Logo: to the web site of Uppsala University

uu.sePublications from Uppsala University
Planned maintenance
A system upgrade is planned for 10/12-2024, at 12:00-13:00. During this time DiVA will be unavailable.
Change search
Refine search result
1234567 1 - 50 of 1807
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Aakhus, Mark
    et al.
    Rutgers University.
    Ågerfalk, Pär
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Informatics and Media, Information Systems.
    Lennmyr, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Digital Innovation as Design of Digital Practice: Doctors as Designers in Healthcare2018In: Proceedings of the 51st Hawaii International Conference on System Sciences (HICSS), 2018, p. 4594-4601Conference paper (Refereed)
    Abstract [en]

    Medical professionals are increasingly assuming the role of maker and creator. At the same time, digital innovations, as part of evolving information infrastructures, are becoming increasingly prevalent in healthcare. In this paper, we adopt a Schönian approach to understand how a medical professional, who is not an IS designer by trade, engages in the design of digital practice - turning what may appear as a failed digital innovation effort into a successful design of digital practice. Our inquiry suggests three pragmatic principles that call for further investigation: (a) professionals can make a significant contribution to design work by inventing means for fact-based, reflective engagement with the situation; (b) the reorganization of work practice involves organizational design, information system design, and communication design; and (c) developing design as digital practice entails the development of fact-based design practice and must engage practical theories.

    Download full text (pdf)
    fulltext
  • 2.
    Aarnio, Mikko
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Visualization of Peripheral Pain Generating Processes and Inflammation in Musculoskeletal Tissue using [11C]-D-deprenyl PET2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    An objective visualization and quantification of pain-generating processes in the periphery would alter pain diagnosis and represent an important paradigm shift in pain research. Positron emission tomography (PET) radioligand [11C]-D-deprenyl has shown an elevated uptake in painful inflammatory arthritis and whiplash-associated disorder. However, D-Deprenyl’s molecular binding target and uptake mechanism in inflammation and musculoskeletal injuries are still unknown. The present thesis aimed to gain insight into the mechanisms of D-deprenyl binding and uptake and to verify whether pain-associated sites and inflammation in acute musculoskeletal injury could be visualized, objectively quantified and followed over time with [11C]-D-deprenyl PET-computed tomography (PET/CT).

    To identify the D-deprenyl binding target, a high-throughput analysis and competitive radioligand binding studies were performed. D-deprenyl inhibited monoamine oxidase A (MAO-A) activity by 55%, MAO-B activity by 99% and angiotensin-converting enzyme (ACE) by 70%, which identified these enzymes as higher-affinity targets. Furthermore, radioligand receptor binding assays pointed favorably towards the concept of MAO-B as the primary target. To investigate the biochemical characteristics of the binding site, we used radioligand binding assays to assess differences in the binding profile in inflamed human synovial membranes exhibiting varying levels of inflammation. D-deprenyl bound to a single, saturable population of membrane-bound protein in synovial membrane homogenates and the level of inflammation correlated with an increase in D-deprenyl binding affinity.

    To verify whether D-deprenyl can visualize pain-generating processes, patients with musculoskeletal injuries were investigated and followed-up with [11C]-D-deprenyl PET/CT. In the study of eight patients with ankle sprain, the molecular aspects of inflammation and tissue injury could be visualized, objectively quantified and followed over time with [11C]-D-deprenyl PET/CT. The pain coexisted with increased [11C]-D-deprenyl uptake. In the study of 16 whiplash patients, an altered [11C]-D-deprenyl uptake in the cervical bone structures and facet joints was associated with subjective pain levels and self-rated disability.

    To further evaluate D-Deprenyl’s usefulness as a marker of inflammation, three PET tracers were compared in an animal PET/CT study. Preliminary findings showed that [11C]-D-deprenyl had an almost identical uptake pattern when compared with [11C]-L-deprenyl. The two deprenyl enantiomers showed no signs of specific binding or trapping and therefore may not be useful to study further in models of inflammatory pain, surgical pain, or both.

    This thesis demonstrates that D-deprenyl visualizes painful inflammation in musculoskeletal injuries and that the probable underlying mechanism of [11C]-D-deprenyl uptake is binding to MAO.

    List of papers
    1. High-throughput screening and radioligand binding studies reveal monoamine oxidase-B as the primary binding target for D-deprenyl
    Open this publication in new window or tab >>High-throughput screening and radioligand binding studies reveal monoamine oxidase-B as the primary binding target for D-deprenyl
    Show others...
    2016 (English)In: Life Sciences, ISSN 0024-3205, E-ISSN 1879-0631, Vol. 152, p. 231-237Article in journal (Refereed) Published
    Abstract [en]

    Aims: D-deprenyl is a useful positron emission tomography tracer for visualization of inflammatory processes. Studies with [C-11]-D-deprenyl showed robust uptake in peripheral painful sites of patients with rheumatoid arthritis or chronic whiplash injury. The mechanism of preferential D-deprenyl uptake is not yet known, but the existence of a specific binding site was proposed. Thus, in the present study, we sought to identify the binding site for D-deprenyl and verify the hypothesis about the possibility of monoamine oxidase enzymes as major targets for this molecule. Main methods: A high-throughput analysis of D-deprenyl activity towards 165 G-protein coupled receptors and 84 enzyme targets was performed. Additionally, binding studies were used to verify the competition of [H-3]D-deprenyl with ligands specific for targets identified in the high-throughput screen. Key findings: Our high-throughput investigation identified monoamine oxidase-B, monoamine oxidase-A and angiotensin converting enzyme as potential targets for D-deprenyl. Further competitive [3H] D-deprenyl binding studies with specific inhibitors identified monoamine oxidase-B as the major binding site. No evident high-affinity hits were identified among G-protein coupled receptors. Significance: Our study was the first to utilize a high-throughput screening approach to identify putative D-deprenyl targets. It verified 249 candidate proteins and confirmed the role of monoamine oxidase - B in D-deprenyl binding. Our results add knowledge about the possible mechanism of D-deprenyl binding, which might aid in explaining the increased uptake of this compound in peripheral inflammation. Monoamine oxidase-B will be further investigated in future studies utilizing human inflamed synovium.

