had a higher intake of vegetables, while Link÷ping men had a higher intake of fruit and berries. Conclusion: The observed differences in food consumption and dietary composition are partly consistent with the higher CHD mortality among Lithuanian men. However, data on biomarkers indicate that other dietary and lifestyle factors play a role.

  • 31.
    Larsby, Birgitta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Technical Audiology. Linköping University, Faculty of Health Sciences.
    Hergils, Leif
    Östergötlands Läns Landsting.
    Billermark, Erica
    Östergötlands Läns Landsting.
    A comparative study of the glycerol test, electrocochleography (ECoG) and measurement of the travelling wave velocity  in diagnosis of Meniere's disease1999Conference paper (Other academic)
  • 32.
    Svärd, Anna
    et al.
    Rheumatology Clinic, Falun Hospital, Falun.
    Kastbom, Alf
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences.
    Söderlin, Maria K.
    Spenshult Rheumatology Centre, Oskarström, Sweden.
    Reckner-Olsson, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Occupational and Environmental Medicine. Linköping University, Faculty of Health Sciences.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    A Comparison Between IgG- and IgA-class Antibodies to Cyclic Citrullinated Peptides and to Modified Citrullinated Vimentin in Early Rheumatoid Arthritis and Very Early Arthritis2011In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 38, no 7, 1265-1272 p.Article in journal (Refereed)
    Abstract [en]

    Objective. Because of their slightly higher sensitivity, it has been argued that antibodies to modified citrullinated vimentin (anti-MCV) are superior to antibodies to cyclic citrullinated peptides (anti-CCP), while others claim that anti-CCP is preferable because of higher diagnostic specificity for rheumatoid arthritis (RA). We evaluated IgG- and IgA-class anti-MCV and anti-CCP as diagnostic and prognostic markers in early arthritis. less thanbrgreater than less thanbrgreater thanMethods. Two Swedish arthritis populations were examined: 215 patients with early RA (andlt;= 12 months duration) from the Swedish TIRA-1 cohort, and 69 patients with very early arthritis (andlt;= 3 months duration) from the Kronoberg Arthritis Incidence cohort, in which 22% were diagnosed with RA. IgG anti-CCP and anti-MCV antibodies were analyzed with commercial kits. These tests were modified for IgA-class antibody detection. less thanbrgreater than less thanbrgreater thanResults were related to disease course, smoking habits, and shared epitope status. Results. In the TIRA-1 cohort, occurrence of IgG anti-MCV and IgG anti-CCP showed a 93% overlap, although IgG anti-MCV had higher diagnostic sensitivity. Twenty-four percent tested positive for IgA anti-MCV compared to 29% for IgA anti-CCP. In the Kronoberg Arthritis Incidence cohort, 15% tested positive for IgG anti-MCV and 6% for IgA anti-MCV, compared to 10% positive for IgG anti-CCP and 3% positive for IgA anti-CCP, revealing that anti-CCP had higher diagnostic specificity for RA. As previously reported for IgA anti-CCP, IgA anti-MCV antibodies occurred in a small proportion of high-level IgG antibody-positive sera and were associated with a more aggressive disease course. Smokers were more often positive for antibodies to citrullinated proteins, most strikingly among the patients who were IgA anti-MCV-positive. less thanbrgreater than less thanbrgreater thanConclusion. The occurrences of IgG-class anti-MCV and anti-CCP in early RA largely overlap. The sensitivity of anti-MCV is slightly higher, while the diagnostic specificity is higher for anti-CCP. In both instances a positive test predicts an unfavorable disease course, possibly slightly more so for anti-MCV. Although associated with a more active disease over time, IgA-class anti-CCP or anti-MCV do not add any diagnostic advantage.

  • 33.
    Magnusson, Karin
    Linköping University, Department of Medical and Health Sciences.
    A comparison of persons who got Motivational Interviewing (MI) or not to promote physical activity, and prediction of factors influencing change of physical activity level after two years2010Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Introduction: Physical inactivity, related lifestyle diseases and back pain are severe problems in today’s society. One way to increase physical activity level is through Motivational Interviewing (MI).

     

    Purpose: Comparing participants who were in need of MI for physical activity due to risk of heart- and coronary disease with participants not in need of MI, and to describe whether MI for physical activity and other factors can predict change of physical activity level.

     

    Method: A cohort was followed during two years and measured on lifestyle factors, socioeconomic and psychological factors, general health, motivation to change lifestyle and back pain by questionnaires. Based on risk of heart and coronary disease, participants underwent an MI-session for increased physical activity (n=393) or no MI-session (n=380) at baseline.

     

    Results: Besides having a deteriorated lifestyle, the majority of participants who received MI were females, had lower self-estimated economy, had lower health-related quality of life, scored lower on psychological factors and had comorbidity and back pain to a larger extent. Factors related to increase of physical activity level included being physically inactive at baseline, being a female, not having MI and not having disability due to back pain.

     

    Conclusion: Participants in the MI-group had poorer health and more back pain. Having MI did not predict an increase of physical activity, but a low level of physical activity in the past and being a female did play a part in the prediction. More research is needed on MI for increase of physical activity level for an individual with risk of heart- and coronary disease and/or with back pain.

  • 34.
    Eldh, Ann Catrine
    et al.
    Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm and School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Ekman, Inger
    Sahlgrenska Academy at Göteborg University, Institute of Health and Care Sciences, Göteborg.
    Ehnfors, Margareta
    Örebro universitet, Institutionen för hälsovetenskap och medicin, Örebro.
    A comparison of the concept of patient participation and patients' descriptions as related to healthcare definitions.2010In: International journal of nursing terminologies and classifications : the official journal of NANDA International, ISSN 1744-618X, Vol. 21, no 1, 21-32 p.Article in journal (Refereed)
    Abstract [en]

    PURPOSE. To depict what patients describe as patient participation and whether descriptions of patient participation are affected by gender, age, healthcare contact, and duration of disease. DATA SOURCES. Current patients (n= 362) responded to a questionnaire on participation. DATA SYNTHESIS. Patients' descriptions focused on having knowledge, rather than being informed, and on interacting with health professionals, rather than merely partaking in decision making. CONCLUSIONS. Patients' descriptions of participation correspond with the International Classification of Functioning, Disability and Health's definition, which includes "being involved in a life situation." Healthcare legislation and professionals employ a narrower concept of patient participation as defined by, e.g., Medical Subject Headings. PRACTICE IMPLICATIONS. Findings suggest that health professionals need to embrace what patients describe as participation.

