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  • 1.
    Almroth, Henrik
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Andersson, Torbjorn
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Fengsrud, Espen
    Örebro University, School of Health Sciences. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Friberg, Leif
    Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
    Linde, P.
    Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Rosenqvist, Mårten
    Stockholm South Hospital, Karolinska Institutet, Stockholm, Sweden.
    Englund, A.
    Stockholm South Hospital, Karolinska Institutet, Stockholm, Sweden.
    The safety of flecainide treatment of atrial fibrillation: long-term incidence of sudden cardiac death and proarrhythmic events2011In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 270, no 3, p. 281-290Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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

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

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

  • 2.
    Bengtsson, Torbjörn
    et al.
    Department of Medical and Health Sciences, Cardiovascular Inflammation Research Centre, Linköping University, Linköping, Sweden; Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Karlsson, H
    Department of Clinical and Experimental Medicine, Cardiovascular Inflammation Research Centre, Linköping University, Linköping, Sweden.
    Gunnarsson, P
    Department of Medical and Health Sciences, Cardiovascular Inflammation Research Centre, Linköping University, Linköping, Sweden.
    Skoglund, C
    Department of Medical and Health Sciences, Cardiovascular Inflammation Research Centre, Linköping University, Linköping, Sweden.
    Elison, C
    Department of Clinical and Experimental Medicine, Cardiovascular Inflammation Research Centre, Linköping University, Linköping, Sweden.
    Leanderson, P
    Department of Clinical and Experimental Medicine, Cardiovascular Inflammation Research Centre, Linköping University, Linköping, Sweden.
    Lindahl, M
    Department of Clinical and Experimental Medicine, Cardiovascular Inflammation Research Centre, Linköping University, Linköping, Sweden.
    The periodontal pathogen Porphyromonas gingivalis cleaves apoB-100 and increases the expression of apoM in LDL in whole blood leading to cell proliferation2008In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 263, no 5, p. 558-571Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 3.
    Coorevits, Pascal
    et al.
    Ghent University, Ghent, Belgium; The European Institute for Health Records (EuroRec), Sint-Martens-Latem, Belgium.
    Sundgren, M
    AstraZeneca R&D, Mölndal, Sweden.
    Klein, Gunnar O.
    University of Science and Technology, Trondheim, Norway.
    Bahr, A
    Sanofi R&D, Chilly-Mazarin, France.
    Claerhout, B
    Custodix NV, Sint-Martens-Latem, Belgium.
    Daniel, C
    Paris Descartes University INSERM, Paris, France.
    Dugas, M
    University of Münster, Münster, Germany.
    Dupont, D
    Data Mining International SA, Geneva, Switzerland.
    Schmidt, A
    Pharma Product Development, F Hoffmann-La Roche Ltd, Basel, Switzerland.
    Singleton, P
    Cambridge Health Informatics, Cambridge, UK.
    De Moor, G
    Ghent University, Ghent, Belgium; The European Institute for Health Records (EuroRec), Sint-Martens-Latem, Belgium.
    Kalra, D
    University College London, London, UK.
    Electronic health records: new opportunities for clinical research2013In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 274, no 6, p. 547-60Article in journal (Refereed)
    Abstract [en]

    Clinical research is on the threshold of a new era in which electronic health records (EHRs) are gaining an important novel supporting role. Whilst EHRs used for routine clinical care have some limitations at present, as discussed in this review, new improved systems and emerging research infrastructures are being developed to ensure that EHRs can be used for secondary purposes such as clinical research, including the design and execution of clinical trials for new medicines. EHR systems should be able to exchange information through the use of recently published international standards for their interoperability and clinically validated information structures (such as archetypes and international health terminologies), to ensure consistent and more complete recording and sharing of data for various patient groups. Such systems will counteract the obstacles of differing clinical languages and styles of documentation as well as the recognized incompleteness of routine records. Here, we discuss some of the legal and ethical concerns of clinical research data reuse and technical security measures that can enable such research while protecting privacy. In the emerging research landscape, cooperation infrastructures are being built where research projects can utilize the availability of patient data from federated EHR systems from many different sites, as well as in international multilingual settings. Amongst several initiatives described, the EHR4CR project offers a promising method for clinical research. One of the first achievements of this project was the development of a protocol feasibility prototype which is used for finding patients eligible for clinical trials from multiple sources.

