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  • 1.
    Aalto, Anne
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Radiology. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Sjoewall, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Davidsson, Leif
    Linköping University, Department of Medicine and Care, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping.
    Forsberg, Pia
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Smedby, Örjan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Radiology. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Brain magnetic resonance imaging does not contribute to the diagnosis of chronic neuroborreliosis2007In: Acta Radiologica, ISSN 0284-1851, E-ISSN 1600-0455, Vol. 48, no 7, p. 755-762Article in journal (Refereed)
    Abstract [en]

    Background: Borrelia infections, especially chronic neuroborreliosis ( NB), may cause considerable diagnostic problems. This diagnosis is based on symptoms and findings in the cerebrospinal fluid but is not always conclusive. Purpose: To evaluate brain magnetic resonance imaging ( MRI) in chronic NB, to compare the findings with healthy controls, and to correlate MRI findings with disease duration. Material and Methods: Sixteen well- characterized patients with chronic NB and 16 matched controls were examined in a 1.5T scanner with a standard head coil. T1- ( with and without gadolinium), T2-, and diffusion- weighted imaging plus fluid- attenuated inversion recovery ( FLAIR) imaging were used. Results: White matter lesions and lesions in the basal ganglia were seen in 12 patients and 10 controls ( no significant difference). Subependymal lesions were detected in patients down to the age of 25 and in the controls down to the age of 43. The number of lesions was correlated to age both in patients ( rho=0.83, P < 0.01) and in controls ( rho=0.61, P < 0.05), but not to the duration of disease. Most lesions were detected with FLAIR, but many also with T2- weighted imaging. Conclusion: A number of MRI findings were detected in patients with chronic NB, although the findings were unspecific when compared with matched controls and did not correlate with disease duration. However, subependymal lesions may constitute a potential finding in chronic NB.

  • 2.
    Agvald-Ohman, C
    et al.
    Karolinska University.
    Struwe, J
    Karolinska Institute.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Walther, Sten
    Linköping University, Department of Medicine and Health Sciences, Physiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    PROMOTING INFECTION CONTROL IN THE ICU USING A TARGETED PUSH-AND-PULL INTERVENTION2009In: in INTENSIVE CARE MEDICINE, vol 35, 2009, Vol. 35, p. 176-176Conference paper (Refereed)
    Abstract [en]

    n/a

  • 3.
    Agvald-Öhman, Christina
    et al.
    Anestesioch intensivvårdskliniken, Karolinska universitetssjukhuset, Huddinge, CLINTEC, Karolinska institutet, Stockholm, Sweden.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Struwe, Johan
    Strama och avdelningen för epidemiologi, Smittskyddsinstitutet, Stockholm, Sweden.
    Walther, Sten M.
    Linköping University, Department of Medicine and Health Sciences, Physiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    »Skjut på« och »dra« metod för att minska vårdrelaterade infektioner på IVA: Pilotprojekt med aktiv uppföljning2010In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 107, no 1-2Article in journal (Refereed)
    Abstract [sv]

    Vårdrelaterade infektioner är ett särskilt stort problem inom intensivvården där patienterna är kritiskt sjuka och har många riskfaktorer.

    För att minska frekvensen vårdrelaterade infektioner måste ett strukturerat arbete bedrivas från flera olika utgångspunkter.

    Vi måste bli bättre på att dia­gnostisera, dokumentera och förebygga dessa infektioner.

    Kombinerad intervention av typen »push« och »pull« visade på lovande resultat med införande av bättre diagnostiska metoder och en upplevelse av ökad motivation hos personalen efter besöket.

  • 4.
    Almroth, Gabriel
    et al.
    Linköping University, Department of Medicine and Care, Nephrology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Lonn, J
    University of Örebro, Sweden .
    Uhlin, Fredrik
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Andersson, B
    Sahlgrens University Hospital, Sweden .
    Hahn-Zoric, M
    Sahlgrens University Hospital, Sweden .
    Fibroblast Growth Factor 23, Hepatocyte Growth Factor, Interleukin-6, High-Sensitivity C-Reactive Protein and Soluble Urokinase Plasminogen Activator Receptor. Inflammation Markers in Chronic Haemodialysis Patients?2013In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 78, no 3, p. 285-290Article in journal (Refereed)
    Abstract [en]

    Sera from 84 haemodialysis (HD) patients and 68 healthy blood donors were analysed with commercially available ELISA techniques for fibroblast growth factor 23 (FGF-23), hepatocyte growth factor (HGF), interleukin-6 (Il-6), high-sensitivity C-reactive protein (hs-CRP) and soluble urokinase plasminogen activator receptor (suPAR), to find a possible correlation of FGF-23 and HGF with the earlier recognized inflammatory markers Il-6 and hs-CRP or suPAR. All patients studied had significantly elevated levels of FGF-23, HGF, hs-CRP and suPAR as compared to the controls. Il-6 and hs-CRP correlated for patients (R=0.6) as well as for patients and controls altogether. Ln (natural logarithm) of HGF correlated weakly with Ln Il-6 and Ln CRP (R 0.28-0.37). Ln FGF-23 correlated only with Ln HGF (r=-0.25) in controls. Ln HGF correlated with ln suPAR (r=0.6) in both patients and controls. Although elevated as compared to controls, we found no correlation of FGF-23 with the recognized inflammatory markers Il-6, hs-CRP, nor HGF or the new marker suPAR in HD patients. Ln HGF correlated with Ln Il-6, Ln CRP and Ln suPAR. Although probably involved in vessel disease, FGF-23 and HGF may play other roles than acting in inflammatory vessel disease in HD patients. Further studies are necessary to evaluate the role of these immunological markers in chronic haemodialysis patients with atherosclerosis.

  • 5.
    Almroth, Gabriel
    et al.
    Linköping University, Department of Medical and Health Sciences, Nephrology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Lönn, J
    School of Health and Medical Sciences, Örebro, Sweden.
    Uhlin, Fredrik
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Andersson, B
    Hahn-Zoric, M
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Tillväxtfaktorer och inflammationsmarkörer vid kronisk njursvikt2013In: Njurmedicinskt vårmöte Jönköping 12-14 maj 2013, 2013Conference paper (Refereed)
  • 6.
    Ammerlaan, H S M
    et al.
    University of Medical Centre Utrecht, Netherlands.
    Harbarth, S
    Geneva University Hospital and Medical Sch, Switzerland.
    Buiting, A G M
    John Radcliffe Hospital, England.
    Crook, D W
    Amphia Hospital, Netherlands.
    Fitzpatrick, F
    Beaumont Hospital, Ireland.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Herwaldt, L A
    University of Iowa, IA USA.
    van Keulen, P H J
    Amphia Hospital, Netherlands.
    Kluytmans, J A J W
    St Elizabeth Hospital, Netherlands.
    Kola, A
    Charite University of Medical Berlin, Germany.
    Kuchenbecker, R S
    University of Federal Rio Grande do Sul, Brazil.
    Lingaas, E
    University of Oslo, Norway.
    Meessen, N
    University of Medical Centre Groningen, Netherlands.
    Morris-Downes, M -m.
    Beaumont Hospital, Ireland.
    Pottinger, J M.
    University of Iowa Hospital and Clin, IA USA.
    Rohner, P
    Geneva University Hospital and Medical Sch, Switzerland.
    dos Santos, R P.
    University of Federal Rio Grande do Sul, Brazil.
    Seifert, H
    University of Cologne, Germany.
    Wisplinghoff, H
    University of Cologne, Germany.
    Ziesing, S
    Hannover Medical Sch, Germany.
    Walker, A S.
    John Radcliffe Hospital, England.
    Bonten, M J M.
    University of Medical Centre Utrecht, Netherlands.
    Secular Trends in Nosocomial Bloodstream Infections: Antibiotic-Resistant Bacteria Increase the Total Burden of Infection2013In: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, Vol. 56, no 6, p. 798-805Article in journal (Refereed)
    Abstract [en]

    Background. It is unknown whether rising incidence rates of nosocomial bloodstream infections (BSIs) caused by antibiotic-resistant bacteria (ARB) replace antibiotic-susceptible bacteria (ASB), leaving the total BSI rate unaffected.

    Methods. We investigated temporal trends in annual incidence densities (events per 100 000 patient-days) of nosocomial BSIs caused by methicillin-resistant Staphylococcus aureus (MRSA), ARB other than MRSA, and ASB in 7 ARB-endemic and 7 ARB-nonendemic hospitals between 1998 and 2007.

    Results. 33 130 nosocomial BSIs (14% caused by ARB) yielded 36 679 microorganisms. From 1998 to 2007, the MRSA incidence density increased from 0.2 to 0.7 (annual increase, 22%) in ARB-nonendemic hospitals, and from 3.1 to 11.7 (annual increase, 10%) in ARB-endemic hospitals (P = .2), increasing the incidence density difference between ARB-endemic and ARB-nonendemic hospitals from 2.9 to 11.0. The non-MRSA ARB incidence density increased from 2.8 to 4.1 (annual increase, 5%) in ARB-nonendemic hospitals, and from 1.5 to 17.4 (annual increase, 22%) in ARB-endemic hospitals (P < .001), changing the incidence density difference from −1.3 to 13.3. Trends in ASB incidence densities were similar in both groups (P = .7). With annual increases of 3.8% and 5.4% of all nosocomial BSIs in ARB-nonendemic and ARB-endemic hospitals, respectively (P < .001), the overall incidence density difference of 3.8 increased to 24.4.

    Conclusions.  Increased nosocomial BSI rates due to ARB occur in addition to infections caused by ASB, increasing the total burden of disease. Hospitals with high ARB infection rates in 2005 had an excess burden of BSI of 20.6 per 100 000 patient-days in a 10-year period, mainly caused by infections with ARB.

  • 7.
    Askling, Helena H
    et al.
    Karolinska Institute, Stockholm, Sweden; Karolinska University Hospital, Stockholm, Sweden.
    Lesko, Birgitta
    Swedish National Board of Health & Welfare, Stockholm, Sweden; Swedish Institute for Infectious Disease Control, Stockholm.
    Vene, Sirkka
    Swedish Institute for Infectious Disease Control, Stockholm, Sweden.
    Berndtson, Angerd
    Swedish Institute for Infectious Disease Control, Stockholm, Sweden.
    Björkman, Per
    Malmö University Hospital, Malmö, Sweden.
    Bläckberg, Jonas
    Lund University Hospital, Lund, Sweden.
    Bronner, Ulf
    Karolinska University Hospital, Stockholm, Sweden.
    Follin, Per
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Hellgren, Urban
    Karolinska University Hospital, Stockholm, Sweden.
    Palmerus, Maria
    County Hospital Ryhov, Jönköping, Sweden.
    Ekdahl, Karl
    European Centre for Disease Prevention and Control, Stockholm, Sweden.
    Tegnell, Anders
    Swedish National Board of Health & Welfare, Stockholm, Sweden.
    Struwe, Johan
    Swedish Institute for Infectious Disease Control, Stockholm, Sweden.
    Serologic Analysis of Returned Travelers with Fever, Sweden2009In: Emerging Infectious Diseases, ISSN 1080-6040, E-ISSN 1080-6059, Vol. 15, no 11, p. 1805-1808Article in journal (Refereed)
    Abstract [en]

    We studied 1,432 febrile travelers from Sweden who had returned from malaria-endemic areas during March 2005-March 2008. In 383 patients, paired serum samples were blindly analyzed for influenza and 7 other agents. For 21% of 115 patients with fever of unknown origin, serologic analysis showed that influenza was the major cause.

  • 8.
    Bjornsson, Einar
    et al.
    Sahlgrens University Hospital.
    Verbaan, Hans
    Lund University.
    Oksanen, Antti
    Karolinska University Hospital.
    Frydén, Aril
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Johansson, Jonas
    Roche, Stockholm.
    Friberg, Sarah
    Roche, Stockholm.
    Dalgard, Olav
    University of Oslo.
    Kalaitzakis, Evangelos
    Sahlgrens University Hospital.
    Health-related quality of life in patients with different stages of liver disease induced by hepatitis C2009In: SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, ISSN 0036-5521, Vol. 44, no 7, p. 878-887Article in journal (Refereed)
    Abstract [en]

    Objective. Patients with hepatitis C have been shown to have impaired health-related quality of life (HRQoL). The aim of this study was to determine HRQoL in patients in different stages of hepatitis C virus (HCV) and to compare HRQoL in HCV cirrhosis with non-HCV-induced cirrhosis. Material and methods. Out of 489 consecutive patients who fulfilled the inclusion criteria, 472 (96%) agreed to participate in the study: 158 patients with mild/moderate fibrosis with chronic hepatitis C (CHC group), 76 patients with HCV compensated cirrhosis (CC), 53 patients with HCV decompensated (DC) cirrhosis, 52 non-cirrhotic patients with sustained viral response (SVR), and a control group consisting of 32 patients with non-HCV CC and 101 with non-HCV DC who completed the Short Form-36 (SF-36) and EQ-5D questionnaire. Results. The CHC group had significantly lower SF-36 scores than healthy controls, with the exception of scores for the dimensions physical function and bodily pain. HCV patients with DC had lower scores in all SF-36 dimensions in comparison with those of the CHC group, as well as in physical and mental component summaries (Pandlt;0.001). In comparison with the CHC group, the HCV CC group had lower scores on the SF-36 general health dimension (p andlt;0.05) and lower SF-36 physical component summary (PCS) scores (p andlt;0.05). No major differences were seen in patients with HCV- and non-HCV-induced cirrhosis. Conclusions. Impairment in HRQoL in patients with HCV was associated with the severity of liver disease, patients with decompensated cirrhosis exhibiting the highest impairment in HRQoL. The etiology of liver disease does not seem to be important in determining HRQoL in cirrhosis.