  • 35.
    Ahlstrom, G.
    et al.
    Ahlström, G., Department of Health Sciences, University of Örebro, SE-701 82 Örebro, Sweden.
    Lindvall, Björn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Neurology . Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Wenneberg, S.
    Department of Health Sciences, University of Örebro, SE-701 82 Örebro, Sweden.
    Gunnarsson, L.G.
    Department of Neurology and Neurophysiology, Örebro University Hospital, Örebro, Sweden.
    A comprehensive rehabilitation programme tailored to the needs of adults with muscular dystrophy2006In: Clinical Rehabilitation, ISSN 0269-2155, Vol. 20, no 2, 132-141 p.Article in journal (Refereed)
    Abstract [en]

    Objective: To assess if activities of daily living (ADL), coping and quality of life could be improved in adults with muscular dystrophy through a comprehensive rehabilitation programme. Design: Quasi-experimental, controlled clinical study comparing patients with similar age and disease aspects. Setting: Two different counties in Sweden, being either study or control setting. Subjects: The study group comprised 37 adults (21 women, 16 men, mean age 50 years), while the control group comprised 39 people (25 women, 14 men, mean age 46 years). Interventions: Four rehabilitation sessions tailored to different medical, physical and psychosocial needs of the patients, comprising a total of 10 days over a period of 18 months. Main measures: ADL, the Mental Adjustment to Cancer Scale measuring coping strategies, the Sickness Impact Profile measuring health-related quality of life, the Hospital Anxiety and Depression Scale, and the Psychosocial Well-being Questionnaire. Results: No significant differences were found between groups with regard to the outcome measures. There was increased dependence on others in ADL after 18 months in both groups, but it was more pronounced in the control group. Furthermore, a clear trend was observed in the data with regard to coping patterns, the control group using more coping strategies such as 'Helplessness/hopelessness' (P = 0.057), 'Anxious preoccupation' (P = 0.085) and 'Fatalistic' (P = 0.073) when being compared to the study group. Conclusions: No apparent effects on ADL were found from the rehabilitation programme, although there was a tendency of reduction of maladaptive coping patterns in the study group. This initial study may provide the rationale and basis for a randomized controlled trial. © 2006 Edward Arnold (Publishers) Ltd.

  • 36.
    Johannesson, M
    et al.
    Linköping University, Department of Department of Health and Society.
    Hedbrant, Johan
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, Faculty of Science & Engineering.
    Jönsson, B
    Linköping University, Department of Department of Health and Society.
    A computer simulation model for cost-effectiveness analysis of cardiovascular disease prevention.1991In: Médecine et informatique, ISSN 0307-7640, Vol. 16, no 4, 355-362 p.Article in journal (Refereed)
    Abstract [en]

    In this paper a computer simulation model for cost-effectiveness analysis of cardiovascular disease prevention is presented. Cost-effectiveness analysis makes it possible to compare the cost-effectiveness of different interventions in order to maximize the health effects for a given amount of resources. The computer simulation model was written in Turbo-Pascal to be used on an IBM-PC-compatible. The model was based on the 8-year logistic multivariate risk equations for CHD and stroke from the Framingham Heart Study, but the regression coefficients can easily be changed if local data exist. The main advantages with the model are that it is easy to use, transparent, and flexible. The model was mainly developed for scientific purposes, but should be useful also for educational purposes and clinical decision analysis. The modelling approach used should also be useful in many other medical areas.

  • 37.
    Johannesson, Magnus
    et al.
    Linköping University, Department of Thematic Studies, Health and Society. Linköping University, Faculty of Arts and Sciences.
    Hedbrant, Johan
    Center of Technology Transfer, Institute of Technology, Linköping Universitgy, Sweden.
    Jönsson, Bengt
    Linköping University, Department of Thematic Studies, Health and Society. Linköping University, Faculty of Arts and Sciences.
    A computer simulation model for cost-effectiveness analysis of cardiovascular disease prevention1991Report (Other academic)
    Abstract [en]

    In this paper a computer simulation model for cost-effectiveness analysis of cardiovascular disease prevention is presented. The computer simulation model was written in Turbo Pascal to be used on an IBM-PC compatible. The model was based on the 8-year logistic multivariate risk equations for coronary heart disease (CHD) and stroke from the Framingham heart study, but the regression coefficients can easily be changed if local data exists. The main advantages of the model are that it is easy to use, transparent, and flexible. The model was mainly developed for scientific purposes, but should be useful also for educational purposes and clinical decision analysis. The modelling approach should also be useful in many other medical areas.