  • 4.
    Eggers, K. M.
    et al.
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Hjort, M.
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Baron, T.
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Jernberg, T.
    Department of Clinical Sciences, Cardiology, Danderyd Hospital, Karolinska Institute, Stockholm, Sweden.
    Nordenskjöld, A. M.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Cardiology.
    Tornvall, P.
    Department of Clinical Science and Education, Södersjukhuset, Karolinska Institute, Stockholm, Sweden.
    Lindahl, B.
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Morbidity and cause-specific mortality in first-time myocardial infarction with nonobstructive coronary arteries2019In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 285, no 4, p. 419-428Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) is receiving increasing interest as a prognostically adverse entity distinct from myocardial infarction with significant coronary artery disease (MI-CAD). However, data are still limited regarding long-term cardiovascular morbidity and cause-specific mortality in MINOCA.

    METHODS: This is a registry-based cohort study using data from patients admitted to Swedish coronary care units. We investigated various nonfatal outcomes (recurrent MI, hospitalization for heart failure or stroke) and fatal outcomes (cardiovascular, respiratory or cancer-related mortality) in 4069 patients without apparent acute cardiovascular disease, used as non-MI controls, 7266 patients with first-time MINOCA and 69 267 patients with first-time MI-CAD.

    RESULTS: Almost all event rates (median follow-up 3.8 years) increased in a stepwise fashion across the three cohorts [rates of major adverse events (MAE; composite of all-cause mortality, recurrent MI, hospitalization for heart failure or stroke): n = 268 (6.6%), n = 1563 (21.5%), n = 17 777 (25.7%), respectively]. Compared to non-MI controls, MINOCA patients had an adjusted hazard ratio (HR) of 2.12 (95% confidence interval 1.84-2.43) regarding MAE. MINOCA patients had a substantial risk of cardiovascular mortality and the highest numerical risks of respiratory and cancer-related mortality. Male sex, previous heart failure and chronic obstructive pulmonary disease had a stronger prognostic impact in MINOCA than in MI-CAD. Female MINOCA patients with atrial fibrillation were at particular risk.

    CONCLUSIONS: Patients with first-time MINOCA have a considerable risk of adverse events. This stresses the need for a comprehensive search of the cause of MINOCA, thorough treatment of underlying disease triggers and close follow-up.

  • 5.
    Elfström, Peter
    et al.
    Örebro University, School of Health and Medical Sciences.
    Hamsten, Anders
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Ekbom, Anders
    Ludvigsson, Jonas F.
    Cardiomyopathy, pericarditis and myocarditis in a population-based cohort of inpatients with coeliac disease2007In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 262, no 5, p. 545-554Article in journal (Refereed)
    Abstract [en]

    Objectives: We investigated the risk of myocarditis, cardiomyopathy, and pericarditis in patients with celiac disease (CD) from a general population cohort.Subjects and methods: Through the Swedish national registers we identified 9363 children and 4969 adults with a diagnosis of CD (1964–2003). These individuals were matched with upto five reference individuals for age, sex, calendar year and county (n = 69 851). Cox regression estimated hazard ratios (HRs) for later heart disease. Main outcome measures: Myocarditis, cardiomyopathy (any or dilated), and pericarditis defined according torelevant international classification of disease codes in the Swedish national inpatient register.Results: Celiac disease diagnosed in childhood was not associated with later myocarditis (HR = 0.2; 95% CI = 0.0–1.5), cardiomyopathy of any type (HR = 0.8; 95% CI = 0.2–3.7), or pericarditis (HR = 0.4; 95% CI = 0.1–1.9). Restricting our analyses to adulthood CD and heart disease diagnosed from 1987 and onwards in departments of cardiology ⁄ internal medicine, we found no association between CD and later myocarditis (HR = 2.1; 95% CI = 0.4–11.7), dilated cardiomyopathy (HR = 1.7; 95% CI = 0.4– 6.5) or pericarditis (HR = 1.5; 95% CI = 0.5–4.0).Conclusion: This study found no association between CD, later myocarditis, cardiomyopathy or pericarditis

  • 6.
    Emilsson, Louise
    et al.
    Örebro University, School of Medicine, Örebro University, Sweden. Primary Care Research Unit, Vårdcentralen Värmlands Nysäter, Värmland County, Värmlands Nysäter, Sweden; Department of Health Management and Health Economy, Institute of Health and Society, University of Oslo, Oslo, Norway.
    Lindahl, B.
    Department of Medical Sciences, Cardiology, and Uppsala Clinical Research Center, University of Uppsala, Uppsala, Sweden.
    Köster, M.
    National Board of Health and Welfare, Stockholm, Sweden .
    Lambe, M.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Regional Cancer Centre, Uppsala, Sweden.
    Ludvigsson, Jonas F.
    Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Paediatrics, Örebro University Hospital, Örebro, Sweden.
    Review of 103 Swedish healthcare quality registries2015In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 277, no 1, p. 94-136Article in journal (Refereed)
    Abstract [en]

    Background and objectives: In the past two decades, an increasing number of nationwide, Swedish Healthcare Quality Registries (QRs) focusing on specific disorders have been initiated, mostly by physicians. Here, we describe the purpose, organization, variables, coverage and completeness of 103 Swedish QRs.