    Keywords
    D-deprenyl High-throughput screening Binding site
    National Category
    Pharmaceutical Sciences Clinical Medicine
    Identifiers
    urn:nbn:se:uu:diva-291492 (URN)10.1016/j.lfs.2016.03.058 (DOI)000375728500028 ()27058977 (PubMedID)
    Funder
    Berzelii Centre EXSELENT, 2013-01495
    Available from: 2016-05-03 Created: 2016-05-03 Last updated: 2022-01-29Bibliographically approved
    2. Characterization of the binding site for d-deprenyl in human inflamed synovial membrane.
    Open this publication in new window or tab >>Characterization of the binding site for d-deprenyl in human inflamed synovial membrane.
    Show others...
    2018 (English)In: Life Sciences, ISSN 0024-3205, E-ISSN 1879-0631, Vol. 194, p. 26-33Article in journal (Refereed) Published
    Abstract [en]

    Aims: D-Deprenyl when used as a positron emission tomography tracer visualizes peripheral inflammation. The major aim of the current study was to identify and investigate the properties of the binding target for D-deprenyl in synovial membrane explants from arthritic patients.

    Main methods: Thirty patients diagnosed with arthritis or osteoarthritis were enrolled into the study. Homologous and competitive radioligand binding assays utilizing [H-3]D-deprenyl were performed to investigate the biochemical characteristics of the binding site and assess differences in the binding profile in synovial membranes exhibiting varying levels of inflammation.

    Key findings: The [H-3]D-deprenyl binding assay confirmed the existence of a single, saturable population of membrane-bound protein binding sites in synovial membrane homogenates. The macroscopically determined level of inflammation correlated with an increase in [H-3]D-deprenyl binding affinity, without significant alterations in binding site density. Selective monoamine oxidase B inhibitor, selegiline competed for the same site as [H-3]D-deprenyl, but failed to differentiate the samples with regard to their inflammation grade. A monoamine oxidase A inhibitor, pirlindole mesylate showed only weak displacement of [H-3]D-deprenyl binding. No significant alterations in monoamine oxidase B expression was detected, thus it was not confirmed whether it could serve as a marker for ongoing inflammation.

    Significance: Our study was the first to show the biochemical characteristics of the [H-3]D-deprenyl binding site in inflamed human synovium. We confirmed that d-deprenyl could differentiate between patients with varying severity of synovitis in the knee joint by binding to a protein target distinct from monoamine oxidase B.

    Keywords
    Arthritis, Binding target, Monoamine oxidase B, Synovium, d-Deprenyl
    National Category
    Pharmaceutical Sciences
    Research subject
    Pharmaceutical Biochemistry; Medical Biochemistry
    Identifiers
    urn:nbn:se:uu:diva-347601 (URN)10.1016/j.lfs.2017.12.003 (DOI)000425052000004 ()29221756 (PubMedID)
    Funder
    Swedish Research Council, 9459
    Available from: 2018-04-04 Created: 2018-04-04 Last updated: 2022-01-29Bibliographically approved
    3. Visualization of painful inflammation in patients with pain after traumatic ankle sprain using [(11)C]-D-deprenyl PET/CT.
    Open this publication in new window or tab >>Visualization of painful inflammation in patients with pain after traumatic ankle sprain using [(11)C]-D-deprenyl PET/CT.
    Show others...
    2017 (English)In: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, Vol. 17, no 1, p. 418-424Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND AND AIMS: Positron emission tomography (PET) with the radioligand [(11)C]-D-deprenyl has shown increased signal at location of pain in patients with rheumatoid arthritis and chronic whiplash injury. The binding site of [(11)C]-D-deprenyl in peripheral tissues is suggested to be mitochondrial monoamine oxidase in cells engaged in post-traumatic inflammation and tissue repair processes. The association between [(11)C]-D-deprenyl uptake and the transition from acute to chronic pain remain unknown. Further imaging studies of musculoskeletal pain at the molecular level would benefit from establishing a clinical model in a common and well-defined injury in otherwise healthy and drug-naïve subjects. The aim of this study was to investigate if [(11)C]-D-deprenyl uptake would be acutely elevated in unilateral ankle sprain and if tracer uptake would be reduced as a function of healing, and correlated with pain localizations and pain experience.

    METHODS: Eight otherwise healthy patients with unilateral ankle sprain were recruited at the emergency department. All underwent [(11)C]-D-deprenyl PET/CT in the acute phase, at one month and 6-14 months after injury.

    RESULTS: Acute [(11)C]-D-deprenyl uptake at the injury site was a factor of 10.7 (range 2.9-37.3) higher than the intact ankle. During healing, [(11)C]-D-deprenyl uptake decreased, but did not normalize until after 11 months. Patients experiencing persistent pain had prolonged [(11)C]-D-deprenyl uptake in painful locations.