  • 38.
    Peng, S.
    et al.
    Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
    Westermark, Gunilla
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology.
    Naslund, J.
    Näslund, J., Department of Clinical Neuroscience, Occupational Therapy, and Elderly Care Research (NEUROTEC), Section for Geriatrics, Karolinska Institute, Huddinge, Sweden.
    Häggqvist, Bo
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology .
    Glennert, J.
    Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
    Westermark, P.
    Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden.
    A computer-based training system for breast fine needle aspiration cytology2002In: Journal of Pathology, ISSN 0022-3417, Vol. 196, no 1, 113-121 p.Article in journal (Refereed)
    Abstract [en]

    Fine-needle aspiration (FNA) cytology is a rapid and inexpensive technique used extensively in the diagnosis of breast disease. To remove diagnostic subjectivity, a diagnostic decision support system (DDSS) called CytoInform© has been developed, based on a Bayesian belief network (BBN) for the diagnosis of breast FNAs. In addition to acting as a DDSS, the system implements a computer-based training (CBT) system, providing a novel approach to breast cytology training. The system guides the trainee cytopathologist through the diagnostic process, allowing the user to grade each diagnostic feature using a set of on-screen reference images as visual clues. The trainee positions a slider on a spectrum relative to these images, reflecting the similarity between the reference image and the microscope image. From this, an evidence vector is generated, allowing the current diagnostic probability to be updated by the BBN. As the trainee assesses each clue, the evidence entered is compared with that of the expert through the use of a defined teaching file. This file records the relative severity of each clue and a tolerance band within which the trainee must position the slider. When all clues in the teaching case have been completed, the system informs the user of inaccuracies and offers the ability to reassess problematic features. In trials with two pathologists of different experience and a series of ten cases, the system provided an effective tool in conveying diagnostic evidence and protocols to trainees. This is evident from the fact that each pathologist only misinterpreted one case and a total of 86%/88% (experienced/inexperienced) of all clues assessed were interpreted correctly. Significantly, in all cases that produced the correct final diagnostic probability, the route taken to that solution was consistent with the expert's solution. Copyright © 2001 John Wiley & Sons, Ltd.

  • 39.
    Larsby, Birgitta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Technical Audiology. Linköping University, Faculty of Health Sciences.
    Thell, Jan
    Östergötlands Läns Landsting.
    Ödkvist, LM
    Östergötlands Läns Landsting.
    A computerized smooth pursuit test.1986In: Claussen C-F, Kirtane MV, editors. Vertigo, nausea,tinnitus and hearing loss in cardiovasculr disease.: Elsevier SciencePublishers B.V.; 1986 / [ed] Claussen C-F, Kirtane MV, editors., 1986, 313-318 p.Conference paper (Other academic)
  • 40.
    Petersson, Ulla
    et al.
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Primary Health Care in Motala.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences.
    Nilsson, Peter
    Department of Clinical Sciences, Lund University, University Hospital, Malmö , Sweden.
    A consultation-based method is equal to SCORE and an extensive laboratory-based method in predicting risk of future cardiovascular disease2009In: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 16, no 5, 536-540 p.Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: As cardiovascular disease (CVD) is one of the most common causes of mortality worldwide, much interest has been focused on reliable methods to predict cardiovascular risk.

    DESIGN: A cross-sectional, population-based screening study with 17-year follow-up in Southern Sweden.

    METHODS: We compared a non-laboratory, consultation-based risk assessment method comprising age, sex, present smoking, prevalent diabetes or hypertension at baseline, blood pressure (systolic >/=140 or diastolic >/=90), waist/height ratio and family history of CVD to Systemic COronary Risk Evaluation (SCORE) and a third model including several laboratory analyses, respectively, in predicting CVD risk. The study included clinical baseline data on 689 participants aged 40-59 years without CVD. Blood samples were analyzed for blood glucose, serum lipids, insulin, insulin-like growth factor-I, insulin-like growth factor binding protein-1, C-reactive protein, asymmetric dimethyl arginine and symmetric dimethyl arginine. During 17 years, the incidence of total CVD (first event) and death was registered.

    RESULTS: A non-laboratory-based risk assessment model, including variables easily obtained during one consultation visit to a general practitioner, predicted cardiovascular events as accurately [hazard ratio (HR): 2.72; 95% confidence interval (CI): 2.18-3.39, P<0.001] as the established SCORE algorithm (HR: 2.73; 95% CI: 2.10-3.55, P<0.001), which requires laboratory testing. Furthermore, adding a combination of sophisticated laboratory measurements covering lipids, inflammation and endothelial dysfunction, did not confer any additional value to the prediction of CVD risk (HR: 2.72; 95% CI: 2.19-3.37, P<0.001). The c-statistics for the consultation model (0.794; 95% CI: 0.762-0.823) was not significantly different from SCORE (0.767; 95% CI: 0.733-0.798, P=0.12) or the extended model (0.806; 95% CI: 0.774-0.835, P=0.55).

    CONCLUSION: A risk algorithm based on non-laboratory data from a single primary care consultation predicted long-term cardiovascular risk as accurately as either SCORE or an elaborate laboratory-based method in a defined middle-aged population.

  • 41.
    Annerbäck, Eva-Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Centre for Clinical Research in Sörmland, Uppsala University, Sweden .
    Sahlqvist, Lota
    Centre for Clinical Research in Sörmland, Uppsala University, Sweden .
    Wingren, Gun
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    A cross-sectional study of victimisation of bullying among schoolchildren in Sweden: Background factors and self-reported health complaints2014In: Scandinavian Journal of Public Health, ISSN 1403-4948, E-ISSN 1651-1905, Vol. 42, no 3, 270-277 p.Article in journal (Refereed)
    Abstract [en]

    AIM:

    To examine background factors for bullying and associations between bullying victimisation and health problems.

    METHODS:

    A cross-sectional study on all pupils in grades 7 and 9 in a Swedish county was conducted in 2011 (n=5248). Data have been analysed with bi- and multivariate models.

    RESULTS:

    14% of the children reported that they had been bullied during the past 2 months. Background factors for bullying were: gender (girls more often); age (younger students more often); disability/disease; high body mass index, and having parents born abroad. There were strong associations between being bullied and poor health and self-harm. Associations with poor general health for boys and girls and mental health problems for girls showed stronger associations with higher frequency of bullying than with lower. For boys, physical bullying had stronger correlations with poor general health than written-verbal bullying.