    Methods: From March to September 2013, we examined the 2012 applications of 103 QRs to the Swedish Association of Local Authorities and Regions (SALAR) and also studied the annual reports from the same QRs. After initial data abstraction, the coordinator of each QR was contacted at least twice between June and October 2013 and asked to confirm the accuracy of the data retrieved from the applications and reports.

    Results: About 60% of the QRs covered 80% of their target population (completeness). Data recorded in Swedish QRs include aspects of disease management (diagnosis, clinical characteristics, treatment and lead times). In addition, some QRs retrieve data on self-reported quality of life (EQ5D, SF-36 and disease-specific measures), lifestyle (smoking) and general health status (World Health Organization performance status, body mass index and blood pressure).

    Conclusion: Detailed clinical data available in Swedish QRs complement information from government-administered registries and provide an important source not only for assessment and development of quality of care but also for research.

  • 7.
    Freund-Levi, Yvonne
    et al.
    Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Vedin, I
    Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Cederholm, T
    Department of Public Health and Caring Sciences, Uppsala University Hospital, Uppsala, Sweden; Division of Clinical Nutrition and Metabolism, Uppsala University Hospital, Uppsala, Sweden.
    Basun, H
    Department of Public Health and Caring Sciences, Uppsala University Hospital, Uppsala, Sweden; Geriatrics, Uppsala University Hospital, Uppsala, Sweden.
    Faxén Irving, G
    Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Eriksdotter, M
    Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Hjorth, E
    Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Schultzberg, M
    Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Vessby, B
    Department of Public Health and Caring Sciences, Uppsala University Hospital, Uppsala, Sweden; Geriatrics, Uppsala University Hospital, Uppsala, Sweden.
    Wahlund, L-O
    Department of Neurobiology, Caring Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Salem, N
    National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville MD, United States.
    Palmblad, J
    Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Transfer of omega-3 fatty acids across the blood-brain barrier after dietary supplementation with a docosahexaenoic acid-rich omega-3 fatty acid preparation in patients with Alzheimer's disease: the OmegAD study2014In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 275, no 4, p. 428-436Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Little is known about the transfer of essential fatty acids (FAs) across the human blood-brain barrier (BBB) in adulthood. In this study, we investigated whether oral supplementation with omega-3 (n-3) FAs would change the FA profile of the cerebrospinal fluid (CSF).

    METHODS: A total of 33 patients (18 receiving the n-3 FA supplement and 15 receiving placebo) were included in the study. These patients were participants in the double-blind, placebo-controlled randomized OmegAD study in which 204 patients with mild Alzheimer's disease (AD) received 2.3 g n-3 FA [high in docosahexaenoic acid (DHA)] or placebo daily for 6 months. CSF FA levels were related to changes in plasma FA and to CSF biomarkers of AD and inflammation.

    RESULTS: At 6 months, the n-3 FA supplement group displayed significant increases in CSF (and plasma) eicosapentaenoic acid (EPA), DHA and total n-3 FA levels (P < 0.01), whereas no changes were observed in the placebo group. Changes in CSF and plasma levels of EPA and n-3 docosapentaenoic acid were strongly correlated, in contrast to those of DHA. Changes in DHA levels in CSF were inversely correlated with CSF levels of total and phosphorylated tau, and directly correlated with soluble interleukin-1 receptor type II. Thus, the more DHA increased in CSF, the greater the change in CSF AD/inflammatory biomarkers.

    CONCLUSIONS: Oral supplementation with n-3 FAs conferred changes in the n-3 FA profile in CSF, suggesting transfer of these FAs across the BBB in adults.