  • 9.
    Brodszki, N B
    et al.
    Lund University Hospital.
    Matsols, H
    Falu Lasarett.
    Fasth, A
    Drottning Silvias Barnoch Ungdomssjukhus.
    Friman, V
    Sahlgrens University Hospital.
    Lofdahl, K
    Sahlgrens University Hospital.
    Oskarsdottir, S
    Drottning Silvias Barnoch Ungdomssjukhus.
    Marthinsen, L
    Lanssjukhuset, Halmstad.
    Olinder-Nielsen, A M
    Lanssjukhuset Ryhov.
    Wagstrom, P
    Lanssjukhuset Ryhov.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
    Jonsson, G
    Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Aurivillius, M
    University Sjukhuset, Malmö.
    Lanbeck, P
    University Sjukhuset, Malmö.
    Granert, C
    Karolinska University Sjukhuset.
    Gustafson, R
    Karolinska University Sjukhuset.
    Hammarstrom, L
    Karolinska University Sjukhuset.
    Ahlin, A
    Sachsska Barnsjukhuset.
    West, C
    Norrlands University Sjukhus.
    Gunther, G
    Uppsala University.
    Pauksen, K
    Uppsala University.
    Arneborn, P
    Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Björkqvist, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    Bjorkander, J
    Lanssjukhuset Ryhov.
    Swedish guidelines for the assessment, diagnosis and management of 6 primary immunodeficiency states: CVID, IgG subclass deficiency, IgA deficiency, XLA, SCID and CGD2008In: CLINICAL AND EXPERIMENTAL IMMUNOLOGY,ISSN 0009-9104: Volume 154, 2008, Vol. 154, p. 140-141Conference paper (Refereed)
  • 10.
    Brouqui, P.
    et al.
    CHU Nord and URMITE IRD-CNRS UMR.
    Puro, V.
    National Institute for Infectious Diseases L Spallanzani, Rome.
    Fusco, F.M.
    National Institute for Infectious Diseases L Spallanzani, Rome.
    Bannister, B.
    Royal Free Hospital, London.
    Schilling, S.
    J W Goethe University.
    Follin, Per
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Gottschalk, R.
    Public Health Office, Frankfurt.
    Hemmer, R.
    Luxembourg Central Hospital.
    Maltezou, H.C.
    Hellenic Centre for Diseases Control and Prevention.
    Ott, K.
    West Tallinn Central Hospital.
    Peleman, R.
    University Hospital of Gent.
    Perronne, C.
    Raymond Poincaré University Hospital.
    Sheehan, G.
    Mater Misericordiae Hospital.
    Siikamaki, H.
    Helsinki University Central Hospital.
    Skinhoj, P.
    Rigshospitalet, Copenhagen.
    Ippolito, G.
    National Institute for Infectious Diseases L Spallanzani, Rome.
    Infection control in the management of highly pathogenic infectious diseases: consensus of the European Network of Infectious Disease2009In: The Lancet Infectious Diseases, ISSN 1473-3099, Vol. 9, no 5, p. 301-311Article, review/survey (Refereed)
    Abstract [en]

    The European Network for Infectious Diseases (EUNID) is a network of clinicians, public health epidemiologists, microbiologists, infection control, and critical-care doctors from the European member states, who are experienced in the management of patients with highly infectious diseases. We aim to develop a consensus recommendation for infection control during clinical management and invasive procedures in such patients. After an extensive literature review, draft recommendations were amended jointly by 27 partners from 15 European countries. Recommendations include repetitive training of staff to ascertain infection control, systematic use of cough and respiratory etiquette at admission to the emergency department, fluid sampling in the isolation room, and analyses in biosafety level 3/4 laboratories, and preference for point-of-care bedside laboratory tests. Children should be cared for by paediatricians and intensive-care patients should be cared for by critical-care doctors in high-level isolation units (HLIU). Invasive procedures should be avoided if unnecessary or done in the HLIU, as should chest radiography, ultrasonography, and renal dialysis. Procedures that require transport of patients out of the HLIU should be done during designated sessions or hours in secure transport. Picture archiving and communication systems should be used. Post-mortem examination should be avoided; biopsy or blood collection is preferred.

  • 11.
    Börgeson, Emma
    et al.
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Lönn, Johanna
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Bergström, Ida
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Brodin Patcha, Veronika
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Ramström, Sofia
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Sarndahl, Eva
    University Orebro.
    Bengtsson, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences.
    Lipoxin A(4) Inhibits Porphyromonas gingivalis-Induced Aggregation and Reactive Oxygen Species Production by Modulating Neutrophil-Platelet Interaction and CD11b Expression2011In: INFECTION AND IMMUNITY, ISSN 0019-9567, Vol. 79, no 4, p. 1489-1497Article in journal (Refereed)
    Abstract [en]

    Porphyromonas gingivalis is an etiological agent that is strongly associated with periodontal disease, and it correlates with numerous inflammatory disorders, such as cardiovascular disease. Circulating bacteria may contribute to atherogenesis by promoting CD11b/CD18-mediated interactions between neutrophils and platelets, causing reactive oxygen species (ROS) production and aggregation. Lipoxin A(4) (LXA(4)) is an endogenous anti-inflammatory and proresolving mediator that is protective of inflammatory disorders. The aim of this study was to investigate the effect of LXA(4) on the P. gingivalis-induced activation of neutrophils and platelets and the possible involvement of Rho GTPases and CD11b/CD18 integrins. Platelet/leukocyte aggregation and ROS production was examined by lumiaggregometry and fluorescence microscopy. Integrin activity was studied by flow cytometry, detecting the surface expression of CD11b/CD18 as well as the exposure of the high-affinity integrin epitope, whereas the activation of Rac2/Cdc42 was examined using a glutathione S-transferase pulldown assay. The study shows that P. gingivalis activates Rac2 and Cdc42 and upregulates CD11b/CD18 and its high-affinity epitope on neutrophils, and that these effects are diminished by LXA(4). Furthermore, we found that LXA(4) significantly inhibits P. gingivalis-induced aggregation and ROS generation in whole blood. However, in platelet-depleted blood and in isolated neutrophils and platelets, LXA(4) was unable to inhibit either aggregation or ROS production, respectively. In conclusion, this study suggests that LXA(4) antagonizes P. gingivalis-induced cell activation in a manner that is dependent on leukocyte-platelet interaction, likely via the inhibition of Rho GTPase signaling and the downregulation of CD11b/CD18. These findings may contribute to new strategies in the prevention and treatment of periodontitis-induced inflammatory disorders, such as atherosclerosis.

  • 12.
    Cardell, Kristina
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Studies on Hepatitis B Vaccination and Factors Associated withthe Vaccine Response2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Hepatitis B virus causes liver disease and up to 2 billion people have been in contact with the virus world wide. It can cause both acute and chronic disease. The routes for transmission are through blood, mother to infant at time of delivery and sexually. Chronic hepatitis B infection is a risk factor for development of liver cirrhosis and hepatocellular carcinoma. Prevention of hepatitis B virus infection is highly desirable. Since the early1980s hepatitis B vaccine has been available. It can effectively prevent the disease and has been found to be safe. The World Health Organisation, WHO, has recommended all countries to implement the vaccine in their children’s vaccination programmes and many countries have followed this recommendation. In Sweden so far the recommendation is vaccination of identified risk groups for hepatitis B. Health care workers who are at risk of having blood contact in their work is one such risk group.

    In a large study on health care workers who were intradermally vaccinated with the hepatitis B vaccine, 960/1406 (68.3%) developed protective levels of antibodies to HBsAg (anti-HBs; defined as >10 mIU/mL) after three doses. After administering of an additional fourth dose to non-responders the response rate was 1187/1335 (88.9%). Risk factors for non-response were smoking and age above 40 years. Also, the vaccine response rates improved during the study and a risk of giving a too small dose with intradermal administration was also identified. This suggests that intradermal administration is dependent on well trained personnel.

    A genetic factor which has been proposed to be associated with a non-responder status to HBV vaccination is the HLA haplotype of the host. In a study in on 69 responders and 53 non-responders the haplotypes were therefore determined. It was found that [DQB1*0602; DQA1*0102; DR15] and [DQB1*0603; DQA1*0103; DRB1*1301] were more likely to be found in responders (p<0.025 and p<0.05 respectively). In non-responders the haplotype [DQB1*0604; DQA1*0102; DRB1*1302] was found more frequently (p<0.005). This study supports that the HLA class II of the host is involved in the ability to respond to the HBV vaccination.

    To further test the genetic link between the HLA of the host and a non-responder status, relatives to known intradermal non-responders with known haplotypes for DQA1, DQB1 and DRB1 were vaccinated in the same way, intradermally. The response rate in the relatives was 15/26 (58%) which is lower than expected suggesting a genetic influence on the vaccine response. In this study 5/6 with the haplotype [DQB1*0604; DQA1*0102; DRB1*1302] were non-responders which is in line with the previous data that this haplotype is correlated to hepatitis B vaccine non-response.

    Finally, to test a strategy by which we could induce an effective anti-HBs seroconversion in non-responders we revaccinated these with the combined hepatitis A and B vaccine intramuscularly at a double dose. Already after the first revaccination dose 26/44 (60%) responded with protective antibodies compared to 2/20 (10%) in a vaccine naïve reference group, suggesting an anamnestic response. After three doses 42/44 (95%) responded in the non-responder group and 20/20 (100%) in the reference group. All participants in the study responded to the hepatitis A antigen.

    In conclusion these studies show that intradermal vaccine administration can be used and is effective, and that the ability to respond is influenced by several, including genetic, factors. Importantly a non-responder status to hepatitis B vaccination is not absolute, a double dose of the combined HAV and HBV vaccine effectively overcomes this non-response in most individuals.

    List of papers
    1. Intradermal hepatitis B vaccination in health care workers. Response rate and experiences from vaccination in clinical practise
    Open this publication in new window or tab >>Intradermal hepatitis B vaccination in health care workers. Response rate and experiences from vaccination in clinical practise
    1999 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 31, no 2, p. 197-200Article in journal (Refereed) Published
    Abstract [en]

    Health care workers at risk for hepatitis B virus infection are recommended for vaccination. Low-dose intradermal (i.d.) administration of vaccine has been suggested as a less expensive alternative to intramuscular (i.m.) inoculation. To evaluate the i.d. vaccination route, health care workers were included in a prospective study. The subjects were vaccinated with 0.1 ml (= 2 microg) recombinant vaccine (Engerix B, SmithKline Beecham) i.d. at 0, 1 and 6 months. Two months after the third vaccination, measurement of the anti-HBs level was conducted. An anti-HBs level > or =10 IU/l was considered protective. Those with an anti-HBs level <10 IU/l were given a fourth dose with new serological control after another 2 months. The results are based on the 1406 subjects that it was possible to evaluate. The seroconversion rate to protective anti-HBs level after 3 doses was 68% and after 3 or 4 doses 89%. Factors associated with a lower response rate were increasing age (p<0.05) and smoking (p<0.001). Sex or body mass index had no influence on the results. Vaccination technique seems to be of utmost importance when the i.d. route is used. Well instructed and experienced nurses are required and quality control with follow-up of overall seroconversion rate within each centre is needed.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-20796 (URN)10.1080/003655499750006272 (DOI)10447332 (PubMedID)
    Available from: 2009-09-21 Created: 2009-09-21 Last updated: 2017-12-13Bibliographically approved
    2. Haplotypes comprising subtypes of the DQB1*06 allele direct the antibody response after immunisation with hepatitis B surface antigen
    Open this publication in new window or tab >>Haplotypes comprising subtypes of the DQB1*06 allele direct the antibody response after immunisation with hepatitis B surface antigen
    1998 (English)In: Tissue Antigens, ISSN 0001-2815, E-ISSN 1399-0039, Vol. 52, no 4, p. 374-380Article in journal (Refereed) Published
    Abstract [en]

    Two HLA class II haplotypes, HLA-[DQB1*0602; DQA1*0102; DR15] and HLA-[DQB1*0603; DQA1*0103; DRB1*1301] were found to be less common in 52 nonresponders compared with 68 responders, P<0.025 and P<0.05 respectively, after vaccination with hepatitis B surface antigen (HBsAg). Another haplotype, HLA-[DQB1*0604; DQA1*0102; DRB1*1302], had a significantly higher frequency in the nonresponders (P<0.005). The nonresponders and responders were nonsmoking, healthy individuals with an antibody concentration of <10 IU/l and >100 IU/l respectively. The three haplotypes comprise either of three different DQB1*06 subtypes. Two of the seven amino acids that differ between the two responder alleles DQB1*0602 and *0603 and the nonresponder allele *0604 are located in the peptide-binding groove of the DQB1 molecule. In addition to this finding, amino acid 86 in the DRB1 molecule seems to determine the response against HBsAg. DRB1*1301 and DR15 in the responder haplotypes have a Val at this position while the nonresponder haplotype has a Gly. These results suggest a role for both the DQB1*06 alleles and the DRB1 alleles *1301, *1302 and DR15 to direct either a response or a nonresponse against HBsAg. Sixteen HLA class II genotypes were found to be shared by 25 nonresponders and 32 responders. This finding of HLA-identical nonresponders and responders indicates an influence of other genetic factors in addition to the HLA system in the response to HBsAg.

    Keywords
    Frequency, haplotype, HIA class II, nonresponders, nonsmoking, responders
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-20797 (URN)10.1111/j.1399-0039.1998.tb03058.x (DOI)9820601 (PubMedID)
    Available from: 2009-09-21 Created: 2009-09-21 Last updated: 2017-12-13Bibliographically approved
    3. Hepatitis B vaccination in relatives to known non-responders: A family study
    Open this publication in new window or tab >>Hepatitis B vaccination in relatives to known non-responders: A family study
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Hepatitis B can be prevented by hepatitis B vaccine in most individuals. However about 5 –10% of all individuals fail to produce a protective antibody level to hepatitis B surface antigen(anti-HBs), after standard vaccination procedure with three vaccine doses. The mechanismsfor non-response are multi-factorial and not clearly understood. Non-response in this studywas defined as anti-HBs < 10 mIU/ml after at least 4 doses of intradermal hepatitis B vaccine.In this study we vaccinated relatives to known non-responders to hepatitis B vaccine. Thestudy subjects were chosen among relatives to non-responders with known HLA class IIhaplotypes. Recombinant hepatitis B vaccine was administered intradermally at 0, 1 and 6months. For those with anti-HBs <10 mIU/ml after three doses an additional dose was givenfollowed by new anti-HBs measurement. A total of 8 probands and 26 relatives wereincluded. Of the 26 relatives 15/26 (58%) responded to the vaccination schedule compared tothe expected 90-95%. This data therefore support the theory that genetic factors play animportant role in the antibody response to hepatitis B vaccine. The study population wasthough too small to conclude the role of specific genetic factors related to response and nonresponse.