    CONCLUSIONS:

    Bullying is a serious public health problem among young people and healthcare professionals have an important task in identifying exposed children. Children who are "different" are more exposed to bullying, which implies that school personnel, parents, and other adults in these children's social networks can play an important role in paying attention to and preventing the risk of bullying.

    .

  • 42.
    Mirazimi, Ali
    et al.
    Department of Virology, Swedish Institute for Infectious Disease Control/Karolinska Institute, Solna, Sweden.
    Magnusson, Karl-Eric
    Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Svensson, Lennart
    Linköping University, Department of Molecular and Clinical Medicine, Molecular Virology. Linköping University, Faculty of Health Sciences.
    A cytoplasmic region of the NSP4 enterotoxin of rotavirus is involved in retention in the endoplasmic reticulum2003In: Journal of General Virology, ISSN 0022-1317, E-ISSN 1465-2099, Vol. 84, no 4, 875-883 p.Article in journal (Refereed)
    Abstract [en]

    The rotavirus genome encodes two glycoproteins, one structural (VP7) and one non-structural (NSP4), both of which mature and remain in the endoplasmic reticulum (ER). While three amino acids in the N terminus have been proposed to function as a retention signal for VP7, no information is yet available on how NSP4 remains associated with the ER. In this study, we have investigated the ER retention motif of NSP4 by producing various C-terminal truncations. Deleting the C terminus by 52 amino acids did not change the intracellular distribution of NSP4, but an additional deletion of 38 amino acids diminished the ER retention and resulted in the expression of NSP4 on the cell surface. Brefeldin A treatment prevented NSP4 from reaching the cell surface, suggesting that C-terminal truncated plasma membrane NSP4 is transported through the normal secretory pathway. On the basis of these results, we propose that the region between amino acids 85 and 123 in the cytoplasmic region of NSP4 are involved in ER retention.

  • 43.
    Wiréhn, Ann-Britt
    Linköping University, Department of Medicine and Health Sciences, Health and Society. Linköping University, Faculty of Health Sciences.
    A Data-Rich World: Population‐based registers in healthcare research2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Advances and integration of information and communication technologies into healthcare systems offer new opportunities to improve public health worldwide. In Sweden, there are already unique possibilities for epidemiological research from registers because of a long tradition of centralized data collection into population-based registers and their allowance for linkage. The growing efficiency of automated digital storage provides growing volumes of archived data that increases the potential of analyses further.

    The purpose of this thesis can be divided into two parallel themes: illustrations and discussions of the use and usefulness of population-based registers on the one hand, and specific research questions in epidemiology and healthcare research on the other. The research questions are addressed in separate papers.

    From the Swedish Cancer Registry, 25 years of incidence data on testicular cancer was extracted for a large cohort. Record linkage to survey data on serum cholesterol showed a highly significant positive association, suggesting that elevated serum cholesterol concentration is a risk factor for testicular cancer. Since the finding is the first of its kind and because of wide confidence intervals further studies are needed to confirm the association.

    Östergötland County council’s administra-tive database (the Care Data Warehouse in Östergötland (CDWÖ)) provided data for preva-lence estimations of four common chronic diseases.

    The prevalence rate agreed very well with previous estimates for diabetes and fairly well with those for asthma. For hypertension and chronic obstructive pulmonary disease, the observed rates were lower than previous prevalence estimates. Data on several consecutive years covering all healthcare levels are needed to achieve valid prevalence estimates.

    CDWÖ data was also used to analyse the impact of diabetes on the prevalence of ischemic heart disease. Women had higher diabetes/non-diabetes prevalence rate ratios across all ages. The relative gender difference remained up to the age of 65 years and thereafter decreased considerably.

    The age-specific direct healthcare cost of diabetes was explored using data from the CDWÖ, the county council’s Cost Per Patient database and the Swedish Prescribed Drug Register. The cost per patient and the relative magnitude of different cost components varied considerably by age, which is important to consider in the future planning of diabetes management.

    The Cancer Registry was established mainly as a basis for epidemiological surveillance and research, exemplified in this thesis by a study on testicular cancer. In contrast, the newly established and planned healthcare databases in different Swedish counties are mainly for managerial purposes. As is shown in this thesis, these new databases may also be used to address problems in epidemiology and healthcare research.

    List of papers
    1. Serum cholesterol and testicular cancer incidence in 45 000 men followed for 25 years
    Open this publication in new window or tab >>Serum cholesterol and testicular cancer incidence in 45 000 men followed for 25 years
    2005 (English)In: British Journal of Cancer, ISSN 0007-0920, Vol. 92, no 9, 1785-1786 p.Article in journal (Refereed) Published
    Abstract [en]

    In a 25-year follow-up study of 44 864 men with measured serum cholesterol levels, the testicular cancer hazard ratios for the serum cholesterol categories 5.7–6.9 and ≥7.0 mmol l-1 vs the reference category (<5.7 mmol l-1) were 1.3 and 4.5, respectively; P-value for trend=0.005. This highly significant association suggests that high-serum cholesterol is a risk factor for testicular cancer.

    Keyword
    epidemiology, testicular neoplasm, cholesterol
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-12757 (URN)10.1038/sj.bjc.6602539 (DOI)
    Available from: 2007-11-06 Created: 2007-11-06 Last updated: 2011-02-03
    2. Estimating disease prevalence using a population-based administrative healthcare database
    Open this publication in new window or tab >>Estimating disease prevalence using a population-based administrative healthcare database
    2007 (English)In: Scandinavian Journal of Public Health, ISSN 1403-4948, Vol. 35, no 4, 424-431 p.Article in journal (Refereed) Published
    Abstract [en]

    Aims: In Östergötland County, Sweden, all data on hospital care and primary healthcare (PHC) have been entered in a diagnosis-related administrative database since 1999. This database was used to estimate the prevalence of four chronic diseases and to examine the capture of data in PHC, outpatient hospital care, and inpatient hospital care, considered in different time frames.