  • 8.
    Fröbert, Ole
    et al.
    Örebro University, School of Medical Sciences. Department of Cardiology.
    Frøbert, Anne Mette
    Department of Chemistry and Bioscience, Aalborg University, Aalborg, Denmark.
    Kindberg, Jonas
    Department of Wildlife, Fish and Environmental Studies, Swedish University of Agricultural Sciences, Umeå, Sweden; Norwegian Institute for Nature Research, Trondheim, Norway.
    Arnemo, Jon M.
    Department of Forestry and Wildlife Management, Inland Norway University of Applied Sciences, Koppang, Norway.
    Overgaard, Michael T.
    Department of Chemistry and Bioscience, Aalborg University, Aalborg, Denmark.
    The brown bear as a translational model for sedentary lifestyle related diseases2019In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796Article in journal (Refereed)
    Abstract [en]

    Sedentary lifestyle accelerates biological aging, is a major risk factor for developing metabolic syndrome and is associated with cardiovascular disease, diabetes mellitus, kidney failure, sarcopenia and osteoporosis. In contrast to the linear path to worsening health in humans with metabolic syndrome, brown bears have developed a circular metabolic plasticity enabling these animals to tolerate obesity and a "sedentary lifestyle" during hibernation and exit the den metabolically healthy in spring. Bears are close to humans physiology-wise, much closer than rodents, the preferred experimental animals in medical research, and may better serve as translational model to develop treatments for lifestyle-related diseases. In this review aspects of brown bear hibernation survival strategies are outlined and conceivable experimental strategies to learn from bears are described.

  • 9. Iggman, D.
    et al.
    Gustafsson, Inga-Britt
    Örebro University, School of Hospitality, Culinary Arts & Meal Science.
    Berglund, L.
    Vessby, B.
    Marckmann, P.
    Riserus, U.
    Replacing dairy fat with rapeseed oil causes rapid improvement of hyperlipidaemia: a randomized controlled study2011In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 270, no 4, p. 356-364Article in journal (Refereed)
    Abstract [en]

    Background. Rapeseed oil (RO), also known as canola oil, principally contains the unsaturated fatty acids 18:1n-9, 18:2n-6 and 18:3n-3 and may promote cardiometabolic health. Objective. To investigate the effects on lipoprotein profile, factors of coagulation and insulin sensitivity of replacing a diet rich in saturated fat from dairy foods (DF diet) with a diet including RO-based fat (RO diet). Design. During a 2 x 3-week randomized, controlled, cross-over trial, 20 free-living hyperlipidaemic subjects were provided with isocaloric test diets that differed in fat composition alone. Blood lipoprotein profile, coagulation and fibrinolytic factors and insulin sensitivity (euglycaemic clamp) were determined before and after the dietary intervention. Results. All subjects completed the study, and compliance was high according to changes in serum fatty acids. The RO diet, but not the DF diet, reduced the levels of serum cholesterol (-17%), triglycerides (-20%) and low-density lipoprotein cholesterol (-17%), cholesterol/high-density lipoprotein (HDL) cholesterol ratio (-21%), apolipoprotein (apo) B/apo A-I ratio (-4%) and factor VII coagulant activity (FVIIc) (-5%) from baseline. These changes were significantly different between the diets (P = 0.05 to P < 0.0001), except for FVIIc (P = 0.1). The RO diet, but not the DF diet, modestly increased serum lipoprotein( a) (+6%) and tended to increase the glucose disappearance rate (K-value, +33%). HDL cholesterol, insulin sensitivity, fibrinogen and tissue plasminogen activator inhibitor-1 levels did not change from baseline or differ between the two diets. Conclusions. In a diet moderately high in total fat, replacing dairy fat with RO causes a rapid and clinically relevant improvement in serum lipoprotein profile including lowering of triglycerides in hyperlipidaemic individuals.

  • 10.
    Jendle, Johan
    et al.
    Department of Internal Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Karlberg, B. E.
    Department of Internal Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Intrapulmonary administration of insulin to healthy volunteers1996In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 240, no 2, p. 93-98Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To study the biological effects of nebulized insulin, administered intrapulmonary, to healthy volunteers.

    DESIGN: A double-blind, randomized, controlled intervention study.

    SETTING: The department of Internal Medicine, University Hospital, Linköping, Sweden.

    SUBJECTS: Eight healthy, non-smoking volunteers, with a mean age of 28 (range 22 to 56) years.

    INTERVENTIONS: Regular human insulin 100 U mL-1 (Actrapid) or 0.9% saline was given randomly as an oral inhalation. Insulin was given in three different doses (40, 80 and 160 U). Aerosol was generated by a new jet nebulizer.

    MAIN OUTCOME MEASURES: Blood glucose, serum insulin, and serum C-peptide.

    RESULTS: After the 160 U insulin dose the blood glucose concentration (mean +/- SE) fell from 4.3 +/- 0.2 to 2.8 +/- 0.2 mmol L-1 (P < 0.001), concomitant with an increase in mean serum insulin concentrations, rising from 9.5 +/- 1.5 to 26.1 +/- 2.5 mU L-1 (P < 0.001). Serum C-peptide concentrations simultaneously decreased from 0.48 +/- 0.03 to 0.12 +/- 0.02 mmol L-1 (P < 0.001). All changes were dose dependent. No adverse reactions were noted and no significant changes in lung function tests.