    CONCLUSIONS AND IMPLICATIONS: The data provide further support that [(11)C]-D-deprenyl PET can visualize, quantify and follow processes in peripheral tissue that may relate to soft tissue injuries, inflammation and associated nociceptive signaling. Such an objective correlate would represent a progress in pain research, as well as in clinical pain diagnostics and management.

    Place, publisher, year, edition, pages
    Walter de Gruyter, 2017
    Keywords
    Ankle injuries, Carbon-11, Deprenyl, Inflammation, PET, Pain
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-333782 (URN)10.1016/j.sjpain.2017.10.008 (DOI)000419851500070 ()29126847 (PubMedID)
    Available from: 2017-11-16 Created: 2017-11-16 Last updated: 2019-09-25Bibliographically approved
    4. Whiplash injuries associated with experienced pain and disability can be visualized with [11C]-D-deprenyl PET/CT
    Open this publication in new window or tab >>Whiplash injuries associated with experienced pain and disability can be visualized with [11C]-D-deprenyl PET/CT
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    The understanding of etiological mechanisms of whiplash associated disorder is still inadequate. Objective visualization and quantification of peripheral musculoskeletal injury and possible painful inflammation in whiplash associated disorder would facilitate diagnosis, strengthen patients’ subjective pain reports and aid clinical decisions eventually leading to better treatments. In the current study, we further evaluated the potential to use [11C]D-deprenyl PET/CT to visualize inflammation after whiplash injury. Sixteen patients with whiplash injury grade II were recruited at the emergency department and underwent [11C]D-deprenyl PET/CT in the acute phase and at 6 months after injury. Subjective pain levels, self rated neck disability and active cervical range of motion were recorded at each imaging session. Results showed that the molecular aspects of inflammation and possible tissue injuries after acute whiplash injury could be visualized, objectively quantified and followed over time with [11C]-D-deprenyl PET/CT. An altered [11C]D-deprenyl uptake in the cervical bone structures and facet joints was associated with subjective pain levels and self rated disability during both imaging occasions. These findings may contribute to a better understanding of affected peripheral structures in whiplash injury and strengthens the idea that PET/CT detectable organic lesions in peripheral tissue may be relevant for the development of persistent pain and disability in whiplash injury.

    Perspective: This article presents a novel way of objectively visualizing possible structural damage and inflammation that cause pain and disability in whiplash injury. This PET method can bring an advance in pain research and eventually would facilitate the clinical management of patients in pain.

    Keywords
    Whiplash; deprenyl; inflammation; pain; PET; carbon-11
    National Category
    Medical and Health Sciences
    Research subject
    Molecular Medicine; Medical Cell Biology
    Identifiers
    urn:nbn:se:uu:diva-347602 (URN)
    Available from: 2018-04-04 Created: 2018-04-04 Last updated: 2018-04-12
    5. Evaluation of  PET tracers [11C]D-deprenyl, [11C]L-dideuteriumdeprenyl and [18F]FDG for Visualization of Acute Inflammation in a Rat Model of Pain - Preliminary Findings.
    Open this publication in new window or tab >>Evaluation of  PET tracers [11C]D-deprenyl, [11C]L-dideuteriumdeprenyl and [18F]FDG for Visualization of Acute Inflammation in a Rat Model of Pain - Preliminary Findings.
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Purpose: Positron emission tomography with the radioligand [11C]D-deprenyl has shown an increased signal at the location of pain in patients with ankle sprains, rheumatoid arthritis and chronic whiplash injury, but the mechanism of this tracer uptake and its exact binding site in inflammation or tissue injury is still unclear. The aim of this study was to further evaluate [11C]D-deprenyl´s usefulness as a marker of acute inflammation.

    Methods: An animal PET/CT study was performed three days after the induction of a rat model of inflammatory or surgical pain. Fourteen adult male Sprague-Dawley rats and three tracers [11C]D-deprenyl, [11C]L-dideuterumdeprenyl and [18F]fluorodeoxyglucose were used.

    Results: No [11C]D-deprenyl accumulation was seen in a rat model of musculoskeletal pain. In the rat model of inflammatory pain all three ligands were shown to visualize the inflamed ankle joint with much lower uptake in the control ankle joint. The uptake was largest with [11C]D-deprenyl and [11C]L- dideuteriumdeprenyl, where approximately 1 % of the injected dose could be found in the affected ankle joint during the first minutes, whereas the uptake of [18F]FDG was approximately 0.5 % of the injected dose. However, the ratio of uptake of the injected ankle joint versus the control ankle joint was much higher for [18F]FDG (around 10 fold increase) than for the two deprenyl enantiomers (2 – 3 fold increase). The uptake pattern of [11C]D-deprenyl and [11C]L-dideuteriumdeprenyl did not show signs of specific binding or irreversible trapping.

    Conclusions: Contrary to our expectations, of the three tracers only [18F]FDG may be used as markers of peripheral inflammation in a rat model of inflammatory pain. However, as a high site-specificity is required, [11C]D-deprenyl and [11C]L-dideyteriumdeprenyl deserve further exploration regarding sensitivity, specificity and uptake mechanisms in human pain syndromes.