    Methods: A case-finding algorithm identified patients with at least one healthcare contact involving a diagnosis of diabetes, hypertension, asthma, or chronic obstructive pulmonary disease (COPD) in 1999—2003. Prevalence rates were calculated as the ratio of the number of identified patients alive to the total number of inhabitants on 31 December 2003 (n~415,000).

    Results: Prevalence rates were 4.4% for diabetes, 10.3% for hypertension, 4.5% for asthma, and 1.2% for COPD. For all four diagnoses, the proportions of patients identified on only one healthcare level were greatest for PHC, reaching rates of 23%, 68%, 53%, and 48%, respectively. The cases identified solely in PHC comprised larger proportions of women and patients over the age of 65 years. Considering the proportion of patients identified in 2003 in relation to the total five-year period gave values of 71%, 50%, 38%, and 58%, respectively, for the four diagnoses.

    Conclusions: The administrative healthcare databases in Sweden today can be important tools in epidemiological research. However, data on several consecutive years and both PHC and hospital data are needed to achieve valid prevalence estimates.

    Keyword
    Asthma, COPD, diabetes mellitus, epidemiology, healthcare, hypertension, inpatients, prevalence, primary outpatients, registries
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-12758 (URN)10.1080/14034940701195230 (DOI)
    Available from: 2007-11-06 Created: 2007-11-06 Last updated: 2009-05-19
    3. Age and Gender Differences in the Impact of Diabetes on the Prevalence of Ischemic Heart Disease: a Population-Based Register Study
    Open this publication in new window or tab >>Age and Gender Differences in the Impact of Diabetes on the Prevalence of Ischemic Heart Disease: a Population-Based Register Study
    2008 (English)In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 79, no 3, 497-502 p.Article in journal (Refereed) Published
    Abstract [en]

    Objective: To explore age and gender differences in the impact of diabetes on the prevalence of ischemic heart disease (IHD) in a defined population.

    Methods: Data were obtained from an administrative health care register covering a population of about 415 000. The study included all patients aged 45-74 years diagnosed between 1999-2003 with IHD (n=11 311) and diabetes (n=10 364) by physicians at all primary health care centres (PHCs) and out- and inpatient clinics at all hospitals in the county of Östergötland, Sweden.

    Results: In the 45-54 year-old age group, diabetes was associated with an increase in IHD prevalence equivalent to ageing about 20 years in women and 10 years in men. The diabetes/nondiabetes IHD prevalence rate ratio (IPR) decreased with age in both men and women (trend p-values < 0.001). The IPR was higher among women than men in each age group, though the female relative excess decreased from 75% higher in the 45-54 year-old age group to 33% higher in the 65-74 year-old age group (trend p-value = 0.018).

    Conclusions: The relative gender difference in the impact of diabetes on IHD in younger middle-aged patients remained up to the age of 65 years, decreasing considerably thereafter.

    Place, publisher, year, edition, pages
    Institutionen för medicin och hälsa, 2008
    Keyword
    aging, coronary disease, diabetes mellitus, prevalence, sex differences
    National Category
    Social Sciences
    Identifiers
    urn:nbn:se:liu:diva-11241 (URN)10.1016/j.diabres.2007.10.009 (DOI)
    Note
    Original publication: Ann-Britt E. Wiréhn, Carl Johan Östgren and John M. Carstensen, Age and Gender Differences in the Impact of Diabetes on the Prevalence of Ischemic Heart Disease: a Population-Based Register Study, 2008, Diabetes Research and Clinical Practice, (79), 3, 497-502. http://dx.doi.org/10.1016/j.diabres.2007.10.009. Copyright: Elsevier B.V., http://www.elsevier.com/Available from: 2008-03-12 Created: 2008-03-12 Last updated: 2011-02-03
    4. Age-specific direct health care costs attributable to diabetesin a Swedish population: a register-based analysis
    Open this publication in new window or tab >>Age-specific direct health care costs attributable to diabetesin a Swedish population: a register-based analysis
    2008 (English)In: Diabetic Medicine, ISSN 0742-3071, Vol. 25, no 6, 732-737 p.Article in journal (Refereed) Published
    Abstract [en]

    Aims: The aim of this population-based study was to explore the age-specific additional direct healthcare cost for patients with diabetes compared with the non-diabetic population.

    Methods: In 1999-2005, patients with diabetes in the Swedish county of Östergötland (n = 20 876) were identified from an administrative database. Cost data on the healthcare expenditure in primary healthcare, out-patient hospital care and in-patient care for the entire county population (n = ∼415 000) in 2005 were extracted from a cost per patient (CPP) database, which includes information on all utilized healthcare resources in the county. Data on drug sales were obtained from the Swedish Prescribed Drug Register.

    Results: The cost per person was 1.8 times higher in patients with diabetes than in the non-diabetic population, 7.7 times higher in children and 1.3 times higher in subjects aged > 75 years. The additional cost per person for diabetes was €1971; €3930 and €1367, respectively, for children and subjects aged > 75 years. The proportion of total additional diabetes costs attributable to in-patient care increased with age from 25 to 50%; in-patient care was the most expensive component at all ages except in children, for whom visiting a specialist was most expensive. The diabetes-related segment of the total healthcare cost was 6.6%, increasing from 2.0% in children to 10.3% in the age group 65-74 years, declining to 6.2% in the oldest age group.

    Conclusions: The direct medical cost of diabetes varies considerably by age. Knowledge about the influence of age on healthcare costs to society will be important in future planning of diabetes management.