    CONCLUSIONS: Intrapulmonary insulin administration to healthy subjects can induce a significant hypoglycaemia and cause a clinically relevant increase in serum insulin concentrations. If similar results can be obtained when administering insulin to diabetic subjects, this insulin administration route can be a future complement to certain groups of patients.

  • 11.
    Katsika, Despina
    et al.
    Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden.
    Tuvblad, Catherine
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Einarsson, Carl
    Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden.
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Marschall, Hans-Ulrich
    Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden.
    Body mass index, alcohol, tobacco and symptomatic gallstone disease: a Swedish twin study2007In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 262, no 5, p. 581-587Article in journal (Refereed)
    Abstract [en]

    Background/Aims: Both genetic and environmental factors are involved in the pathogenesis of gallstone disease (GD). We aimed to examine the association between symptomatic GD and overweight (body mass index, BMI, 25-30 kg m -2), obesity (BMI > 30 kg m-2), alcohol, smoking and smoke-free tobacco by analysing a large twin population.

    Methods: The Swedish Twin Registry (STR) was linked to the Swedish Hospital Discharge and Causes of Death Registries for GD and GD-surgery related diagnoses. Weight, height, use of alcohol, smoking and smoke-free tobacco were provided by STR and analysed for possible associations by conditional logistic regression.

    Results: Overweight and obesity were associated with a significantly higher risk for symptomatic GD in the whole study population (OR 1.86 and OR 3.38; CI: 1.52-2.28 and 2.28-5.02 respectively). High alcohol consumption was associated with a lower risk for GD in the whole population (OR 0.62; CI: 0.51-0.74) with no difference between discordant monozygotic and dizygotic twins (OR 1.08 and OR 0.96; CI: 0.82-1.42 and 0.79-1.16). Smoking or smoke-free tobacco was not correlated with GD.

    Conclusion: Consistent with epidemiological studies, we found positive associations between BMI and the development of symptomatic GD. High alcohol consumption was associated with a decreased risk against GD. Tobacco use has no impact on GD.

  • 12.
    Ludvigsson, Jonas F.
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Adami, H. O.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Clinical Effectiveness Research Group, University of Oslo, Oslo, Norway.
    The urgency to embrace Big Data opportunities in medicine2018In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, no 5, p. 479-480Article in journal (Other academic)
    Abstract [en]

    .

  • 13.
    Ludvigsson, Jonas F.
    et al.
    Department of Paediatrics, Örebro University Hospital, Örebro, Sweden; Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Inghammar, M.
    Section for Respiratory Medicine AND Allergology, Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, Lund, Sweden.
    Ekberg, M.
    Section for Respiratory Medicine AND Allergology, Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, Lund, Sweden.
    Egesten, A.
    Section for Respiratory Medicine AND Allergology, Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, Lund, Sweden.
    A nationwide cohort study of the risk of chronic obstructive pulmonary disease in coeliac disease2012In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 271, no 5, p. 481-489Article in journal (Refereed)
    Abstract [en]

    Objective: Chronic obstructive pulmonary disease (COPD) continues to be an important cause of morbidity, mortality and healthcare costs in the western world. Although smoking is an important trigger of COPD, other factors such as chronic inflammation and malnutrition are known to influence its development. Because coeliac disease (CD) is characterized both by dysregulated inflammation and malnutrition, the possibility of an association between CD and COPD was investigated.

    Methods: Through biopsy data from all Swedish pathology departments, we identified 10990 individuals with CD who were biopsied between 1987 and 2008 (Marsh 3: villous atrophy). As controls, 54129 reference individuals matched for age, sex, county and calendar year of first biopsy were selected. Cox regression analysis was then performed to estimate hazard ratios (HRs) for having a diagnosis of COPD according to the Swedish Patient Register.

    Results: During follow-up, 380 individuals with CD (3.5%) and 1391 (2.6%) controls had an incident diagnosis of COPD, which corresponds to an HR of 1.24 (95% CI: 1.10-1.38) and an excess risk of COPD of 79/100000 person-years in CD. The risk increase remained 5years after biopsy (HR=1.17; 95% CI: 1.00-1.37). Risk estimates did not change with adjustment for type 1 diabetes, thyroid disease, rheumatoid arthritis, country of birth or level of education. Men with CD were at a higher risk of COPD (HR=1.39; 95% CI: 1.18-1.62) than women with CD (HR=1.11; 95% CI: 0.94-1.30). Of note, CD was also associated with COPD before CD diagnosis (odds ratio=1.22; 95% CI: 1.02-1.46).