    Keywords
    deprenyl; inflammation; pain; PET; carbon-11
    National Category
    Medical and Health Sciences
    Research subject
    Anaesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:uu:diva-347604 (URN)
    Available from: 2018-04-04 Created: 2018-04-04 Last updated: 2018-04-12
    Download full text (pdf)
    fulltext
    Download (jpg)
    presentationsbild
  • 3.
    Aarnio, Mikko
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Fredriksson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology. Karolinska Inst, Dept Neurosci, Stockholm, Sweden.
    Gordh, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Wolf, Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Eriksson, Måns
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Statistics.
    Peterson, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Linnman, Clas
    Harvard Med Sch, Boston Childrens Hosp, Dept Anesthesiol, Boston, MA USA.
    Visualization of painful inflammation in patients with pain after traumatic ankle sprain using [(11)C]-D-deprenyl PET/CT.2017In: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, Vol. 17, no 1, p. 418-424Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: Positron emission tomography (PET) with the radioligand [(11)C]-D-deprenyl has shown increased signal at location of pain in patients with rheumatoid arthritis and chronic whiplash injury. The binding site of [(11)C]-D-deprenyl in peripheral tissues is suggested to be mitochondrial monoamine oxidase in cells engaged in post-traumatic inflammation and tissue repair processes. The association between [(11)C]-D-deprenyl uptake and the transition from acute to chronic pain remain unknown. Further imaging studies of musculoskeletal pain at the molecular level would benefit from establishing a clinical model in a common and well-defined injury in otherwise healthy and drug-naïve subjects. The aim of this study was to investigate if [(11)C]-D-deprenyl uptake would be acutely elevated in unilateral ankle sprain and if tracer uptake would be reduced as a function of healing, and correlated with pain localizations and pain experience.

    METHODS: Eight otherwise healthy patients with unilateral ankle sprain were recruited at the emergency department. All underwent [(11)C]-D-deprenyl PET/CT in the acute phase, at one month and 6-14 months after injury.

    RESULTS: Acute [(11)C]-D-deprenyl uptake at the injury site was a factor of 10.7 (range 2.9-37.3) higher than the intact ankle. During healing, [(11)C]-D-deprenyl uptake decreased, but did not normalize until after 11 months. Patients experiencing persistent pain had prolonged [(11)C]-D-deprenyl uptake in painful locations.

    CONCLUSIONS AND IMPLICATIONS: The data provide further support that [(11)C]-D-deprenyl PET can visualize, quantify and follow processes in peripheral tissue that may relate to soft tissue injuries, inflammation and associated nociceptive signaling. Such an objective correlate would represent a progress in pain research, as well as in clinical pain diagnostics and management.

  • 4.
    Aarnio, Mikko
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Lampa, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. PET Centre, Department of Medical Imaging, Uppsala University Hospital, Sweden.
    Gordh, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Linnman, Clas
    Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, United States.
    Whiplash injuries associated with experienced pain and disability can be visualized with [11C]-D-deprenyl positron emission tomography and computed tomography2022In: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 163, no 3, p. 489-495Article in journal (Refereed)
    Abstract [en]

    Knowledge of etiological mechanisms underlying whiplash-associated disorders is incomplete. Localisation and quantification of peripheral musculoskeletal injury and inflammation in whiplash-associated disorders would facilitate diagnosis, strengthen patients' subjective pain reports, and aid clinical decisions, all of which could lead to improved treatment. In this longitudinal observational study, we evaluated combined [11C]-D-deprenyl positron emission tomography and computed tomography after acute whiplash injury and at 6-month follow-up. Sixteen adult patients (mean age 33 years) with whiplash injury grade II were recruited at the emergency department. [11C]-D-deprenyl positron emission tomography and computed tomography, subjective pain levels, self-rated neck disability, and active cervical range of motion were recorded within 7 days after injury and again at 6-month follow-up. Imaging results showed possible tissue injuries after acute whiplash with an altered [11C]-D-deprenyl uptake in the cervical bone structures and facet joints, associated with subjective pain locale and levels, as well as self-rated disability. At follow-up, some patients had recovered and some showed persistent symptoms and reductions in [11C]-D-deprenyl uptake correlated to reductions in pain levels. These findings help identify affected peripheral structures in whiplash injury and strengthen the idea that positron emission tomography and computed tomography detectable organic lesions in peripheral tissue are relevant for the development of persistent pain and disability in whiplash injury.

    Download full text (pdf)
    fulltext
  • 5.
    Abu Hamdeh, Sami
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Emami Khoonsari, Payam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Shevchenko, Ganna
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Gordh, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Ericson, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery.
    Kultima, Kim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Enblad: Neurosurgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Increased CSF Levels of Apolipoproteins and Complement Factors in Trigeminal Neuralgia Patients-In Depth Proteomic Analysis Using Mass Spectrometry2020In: Journal of Pain, ISSN 1526-5900, E-ISSN 1528-8447, Vol. 21, no 9-10, p. 1075-1084Article in journal (Refereed)
    Abstract [en]

    The main cause of trigeminal neuralgia (TN) is compression of a blood vessel at the root entry zone of the trigeminal nerve. However, a neurovascular conflict does not seem to be the only etiology and other mechanisms are implicated in the development of the disease. We hypothesized that TN patients may have distinct protein expression in the CSF. In this study, lumbar CSF from TN patients (n = 17), scheduled to undergo microvascular decompression, and from controls (n = 20) was analyzed and compared with in depth mass spectrometry TMTbased quantitative proteomics. We identified 2552 unique proteins, of which 46 were significantly altered (26 increased, and 20 decreased, q-value < .05) in TN patients compared with controls. An over-representation analysis showed proteins involved in high-density lipoprotein, such as Apolipoprotein A4, Apolipoprotein M, and Apolipoprotein A1, and the extracellular region, including proteins involved in the complement cascade to be over-represented. We conclude that TN patients have distinct protein expression in the CSF compared to controls. The pathophysiological background of the protein alterations found in this study warrants further investigation in future studies. Perspective: In this article, cerebrospinal fluid from patients with trigeminal neuralgia was analyzed using in depth shotgun proteomics, revealing 46 differentially expressed proteins compared to controls. Among these, apolipoproteins and proteins involved in the complement system were elevated and signif-icantly over-represented, implying an inflammatory component in the pathophysiology of the disease.