    Keywords
    Hepatitis B vaccine, non-responders, genetics
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-20798 (URN)
    Available from: 2009-09-21 Created: 2009-09-21 Last updated: 2010-01-14Bibliographically approved
    4. Excellent response rate to a double dose of the combined hepatitis A and B vaccine in previous nonresponders to hepatitis B vaccine
    Open this publication in new window or tab >>Excellent response rate to a double dose of the combined hepatitis A and B vaccine in previous nonresponders to hepatitis B vaccine
    2008 (English)In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 198, no 3, p. 299-304Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Hepatitis B vaccine has been shown to be highly efficient in preventing hepatitis B. However, 5%-10% of individuals fail to develop protective levels (>or=10 mIU/mL) of antibodies to hepatitis B surface antigen (anti-HBs) and are considered to be nonresponders.

    METHODS: A total of 48 nonresponders and 20 subjects naive to the HBV vaccine received a double dose of combined hepatitis A and B vaccine (Twinrix) at 0, 1, and 6 months. The levels of anti-HBs and antibodies to hepatitis A virus (anti-HAV) were determined before vaccination and 1 month after each dose.

    RESULTS: Among 44 nonresponders, protective anti-HBs levels were found in 26 (59%) after the first dose and in 42 (95%) after the third dose. Among the control subjects, the corresponding figures were 10% and 100%, respectively. All subjects seroconverted to anti-HAV. The titers of both anti-HBs and anti-HAV were lower in the previously nonresponsive subjects (P< .01).

    CONCLUSION: Revaccination of nonresponders to the standard hepatitis B vaccine regimen with a double dose of the combined hepatitis A and B vaccine was highly effective. This is most likely explained by the increased dose, a positive bystander effect conferred by the hepatitis A vaccine, or both.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-20799 (URN)10.1086/589722 (DOI)18544037 (PubMedID)
    Available from: 2009-09-21 Created: 2009-09-21 Last updated: 2017-12-13Bibliographically approved
  • 13.
    Cardell, Kristina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Infectious Diseases UHL.
    Frydén, Aril
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Infectious Diseases UHL.
    Normann, Bengt
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Intradermal hepatitis B vaccination in health care workers. Response rate and experiences from vaccination in clinical practise1999In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 31, no 2, p. 197-200Article in journal (Refereed)
    Abstract [en]

    Health care workers at risk for hepatitis B virus infection are recommended for vaccination. Low-dose intradermal (i.d.) administration of vaccine has been suggested as a less expensive alternative to intramuscular (i.m.) inoculation. To evaluate the i.d. vaccination route, health care workers were included in a prospective study. The subjects were vaccinated with 0.1 ml (= 2 microg) recombinant vaccine (Engerix B, SmithKline Beecham) i.d. at 0, 1 and 6 months. Two months after the third vaccination, measurement of the anti-HBs level was conducted. An anti-HBs level > or =10 IU/l was considered protective. Those with an anti-HBs level <10 IU/l were given a fourth dose with new serological control after another 2 months. The results are based on the 1406 subjects that it was possible to evaluate. The seroconversion rate to protective anti-HBs level after 3 doses was 68% and after 3 or 4 doses 89%. Factors associated with a lower response rate were increasing age (p<0.05) and smoking (p<0.001). Sex or body mass index had no influence on the results. Vaccination technique seems to be of utmost importance when the i.d. route is used. Well instructed and experienced nurses are required and quality control with follow-up of overall seroconversion rate within each centre is needed.

  • 14.
    Cardell, Kristina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Infectious Diseases UHL.
    Lindblom, Bertil
    Linköping University, Department of Clinical and Experimental Medicine, Forensic Medicine . Linköping University, Faculty of Health Sciences.
    Frydén, Aril
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Infectious Diseases UHL.
    Hepatitis B vaccination in relatives to known non-responders: A family studyManuscript (preprint) (Other academic)
    Abstract [en]

    Hepatitis B can be prevented by hepatitis B vaccine in most individuals. However about 5 –10% of all individuals fail to produce a protective antibody level to hepatitis B surface antigen(anti-HBs), after standard vaccination procedure with three vaccine doses. The mechanismsfor non-response are multi-factorial and not clearly understood. Non-response in this studywas defined as anti-HBs < 10 mIU/ml after at least 4 doses of intradermal hepatitis B vaccine.In this study we vaccinated relatives to known non-responders to hepatitis B vaccine. Thestudy subjects were chosen among relatives to non-responders with known HLA class IIhaplotypes. Recombinant hepatitis B vaccine was administered intradermally at 0, 1 and 6months. For those with anti-HBs <10 mIU/ml after three doses an additional dose was givenfollowed by new anti-HBs measurement. A total of 8 probands and 26 relatives wereincluded. Of the 26 relatives 15/26 (58%) responded to the vaccination schedule compared tothe expected 90-95%. This data therefore support the theory that genetic factors play animportant role in the antibody response to hepatitis B vaccine. The study population wasthough too small to conclude the role of specific genetic factors related to response and nonresponse.

  • 15.
    Cardell, Kristina
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Widell, A
    Department of Medical Microbiology Lund University.
    Frydén, Aril
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    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.
    Månsson, A-S
    Department of Medical Microbiology Lund University.
    FranzÉn, Stefan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Lymer, U-B
    Department of Natural Sciences and Biomedicine, School of Health Sciences Jönköping University.
    Isaksson, Barbro
    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.
    Nosocomial hepatitis C in a thoracic surgery unit, retrospective findings generating a prospective study2008In: Journal of Hospital Infection, ISSN 0195-6701, E-ISSN 1532-2939, Vol. 68, no 4, p. 322-328Article in journal (Refereed)
    Abstract [en]

    We describe the transmission of hepatitis C virus (HCV) to two patients from a thoracic surgeon who was unaware of his hepatitis C infection. By partial sequencing of the non-structural 5B gene and phylogenetic analysis, the viruses from both patients were found to be closely related to genotype 1a strain from the surgeon. Two further hepatitis C cases were found in relation to the thoracic clinic. Their HCV sequences were related to each other but were of genotype 2b and the source of infection was never revealed. To elucidate the magnitude of the problem, we conducted a prospective study for a period of 17 months in which patients who were about to undergo thoracic surgery were asked to participate. Blood samples were drawn prior to surgery and at least four months later. The postoperative samples were then screened for anti-HCV and, if positive, the initial sample was also analysed. The only two patients (0.4%) identified were confirmed anti-HCV positive before surgery, and none out of 456 evaluable cases seroconverted to anti-HCV during the observation period. Despite the retrospectively identified cases, nosocomial hepatitis C is rare in our thoracic unit. The study points out the risk of transmission of hepatitis C from infected personnel and reiterates the need for universal precautions. © 2008 The Hospital Infection Society.

  • 16.
    Cardell, Kristina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Åkerlind, Britt
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Sällberg, Matti
    Division of Clinical Virology, Karolinska Institute at Karolinska University Hospital, Huddinge, Sweden.
    Frydén, Aril
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Infectious Diseases UHL.
    Excellent response rate to a double dose of the combined hepatitis A and B vaccine in previous nonresponders to hepatitis B vaccine2008In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 198, no 3, p. 299-304Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Hepatitis B vaccine has been shown to be highly efficient in preventing hepatitis B. However, 5%-10% of individuals fail to develop protective levels (>or=10 mIU/mL) of antibodies to hepatitis B surface antigen (anti-HBs) and are considered to be nonresponders.

    METHODS: A total of 48 nonresponders and 20 subjects naive to the HBV vaccine received a double dose of combined hepatitis A and B vaccine (Twinrix) at 0, 1, and 6 months. The levels of anti-HBs and antibodies to hepatitis A virus (anti-HAV) were determined before vaccination and 1 month after each dose.

    RESULTS: Among 44 nonresponders, protective anti-HBs levels were found in 26 (59%) after the first dose and in 42 (95%) after the third dose. Among the control subjects, the corresponding figures were 10% and 100%, respectively. All subjects seroconverted to anti-HAV. The titers of both anti-HBs and anti-HAV were lower in the previously nonresponsive subjects (P< .01).

    CONCLUSION: Revaccination of nonresponders to the standard hepatitis B vaccine regimen with a double dose of the combined hepatitis A and B vaccine was highly effective. This is most likely explained by the increased dose, a positive bystander effect conferred by the hepatitis A vaccine, or both.

  • 17.
    Cedergren, Jan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences.
    Follin, Per
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Forslund, Tony
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology . Linköping University, Faculty of Health Sciences.
    Lindmark, Maria
    Linköping University, Department of Medicine and Care. Linköping University, Faculty of Health Sciences.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology . 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, Centre for Medicine, Department of Rheumatology in Östergötland.
    Inducible nitric oxide synthase (NOS II) is constitutive in human neutrophils2003In: APMIS, ISSN 0903-4641, Vol. 111, no 10, p. 963-968Article in journal (Refereed)
    Abstract [en]

    The objective was to study the expression of inducible nitric oxide synthase (NOS II) in and NO production by human blood neutrophils and in in vivo exudated neutrophils. Cellular expression of NOS II was evaluated by flow cytometry in whole blood, in isolated blood neutrophils, and in neutrophils obtained by exudation in vivo into skin chambers. Neutrophil NOS II was also demonstrated by Western blotting. Uptake of 3H-labelled L-arginine was studied in vitro and NOS activity measured in a whole cell assay by the conversion of 3H-arginine to 3H-citrulline. In contrast to unseparated blood cells, NOS II was demonstrable both in isolated blood neutrophils and exudated cells. The failure to detect NOS II by flow cytometry in whole blood cells thus proved to be due to the quenching effect of hemoglobin. Western blotting revealed a 130 kD band corresponding to NOS II in isolated blood neutrophils, but detection was dependent on diisopropylfluorophosphate for proteinase inhibition. L-arginine was taken up by neutrophils, but enzymatic activity could not be demonstrated. We conclude that human neutrophils constitutively express NOS II, but that its demonstration by FITC-labelling is inhibited by hemoglobin-mediated quenching in whole blood samples.

  • 18.
    Chabok, Abbas
    et al.
    Uppsala University.
    Tärnberg, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences.
    Smedh, Kenneth
    Uppsala University.
    Påhlman, Lars
    Uppsala University.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences.
    Lindberg, Christian
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Prevalence of fecal carriage of antibiotic-resistant bacteria in patients with acute surgical abdominal infections2010In: SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, ISSN 0036-5521, Vol. 45, no 10, p. 1203-1210Article in journal (Refereed)
    Abstract [en]

    Objective. Antibiotic resistance is increasing worldwide. The aims of the current study were to determine the fecal carriage of antibiotic-resistant bacteria and antibiotic treatment in surgical patients admitted to hospital due to acute intra-abdominal infections. Materials and methods. Eight Swedish surgical units participated in this prospective multicenter investigation. Rectal swabs were obtained on admission to hospital. Cultures were performed on chromogenic agar and antibiotic susceptibility testing was performed using the disk diffusion method. Extended-spectrum beta-lactamase (ESBL)phenotype was confirmed by Etest. Results. Rectal samples were obtained and analyzed from 208 patients with intra-abdominal surgical infections. Surgery was performed in 134 patients (65%). Cephalosporins were the most frequently used empirical antibiotic therapy. The highest rates of resistance among Enterobacteriaceae were detected for ampicillin (54%), tetracycline (26%), cefuroxime (26%) and trimethoprim-sulfamethoxazole (20%). The prevalence of decreased susceptibility (I + R) for the other antibiotics tested was for ciprofloxacin 20%, piperacillin-tazobactam 17%, cefotaxime 14%, ertapenem 12%, gentamicin 3% and imipenem 0%. ESBL-producing Enterobacteriaceae were found in samples from 10 patients (5%). Three patients had five E. coli isolates producing AmpC enzymes. Conclusions. This study shows a high rate of resistance among Enterobacteriaceae against antibiotics which are commonly used in Sweden and should have implications for the future choice of antibiotics for surgical patients.

  • 19.
    Dalgard, Olav
    et al.
    and Infectious Disease Department, Ullevål University Hospital, Oslo, Norway and Medical Department, Aker University Hospital, Oslo, Norway.
    Bjøro, Kristian
    Medical Department, Rikshospitalet, Oslo, Norway.
    Ring-Larsen, Helmer
    Liver Unit, Rigshospitalet, Copenhagen, Denmark and Faculty of Pharmacology and Pharmacotherapy, University of Copenhagen, Copenhagen, Denmark.
    Bjornsson, Einar
    Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden.
    Holberg-Petersen, Mona
    Department of Microbiology, Ullevål University Hospital, Oslo, Norway.
    Skovlund, Eva
    School of Pharmacy, University of Oslo, Oslo, Norway.
    Reichard, Olle
    Karolinska University Hospital, Stockholm, Sweden.
    Myrvang, Bjørn
    Infectious Disease Department, Ullevål University Hospital, Oslo, Norway.
    Sundelöf, Bo
    Medical Department, Gävle Hospital, Gävle, Sweden.
    Ritland, Ståle
    Medical Department, Buskerud University Hospital, Drammen, Norway.
    Hellum, Kjell
    Medical Department, Akershus University Hospital, Nordbyhagen, Norway.
    Frydén, Aril
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Florholmen, Jon
    Medical Department, Tromsø University Hospital, Tromsø, Norway.
    Verbaan, Hans
    Medical Department, Malmö University Hospital, Malmö, Sweden.
    Pegylated interferon alfa and ribavirin for 14 versus 24 weeks in patients with hepatitis C virus genotype 2 or 3 and rapid virological response2008In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 47, no 1, p. 35-42Article in journal (Refereed)
    Abstract [en]

    A recent nonrandomized pilot trial showed that hepatitis C virus (HCV) patients with genotype 2/3 and rapid virological response (RVR) had a 90% sustained virological response (SVR) rate after 14 weeks of treatment. We aimed to assess this concept in a randomized controlled trial. In the trial, 428 treatment-naïve HCV RNA–positive patients with genotype 2 or 3 were enrolled. Patients with RVR were randomized to 14 (group A) or 24 (group B) weeks of treatment. Patients were treated with pegylated interferon α-2b (1.5 μg/kg) subcutaneously weekly and ribavirin (800-1400 mg) orally daily. The noninferiority margin was set to be 10% between the two groups with a one-sided 2.5% significance level. RVR was obtained in 302 of 428 (71%), and 298 of these were randomized to group A (n = 148) or group B (n = 150). In the intention-to-treat analysis, SVR rates were 120 of 148 (81.1%) in group A and 136 of 150 (90.7%) in group B (difference, 9.6%; 95% confidence interval, 1.7-17.7). Among patients with an HCV RNA test 24 weeks after the end of treatment, 120 of 139 (86.3%) patients in group A achieved SVR compared with 136 of 146 (93.2%) in group B (difference, 6.9%; 95% confidence interval, −0.1 to +13.9). Conclusion: We cannot formally claim that 14 weeks of treatment is noninferior to 24 weeks of treatment. However, the SVR rate after 14 weeks of treatment is high, and although longer treatment may give slightly better SVR, we believe economical savings and fewer side effects make it rational to treat patients with genotype 2 or 3 and RVR for only 14 weeks.