    Keyword
    Diabetes, Economics, Healthcare delivery, Prevalence, Registers
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-12760 (URN)10.1111/j.1464-5491.2008.02444.x (DOI)
    Available from: 2007-11-06 Created: 2007-11-06 Last updated: 2009-08-21
  • 44.
    Kindberg, Elin
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology . Linköping University, Faculty of Health Sciences.
    Mickiene, Aukse
    Department of Medicine Karolinska University Hospital Huddinge.
    Ax, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Åkerlind, Britt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Vene, Sirkka
    5Swedish Institute for Infectious Disease Control Karolinska Institutet, Stockholm.
    Lindquist, Lars
    Department of Medicine Karolinska University Hospital Huddinge.
    Lundkvist, Åke
    Swedish Institute for Infectious Disease Control Karolinska Institutet, Stockholm.
    Svensson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Molecular Virology . Linköping University, Faculty of Health Sciences.
    A deletion in the chemokine receptor 5 (CCR5) gene is associated with tickborne encephalitis2008In: Journal of Infectious Diseases, ISSN 0022-1899, Vol. 197, no 2, 266-269 p.Article in journal (Refereed)
    Abstract [en]

    Tickborne encephalitis (TBE) virus infections can be asymptomatic or cause moderate to severe injuries of the central nervous system. Why some individuals develop severe disease is unknown, but a role for host genetic factors has been suggested. To investigate whether chemokine receptor CCR5 is associated with TBE, CCR5Δ32 genotyping was performed among Lithuanian patients with TBE (n = 129) or with aseptic meningoencephalitis (n = 76) as well as among control subjects (n = 134). We found individuals homozygous for CCR5Δ32 (P = .026) only among patients with TBE and a higher allele prevalence among patients with TBE compared with the other groups studied. CCR5Δ32 allele prevalence also increased with the clinical severity of disease. © 2007 by the Infectious Diseases Society of America. All rights reserved.

  • 45.
    Karlsson, Thomas
    et al.
    Linköping University, Faculty of Arts and Sciences. Linköping University, Department of Behavioural Sciences, Cognition, Development and Disability.
    Johansson, I.
    Adolfsson, R.
    Nilsson, L-G.
    Dubuc, S.
    A demonstration of a remarkable memory capacity in Alzheimer's Disease2003In: Dementia and Geriatric Cognitive Disorders, ISSN 1420-8008, Vol. 15Article in journal (Refereed)
  • 46.
    Holm, E
    et al.
    Umeå.
    Timpka, Toomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, Division of Preventive and Social Medicine and Public Health Science. Östergötlands Läns Landsting, Centre for Public Health Sciences, Centre for Public Health Sciences.
    A discrete time-space geography for epidemiology: from mixing groups to pockets of local order in pandemic simulations.2007In: MEDINFO 2007 - Proceedings of the 12th World Congress on Health (Medical) Informatics – Building Sustainable Health Systems / [ed] Klaus A. Kuhn, James R. Warren, Tze-Yun Leong, 2007, Vol. 12, no 1, 464- p.Conference paper (Refereed)
    Abstract [en]

    The World Health Organization urges all nations to develop and maintain national influenza preparedness plans. Important components of such plans are forecasts of morbidity and mortality based on local social and geographic conditions. Most methodologies for simulations of epidemic outbreaks are implicitly based on the assumption that the frequency and duration of social contacts that lead to disease transmission is affected by geography, i.e. the spatial distribution of physical meeting places. In order to increase the effectiveness of the present methods for simulation of infectious disease outbreaks, the aim of this study is to examine two social geographic issues related to such models. We display how the social geographic characteristics of mixing networks, in particular when these significantly deviate from the random-mixing norm, can be represented in order to enhance the understanding and prediction of epidemic patterns in light of a possible future destructive influenza pandemic. We conclude that social geography, social networks and simulation models of directly transmitted infectious diseases are fundamentally linked.

  • 47.
    Svärd, Anna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Kastbom, Alf
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
    Sommarin, Yngve
    EuroDiagnostica AB, Malmö.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
    A disease-modifying role for mucosal IgA antibodies to citrullinated antigens?2012In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 71, no Issue suppl. 1, A38-A39 p.Article in journal (Refereed)
    Abstract [en]

    Objective

    The aim of this study was to investigate whether immunoglobulin A (IgA) antibodies to cyclic citrullinated peptides CCP) can be detected in saliva of patients with established heumatoid arthritis (RA) and if it relates to clinical manifestations.

    Methods

    Salivary samples were collected (by ‘passive drooling’) from 63 consecutive patients with established RA at a visit to the rheumatology outpatient clinic (Falun, Sweden), and from 20 healthy persons (hospital staff). The samples were centrifuged and kept frozen at −70°C until analysis. IgA-class anti-CCP antibodies in saliva were analysed by adaptation of commercial ELISA (Immunoscan RA, Euro-Diagnostica AB, Malmo, Sweden) using polyclonal rabbit antihuman α-chain specific antibodies conjugated with horseradish peroxidase(DakoCytomation, Glostrup, Denmark) as secondary antibody. To ensure specificity of the reaction, a corresponding ELISA was set up to analyse IgA antibodies to control antigen(cyclic arginine peptide, CAP), and anti-CCP/anti-CAP ratios were calculated. Also, inhibition studies were performed by preincubation of sera with soluble CCP or CAP. Clinical and laboratory data on disease activity, that is, C reactive protein (CRP), erythrocyte sedimentation rate (ESR), and 28-joint count disease activity score (DAS28) as well as radiological outcome (occurrence or absence of erosions as judged by a radiologist in diagnostic routine) were achieved retrospectively via the patients’ medical records.

    Results

    Background reactivity against CCP was found in virtually all patients and healthy subjects, whereas a positive anti-CCP/anti-CAP ratio (≥1.5) was found in 14 out of 63 RA patients (22%) and in one healthy subject (5%). Salivary IgA-reactivity with CCP was dose-dependently inhibited by soluble CCP (but not with CAP) in sera with anti-CCP/anti- CAP ratios ≥1.5. No IgG-reactivity to CCP was found in saliva, although all patients with salivary IgA anti-CCP tested IgG anti-CCP-positive in serum. Furthermore, less than half of those testing IgA-positive in saliva were IgA anti-CCP positive in serum, strongly arguing against passive leakage of anti-CCP antibodies from blood to saliva. The patients testing positive for salivary IgA antibodies had lower average disease activity measures (CRP, ESR, DAS28) at presentation and fewer developed bony erosions within 6 years after presentation (p=0.043, Fisher’s exact test).