  • 6.
    Acosta, Cecilia M.
    et al.
    Univ Nacl Mar Del Plata, Hosp Privado Comunidad, Dept Anaesthesiol, Mar Del Plata, Argentina.
    Lopez Vargas, Maria Paz
    Univ Nacl Mar Del Plata, Hosp Privado Comunidad, Dept Anaesthesiol, Mar Del Plata, Argentina.
    Oropel, Facundo
    Univ Nacl Mar Del Plata, Hosp Privado Comunidad, Dept Anaesthesiol, Mar Del Plata, Argentina.
    Valente, Lisandro
    Univ Nacl Mar Del Plata, Hosp Privado Comunidad, Dept Anaesthesiol, Mar Del Plata, Argentina.
    Ricci, Lila
    Univ Nacl Mar Del Plata, Fac Ciencias Exactas, Dept Math, Mar Del Plata, Argentina.
    Natal, Marcela
    Univ Nacl Mar Del Plata, Fac Ciencias Exactas, Dept Math, Mar Del Plata, Argentina.
    Suarez Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Univ Autonoma Madrid, Hosp Univ Princesa, Inst Carlos III, CIBERES, Madrid, Spain; Univ Autonoma Madrid, Hosp Univ Princesa, Dept Crit Care, Madrid, Spain.
    Tusman, Gerardo
    Univ Nacl Mar Del Plata, Hosp Privado Comunidad, Dept Anaesthesiol, Mar Del Plata, Argentina.
    Prevention of atelectasis by continuous positive airway pressure in anaesthetised children: A randomised controlled study2021In: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 38, no 1, p. 41-48Article in journal (Refereed)
    Abstract [en]

    BACKGROUND 

    Continuous positive airway pressure (CPAP) prevents peri-operative atelectasis in adults, but its effect in children has not been quantified.

    OBJECTIVE 

    The aim of this study was to evaluate the role of CPAP in preventing postinduction and postoperative atelectasis in children under general anaesthesia.

    DESIGN 

    A randomised controlled study.

    SETTING 

    Single-institution study, community hospital, Mar del Plata. Argentina.

    PATIENTS 

    We studied 42 children, aged 6 months to 7 years, American Society of Anesthesiologists physical status class I, under standardised general anaesthesia.

    INTERVENTIONS 

    Patients were randomised into two groups: Control group (n = 21): induction and emergence of anaesthesia without CPAP; and CPAP group (n = 21): 5 cmH2O of CPAP during induction and emergence of anaesthesia. Lung ultrasound (LUS) imaging was performed before and 5 min after anaesthesia induction. Children without atelectasis were ventilated in the same manner as the Control group with standard ventilatory settings including 5 cmH2O of PEEP. Children with atelectasis received a recruitment manoeuvre followed by standard ventilation with 8 cmH2O of PEEP. Then, at the end of surgery, LUS images were repeated before tracheal extubation and 60 min after awakening.

    MAIN OUTCOME MEASURES 

    Lung aeration score and atelectasis assessed by LUS.

    RESULTS 

    Before anaesthesia, all children were free of atelectasis. After induction, 95% in the Control group developed atelectasis compared with 52% of patients in the CPAP group (P < 0.0001). LUS aeration scores were higher (impaired aeration) in the Control group than the CPAP group (8.8 ± 3.8 vs. 3.5 ± 3.3 points; P < 0.0001). At the end of surgery, before tracheal extubation, atelectasis was observed in 100% of children in the Control and 29% of the CPAP group (P < 0.0001) with a corresponding aeration score of 9.6 ± 3.2 and 1.8 ± 2.3, respectively (P < 0.0001). After surgery, 30% of children in the Control group and 10% in the CPAP group presented with residual atelectasis (P < 0.0001) also corresponding to a higher aeration score in the Control group (2.5 ± 3.1) when compared with the CPAP group (0.5 ± 1.5; P < 0.01).

    CONCLUSION 

    The use of 5 cmH2O of CPAP in healthy children of the studied age span during induction and emergence of anaesthesia effectively prevents atelectasis, with benefits maintained during the first postoperative hour.

    TRIAL REGISTRY 

    Clinicaltrials.gov NCT03461770.