  • 20.
    Darelid, Johan
    et al.
    Department of Infectious Diseases, Ryhov Hospital, Jönköping, Sweden.
    Löfgren, Sture
    Department of Clinical Bacteriology, Ryhov Hospital, Jönköping, Sweden.
    Malmvall, Bo-Eric
    Department of Infectious Diseases, Ryhov Hospital, Jönköping, Sweden.
    Olinder-Nielsen, Ann-Margareth
    Department of Infectious Diseases, Ryhov Hospital, Jönköping, Sweden.
    Briheim, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Hallander, H.
    Swedish Inst. Infect. Dis. Control, Stockholm, Sweden.
    Legionella pneumophila serogroup 1 antibody kinetics in patients with Legionnaires' disease: implications for serological diagnosis2003In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 35, no 1, p. 15-20Article in journal (Refereed)
    Abstract [en]

    To evaluate current serological criteria for Legionella pneumophila serogroup 1 (Lp1), the antibody response was prospectively studied in all patients hospitalized for Legionnaires' disease in a Swedish county during 11 y (n = 62). A 4-fold or greater rise in antibody titre to ≥ 128 (the minimum convalescent antibody level for diagnosis, as recommended by the Centers for Disease Control and Prevention), using the indirect immunofluorescence antibody test, was found in 21/52 (40%) of tested patients. By referring to the titre levels in healthy residents from the local population (World Health Organization criteria), 45/52 (87%) cases were confirmed serologically. In 21 patients followed longitudinally for 10 y, the median antibody titre fell from 256 (range 32-1024) to 16 (range 2-128) in 3 y. No booster reactions were observed in any patient. After 10 y, the geometric mean titre of this clinical cohort had reached the same level as observed in the background population 5 y earlier. Titre levels in subjects exposed to Legionella from a municipal water system indicate that only 1 out of 10 of all infections are identified clinically. Indirect immunofluorescent antibody testing with local reference sera is a sensitive method for laboratory confirmation of Lp1 in an unselected pneumonia population.

  • 21.
    Ekdahl, Christer
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Infective Endocarditis: aspects of pathophysiology, epidemiology, management and prognosis2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Infective endocarditis (IE) is a rare but complex disease that is fatal if untreated. With a modern combination of antimicrobial therapy and heart valve surgery, mortality is still 10-20 %. The structure of the endocarditis vegetation impedes the penetration of phagocytic cells such as monocytes and granulocytes. This leads to high bacterial counts inside the vegetation and the need for long treatment courses with a combination of intravenously administered bactericidal antibiotics.

    The aim of this thesis was to study the changes in epidemiology, management, and mortality at our hospital between 1980 and 2001, and to identify prognostic factors associated with mortality. To assess the issue of referral bias, differences between referred episodes and episodes from our local community were studied. Additional aims were to study the occurrence of the pro-chemotactic cytokines IL-8 and TNF-α in heart valves and vegetations during the active phase of IE, and to study the effect of the glycopeptide antibiotic vancomycin in dense staphylococcal cultures in vitro. As it is a rare and complex disease, management of IE is usually complicated for non-specialists. For this reason a computerised decision support system for IE was developed and evaluated.

    Between 1980 and 2001, the occurrence of Staphylococcus aureus IE and the use of early heart valve surgery increased significantly, regardless of whether the episodes were referred or of local origin. Glycopeptide antibiotics, mainly vancomycin, were used more frequently, especially among referred patients. Referred patients were younger, predominantly male, had more complications, and received surgical treatment more often than patients from our local community. The reason for the lower frequency of female patients in the referral cohort cannot be explained by more comorbidity or fewer complications. The differences between referred and local episodes seen in our study highlight the need for assessment and adjustment for referral bias in IE studies (Paper I).

    In six patients who needed early heart valve surgery, the largest numbers of IL-8-containing cells, and the greatest amount of inflammation, were seen in patients with short preoperative antimicrobial treatment courses. No such relationships were seen with respect to TNF-α-containing cells. The IL-8-containing cells and the inflammatory cells were predominantly scattered in the heart valve stroma or in the margin of the vegetation (Paper II). The primary effect of IL-8 is to stimulate chemotaxis of polymorphonuclear neutrophil granulocytes. This indicates that there is no deficiency of IL-8 in the area close to the vegetation as a cause of the localised agranulocytosis often present inside the vegetation.

    Our study revealed a need for computerised decision support systems (DSSs) in the field of IE, but to be used in clinical practice these DSSs need be part of knowledge bases covering larger domains (Paper IV). Some of our initial ideas described in Paper III, especially the use of Internet technology and the combination of rule-based advice and explanatory hypertext, will probably be included in these knowledge bases.

    In vitro, there is a rapid reduction of free vancomycin in broth containing dense staphylococcal cultures. Consequently, there is a simultaneous increase in broth MICs, particularly in high inocula, which is not caused by a development of resistance (Paper V). These findings need further evaluation in vivo, but indicate that the dosing regimen of vancomycin is of particular importance in staphylococcal infections with dense inocula, e.g. infective endocarditis.

    Diabetes mellitus and moderate to severe heart failure were independent risk factors for 6-month mortality in left-sided, Duke definite IE episodes, regardless of referral or local origin of the episodes. Early heart valve surgery had a positive impact on the 6-month mortality in the referral cohort of episodes, which may be due to referral bias (Paper VI).

    List of papers
    1. Changes in left-sided infective endocarditis over two decades at a Swedish university hospital: and evaluation of the importance of referral bias
    Open this publication in new window or tab >>Changes in left-sided infective endocarditis over two decades at a Swedish university hospital: and evaluation of the importance of referral bias
    Manuscript (Other academic)
    Identifiers
    urn:nbn:se:liu:diva-13331 (URN)
    Available from: 2008-06-18 Created: 2008-06-18 Last updated: 2010-01-13
    2. IL-8 and tumor necrosis factor alpha in heart valves from patients with infective endocarditis
    Open this publication in new window or tab >>IL-8 and tumor necrosis factor alpha in heart valves from patients with infective endocarditis
    Show others...
    2002 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, Vol. 34, no 10, p. 759-762Article in journal (Refereed) Published
    Abstract [en]

    The embedding of bacteria in the vegetation of infective endocarditis impedes the penetration of phagocytic cells. IL-8 has a stimulating effect on the immune system, particularly with respect to chemotaxis and activation of granulocytes. Tumor necrosis factor alpha (TNF-) is 1 of the major proinflammatory cytokines. IL-8 and TNF- were visualized by means of immunohistochemistry in paraffin-embedded heart valve biopsies from 6 patients with infective endocarditis who required cardiac surgery during the active phase of the infection. In 5/6 patients there were signs of inflammation, and in these patients IL-8- and TNF- -containing cells were visualized in the heart valve stromas or vegetations. The largest numbers of IL-8-containing cells, and the greatest amount of inflammation, were seen in patients with short preoperative treatment courses. No such relationships were seen with respect to TNF- -containing cells. These observations may suggest that the occurrence of IL-8-containing cells in infected heart valves could be used as a marker of disease activity.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13332 (URN)10.1080/00365540210147912 (DOI)
    Available from: 2008-06-18 Created: 2008-06-18 Last updated: 2009-08-17
    3. Extended telemedical consultation using Arden Syntax based decision support, hypertext and WWW technique
    Open this publication in new window or tab >>Extended telemedical consultation using Arden Syntax based decision support, hypertext and WWW technique
    Show others...
    1997 (English)In: Methods of Information in Medicine, ISSN 0026-1270, Vol. 36, no 2, p. 108-114Article in journal (Refereed) Published
    Abstract [en]

    There is an obvious need for geographic distribution of expert knowledge among several health care units without increasing the cost of on-site expertise in locations where health care is provided. This paper describes the design of a knowledge-based decision-support system for extended consultation in clinical medicine. The system is based on Arden Syntax for Medical Logic Modules and hypertext using World Wide Web technology. It provides advice and explanations regarding the given advice. The explanations are presented in a hypertext format allowing the user to browse related information and to verify the relevance of the given advice. The system is intended to be used in a closed local network. With special precautions regarding issues of safety and patient security, the system can be used over wider areas such as in rural medicine. A prototype has been developed in the field of clinical microbiology and infectious diseases regarding infective endocarditis.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13333 (URN)9242006 (PubMedID)
    Available from: 2008-06-18 Created: 2008-06-18 Last updated: 2017-12-13
    4. A study of the usage of a decision-support system for infective endocarditis
    Open this publication in new window or tab >>A study of the usage of a decision-support system for infective endocarditis
    2000 (English)In: Medical informatics and the Internet in medicine (Print), ISSN 1463-9238, E-ISSN 1464-5238, Vol. 25, no 1, p. 1-18Article in journal (Refereed) Published
    Abstract [en]

    The objective of this study was to examine a design for a World Wide Web-based decision-support system in use by clinically active physicians. A prototype implementation of the design concerned management of infective endocarditis patient cases. The design was based on an integration of hypertext and rule-based knowledge. In the study sessions, physicians in the field of internal medicine worked on managing authentic patient cases in a laboratory setting. Data was collected from interviews with the physicians using video recordings and stimulated recall technique. The qualitative data was analysed according to the constant comparative method in order to develop a model of the physicians' usage of the system. The resulting model describes perceived contributions and criteria for usefulness of the system. The ways the physicians used the system showed that it was able to provide patient-specific support for confirming clinical decisions, for higher-level patient management, and for preparing for and initiating expert consultations. Users also stated that new medical knowledge could be gained as a side effect of using the system.

    Keywords
    Decision-support System, Endocarditis, Qualitative Methodology, Evaluation
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13334 (URN)10.1080/146392300298229 (DOI)
    Available from: 2008-06-18 Created: 2008-06-18 Last updated: 2017-12-13
    5. Rapid decrease of free vancomycin in dense staphylococcal cultures
    Open this publication in new window or tab >>Rapid decrease of free vancomycin in dense staphylococcal cultures
    Show others...
    2005 (English)In: European journal of clinical microbiology and infectious diseases, ISSN 0934-9723, Vol. 24, no 9, p. 596-602Article in journal (Refereed) Published
    Abstract [en]

    Bacterial numbers in broth cultures were determined by bioluminescence assay of intracellular bacterial ATP. Broth MICs for strains of Staphylococcus epidermidis (ATCC 14990 and 35984) and Staphylococcus aureus (ATCC 25923, 29213 and 6538) were determined for cultures with different inocula (105–108 bacteria/ml) after 24 h of incubation in supplemented Mueller–Hinton broth containing vancomycin. All of the tested strains except one were susceptible to methicillin, and all of the strains were susceptible to vancomycin. Free vancomycin concentrations in the broth cultures of all strains were determined with an agar well bioassay after 24 h of incubation. Free vancomycin concentrations and bacterial numbers of ATCC 35984 and ATCC 29213 were also determined after 0.5, 2, 4, and 8 h. In a low inoculum (105 bacteria/ml), the broth MICs were 1–4 μg/ml. In a high inoculum (∼108 bacteria/ml), the broth MICs increased two- to fourfold to 4–8 μg/ml. In dense inocula (∼109–1010 bacteria/ml), the concentrations of free vancomycin in the broth were reduced, in most cases below the detection limit of the bioassay (≤0.5 μg/ml). This reduction of free vancomycin was fast, occurring in initially dense inocula in less than 30 min. No emergence of resistance was seen. These results show a rapid reduction of free vancomycin in the broth and a simultaneous increase in broth MICs in high inocula, without development of resistance. This indicates that the dosing regimen of vancomycin is of particular importance in staphylococcal infections with dense inocula, e.g. infective endocarditis.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13335 (URN)10.1007/s10096-005-0011-0 (DOI)
    Available from: 2008-06-18 Created: 2008-06-18
    6. Prognostic factors for 6-month mortality in infective endocarditis: a retrospective study in a Swedish referral hospital
    Open this publication in new window or tab >>Prognostic factors for 6-month mortality in infective endocarditis: a retrospective study in a Swedish referral hospital
    Manuscript (Other academic)
    Identifiers
    urn:nbn:se:liu:diva-13336 (URN)
    Available from: 2008-06-18 Created: 2008-06-18 Last updated: 2010-01-13
  • 22.
    Ekdahl, Christer
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Broqvist, Mats
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Franzén, Stefan
    Ljunghusen, Olof
    Maller, Rolf
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Sander, Birgitta
    IL-8 and tumor necrosis factor alpha in heart valves from patients with infective endocarditis2002In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, Vol. 34, no 10, p. 759-762Article in journal (Refereed)
    Abstract [en]

    The embedding of bacteria in the vegetation of infective endocarditis impedes the penetration of phagocytic cells. IL-8 has a stimulating effect on the immune system, particularly with respect to chemotaxis and activation of granulocytes. Tumor necrosis factor alpha (TNF-) is 1 of the major proinflammatory cytokines. IL-8 and TNF- were visualized by means of immunohistochemistry in paraffin-embedded heart valve biopsies from 6 patients with infective endocarditis who required cardiac surgery during the active phase of the infection. In 5/6 patients there were signs of inflammation, and in these patients IL-8- and TNF- -containing cells were visualized in the heart valve stromas or vegetations. The largest numbers of IL-8-containing cells, and the greatest amount of inflammation, were seen in patients with short preoperative treatment courses. No such relationships were seen with respect to TNF- -containing cells. These observations may suggest that the occurrence of IL-8-containing cells in infected heart valves could be used as a marker of disease activity.