    Conclusion: Patients with CD seem to be at a moderately increased risk of COPD both before and after CD diagnosis.

  • 14. Moberg, Erik
    et al.
    Hjerpe, E
    Ehrsson, R
    Möller, Claes
    Örebro University, School of Health and Medical Sciences.
    Angelin, B
    Is endometroid cancer of the ovaries a late manifestation of Alström syndrome?2009In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 265, no 2, p. 296-298Article in journal (Refereed)
  • 15.
    Mollazadegan, K.
    et al.
    Dept Med, Clin Epidemiol Unit, Karolinska Inst, Stockholm, Sweden; St Erik Eye Hosp, Karolinska Inst, Stockholm, Sweden.
    Sanders, D. S.
    Gastroenterol & Liver Unit, Royal Hallamshire Hosp, Sheffield, England; Univ Sheffield, Sheffield, England.
    Ludvigsson, Johnny J.
    Dept Clin & Expt Med, Div Pediat, Linköping Univ, Linköping, Sweden; Pediat Clin, Linköping Univ Hosp, Linköping, Sweden.
    Ludvigsson, Jonas F.
    Örebro University Hospital. Dept Med, Clin Epidemiol Unit, Karolinska Inst, Stockholm, Sweden; Dept Pediat, Örebro University Hospital, Örebro, Sweden.
    Long-term coeliac disease influences risk of death in patients with type 1 diabetes2013In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 274, no 3, p. 273-280Article in journal (Refereed)
    Abstract [en]

    Aim. The aim of this study was to examine mortality in patients with both type 1 diabetes (T1D) and coeliac disease (CD). Methods. Between 1969 and 2008, we identified individuals with CD through biopsy reports from all pathology departments (n = 28) in Sweden. T1D was defined as a diagnosis of diabetes recorded in the Swedish National Patient Register between 1964 and 2009 in individuals aged <= 30 years. During follow-up, we identified 960 patients with both T1D and CD. For each individual with T1D and CD, we selected up to five subjects with T1D alone (i.e. no CD), matched for sex, age and calendar period of diagnosis, as the reference group (n = 4608). Using a stratified Cox regression analysis with CD as a time-dependent covariate, we estimated the risk of death in patients with both T1D and CD compared with those with T1D alone. Results. Stratifying for time since CD diagnosis, CD was not a risk factor for death in patients with T1D during the first 5 years after CD diagnosis [hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.43-1.73], but thereafter the HR for mortality increased as a function of follow-up time (5 to <10 years, HR 1.44, 95% CI 0.74-2.79; 10 to <15 years, HR 1.88, 95% CI 0.81-4.36). Having a CD diagnosis for >= 15 years was associated with a 2.80-fold increased risk of death in individuals with T1D (95% CI 1.28-6.12). Conclusion. A diagnosis of CD for >= 15 years increases the risk of death in patients with T1D.

  • 16.
    Persson, I.
    et al.
    Med Prod Agcy, Uppsala, Sweden.
    Granath, F.
    Dept Med, Clin Epidemiol Unit, Karolinska Inst, Stockholm, Sweden.
    Askling, J.
    Dept Med, Rheumatol Unit, Karolinska Inst, Stockholm, Sweden..
    Ludvigsson, Jonas F.
    Örebro University Hospital. Unit of Clinical Epidemiology, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Paediatrics, Örebro University Hospital, Örebro, Sweden.
    Olsson, T.
    Dept Clin Neurosci, Karolinska Inst, Stockholm, Sweden.
    Feltelius, N.
    Med Prod Agcy, Uppsala, Sweden; Dept Med, Rheumatol Unit, Karolinska Inst, Stockholm, Sweden.
    Risks of neurological and immune-related diseases, including narcolepsy, after vaccination with Pandemrix: a population- and registry-based cohort study with over 2 years of follow-up2014In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 275, no 2, p. 172-190Article in journal (Refereed)
    Abstract [en]

    Objectives: To investigate the association between vaccination with Pandemrix and risk of selected neurological and immune-related diseases including narcolepsy.

    Design: Population-based prospective cohort study using data from regional vaccination registries and national health registries.

    Setting: Seven healthcare regions in Sweden comprising 61% of the Swedish population.

    Subjects: Study population of 3347467 vaccinated and 2497572 nonvaccinated individuals (vaccination coverage approximate to 60%) followed between 2009 and 2011 for 6.9 million person-years after exposure and 6.0 million person-years without exposure.