  • 7.
    Acosta, Cecilia M.
    et al.
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesiol, Mar Del Plata, Argentina..
    Poliotto, Sergio
    Hosp Privado Comun, Dept Pediat Surg, Mar Del Plata, Argentina..
    Abrego, Diego
    Hosp Privado Comun, Dept Pediat Surg, Mar Del Plata, Argentina..
    Bradley, Dolores
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesiol, Mar Del Plata, Argentina..
    de Esteban, Santiago
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesiol, Mar Del Plata, Argentina..
    Mir, Francisco
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesiol, Mar Del Plata, Argentina..
    Ricci, Lila
    Univ Nacl Mar Del Plata, Fac Ciencias Exactas, Dept Math, Mar Del Plata, Argentina..
    Natal, Marcela
    Univ Nacl Mar Del Plata, Fac Ciencias Exactas, Dept Math, Mar Del Plata, Argentina..
    Wallin, Mats
    Karolinska Inst, Dept Physiol & Pharmacol, Solna Stockholm, Sweden.;Getinge Crit Care AB, Solna, Sweden..
    Hallbäck, Magnus
    Getinge Crit Care AB, Solna, Sweden..
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Hedenstierna laboratory. CIBERES Network Biomed Res Ctr, Madrid, Spain.;Univ Autonoma Madrid, Hosp Univ La Princesa, Dept Crit Care, Madrid, Spain..
    Tusman, Gerardo
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesiol, Mar Del Plata, Argentina.;Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, Cordoba 4545, RA-7600 Buenos Aires, Argentina..
    Effect of an Individualized Lung Protective Ventilation on Lung Strain and Stress in Children Undergoing Laparoscopy: An Observational Cohort Study2024In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 140, no 3, p. 430-441Article in journal (Refereed)
    Abstract [en]

    Background: Exaggerated lung strain and stress could damage lungs in anesthetized children. The authors hypothesized that the association of capnoperitoneum and lung collapse in anesthetized children increases lung strain-stress. Their primary aim was to describe the impact of capnoperitoneum on lung strain-stress and the effects of an individualized protective ventilation during laparoscopic surgery in children.

    Methods: The authors performed an observational cohort study in healthy children aged 3 to 7 yr scheduled for laparoscopic surgery in a community hospital. All received standard protective ventilation with 5 cm H2O of positive end-expiratory pressure (PEEP). Children were evaluated before capnoperitoneum, during capnoperitoneum before and after lung recruitment and optimized PEEP (PEEP adjusted to get end-expiratory transpulmonary pressure of 0), and after capnoperitoneum with optimized PEEP. The presence of lung collapse was evaluated by lung ultrasound, positive Air-Test (oxygen saturation measured by pulse oximetry 96% or less breathing 21% O2 for 5 min), and negative end-expiratory transpulmonary pressure. Lung strain was calculated as tidal volume/end-expiratory lung volume measured by capnodynamics, and lung stress as the end-inspiratory transpulmonary pressure.

    Results: The authors studied 20 children. Before capnoperitoneum, mean lung strain was 0.20 ± 0.07 (95% CI, 0.17 to 0.23), and stress was 5.68 ± 2.83 (95% CI, 4.44 to 6.92) cm H2O. During capnoperitoneum, 18 patients presented lung collapse and strain (0.29 ± 0.13; 95% CI, 0.23 to 0.35; P < 0.001) and stress (5.92 ± 3.18; 95% CI, 4.53 to 7.31 cm H2O; P = 0.374) increased compared to before capnoperitoneum. During capnoperitoneum and optimized PEEP, children presenting lung collapse were recruited and optimized PEEP was 8.3 ± 2.2 (95% CI, 7.3 to 9.3) cm H2O. Strain returned to values before capnoperitoneum (0.20 ± 0.07; 95% CI, 0.17 to 0.22; P = 0.318), but lung stress increased (7.29 ± 2.67; 95% CI, 6.12 to 8.46 cm H2O; P = 0.020). After capnoperitoneum, strain decreased (0.18 ± 0.04; 95% CI, 0.16 to 0.20; P = 0.090), but stress remained higher (7.25 ± 3.01; 95% CI, 5.92 to 8.57 cm H2O; P = 0.024) compared to before capnoperitoneum.

    Conclusions: Capnoperitoneum increased lung strain in healthy children undergoing laparoscopy. Lung recruitment and optimized PEEP during capnoperitoneum decreased lung strain but slightly increased lung stress. This little rise in pulmonary stress was maintained within safe, lung-protective, and clinically acceptable limits.

  • 8.
    Acosta, Cecilia M.
    et al.
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, Cordoba 4545, RA-7600 Buenos Aires, DF, Argentina..
    Tusman, Gerardo
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, Cordoba 4545, RA-7600 Buenos Aires, DF, Argentina..
    Costantini, Mauro
    Hosp Privado Comunidad Mar Del Plata, Dept Anesthesia, Cordoba 4545, RA-7600 Buenos Aires, DF, Argentina..
    Echevarria, Camila
    Hosp Privado Comunidad Mar Del Plata, Dept Radiol, Buenos Aires, DF, Argentina..
    Pollioto, Sergio
    Hosp Privado Comunidad Mar Del Plata, Dept Pediat Surg, Buenos Aires, DF, Argentina..
    Abrego, Diego
    Hosp Privado Comunidad Mar Del Plata, Dept Pediat Surg, Buenos Aires, DF, Argentina..
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain..
    Bohm, Stephan H.
    Swisstom AG, Landquart, Switzerland..
    Doppler images of intra-pulmonary shunt within atelectasis in anesthetized children2016In: Critical Ultrasound Journal, ISSN 2036-3176, E-ISSN 2036-7902, Vol. 8, article id 19Article in journal (Refereed)
    Abstract [en]

    Background: Doppler images of pulmonary vessels in pulmonary diseases associated with subpleural consolidations have been described. Color Doppler easily identifies such vessels within consolidations while spectral Doppler analysis allows the differentiation between pulmonary and bronchial arteries. Thus, Doppler helps in diagnosing the nature of consolidations. To our knowledge, Doppler analysis of pulmonary vessels within anesthesia-induced atelectasis has never been described before. The aim of this case series is to demonstrate the ability of lung ultrasound to detect the shunting of blood within atelectatic lung areas in anesthetized children.