  • 23.
    Ekdahl, Christer
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
    Hällgren, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
    Nilsson, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences.
    Svensson, E.
    Division of Clinical Bacteriology, Department of Laboratory Medicine, Sahlgrenska University Hospital, Sweden.
    Nilsson, Lennart E.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences.
    Rapid decrease of free vancomycin in dense staphylococcal cultures2005In: European journal of clinical microbiology and infectious diseases, ISSN 0934-9723, Vol. 24, no 9, p. 596-602Article in journal (Refereed)
    Abstract [en]

    Bacterial numbers in broth cultures were determined by bioluminescence assay of intracellular bacterial ATP. Broth MICs for strains of Staphylococcus epidermidis (ATCC 14990 and 35984) and Staphylococcus aureus (ATCC 25923, 29213 and 6538) were determined for cultures with different inocula (105–108 bacteria/ml) after 24 h of incubation in supplemented Mueller–Hinton broth containing vancomycin. All of the tested strains except one were susceptible to methicillin, and all of the strains were susceptible to vancomycin. Free vancomycin concentrations in the broth cultures of all strains were determined with an agar well bioassay after 24 h of incubation. Free vancomycin concentrations and bacterial numbers of ATCC 35984 and ATCC 29213 were also determined after 0.5, 2, 4, and 8 h. In a low inoculum (105 bacteria/ml), the broth MICs were 1–4 μg/ml. In a high inoculum (∼108 bacteria/ml), the broth MICs increased two- to fourfold to 4–8 μg/ml. In dense inocula (∼109–1010 bacteria/ml), the concentrations of free vancomycin in the broth were reduced, in most cases below the detection limit of the bioassay (≤0.5 μg/ml). This reduction of free vancomycin was fast, occurring in initially dense inocula in less than 30 min. No emergence of resistance was seen. These results show a rapid reduction of free vancomycin in the broth and a simultaneous increase in broth MICs in high inocula, without development of resistance. This indicates that the dosing regimen of vancomycin is of particular importance in staphylococcal infections with dense inocula, e.g. infective endocarditis.

  • 24.
    Ekdahl, Christer
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Karlsson, Daniel
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Health Sciences.
    Wigertz, Ove
    Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Forsum, Urban
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    A study of the usage of a decision-support system for infective endocarditis2000In: Medical informatics and the Internet in medicine (Print), ISSN 1463-9238, E-ISSN 1464-5238, Vol. 25, no 1, p. 1-18Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to examine a design for a World Wide Web-based decision-support system in use by clinically active physicians. A prototype implementation of the design concerned management of infective endocarditis patient cases. The design was based on an integration of hypertext and rule-based knowledge. In the study sessions, physicians in the field of internal medicine worked on managing authentic patient cases in a laboratory setting. Data was collected from interviews with the physicians using video recordings and stimulated recall technique. The qualitative data was analysed according to the constant comparative method in order to develop a model of the physicians' usage of the system. The resulting model describes perceived contributions and criteria for usefulness of the system. The ways the physicians used the system showed that it was able to provide patient-specific support for confirming clinical decisions, for higher-level patient management, and for preparing for and initiating expert consultations. Users also stated that new medical knowledge could be gained as a side effect of using the system.

  • 25.
    Eklund, Daniel
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Persson, Hans Lennart
    Linköping University, Department of Medical and Health Sciences, Pulmonary Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Respiratory Medicine.
    Larsson, Marie C.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Welin, Amanda
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Idh, Jonna
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Paues, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Fransson, Sven-Göran
    Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Stendahl, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Lerm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Vitamin D enhances IL-1β secretion and restricts growth of Mycobacterium tuberculosis in macrophages from TB patients2013In: International Journal of Mycobacteriology, ISSN 2212-5531, Vol. 2, no 1, p. 18-25Article in journal (Refereed)
    Abstract [en]

    The emergence of multidrug-resistant strains of Mycobacterium tuberculosis (MTB), the bacterium responsible for tuberculosis (TB), has rekindled the interest in the role of nutritional supplementation of micronutrients, such as vitamin D, as adjuvant treatment. Here, the growth of virulent MTB in macrophages obtained from the peripheral blood of patients with and without TB was studied. The H37Rv strain genetically modified to express Vibrio harveyi luciferase was used to determine the growth of MTB by luminometry in the human monocyte-derived macrophages (hMDMs) from study subjects. Determination of cytokine levels in culture supernatants was performed using a flow cytometry-based bead array technique. No differences in intracellular growth of MTB were observed between the different study groups. However, stimulation with 100 nM 1,25-dihydroxyvitamin D significantly enhanced the capacity of hMDMs isolated from TB patients to control the infection. This effect was not observed in hMDMs from the other groups. The interleukin (IL)-1β and IL-10 release by hMDMs was clearly increased upon stimulation with 1,25-dihydroxyvitamin D. Furthermore, the 1,25-dihydroxyvitamin D stimulation also led to elevated levels of TNF-α (tumor necrosis factor-alpha) and IL-12p40. It was concluded that vitamin D triggers an inflammatory response in human macrophages with enhanced secretion of cytokines, as well as enhancing the capacity of hMDMs from patients with active TB to restrict mycobacterial growth.

  • 26.
    Erlandsson, Marcus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Burman, Lars G.
    Swedish Institute for Infectious Disease Control, Stockholm, Sweden.
    Cars, Otto
    Swedish Institute for Infectious Disease Control, Stockholm, Sweden.
    Gill, Hans
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Nilsson, Lennart E.
    Walther, Sten
    Linköping University, Department of Medicine and Health Sciences, Physiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    ICU-STRAMA Study Group,
    Prescription of antibiotic agents in Swedish intensive care units is empiric and adequate2007In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 39, no 1, p. 63-69Article in journal (Refereed)
    Abstract [en]

    Since the prescription of antibiotics in the hospital setting is often empiric, particularly in the critically ill, and therefore fraught with potential error, we analysed the use of antibiotic agents in Swedish intensive care units (ICUs). We examined indications for antibiotic treatment, agents and dosage prescribed among 393 patients admitted to 23 ICUs at 7 tertiary care centres, 11 secondary hospitals and 5 primary hospitals over a 2-week period in November 2000. Antibiotic consumption was higher among ICU patients in tertiary care centres with a median of 84% (range 58-87%) of patients on antibiotics compared to patients in secondary hospitals (67%, range 35-93%) and in primary hospitals (38%, range 24-80%). Altogether 68% of the patients received antibiotics during the ICU stay compared to 65% on admission. Cefuroxime was the most commonly prescribed antibiotic before and during admission (28% and 24% of prescriptions, respectively). A date for decision to continue or discontinue antibiotic therapy was set in 21% (6/29) of patients receiving prophylaxis, in 8% (16/205) receiving empirical treatment and in 3% (3/88) when culture-based therapy was given. No correlation between antibiotic prescription and laboratory parameters such as CRP levels, leukocyte and thrombocyte counts, was found. The treatment was empirical in 64% and prophylactic in 9% of cases. Microbiological data guided prescription more often in severe sepsis (median 50%, range 40-60% of prescriptions) than in other specified forms of infection (median 32%, range 21-50%). The empirically chosen antibiotic was found to be active in vitro against the pathogens found in 55 of 58 patients (95%) with a positive blood culture. This study showed that a high proportion of ICU patients receive antimicrobial agents and, as expected, empirical-based therapy is more common than culture-based therapy. Antibiotics given were usually active in vitro against the pathogen found in blood cultures. We ascribe this to a relatively modest antibiotic resistance problem in Swedish hospitals.

  • 27.
    Erlandsson, Marcus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
    Gill, Hans
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Nilsson, Lennart E.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences.
    Walther, Sten
    Department of Anaesthesiology, Ullevål University Hospital, University of Oslo, Oslo, Norway.
    Giske, Christian G.
    Division of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden.
    Jonas, Daniel
    Institute of Environmental Medicine and Hospital Epidemiology, University Medical Centre, Freiburg, Germany.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Nordlinder, David
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
    Antibiotic susceptibility patterns and clones of Pseudomonas aeruginosa in Swedish ICUs2008In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 40, no 6-7, p. 487-494Article in journal (Refereed)
    Abstract [en]

    Pseudomonas aeruginosa is 1 of the bacteria most adaptive to anti-bacterial treatment. Previous studies have shown nosocomial spread and transmission of clonal strains of P. aeruginosa in European hospitals. In this study we investigated antibiotic susceptibility and clonality in 101 P. aeruginosa isolates from 88 patients admitted to 8 Swedish ICUs during 2002. We also compared phenotypes and genotypes of P. aeruginosa and carried out cluster analysis to determine if phenotypic data can be used for surveillance of clonal spread. All isolates were collected on clinical indication as part of the NPRS II study in Sweden and were subjected to AFLP analysis for genotyping. 68 isolates with unique genotypes were found. Phenotyping was performed using MIC values for 5 anti-pseudomonal agents. Almost 6% of the isolates were multi-drug resistant (MDR), and this figure rose to almost 8% when intermediate isolates were also included. We found probable clonal spread in 9 cases, but none of them was found to be an MDR strain. Phenotypical cluster analysis produced 40 clusters. Comparing partitions did not demonstrate any significant concordance between the typing methods. The conclusion of our study is that cross-transmission and clonal spread of MDR P. aeruginosa does not present a clinical problem in Swedish ICUs, but probable cross-transmission of non-MDR clones indicate a need for improved hygiene routines bedside. The phenotype clusters were not concordant with genotype clusters, and genotyping is still recommended for epidemiological tracking.

  • 28.
    Erlandsson, Marcus
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
    Hoffmann, Mikael
    Isaksson, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Lindgren, Sune
    Sörén, L.
    Department of Clinical Microbiology, County Hospital, Jönköping .
    Walther, Sten
    Linköping University, Department of Medicine and Health Sciences, Physiology . Linköping University, Faculty of Health Sciences.
    Surveillance of Antibiotic Resistance in ICUs in Southeastern Sweden1999In: Acta Anaesthesiol Scand, Vol. 43, no 8, p. 815-820Article in journal (Refereed)
    Abstract [en]

    Background: A study was designed to assess a computer-based program for continuous registration of antibiotic resistance, statistics concerning severity of illness, and consumption of antibacterial drugs.

    Methods: The frequency of antibiotic resistance among bacteria in eight ICUs in southeastern Sweden was investigated yearly from 1995 through 1997. The antibiotic consumption in the ICUs was registered as defined daily doses (DDD) and compared to severity of illness (APACHE-II scores).

    Results: There was a statistically significant increase in ampicillin resistance among Enterococcus spp. between 1996 and 1997, which was due to a shift from Enterococcus faecalis to Enterococcus faecium. A high prevalence of resistance among coagulase-negative staphylococci to oxacillin (≈ 70%), ciprofloxacin (≈ 50%), fucidic acid (≈ 50%) and netilmicin (≈ 30%) was seen in all ICUs during the whole study period. There was a statistically significant increase in ciprofloxacin resistance among Escherichia coli and Enterococcus spp. The resistance among Enterobacter spp. to cefotaxime decreased but this change was not statistically significant. Efforts were made to avoid betalactam antibiotics, except carbapenems, for treatment of infections caused by Enterobacter spp. and the consumption of cephalosporins decreased whereas the consumption of carbapenems increased. The total antibiotic consumption decreased by 2.5% during the study period. There was no correlation between APACHE II scores and antibiotic consumption.

    Conclusions: Each ICU within a hospital ought to have a program for "on-line" antibiotic resistance surveillance of drugs used in that unit so that changes in empirical treatment can be made when there is an increase in antibiotic-resistant isolates within that unit.

  • 29.
    Follin, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Skin-chamber technique for study of in vivo exudated human neutrophils1999In: JIM - Journal of Immunological Methods, ISSN 0022-1759, E-ISSN 1872-7905, Vol. 232, no 1-2, p. 55-65Article in journal (Refereed)
    Abstract [en]

    The development of new techniques for isolation of neutrophils extravasated in vivo have been essential for studying the dynamics of the inflammatory response in humans. Methods for generating inflammatory skin reactions were first presented in the mid 1950s, and later a skin blistering technique based on suction was introduced. With this procedure, small areas of denuded dermis, called "skin windows", are created and covered with special chambers containing a medium that attracts exudated neutrophils. By comparing the neutrophils collected in such chambers with those isolated from peripheral blood, it is possible to investigate the functional modifications that neutrophils undergo when attracted to an inflammatory process. The skin-blister chamber technique represents an aseptic, non-traumatic and reproducible model of inflammation that can be used to study in vivo activated human neutrophils. The background, methodological aspects and options of this technique are described, together with the functional characteristics of exudated neutrophils. (C) 1999 Elsevier Science B.V. All rights reserved.