    Conclusion

    Salivary IgA antibodies to citrullinated proteins were found in a subset of IgG anti-CCP positive RA patients. In contrast to their serum counterparts, salivary IgA antibodies may associate with a milder/less destructive disease course. This accords with the notion that secretory IgA antibodies exert anti-inflammatory actions, and that they may be associated with induction of systemic tolerance (oral tolerance). The possible disease-modifying role of mucosal immunity to citrullinated proteins needs further investigation!

                    

                                                                    

  • 48.
    Svärd, Anna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Kastbom, Alf
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
    Sommarin, Yngve
    Eurodiagnostica AB.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
    A Disease-Modifying Role for Mucosal IgA Antibodies to Citrullinated Antigens? in ARTHRITIS AND RHEUMATISM, vol 63, issue 10, pp S849-S8492011In: ARTHRITIS AND RHEUMATISM, Wiley-Blackwell , 2011, Vol. 63, no 10, S849-S849 p.Conference paper (Refereed)
    Abstract [en]

    n/a

  • 49.
    Ockander, Marlene
    Linköping University, Department of Department of Health and Society, Division of Preventive and Social Medicine and Public Health Science. Linköping University, Faculty of Health Sciences.
    A female lay perspective on health, disease, and sickness absence2001Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Knowledge about a female perspective on health and disease is important to understand what happens in e.g. the medical meeting. A deeper understanding for the phenomenon of health also has social and economic importance. In Sweden women account for about 60% of the long-term cases of sickness absence.

    Aim: To explore and describe women's perceptions of health and disease and their accounts of sickness absence.

    Methods: The chronic diseases mentioned by elderly women in an interview study are compared with those documented in their respective medical records (n=199). The prevalence of positive diagnoses, overall agreement, and the kappa-coefficient were calculated for each group of diagnoses. Semi-stmctnred interviews were conducted with 82 women who had been on sick leave (60 days or more) or who had disability pension. Sixty of these middle-aged women also carried out a Q-sort.

    Results: The lowest overall agreement between the elderly women report during interviews and their medical records was observed for psychiatric diseases, followed by diseases of the gastrointestinal system. Poor chance-adjusted agreement was found concerning diseases of the gastrointestinal system and diseases of the skin (Paper I). Long-term sickness absence can be said to arise in three distinguishable "spaces": the workspace, the medical-legal space, and the mental space. In the beginning, the women were positive about sick leave as such, which they saw as an opportunity for physical rest. But as time went on, they came to regard sick leave as creating a vicious circle of new problems related to inactivity and isolation. Apart from this vicious circle and chronic physical impairments, certain conditions at the workplace, at the hospital, and the social insurance office transformed seemingly trivial sick leaves into long-term and irreversible sickness absences (Paper II). The women's accounts of being sickness absent contained interpretations of what had happened to them, how things were for the moment, and what they thought the future would bring. Three different accounts could be distinguished: the crisis, the breakpoint, and the migration. The perceptions of their own situation and especially what they thought about their future were associated with their feelings of power to initiative and well-being. The descriptions of life on sick leave are connected to a theory of "loss of work" (Paper III). For these women, to be able to get back to work was found to be equivalent to breaking away from the prospect of isolation and loneliness. Five actors were identified along with suggestions for their actions: the woman who is on sick leave herself, the employer, the health care provider, the social insurance official, and the shop-steward. It was found important to take oneself seriously and also to be taken seriously by others. The results are related to a theory of enduring and suffering (Paper IV). Six accounts representing different conceptions of health, illness, and medicine were identified and described (Paper V).

    Conclusions: The results point to the importance of doing research from different perspectives, using different methods and different sources of information to obtain a deeper understanding of a complex phenomenon like health. Above all, the results presented in this thesis point to a large variation at the individual level in perceptions, which implies the need for care in, for example, the planning of rehabilitation programs. The results also highlight the point that sick leave without follow-up from work, health care, and the social insurance office might have negative consequences on health. Implications for practice are suggested along with proposals for future research.

    List of papers
    1. Patient-doctor Concordance in Elderly Women’s Self-reported Health and Medical Records
    Open this publication in new window or tab >>Patient-doctor Concordance in Elderly Women’s Self-reported Health and Medical Records
    2002 (English)In: Methods of Information in Medicine, ISSN 0026-1270, Vol. 41, no 2, 119-124 p.Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVES: To compare the chronic diseases mentioned by elderly women in an interview study with those documented in their respective medical records.

    METHODS: The prevalence of positive diagnoses, overall agreement, and the kappa-coefficient were calculated for each group of diagnoses.

    RESULTS: The lowest overall agreement was observed for psychiatric diseases, followed by diseases of the gastrointestinal system. Poor chance-adjusted agreement was found concerning diseases of the gastrointestinal system and diseases of the skin.

    CONCLUSIONS: The results suggest that a main reason for discordance was that the elderly women feared "losing face" by reporting some diseases.