    Main outcome measure and analysis: First recorded diagnosis of neurological and immune-related diseases. Relative risks [hazard ratios (HRs) with 95% confidence intervals (CIs)] assessed using Cox regression, adjusted for covariates.

    Results: For all selected neurological and immune-related outcomes under study, other than allergic vaccine reactions (for which we verified an expected increase in risk) and narcolepsy, HRs were close to 1.0 and always below 1.3. We observed a three-fold increased risk of a diagnosis of narcolepsy (HR: 2.92, 95% CI: 1.78-4.79; that is, four additional cases per 100000 person-years) in individuals 20years of age at vaccination and a two-fold increase (HR: 2.18, 95% CI: 1.00-4.75) amongst young adults between 21 and 30years of age. The excess risk declined successively with increasing age at vaccination; no increase in risk was seen after 40years of age.

    Conclusions: For a large number of selected neurological and immune-related diseases, we could neither confirm any causal association with Pandemrix nor refute entirely a small excess risk. We confirmed an increased risk for a diagnosis of narcolepsy in individuals 20years of age and observed a trend towards an increased risk also amongst young adults between 21 and 30years.

  • 17. Tabrizi, F.
    et al.
    Rosenqvist, M.
    Bergfeldt, L.
    Englund, Anders
    Örebro University, School of Health and Medical Sciences.
    Long-term prognosis in patients with bifascicular block: the predictive value of noninvasive and invasive assessment2006In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 260, no 1, p. 31-38Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Patients with bifascicular block (BFB) have a high mortality rate. The purpose of the present study was to identify high-risk patients in a BFB population by performing an extensive cardiac evaluation including noninvasive and invasive tests. DESIGN: Population-based study. SUBJECTS: A total of 100 patients with BFB, of whom 41 had a history of unexplained syncope, were prospectively studied. The mean age was 68 +/- 12. All patients were investigated with Holter-monitoring, an exercise test, an echocardiography, and an invasive electrophysiological study. The severity of congestive heart failure (CHF) was assessed by New York Heart Association (NYHA) classification. Patients in NYHA class IV were excluded. INTERVENTIONS: Patients with syncope were recommended prophylactic pacemaker treatment, which was accepted by 31 patients (76%). Main outcome measures. All-cause mortality and sudden cardiac death (SCD). RESULTS: During a median follow-up of 84 months, 33 patients died, of whom 14 in SCD. In a univariate analysis, high age, a previous myocardial infarction, and CHF were associated with a significantly increased risk of all-cause mortality and SCD. In a Cox multiple regression analysis, CHF was the only independent predictor of all-cause mortality and SCD (P < 0.01). CONCLUSION: Patients with BFB have a poor long-term prognosis. The predictive value of noninvasive and invasive investigations is limited. The only independent predictor of all-cause mortality and SCD in this population was the presence of CHF.