  • 30.
    Fryland, Linda
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Sandin, Linnea
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Wilhelmsson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Lindblom, Pontus
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Nyman, Dag
    Aland Borrelia Grp.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Ekerfelt, Christina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology.
    Biomarkers in blood a few days after a bite by a Borrelia burgdorferi infected tick:: Asymptomatic Borrelia burgdorferi-infected subjects show higher Th1-associated response compared with subjects who later develop Lyme borreliosis2012Manuscript (preprint) (Other academic)
    Abstract [en]

    The clinical outcome following infection with Borrelia (B.) burgdorferi sensu lato (s.l.) differs between individuals, ranging from asymptomatic infection to Lyme borreliosis (LB) with persistent symptoms post-treatment. Previous studies in mice and humans have generated the hypothesis that a successful outcome of B. burgdorferi s.l. infection is associated with an early strong pro-inflammatory T helper (Th)1-like immune response. The aim of this study was to assess the early course of events in B. burgdorferi s.l.-associated inflammation by screening for possible early immune biomarkers in peripheral blood from newly tick-bitten persons. The study subjects bitten by B. burgdorferi s.l.-infected ticks were divided into (1) those later developing clinical LB, (2) those who developed anti-B. burgdorferi s.l. antibodies but not clinical LB, (3) those who neither developed antibodies nor clinical LB. A fourth group consisted of bitten study subjects without development of antibodies or clinical LB. Two sets of samples, both comprising all four groups, were collected in order to repeat the analyses and confirm the data. Sera or plasma collected a few days after the tick bite were analysed for 18 biomarkers (IL-1β, IL-6, CXCL8/IL-8, IL-12p70, IL-17A, IL-27, TNF, CCL18, CCL20, CCL22, CXCL1, CXCL9, CXCL10, CXCL11, calprotectin, MMP-3, MMP-8, MMP-9) by multiplex bead assay and ELISA. In the first set of samples, the neutrophil activation marker calprotectin was increased in subjects who developed clinical LB compared with subjects who developed antibodies against B. burgdorferi s.l. but did not develop LB. However, the finding could not be confirmed in the second set of samples, thus the study failed to identify an early prognostic marker for development of clinical LB. Interestingly, both sets of samples showed increases in two different Th1-associated markers, CXCL10 and IL-12p70, respectively, in subjects who following a bite by a B. burgdorferi s.l.-infected tick developed antibodies against B. burgdorferi s.l. but did not develop LB compared with subjects who developed clinical LB, thus supporting the hypothesis of an early strong Th1-response being important for optimal resolution of B. burgdorferi s.l. infection.

  • 31.
    Fryland, Linda
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Wilhelmsson, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Nyman, Dag
    Aland Borrelia Grp.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Low risk of developing Borrelia burgdorferi infection in the south-east of Sweden after being bitten by a Borrelia burgdorferi-infected tick2011In: INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, ISSN 1201-9712, Vol. 15, no 3, p. E174-E181Article in journal (Refereed)
    Abstract [en]

    Objectives: The risk of developing Lyme borreliosis (LB) from Borrelia burgdorferi sensu lato (Bb)-infected ticks in Sweden is largely unknown. In the current study, we investigated the prevalence of Bb in ticks that had bitten humans and the risk of developing LB from Bb-infected ticks. Methods: Health questionnaires, blood samples, and ticks were collected from 394 tick-bitten study subjects in the County of Ostergotland, Sweden, at the time of the tick bite. Questionnaires and blood samples were also collected 3 months later. Ticks were screened for Bb DNA with PCR, while sera were analyzed for antibodies against Bb using two ELISA assays. Seroconversion, i.e., an at least two-fold increase in anti-Bb antibodies after 3 months, was confirmed using a Strip-Immunoassay. Results: Seventy-five of 397 ticks collected from the study subjects were determined to be Bb-positive. Sixty-four of the tick-bitten subjects had been bitten by Bb-infected ticks. Four of them showed seroconversion and were therefore considered to have an active Bb infection. None of these four subjects had sought health care due to symptoms, but one reported symptoms. Conclusions: Our data suggest that the risk of developing LB after being bitten by a Bb-infected tick is low, and asymptomatic Bb infections appear to be more frequent than symptomatic infections.

  • 32.
    Fusco, F M
    et al.
    National Institute of Infectious Disease L Spallanzani.
    Schilling, S
    University of Frankfurt.
    Puro, V
    National Institute of Infectious Disease L Spallanzani.
    Brodt, H-R
    University of Frankfurt.
    Follin, P
    Västra Götaland Region.
    Jarhall, Boo
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Bannister, B
    Royal Free Hospital, London.
    Maltezou, H C
    Hellen Centre for Disease Control & Prevention.
    Thomson, G
    Health Protection Agency, London.
    Brouqui, P
    CHU Nord.
    Ippolito, G
    National Institute of Infectious Disease L Spallanzani.
    EuroNHID checklists for the assessment of high-level isolation units and referral centres for highly infectious diseases: results from the pilot phase of a European survey2009In: CLINICAL MICROBIOLOGY AND INFECTION, ISSN 1198-743X, Vol. 15, no 8, p. 711-719Article, review/survey (Refereed)
    Abstract [en]

    Healthcare settings have been identified as preferential for the transmission of many agents causing highly infectious diseases (HIDs). Infection control procedures strongly reduce the risk of transmission of HIDs in hospital settings, when adequately applied. The main objective of the European Network for Highly Infectious Diseases (EuroNHID), a network co-funded by the European Commission, is to assess the current capabilities for dealing with HIDs in Europe, specifically in the context of infection control and healthcare worker (HCW) safety, through conducting an on-the-field survey of high-level isolation units (HLIUs)/referral centres for the management of HIDs in participating countries. During the first year of the projects activities, specifically designed, evidence-based checklists were developed. This review introduces the EuroNHID checklists as a standard tool for the assessment of hospital capabilities concerning infection control and HCW safety in the management of patients with HIDs, and presents preliminary results from five HLIUs.

  • 33.
    Fusco, F.M.
    et al.
    Lazzaro Spallanzani.
    Puro, V.
    Lazzaro Spallanzani.
    Baka, A.
    National Health Operations Centre, Athens.
    Bannister, B.
    Royal Free Hospital.
    Brodt, H.-R.
    University Hospital, Johann Wolfgang Goethe Universität.
    Brouqui, P.
    CHU Nord AP-HM.
    Follin, Per
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Gjorup, I.E.
    University of Copenhagen.
    Gottschalk, R.
    Public Health Office, Frankfurt am Main.
    Hemmer, R.
    Centre Hospitalier de Luxembourg.
    Hoepelman, I.M.
    Utrecht University Medical Center.
    Jarhall, Boo
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Kutsar, K.
    National Public Health Institute, Tallinn.
    Lanini, S.
    Lazzaro Spallanzani.
    Lyytikainen, O.
    National Public Health Institute, Department of Infectious Disease, Epidemiology, Helsinki.
    Maltezou, H.C.
    Hellenic Center for Disease Control and Prevention.
    Mansinho, K.
    Centro Hospitalar Lisboa Ocidental.
    Marti, M.C.
    Hospital Universitario Vall dHebron.
    Ott, K.
    West Tallinn Central Hospital.
    Peleman, R.
    University Hospital of Gent.
    Perronne, C.
    Hôpitaux de Paris.
    Sheehan, G.
    Mater Misericordiae Hospital.
    Siikamakii, H.
    Helsinki University Central Hospital.
    Skinhoj, P.
    Rigshospitalet, Copenhagen.
    Trilla, A.
    University of Barcelona.
    Vetter, N.
    Otto Wagner Spital, Wien, Austria.
    Ippolito, G.
    Lazzaro Spallanzani.
    Isolation rooms for highly infectious diseases: an inventory of capabilities in European countries2009In: Journal of Hospital Infection, ISSN 0195-6701, Vol. 73, no 1, p. 15-23Article in journal (Refereed)
    Abstract [en]

    Isolation of patients with highly infectious diseases (HIDs) in hospital rooms with adequate technical facilities is essential to reduce the risk of spreading disease. The European Network for Infectious Diseases (EUNID), a project co-funded by European Commission and involving 16 European Union member states, performed an inventory of high level isolation rooms (HIRs, hospital rooms with negative pressure and anteroom). In participating countries, HIRs are available in at least 211 hospitals, with at least 1789 hospital beds. The adequacy of this number is not known and will depend on prevailing circumstances. Sporadic HID cases can be managed in the available HIRs. HIRs could also have a role in the initial phases of an influenza pandemic. However, large outbreaks due to natural or to bioterrorist events will need management strategies involving healthcare facilities other than HIRs.

  • 34.
    Gardulf, A N N
    et al.
    Karolinska Institute.
    Hansen, S
    Karolinska Institute.
    Steger, B
    Falu Lasarett.
    Fust, R
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Persson, B
    Halmstad Sjukhus.
    Elnersson, K
    Uppsala University Hospital.
    Ericson, E
    Östersunds Sjukhus.
    Hagstedt, C
    Lanssjukhuset Ryhov.
    Johansson, L
    Sahlgrens University Hospital.
    Nicolay, U
    Karolinska Institute.
    Gender differences in the perceptions of PID disease, IgG replacement therapy and life situation - Data from the the national SwePID study2008In: CLINICAL AND EXPERIMENTAL IMMUNOLOGY,ISSN 0009-9104: Volume 154, 2008, Vol. 154, p. 24-24Conference paper (Refereed)
  • 35.
    Gardulf, A N N
    et al.
    Karolinska Institute.
    Hansen, S
    Karolinska University Hospital.
    Steger, B
    Falu Lasarett.
    Fust, R
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Persson, B
    Halmstad Sjukhus.
    Elnersson, K
    Uppsala University Hospital.
    Ericson, E
    Östersunds Sjukhus.
    Hagstedt, C
    Lanssjukhuset Ryhov.
    Johansson, L
    Sahlgrens University Hospital.
    Nicolay, U
    Karolinska Institute.
    Parents views on IgG therapy and life situation having a child suffering from PID - Data from the national SwePID study2008In: CLINICAL AND EXPERIMENTAL IMMUNOLOGY,ISSN 0009-9104: Volume 154, 2008, Vol. 154, p. 25-25Conference paper (Refereed)
  • 36.
    Gardulf, A N N
    et al.
    Karolinska Institute.
    Hansen, S
    Karolinska University Hospital.
    Steger, B
    Falu Lasarett.
    Fust, R
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Persson, B
    Halmstad Sjukhus.
    Elnersson, K
    Uppsala University Hospital.
    Ericson, E
    Östersunds Sjukhus.
    Hagstedt, C
    Lanssjukhuset Ryhov.
    Johansson, L
    Sahlgrens University Hospital.
    Nicolay, U
    Karolinska Institute.
    Patient-reported infections and symptoms before and after IgG therapy - Data from the national SwePID study2008In: CLINICAL AND EXPERIMENTAL IMMUNOLOGY,ISSN 0009-9104: Volume 154, 2008, Vol. 154, p. 24-25Conference paper (Refereed)
  • 37.
    Gibson, Kate L
    et al.
    Nottingham Trent University.
    Duggan, Orla
    Nottingham Trent University.
    Vaughan, Robert
    Guys Hospital, London.
    Kondeatis, Elli
    Guys Hospital, London.
    Nilsson, Bengt-Olof
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
    Wikby, Anders
    Jönköping University.
    Kipling, David
    Cardiff University.
    Dunn-Walters , Deborah K
    Guys Hospital, London.
    B-cell diversity decreases in old age and is correlated with poor health status2009In: AGING CELL, ISSN 1474-9718 , Vol. 8, no 1, p. 18-25Article in journal (Refereed)
    Abstract [en]

    Older people suffer from a decline in immune system, which affects their ability to respond to infections and to raise efficient responses to vaccines. Effective and specific antibodies in responses from older individuals are decreased in favour of non-specific antibody production. We investigated the B-cell repertoire in DNA samples from peripheral blood of individuals aged 86-94 years, and a control group aged 19-54 years, using spectratype analysis of the IGHV complementarity determining region (CDR)3. We found that a proportion of older individuals had a dramatic collapse in their B-cell repertoire diversity. Sequencing of polymerase chain reaction products from a selection of samples indicated that this loss of diversity was characterized by clonal expansions of B cells in vivo. Statistical analysis of the spectratypes enabled objective comparisons and showed that loss of diversity correlated very strongly with the general health status of the individuals; a distorted spectratype can be used to predict frailty. Correlations with survival and vitamin B12 status were also seen. We conclude that B-cell diversity can decrease dramatically with age and may have important implications for the immune health of older people. B-cell immune frailty is also a marker of general frailty.

  • 38.
    Hammar, Mats
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Bergdahl, Björn
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center.
    Öhman, Lena
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Celebrating the Past by Expanding the Future: The Faculty of Health Science, Linköping University 1986–20062006Report (Other academic)
    Abstract [en]

    During the fall of 2006, the Faculty of Health Sciences (FHS) celebrates its 20th birthday. Linköping has a long tradition of health education; our nursing programme started already in 1895 and occupational therapy began in 1965. From the late 1960’s, medical students from Uppsala spent their last seven semesters in Linköping, mainly for clinical studies. After some years, academic and teachers from the young faculty, together with the county council, realized the enormous potential benefits of a complete undergraduate medical programme at Linköping University. Inspired by apparent innovations from McMaster University in Canada, Maastricht in Holland, Ben Gurion in Israel and Tromsø in Norway, these ideas and ideals were gradually turned into reality. In a complicated process, concerning the life or death of the medical faculty, a close co-operation between the University and the County Council of Östergötland was extremely fruitful. A proposal regarding a complete medical programme, and study periods integrated between the other health education programmes, was forwarded to the Swedish government in December 1982 and approved in 1984.

    The new FHS at Linköping University was launched in 1986, and by the end of August the first students began their studies. Already at the start, FHS included several programmes for health professionals: nursing, occupational therapy, physiotherapy, medicine, social welfare and laboratory technology. Speech and language pathology was added in 2003 and the education curriculum for laboratory technicians was developed into a master’s programme in medical biology. A number of important concepts were included in the new programmes. Problem based learning (PBL) was chosen as the fundamental basis for organising studies; using small tutorial groups with supervisors as “coaches” and real patient histories as triggers for learning. Since 2001, realistic cases/scenarios are made available on the Intranet.

    PBL is highly appreciated by the majority of students and teachers. This method of learning focused in contexts, according to pedagogic research, leads to a higher retention of knowledge than in traditional teacher-centered approaches toward learning. Important PBL spin-off effects are in educating students to cooperate in groups, to communicate and argue, to listen to other students’ opinions, to evaluate their own efforts and to identify learning needs. Furthermore, the method implies that students’ learn to independently find and evaluate scientific information, thereby realizing that the truth is somewhat “relative,” since what they find may differ depending on the sources used. Perhaps the most important characteristic of PBL is that it moves the main responsibility for obtaining goals and new knowledge from the teacher to the student.