    Findings: Three anesthetized and mechanically ventilated children were scanned in the supine position using a high-resolution linear probe of 6-12 MHz. Once subpleural consolidations were detected in the most dependent posterior lung regions, the probe was rotated such that its long axis followed the intercostal space. In this oblique position, color Doppler mapping was performed to detect blood flow within the consolidation. Thereafter, pulsed waved spectral Doppler was applied in the previously identified vessels during a short expiratory pause, which prevented interferences from respiratory motion. Different flow patterns were identified which corresponded to both, pulmonary and bronchial vessels. Finally, a lung recruitment maneuver was performed which leads to the complete resolution of the aforementioned consolidation thereby confirming the pathophysiological entity of anesthesia-induced atelectasis.

    Conclusions: Lung ultrasound is a non-invasive imaging tool that not only enables the diagnosis of anesthesia-induced atelectasis in pediatric patients but also analysis of shunting blood within this consolidation.

    Download full text (pdf)
    fulltext
  • 9.
    Adamski, Jan
    et al.
    via media, S-75655 Uppsala, Sweden..
    Goraj, Radoslaw
    Reg Specialist Hosp Olsztyn, Dept Anaesthesiol & Intens Care, Olsztyn, Poland..
    Onichimowski, Dariusz
    Reg Specialist Hosp Olsztyn, Dept Anaesthesiol & Intens Care, Olsztyn, Poland..
    Gawlikowska, Ewa
    Reg Specialist Hosp Olsztyn, Dept Anaesthesiol & Intens Care, Olsztyn, Poland..
    Weigl, Wojciech
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    The differences between two selected intensive care units located in central and northern Europe: preliminary observation2015In: ANAESTHESIOLOGY INTENSIVE THERAPY, ISSN 1642-5758, Vol. 47, no 2, p. 117-124Article in journal (Refereed)
    Abstract [en]

    Background: The aim of this study was to evaluate possible differences in the functioning of two selected intensive care units in Poland and Finland. The activity of the units was analysed over a period of one year. Methods: The following parameters were compared: demography of treated populations, site of admission, category of illness, severity of illness (APACHE-II scale), mean length of stay, demanded workload (TISS-28 scale), mortality (both ICU and hospital) and standardized mortality ratio (SMR). Results: The results of this study indicated that most of the patients in the Polish ICU, regardless of age, diagnosis and APACHE II score, presented significantly longer lengths of stay (14.65 +/- 13.6 vs 4.1 +/- 4.7 days, P = 0.0001), higher mean TISS-28 score (38.9 +/- 9.1 vs 31.2 +/- 6.1, P = 0.0001) and higher ICU and hospital mortality (41.5% vs 10.2% and 44.7% vs 21.8%, respectively, P = 0.0001). The values of SMR were 0.9 and 0.85 for the Finnish and Polish ICUs, respectively. Conclusion: The collected data indicate huge differences in the utilisation of critical care resources. Treatment in Polish ICU is concentrated on much more severely ill patients which might be sometimes accompanied by futility of care. In order to verify and correctly interpret the presented phenomena, further studies are needed.

    Download full text (pdf)
    fulltext
  • 10.
    Adamski, Jan
    et al.
    Satakunta Dist Hosp, Dept Anaesthesia & Intens Care, Pori, Finland..
    Nowakowski, Piotr
    Czerniakowski Hosp, Dept Anaesthesiol & Intens Therapy, Warsaw, Poland..
    Gorynski, Pawel
    Ctr Monitoring Populat Hlth Status, Dept Hyg, Natl Inst Publ Hlth, Warsaw, Poland..
    Onichimowski, Dariusz
    Reg Specialist Hosp, Dept Anaesthesiol & Intens Therapy, Olsztyn, Poland..
    Weigl, Wojciech
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Incidence of in-hospital cardiac arrest in Poland2016In: ANAESTHESIOLOGY INTENSIVE THERAPY, ISSN 1642-5758, Vol. 48, no 5, p. 288-293Article in journal (Refereed)
    Abstract [en]

    Background: In-hospital cardiac arrest with its poor prognosis is a challenging problem in hospitals. The aim of this study was to evaluate in Polish hospitals the frequency of in-hospital cardiac arrests with the subsequent mortality, with special emphasis on the type of unit at which the event occurred, and the patient's demographic data, such as age and sex.

    Methods: The study was a retrospective analysis of data for 2012 registered in the Polish General Hospital Morbidity Study. This research covered all Polish hospitals, excluding only government and psychiatric hospitals. The study inclusion criterion was the incidence of cardiac arrest in any hospital ward, recorded by the respective ICD-10 diagnosis code.

    Results: Of the 7,775,553 patients hospitalized, the diagnosis of cardiac arrest was reported in a total of 22,602 patients, which included 22,317 adults (98.7% of all patients) and 285 children (1.3%). Overall mortality after cardiac arrest among adults was 74.2%, and in children 46.7%. In both absolute numbers and as percentages of all documented cases, cardiac arrests occurred most often at the departments of intensive care, internal medicine, cardiology and emergency medicine. The accompanying mortality was lower than average at the departments of intensive care, cardiology, cardiology high dependency unit and emergency medicine. The median age of patients with cardiac arrest who died in the hospital was higher than the median age of those who survived (72 vs. 64; P < 0.05). Although cardiac arrests were reported more often among men than women (58.2% vs. 41.8%; P < 0.001), the hospital mortality was higher among women (79.2% vs. 71.6%; P < 0.001).