  • 18.
    Uusitupa, M. U.
    et al.
    Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; Research Unit, Kuopio University Hospital, Kuopio, Finland.
    Hermansen, K.
    Department of Medicine and Endocrinology MEA, Aarhus University Hospital, Aarhus, Denmark.
    Savolainen, Markku Juhani
    Institute of Clinical Medicine, Department of Internal Medicine, University of Oulu, Oulu, Finland.
    Schwab, Ursula S.
    Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; Institute of Clinical Medicine, Internal Medicine, Kuopio University Hospital, Kuopio, Finland.
    Kolehmainen, Marjukka
    Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
    Brader, Lea J.
    Department of Medicine and Endocrinology MEA, Aarhus University Hospital, Aarhus, Denmark.
    Mortensen, Lene Sundahl
    Department of Medicine and Endocrinology MEA, Aarhus University Hospital, Aarhus, Denmark.
    Cloetens, Lieselotte
    Biomedical Nutrition, Pure and Applied Biochemistry, Lund University, Lund, Sweden.
    Johansson-Persson, Anna
    Biomedical Nutrition, Pure and Applied Biochemistry, Lund University, Lund, Sweden.
    Önning, Gunilla
    Biomedical Nutrition, Pure and Applied Biochemistry, Lund University, Lund, Sweden.
    Landin-Olsson, Mona
    Department of Endocrinology, Skåne University Hospital, Lund, Sweden.
    Herzig, Karl-Heinz
    Institute of Biomedicine and Biocenter of Oulu, University of Oulu, Oulu, Finland; Department of Psychiatry, Kuopio University Hospital, Kuopio, Finland.
    Hukkanen, Janne
    Institute of Clinical Medicine, Department of Internal Medicine, University of Oulu, Oulu, Finland.
    Rosqvist, Fredrik
    Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden.
    Iggman, David
    Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden; Center for Clinical Research Dalarna, Falun, Sweden.
    Paananen, Jussi
    Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
    Pulkki, Kari J.
    Eastern Finland Laboratory Centre and Department of Clinical Chemistry, University of Eastern Finland, Kuopio, Finland.
    Siloaho, Maritta
    Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; Institute of Clinical Medicine, Department of Internal Medicine, University of Oulu, Oulu, Finland; Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
    Dragsted, Lars Ove
    Department of Nutrition, Exercise and Sport, University of Copenhagen, Copenhagen, Denmark.
    Barri, Thaer A.
    Department of Nutrition, Exercise and Sport, University of Copenhagen, Copenhagen, Denmark.
    Overvad, Kim
    Department of Epidemiology, School of Public Health, Aarhus University, Aarhus, Denmark; Department of Cardiology, Aalborg Hospital, Aarhus University Hospital, Aarhus, Denmark.
    Bach Knudsen, Knud Erik
    Department of Animal Science, Aarhus University, Aarhus, Denmark.
    Hedemann, Mette Skou
    Department of Animal Science, Aarhus University, Aarhus, Denmark.
    Arner, Peter
    Department of Medicine (H7), Karolinska Institute, Stockholm, Sweden.
    Dahlman, Ingrid
    Department of Medicine (H7), Karolinska Institute, Stockholm, Sweden.
    Borge, Grethe Iren
    Nofima, Norwegian Institute of Food, Fisheries and Aquaculture Research, Ås, Norway.
    Baardseth, P.
    Nofima, Norwegian Institute of Food, Fisheries and Aquaculture Research, Ås, Norway.
    Ulven, Stine Marie
    Department of Health, Nutrition and Management, Faculty of Health Sciences, Oslo and Akershus University College of Applied Sciences, Oslo, Norway.
    Gunnarsdottir, Ingibjörg
    Unit for Nutrition Research, University of Iceland and Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland.
    Jónsdóttir, Svandis Erna
    Unit for Nutrition Research, University of Iceland and Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland.
    Thorsdottir, Inga
    Unit for Nutrition Research, University of Iceland and Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland.
    Oresic, Matej
    Örebro University, School of Medical Sciences. Unit for Nutrition Research, University of Iceland and Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland.
    Poutanen, Kaisa S.
    Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; VTT Technical Research Centre of Finland, Espoo, Finland.
    Risérus, Ulf
    Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden.
    Akesson, Björn A.
    Biomedical Nutrition, Pure and Applied Biochemistry, Lund University, Lund, Sweden; Department of Clinical Nutrition, Skåne University Hospital, Lund, Sweden.
    Effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile and inflammation markers in metabolic syndrome: a randomized study (SYSDIET)2013In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 274, no 1, p. 52-66Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Different healthy food patterns may modify cardiometabolic risk. We investigated the effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile, blood pressure and inflammatory markers in people with metabolic syndrome.

    METHODS: We conducted a randomized dietary study lasting for 18-24 weeks in individuals with features of metabolic syndrome (mean age 55 years, BMI 31.6 kg m(-2) , 67% women). Altogether 309 individuals were screened, 200 started the intervention after 4-week run-in period, and 96 (proportion of dropouts 7.9%) and 70 individuals (dropouts 27%) completed the study, in the Healthy diet and Control diet groups, respectively. Healthy diet included whole-grain products, berries, fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products. An average Nordic diet served as a Control diet. Compliance was monitored by repeated 4-day food diaries and fatty acid composition of serum phospholipids.

    RESULTS: Body weight remained stable, and no significant changes were observed in insulin sensitivity or blood pressure. Significant changes between the groups were found in non-HDL cholesterol (-0.18, mmol L(-1) 95% CI -0.35; -0.01, P = 0.04), LDL to HDL cholesterol (-0.15, -0.28; -0.00, P = 0.046) and apolipoprotein B to apolipoprotein A1 ratios (-0.04, -0.07; -0.00, P = 0.025) favouring the Healthy diet. IL-1 Ra increased during the Control diet (difference -84, -133; -37 ng L(-1) , P = 0.00053). Intakes of saturated fats (E%, beta estimate 4.28, 0.02; 8.53, P = 0.049) and magnesium (mg, -0.23, -0.41; -0.05, P = 0.012) were associated with IL-1 Ra.

    CONCLUSIONS: Healthy Nordic diet improved lipid profile and had a beneficial effect on low-grade inflammation.

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