    Other important elements of the various curricula at the FHS are vertical and horizontal integration. In vertical integration, e.g. between clinical and basic science, different sections are interwoven with clear progressive shifts over phases and semesters. This has shown to stimulate profound rather than superficial learning, and probably stimulates better understanding. Horizontal integration focuses on the simultaneous learning of several subjects needed to understand and explain the scenarios used.

    In PBL, teachers are expected to cooperate over departmental borders, a process that often produces positive spin-off effects extending further to research. They take on many different roles as e.g. planners, semester coordinators, tutors, lecturers and clinical supervisors. As such, newcomers may encounter certain frustration. Continuous staff development is critical to assure pedagogical selection and excellence, and thereby the quality of the programmes.

    In PBL, teachers are expected to cooperate over departmental borders, a process that often produces positive spin-off effects extending further to research. They take on many different roles as e.g. planners, semester coordinators, tutors, lecturers and clinical supervisors. As such, newcomers may encounter certain frustration. Continuous staff development is critical to assure pedagogical selection and excellence, and thereby the quality of the programmes.

    The aim to be a medical faculty with a standing among the most progressive worldwide implies continuous evaluation and development. Our mission is to foster the very best in health care; health care extending consideration toward educating competent professionals and conducting quality research with a focus on societal needs and welfare. To fulfil this mission, we need to advance teaching models based on evidence, and continuously improve and develop our educational methods. This process requires cooperation between departments, teachers and students within the university and indeed, throughout the world. Such contacts and collaborations are as important in education as they are in research, and extend an endless source of inspiration. Communication between the different undergraduate programmes at FHS has been extremely fruitful and should further be stimulated. At the faculty level, it is important to provide teachers with credit for efforts and development toward education. To keep integration and innovation at a high level, it is very important to balance the decision power and the distribution of money between departments and programmes.

    The aim of this book is to provide a general overview, in glimpses, of some of the important developments in FHS education; to describe new ideas in progress or those already turned to reality and also, to extend some consideration of publications regarding our educational innovations. We hope these examples provide the essence of inspiration for future work, contributing to improved education and better health for all.

  • 39.
    Hammarskjold, F
    et al.
    Ryhov County Hospital, Sweden .
    Mernelius, S
    Ryhov County Hospital, Sweden .
    Andersson, R. E.
    Ryhov County Hospital, Sweden .
    Berg, Sören
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Lofgren, S
    Ryhov County Hospital, Sweden .
    Malmvall, Bo-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Petzold, M
    University of Gothenburg, Sweden .
    Matussek, A
    Ryhov County Hospital, Sweden .
    Possible transmission of Candida albicans on an intensive care unit: genotype and temporal cluster analyses2013In: Journal of Hospital Infection, ISSN 0195-6701, E-ISSN 1532-2939, Vol. 85, no 1, p. 60-65Article in journal (Refereed)
    Abstract [en]

    Background: Nosocomial transmission of Candida spp. has not been fully explored and previous studies have shown conflicting results. less thanbrgreater than less thanbrgreater thanAim: To evaluate the possible nosocomial transmission of Candida spp. on an intensive care unit (ICU). less thanbrgreater than less thanbrgreater thanMethods: A prospective study was conducted for a period of 19 months, including all patients on our ICU with growth of Candida spp. from surveillance and directed cultures. Molecular typing with repetitive sequence-based polymerase chain reaction was used to define genotype relationships between the Candida albicans and Candida glabrata isolates. Candida isolates obtained from blood cultures taken from patients in our county outside the ICU were used as a reference. Temporal cluster analysis was performed to evaluate genotype distribution over time. less thanbrgreater than less thanbrgreater thanFindings: Seventy-seven patients with 78 ICU stays, representing 12% of all ICU stays, were found to harbour 180 isolates of Candida spp. Molecular typing revealed 27 C. albicans genotypes and 10 of C. glabrata. Possible clustering, indicated by overlapping stays of patients with indistinguishable candida genotypes, was observed on seven occasions with C. albicans and on two occasions with C. glabrata. Two C. albicans genotypes were found significantly more often in the ICU group compared with the reference group. Moreover, C. albicans genotypes isolated from more than one patient were significantly more often found in the ICU group. Temporal cluster analysis revealed a significantly increased number of pairs with indistinguishable genotypes at a 21-day interval, indicating clustering. less thanbrgreater than less thanbrgreater thanConclusion: This study indicates possible transmission of C. albicans between ICU patients based on genotyping and temporal cluster analysis.

  • 40.
    Hammarskjold, F.
    et al.
    Hammarskjöld, F., Department of Anaesthesia and Intensive Care, Ryhov County Hospital, Jönköping, Sweden, Ryhov County Hospital, 551 85 Jönköping, Sweden.
    Wallen, G.
    Wallén, G., Department of Anaesthesia and Intensive Care, Ryhov County Hospital, Jönköping, Sweden.
    Malmvall, Bo-Eric
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases .
    Central venous catheter infections at a county hospital in Sweden: A prospective analysis of colonization, incidence of infection and risk factors2006In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 50, no 4, p. 451-460Article in journal (Refereed)
    Abstract [en]

    Background: Catheter-related infection (CRI) is one of the most serious complications of the use of central venous catheters (CVCs), with an incidence of 2-30/1000 days in different studies. No major prospective study has evaluated the rate of CRI in Scandinavia. Since 1999, we have had a thorough programme for the insertion and care of all CVCs used at our hospital and its outpatient clinics. The purpose of this survey was to study the incidence of catheter tip colonization and CRI and their risk factors, and to compare these data with previous non-Scandinavian studies. Methods: We studied prospectively 605 CVCs in 456 patients in relation to insertion data, patient and catheter characteristics, catheterization time and microbiological cultures. Risk factors were analysed by multivariate analysis. Results: Four hundred and ninety-five (82%) of all CVCs were assessed completely. The total catheterization time was 9010 days. The incidence of positive tip culture was 7.66/1000 days, and the predominant microorganism was coagulase-negative staphylococci. The incidence of CRI was 1.55/1000 days, and the only significant risk factor was the duration of catheterization with a relative risk of 1.009 per day [95% confidence interval (CI), 1.003-1.015]. Of the 14 cases with CRI, six were associated with candida species, and five of these were diagnosed in the intensive care unit. Conclusion: In comparison with non-Scandinavian studies, our practice of strict basic hygiene routines for CVC insertion and care is associated with a low incidence of CRI. However, there was a high proportion of candida species amongst these infections. The only risk factor for CRI was the duration of catheterization. © Acta Anaesthesiologica Scandinavica 2006.

  • 41.
    Hammarskjöld, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Preventing Infections Related to Central Venous and Arterial Catheters2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Central venous catheters (CVCs) are indispensable in modern medical practice. Serious complications associated with CVC use include catheter-related infection (CRI) and catheter related-bloodstream infection (CRBSI) both of which contribute to morbidity, mortality and healthcare costs. Several studies have shown that implementation of basic hygiene routines, for CVC insertion and care, can significantly reduce the number of CRBSIs. However, there are limited data on the long-term effects after such an intervention. CVC infections, in terms of incidences and microorganisms, vary between different units and countries. Studies from Scandinavian hospitals are rare and not published recently. It has been stated that arterial catheters (ACs) are less prone to be responsible for CRI and CRBSI when compared with CVCs. However, recent studies outside Scandinavia have shown that they cause infections in significant numbers. The general view has been that nosocomial Candida infections in ICU patients evolve from the patient’s endogenous flora. However, a few studies have indicated that transmission of Candida spp. can occur between patients on an ICU as is well-described for certain bacteria. Candida spp. are among the most common microorganisms responsible for CRI/CRBSI.

    The aim of this thesis was to study the incidences of, and microorganisms related to CVC (Study 1) and AC (Study 2) infections after implementation of evidence-based routines for insertion and care. The populations studied were patients with CVCs treated throughout the entire hospital (Studies 1 and 4) and patients with ACs treated on the ICU (Study 2). The aim was further to analyse risk factors contributing to these infections (Studies 1, 2 and 4). We also evaluated the long-term effects and endurance, of evidence-based routines, assessed as temporal variations in CVC colonisation and infections over a six-year period (Study 4). As we found that Candida spp. were common causes of CRI/CRBSI in Study 1, we decided to see if transmission of Candida spp. possibly occurred between patients on our ICU (Study 3).

    We found low incidence rates, compared to international studies, for CRI and CRBSI related to the 495 CVCs studied over a short period (16 months, Study 1) and the 2045 CVCs studied over long-term follow-up (six years, Study 4). We found no cases of AC-CRBSI but a low number of AC-CRI in the 600 ACs studied. The type of microorganisms responsible for infections related to CVCs and ACs were similar to those found in international studies. However, the proportion of Candida spp. was high in Studies 1 and 4 evaluating CVC infections. There was no difference in the CVC-catheterisation time for CRI/CRBSI caused by Candida spp. as compared to CRI/CRBSI caused by bacteria. Risk factors for CRI associated with CVCs were chronic haemodialysis (Study 1), all haemodialysis in general (Study 4) and CVCs inserted via the internal jugular vein as compared to the subclavian vein (Study 4). Risk factors for CRI related to ACs were colonisation or infection of a simultaneous CVC and immunosuppression. Genotypes of Candida albicans and Candida glabrata had a heterogeneous distribution between ICU patients over time. Comparison with a reference group and cluster analysis indicated that transmission of Candida spp. between ICU patients is possible.

    In, conclusion, we have found, after implementation of evidence-based routines for CVC and AC insertion and care, low incidences of CRI and CRBSI associated with these catheters. Furthermore, we found that transmission of Candida spp. between patients on the ICU is possible.

    List of papers
    1. Central venous catheter infections at a county hospital in Sweden: A prospective analysis of colonization, incidence of infection and risk factors
    Open this publication in new window or tab >>Central venous catheter infections at a county hospital in Sweden: A prospective analysis of colonization, incidence of infection and risk factors
    2006 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 50, no 4, p. 451-460Article in journal (Refereed) Published
    Abstract [en]

    Background: Catheter-related infection (CRI) is one of the most serious complications of the use of central venous catheters (CVCs), with an incidence of 2-30/1000 days in different studies. No major prospective study has evaluated the rate of CRI in Scandinavia. Since 1999, we have had a thorough programme for the insertion and care of all CVCs used at our hospital and its outpatient clinics. The purpose of this survey was to study the incidence of catheter tip colonization and CRI and their risk factors, and to compare these data with previous non-Scandinavian studies. Methods: We studied prospectively 605 CVCs in 456 patients in relation to insertion data, patient and catheter characteristics, catheterization time and microbiological cultures. Risk factors were analysed by multivariate analysis. Results: Four hundred and ninety-five (82%) of all CVCs were assessed completely. The total catheterization time was 9010 days. The incidence of positive tip culture was 7.66/1000 days, and the predominant microorganism was coagulase-negative staphylococci. The incidence of CRI was 1.55/1000 days, and the only significant risk factor was the duration of catheterization with a relative risk of 1.009 per day [95% confidence interval (CI), 1.003-1.015]. Of the 14 cases with CRI, six were associated with candida species, and five of these were diagnosed in the intensive care unit. Conclusion: In comparison with non-Scandinavian studies, our practice of strict basic hygiene routines for CVC insertion and care is associated with a low incidence of CRI. However, there was a high proportion of candida species amongst these infections. The only risk factor for CRI was the duration of catheterization. © Acta Anaesthesiologica Scandinavica 2006.

    Keywords
    Candida species, Catheter-related infection, Central venous catheter (CVC), Nosocomial infection
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-50078 (URN)10.1111/j.1399-6576.2006.00974.x (DOI)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-12
    2. Low incidence of arterial catheter infections in a Swedish intensive care unit: risk factors for colonisation and infection
    Open this publication in new window or tab >>Low incidence of arterial catheter infections in a Swedish intensive care unit: risk factors for colonisation and infection
    2010 (English)In: Journal of Hospital Infection, ISSN 0195-6701, E-ISSN 1532-2939, Vol. 76, no 2, p. 130-134Article in journal (Refereed) Published
    Abstract [en]

    There is growing concern that arterial catheters (ACs) cause catheter-related infections (CRIs). Limited data are available concerning risk factors for AC-CRI and there are no studies concerning incidence and micro-organisms from northern Europe. The aims of this study were to determine the incidence of, and micro-organisms responsible for, AC colonisation and AC-CRI in a Swedish intensive care unit (ICU), and to determine risk factors contributing to AC colonisation and AC-CRI. We prospectively studied all patients (N=539) receiving ACs (N=691) in a mixed ICU of a county hospital. Six hundred (87%) of all ACs were assessed completely. The total catheterisation time for 482 patients was 2567 days. The incidence of positive tip culture was 7.8 per 1000 catheter-days, with the predominant micro-organism being coagulase-negative staphylococci (CoNS). The incidence of AC-CRI was 2.0 per 1000 catheter-days (with no cases of bacteraemia). All AC-CRIs were caused by CoNS. Multivariate analysis revealed that immunosuppression, central venous catheter (CVC) colonisation and CVC infection were significant risk factors for AC-CRI. We conclude that AC colonisation and infection with systemic symptoms occur at a low rate in our ICU which supports our practice of basic hygiene routines for the prevention of AC-CRI. Colonisation and infection of a simultaneous CVC seem to be risk factors. The role of contemporaneous colonisation and infection of multiple bloodstream catheters has received little attention previously. Further studies are needed to verify the significance of this finding.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-59067 (URN)10.1016/j.jhin.2010.05.021 (DOI)
    Available from: 2010-09-08 Created: 2010-09-08 Last updated: 2017-12-12
    3. Possible transmission of Candida albicans on an intensive care unit: intensive care unit:
    Open this publication in new window or tab >>Possible transmission of Candida albicans on an intensive care unit: intensive care unit:
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Nosocomial transmission of Candida spp. has not fully been explored and previous studies have shown conflicting results.