    Keyword
    diagnosis, women, medical records, patients, medical decision making
    National Category
    Social Sciences
    Identifiers
    urn:nbn:se:liu:diva-26291 (URN)12061118 (PubMedID)10807 (Local ID)10807 (Archive number)10807 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2013-09-05Bibliographically approved
    2. A female lay perspective on the establishment of long-term sickness absence
    Open this publication in new window or tab >>A female lay perspective on the establishment of long-term sickness absence
    2001 (English)In: International Journal of Social Welfare, ISSN 1369-6866, E-ISSN 1468-2397, Vol. 10, no 1, 74-79 p.Article in journal (Refereed) Published
    Abstract [en]

    In Sweden women account for about 60% of the long-term cases of sickness absence. The aim of this study was to describe women's explanations as to how long-term sickness absence arises and becomes permanent, with reference to their personal experience. Semi-structured interviews were performed with 82 middle-aged women who have personal experience of long-term sickness absence. Long-term sickness absence can be said to arise in three distinguishable “spaces”: the work space, the medico-legal space and the mental space. In the beginning, the women were positive about sick-leave as such, which they saw as an opportunity for physical rest. But as time went on, they came to regard sick-leave as creating a vicious circle of new problems related to inactivity and isolation. Apart from this vicious circle and chronic physical impairments, certain conditions at the workplace, at the hospital and the social insurance office transformed seemingly trivial sick-leaves into long-term and irreversible sickness absences

    Keyword
    sickness absence, lay explanation models, women, phenomenology, interview
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-26067 (URN)10.1111/1468-2397.00154 (DOI)10526 (Local ID)10526 (Archive number)10526 (OAI)
    Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2013-09-05Bibliographically approved
    3. Women's experiences of long term sickness absence: Is there a "loss of work syndrome"?
    Open this publication in new window or tab >>Women's experiences of long term sickness absence: Is there a "loss of work syndrome"?
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: In most European countries, long-term sickness absence contribute the greatest number of days that are reimbursed due to sickness absence. This group is growing and it is constituted mainly of women.

    Aim: The present study seeks further knowledge about what happens then and there, i.e., how long-term sickness absent women handle and explain, for themselves and others, this interruption in their daily life.

    Methods: Semi-structured interviews were performed with 82 middle-aged women with personal experience from long-term sickness absence.

    Results: The women's accounts of being sickness absent contained interpretations of what had happen to them, how things were for the moment, and what they thought the future would bring. Three different accounts could be distinguished: the crisis, the breakpoint, and the migration. The perception of their own situation and especially what they thought about their future was associated with their feeling of power to initiative and well-being.

    Conclusion: From our study we have found implications for central topics of importance: time elapse, sense of coherence, reorientation/adaptation, and vital goals.

    Keyword
    Vital goal, life plan, sense of coherence, phenomenology, women, sickness absence
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-80264 (URN)
    Available from: 2012-08-23 Created: 2012-08-23 Last updated: 2013-09-05Bibliographically approved
    4. How to avoid the frightening scenario of long-term sickness absence: The advice from women with personal experience
    Open this publication in new window or tab >>How to avoid the frightening scenario of long-term sickness absence: The advice from women with personal experience
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Aims: The aim of this study was to describe women's perceptions of what can be done to avoid long-term sickness absence.

    Methods: Interviews were conducted with 82 women who had been on sickness absence ( 60 days or more) or had disability pensions.

    Results: For these women, to be able to get back to work was found to be equivalent to breaking away from the prospect of isolation and loneliness. Five actors were identified along with suggestions for their actions: the woman who is on sick leave herself, the employer, the healthcare provider, the social insurance official, and the shop-steward.

    Conclusions: It is important to take oneself seriously and also to be taken seriously by others. Thus, it is important to not wait too long to take action which concerns both the individual herself and all those who get involved in her case at work, at hospital or at the social insurance office. Practical advice to reach recovery and avoid sickness absence is presented.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-80265 (URN)
    Available from: 2012-08-23 Created: 2012-08-23 Last updated: 2013-09-05Bibliographically approved
    5. Accounts of health, illness and medicine in women on long-term sickness absence
    Open this publication in new window or tab >>Accounts of health, illness and medicine in women on long-term sickness absence
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Long-term sickness absence has grown to an important social and economic question and it affects women more than men. The specific aim of the study was to identify patterns of association between ideas of health endorsed by groups of women having a close firsthand experience of long-term sickness absence. Using the Q-methodology, in a group of 60 middle-aged women, six accounts representing different conceptions of health, illness, and medicine were identified. Future studies should be implemented to investigate the prospective value of the categorisation identified in this study e.g. to see whether, and in that case how, these conceptions affect sick leave and rehabilitation.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-80266 (URN)
    Available from: 2012-08-23 Created: 2012-08-23 Last updated: 2013-09-05Bibliographically approved
  • 50.
    Ramström, A Sofia
    et al.
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Fagerberg, I.
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Lindahl, Tomas
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    A flow cytometric assay for the study of dense granule storage and release in human platelets1999In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 10, no 2-3, 153-158 p.Article in journal (Refereed)
    Abstract [en]

    The clinical manifestations of platelet dense (δ) granule defects are easy bruising, as well as epistaxis and bleeding after delivery, tooth extractions and surgical procedures. The observed symptoms may be explained either by a decreased number of granules or by a defect in the uptake/release of granule contents. We have developed a method to study platelet dense granule storage and release. The uptake of the fluorescent marker, mepacrine, into the platelet dense granule was measured using flow cytometry. The platelet population was identified by the size and binding of a phycoerythrin-conjugated antibody against GPIb. Cells within the discrimination frame were analysed for green (mepacrine) fluorescence. Both resting platelets and platelets previously stimulated with collagen and the thrombin receptor agonist peptide SFLLRN was analysed for mepacrine uptake. By subtracting the value for mepacrine uptake after stimulation from the value for uptake without stimulation for each individual, the platelet dense granule release capacity could be estimated. Whole blood samples from 22 healthy individuals were analysed. Mepacrine incubation without previous stimulation gave mean fluorescence intensity (MFI) values of 83±6 (mean ± 1 SD, range 69–91). The difference in MFI between resting and stimulated platelets was 28±7 (range 17–40). Six members of a family, of whom one had a known δ-storage pool disease, were analysed. The two members (mother and son) who had prolonged bleeding times also had MFI values disparate from the normal population in this analysis. The values of one daughter with mild bleeding problems but a normal bleeding time were in the lower part of the reference interval.

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