    Aim: To evaluate the possible nosocomial transmission of Candida spp. on an intensive care unit (ICU).

    Methods: We conducted a prospective study over 19 month, including all patients on our ICU with growth of Candida spp. from surveillance and directed cultures. Molecular typing, with rep-PCR (DiversiLab) was used to define genotype relationships between the C. albicans and C. glabrata isolates. Candida isolates obtained from blood cultures taken from patients in our county outside the ICU, were used as a reference. Temporal cluster analysis was performed to evaluate genotype distribution over time.

    Findings: Seventy-seven patients with 78 ICU stays, representing twelve per cent of all ICU stays, were found to harbour 180 isolates of Candida spp. Molecular typing revealed 27 C. albicans genotypes and ten of C. glabrata. Possible clustering, indicated by overlapping stays of patients with indistinguishable candida genotypes was observed on seven occasions with C. albicans and on two occasions with C. glabrata. Two C. albicans genotypes were found significantly more often in the ICU group compared to the reference group. Moreover, C. albicans genotypes isolated from more than one patient were significantly more often found in the ICU group. Temporal cluster analysis revealed a significantly increased number of pairs with indistinguishable genotypes at a 21-dayinterval, indicating clustering.

    Conclusion: This study indicates transmission of C. albicans between ICU patients based on genotyping and temporal cluster analysis.

    Keywords
    Candida, Molecular typing, Intensive care unit, nosocomial infections
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-89953 (URN)
    Available from: 2013-03-12 Created: 2013-03-12 Last updated: 2013-03-12Bibliographically approved
    4. Sustained low incidence of central venous catheter-related infections in a Swedish county hospital following implementation of a hygiene program: a six year follow-up study
    Open this publication in new window or tab >>Sustained low incidence of central venous catheter-related infections in a Swedish county hospital following implementation of a hygiene program: a six year follow-up study
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: There are limited data on the long term-effects of implementing a central venous catheter (CVC) program for prevention of CVC infections. The aims of this study were to evaluate the incidence of CVC colonization, catheter-related infections (CRI), catheter-related bloodstream infections (CRBSI), and their risk factors, over a six year period.

    Methods: A continuous prospective study aiming to include all CVCs used at our hospital during the years 2004-2009, evaluating colonization, CRI, CRBSI and possible risk factors.

    Results: 2772 CVCs were used during the study period. Data on culture results and catheterization time were available for 2045 CVCs used in 1674 patients. The incidences of colonization, CRI and CRBSI were 7.0, 2.2 and 0.6 per 1000 CVC-days. Analysis of quarterly incidences revealed one occasion with increasing infection rates. Catheterization time was a risk factor for CRI, but not for CRBSI. Other risk factors for CRI were hemodialysis, CVC use in the internal jugular vein compared to the subclavian vein. Hemodialysis was the only risk factor for CRBSI.

    Conclusion: We found that that a CRI prevention program adhered to by the entire staff at a county hospital is successful in keeping CVC infections at a low rate over a long period of time.

    Keywords
    Catheter-related bloodstream infection; Central venous catheter; Nosocomial infection
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-89954 (URN)
    Available from: 2013-03-12 Created: 2013-03-12 Last updated: 2013-03-12Bibliographically approved
  • 42.
    Hammarskjöld, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
    Berg, Sören
    Linköping University, Department of Medicine and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Malmvall, Bo-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
    Low incidence of arterial catheter infections in a Swedish intensive care unit: risk factors for colonisation and infection2010In: Journal of Hospital Infection, ISSN 0195-6701, E-ISSN 1532-2939, Vol. 76, no 2, p. 130-134Article in journal (Refereed)
    Abstract [en]

    There is growing concern that arterial catheters (ACs) cause catheter-related infections (CRIs). Limited data are available concerning risk factors for AC-CRI and there are no studies concerning incidence and micro-organisms from northern Europe. The aims of this study were to determine the incidence of, and micro-organisms responsible for, AC colonisation and AC-CRI in a Swedish intensive care unit (ICU), and to determine risk factors contributing to AC colonisation and AC-CRI. We prospectively studied all patients (N=539) receiving ACs (N=691) in a mixed ICU of a county hospital. Six hundred (87%) of all ACs were assessed completely. The total catheterisation time for 482 patients was 2567 days. The incidence of positive tip culture was 7.8 per 1000 catheter-days, with the predominant micro-organism being coagulase-negative staphylococci (CoNS). The incidence of AC-CRI was 2.0 per 1000 catheter-days (with no cases of bacteraemia). All AC-CRIs were caused by CoNS. Multivariate analysis revealed that immunosuppression, central venous catheter (CVC) colonisation and CVC infection were significant risk factors for AC-CRI. We conclude that AC colonisation and infection with systemic symptoms occur at a low rate in our ICU which supports our practice of basic hygiene routines for the prevention of AC-CRI. Colonisation and infection of a simultaneous CVC seem to be risk factors. The role of contemporaneous colonisation and infection of multiple bloodstream catheters has received little attention previously. Further studies are needed to verify the significance of this finding.

  • 43.
    Hammarskjöld, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Berg, Sören
    Linköping University, Department of Medical and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Thoracic and Vascular Surgery in Östergötland.
    Taxbro, K.
    Department of Anesthesia and Intensive Care, Ryhov County Hospital, Sweden.
    Malmvall, Bo-Erik
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Sustained low incidence of central venous catheter-related infections in a Swedish county hospital following implementation of a hygiene program: a six year follow-up studyManuscript (preprint) (Other academic)
    Abstract [en]

    Background: There are limited data on the long term-effects of implementing a central venous catheter (CVC) program for prevention of CVC infections. The aims of this study were to evaluate the incidence of CVC colonization, catheter-related infections (CRI), catheter-related bloodstream infections (CRBSI), and their risk factors, over a six year period.

    Methods: A continuous prospective study aiming to include all CVCs used at our hospital during the years 2004-2009, evaluating colonization, CRI, CRBSI and possible risk factors.

    Results: 2772 CVCs were used during the study period. Data on culture results and catheterization time were available for 2045 CVCs used in 1674 patients. The incidences of colonization, CRI and CRBSI were 7.0, 2.2 and 0.6 per 1000 CVC-days. Analysis of quarterly incidences revealed one occasion with increasing infection rates. Catheterization time was a risk factor for CRI, but not for CRBSI. Other risk factors for CRI were hemodialysis, CVC use in the internal jugular vein compared to the subclavian vein. Hemodialysis was the only risk factor for CRBSI.

    Conclusion: We found that that a CRI prevention program adhered to by the entire staff at a county hospital is successful in keeping CVC infections at a low rate over a long period of time.

  • 44.
    Hammarskjöld, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Mernelius, S.
    Microbiology Laboratory, Department of Laboratory Services, Division of Medical Services, Ryhov County Hospital, Jönköping, Sweden.
    Andersson, R.
    Department of Surgery, Ryhov County Hospital, Sweden.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Löfgren, S.
    Microbiology Laboratory, Department of Laboratory Services, Division of Medical Services, Ryhov County Hospital, Jönköping, Sweden.
    Malmvall, Bo-Erik
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Petzold, M.
    Centre for Applied Biostatistics, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Matussek, A.
    Microbiology Laboratory, Department of Laboratory Services, Division of Medical Services, Ryhov County Hospital, Jönköping, Sweden.
    Possible transmission of Candida albicans on an intensive care unit: intensive care unit:Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Nosocomial transmission of Candida spp. has not fully been explored and previous studies have shown conflicting results.

    Aim: To evaluate the possible nosocomial transmission of Candida spp. on an intensive care unit (ICU).

    Methods: We conducted a prospective study over 19 month, including all patients on our ICU with growth of Candida spp. from surveillance and directed cultures. Molecular typing, with rep-PCR (DiversiLab) was used to define genotype relationships between the C. albicans and C. glabrata isolates. Candida isolates obtained from blood cultures taken from patients in our county outside the ICU, were used as a reference. Temporal cluster analysis was performed to evaluate genotype distribution over time.

    Findings: Seventy-seven patients with 78 ICU stays, representing twelve per cent of all ICU stays, were found to harbour 180 isolates of Candida spp. Molecular typing revealed 27 C. albicans genotypes and ten of C. glabrata. Possible clustering, indicated by overlapping stays of patients with indistinguishable candida genotypes was observed on seven occasions with C. albicans and on two occasions with C. glabrata. Two C. albicans genotypes were found significantly more often in the ICU group compared to the reference group. Moreover, C. albicans genotypes isolated from more than one patient were significantly more often found in the ICU group. Temporal cluster analysis revealed a significantly increased number of pairs with indistinguishable genotypes at a 21-dayinterval, indicating clustering.

    Conclusion: This study indicates transmission of C. albicans between ICU patients based on genotyping and temporal cluster analysis.

  • 45.
    Hanberger, Håkan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Arman, Dilek
    Gazi University School of Medicine.
    Gill, Hans
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Jindrák, Vlastimil
    Na Homolce Hospital, Praha, Czech Republic.
    Kalenic, Smilja
    Clinical Hospital Centre, Zagreb, Croatia.
    Kurcz, Andrea
    National Centre for Epidemiologia, Budapest, Hungary.
    Licker, Monica
    “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania.
    Naaber, Paul
    United Laboratories, Tartu University Clinics.
    Scicluna, Elizabeth A.
    Mater Dei Hospital, Malta .
    Vanis, Václav
    Na Homolce Hospital, Praha, Czech Republic.
    Walther, Sten M.
    Linköping University, Department of Medicine and Health Sciences, Physiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Surveillance of microbial resistance in European Intensive Care Units: a first report from the Care-ICU programme for improved infection control2009In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 35, no 1, p. 91-100Article in journal (Refereed)
    Abstract [en]

    Purpose: To report initial results from a European ICU surveillance programme focussing on antibiotic consumption, microbial resistance and infection control.

    Methods: Thirty-five ICUs participated during 2005. Microbial resistance, antibiotic consumption and infection control stewardship measures were entered locally into a web-application. Results were validated locally, aggregated by project leaders and fed back to support local audit and benchmarking.

    Results: Median (range) antibiotic consumption was 1,254 (range 348–4,992) DDD per 1,000 occupied bed days. The proportion of MRSA was median 11.6% (range 0–100), for ESBL phenotype of E. coli and K. pneumoniae 3.9% (0–80) and 14.3% (0–77.8) respectively, and for carbapenem-resistant P. aeruginosa 22.5% (0–100). Screening on admission for alert pathogens was commonly omitted, and there was a lack of single rooms for isolation.

    Conclusions: The surveillance programme demonstrated wide variation in antibiotic consumption, microbial resistance and infection control measures. The programme may, by providing rapid access to aggregated results, promote local and regional audit and benchmarking of antibiotic use and infection control practices.

  • 46.
    Hanberger, Håkan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Berg, SörenLinköping University, Faculty of Health Sciences. Linköping University, Department of Medical and Health Sciences, Thoracic Surgery. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Sepsishähtet: handläggning av sepsis på akuten och IVA2008Collection (editor) (Other academic)
    Abstract [sv]

    Sepsis på akuten och IVA baseras på SK-kursen med samma namn. Vi har i andra upplagan flera nya kapitel och hoppas att boken skall bidra till att förbättra vården av patienter med sepsis och andra svåra infektioner.

    Linköping april 2013

    Håkan Hanberger och medförfattare

  • 47.
    Hanberger, Håkan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Edlund, Charlotta
    Medical Product Agency, Uppsala.
    Furebring, Mia
    Uppsala University.
    Giske, Christian G.
    MTC – Karolinska Institutet, Karolinska University Hospital, Stockholm.
    Melhus, Åsa
    Uppsala University.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences.
    Petersson, Johan
    Karolinska Institutet, Stockholm.
    Sjölin, Jan
    Uppsala University.
    Ternhag, Anders
    Swedish Institute for Communicable Disease Control, Solna.
    Werner, Maria
    Södra Älvsborgs Sjukhus, Borås.
    Eliasson, Erik
    Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
    Rational use of aminoglycosides - Review and recommendations by the Swedish Reference Group for Antibiotics (SRGA)2013In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 45, no 3, p. 161-175Article, review/survey (Refereed)
    Abstract [en]

    The Swedish Reference Group for Antibiotics (SRGA) has carried out a risk–benefit analysis of aminoglycoside treatment based on clinical efficacy, antibacterial spectrum, and synergistic effect with beta-lactam antibiotics, endotoxin release, toxicity, and side effects. In addition, SRGA has considered optimal dosage schedules and advice on serum concentration monitoring, with respect to variability in volume of drug distribution and renal clearance. SRGA recommends that aminoglycoside therapy should be considered in the following situations: (1) progressive severe sepsis and septic shock, in combination with broad-spectrum beta-lactam antibiotics, (2) sepsis without shock, in combination with broad-spectrum beta-lactam antibiotics if the infection is suspected to be caused by multi-resistant Gram-negative pathogens, (3) pyelonephritis, in combination with a beta-lactam or quinolone until culture and susceptibility results are obtained, or as monotherapy if a serious allergy to beta-lactam or quinolone antibiotics exists, (4) serious infections caused by multi-resistant Gram-negative bacteria when other alternatives are lacking, and (5) endocarditis caused by difficult-to-treat pathogens when monotherapy with beta-lactam antibiotics is not sufficient. Amikacin is generally more active against extended-spectrum beta-lactamase (ESBL)-producing and quinolone-resistant Escherichia coli than other aminoglycosides, making it a better option in cases of suspected infection caused by multidrug-resistant Enterobacteriaceae. Based on their resistance data, local drug committees should decide on the choice of first-line aminoglycoside. Unfortunately, aminoglycoside use is rarely followed up with audiometry, and in Sweden we currently have no systematic surveillance of adverse events after aminoglycoside treatment. We recommend routine assessment of adverse effects, including hearing loss and impairment of renal function, if possible at the start and after treatment with aminoglycosides, and that these data should be included in hospital patient safety surveillance and national quality registries.

  • 48.
    Hanberger, Håkan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences.
    Erlandsson, Marcus
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Burman, Lars G.
    Swedish Institute for Infectious Diseases Control, Solna, Sweden.