    Conclusion: The frequency of in-hospital cardiac arrests in Polish hospitals and the subsequent mortality is not substantially different from that observed in other countries. However, our study, based on ICD-10 diagnosis codes, gives only limited information about the patients and circumstances of this event. An in-depth analysis of the causes, prognoses, and outcome of in-hospital cardiac arrests could be facilitated by the creation of a national registry.

    Download full text (pdf)
    fulltext
  • 11.
    Adamski, Jan
    et al.
    Satakunta Cent Hosp, Dept Intens Care Med, Sairaalantie 3,PL 317, FIN-28500 Pori, Finland..
    Weigl, Wojciech
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lahtinen, Pasi
    Kuopio Univ Hosp, Dept Anaesthesiol & Intens Care Med, Kuopio, Finland..
    Reinikainen, Matti
    Kuopio Univ Hosp, Dept Anaesthesiol & Intens Care Med, Kuopio, Finland.;Univ Eastern Finland, Fac Hlth Sci, Sch Med, Inst Clin Med, Kuopio, Finland..
    Kaminski, Tadeusz
    Cent Hosp Middle Ostrobothnia, Dept Intens Care Med, Kokkola, Finland..
    Pietiläinen, Laura
    Kuopio Univ Hosp, Dept Anaesthesiol & Intens Care Med, Kuopio, Finland..
    Musialowicz, Tadeusz
    Kuopio Univ Hosp, Dept Anaesthesiol & Intens Care Med, Kuopio, Finland..
    Intensive care patient survival after limiting life-sustaining treatment-The FINNEOL* national cohort study2020In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 64, no 8, p. 1144-1153Article in journal (Refereed)
    Abstract [en]

    Background Few studies have examined survival in intensive care unit (ICU) patients after the restriction of life-sustaining treatment (LST). We aimed to analyse independent factors associated with hospital and 12-month survival rates in ICU patients after treatment restrictions. Methods This retrospective observational study examined all patients treated in adult ICUs from 1 January 2016 until 31 December 2016 included in the Finnish ICU Registry. Multivariable logistic regression analysis was performed to explain the effect on survival. Results Decisions to limit LST were made for 2444 patients (13.7%; 95% CI 13.2-14.2). ICU, hospital, and 12-month survival rates were 71% (95% CI 69-73), 49% (95% CI 47-51), and 24% (95% CI 22-26), respectively. In patients for whom life support was withheld, increased 12-month survival rates were associated with admission from the operating theatre (OR 1.9, 95% CI 1.1-3.4), good pre-hospital physical fitness (OR 4.7, 95% Cl 1.2-16.8) and being housed at home (OR 2.0, 95% Cl 1.4-2.8). Decreased survival rates were associated with admission from a hospital ward (OR 0.67, 95% Cl 0.5-0.9), higher comorbidity (OR 0.6, 95% Cl 0.4-0.9), cancer (OR 0.4, 95%CI 0.2-0.9), greater illness severity (SAPS II; OR 0.98, 95% Cl 0.98-0.99), and higher care intensity (TISS-76; OR 0.93, 95% Cl 0.92-0.95). Conclusion Survival among ICU patients with limited treatment was higher than expected. Advanced age was not associated with higher mortality, potentially because treatment restrictions may be set more easily for older patients.

  • 12.
    Adamski, Jan
    et al.
    Univ Warmia & Mazury, Fac Med Sci, Dept Anaesthesiol & Intens Care, Ul Warszawska 30, PL-10082 Olsztyn, Poland..
    Weigl, Wojciech
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Musialowicz, Tadeusz
    Kuopio Univ Hosp, Dept Anaesthesiol & Intens Care Med, Kuopio, Finland..
    Lahtinen, Pasi
    Cent Hosp South Ostrobothnia, Anaesthesiol & Intens Care Dept, Seinajoki, Finland..
    Reinikainen, Matti
    Kuopio Univ Hosp, Dept Anaesthesiol & Intens Care Med, Kuopio, Finland.;Univ Eastern Finland, Fac Hlth Sci, Sch Med, Inst Clin Med, Kuopio, Finland..
    Predictors of treatment limitations in Finnish intensive care units2022In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 66, no 4, p. 526-538Article in journal (Refereed)
    Abstract [en]

    Background Few studies have examined the factors that predict the limitations of life-sustaining treatment (LST) to patients in intensive care units (ICUs). We aimed to identify variables associated with the decision of withholding of life support (WHLS) at admission, WHLS during ICU stay and the withdrawal of ongoing life support (WDLS). Methods This retrospective observational study comprised 17,772 adult ICU patients who were included in the nationwide Finnish ICU Registry in 2016. Factors associated with LST limitations were identified using hierarchical logistic regression. Results The decision of WHLS at admission was made for 822 (4.6%) patients, WHLS during ICU stay for 949 (5.3%) patients, and WDLS for 669 (3.8%) patients. Factors strongly predicting WHLS at admission included old age (adjusted odds ratio [OR] for patients aged 90 years or older in reference to those younger than 40 years was 95.6; 95% confidence interval [CI], 47.2-193.5), dependence on help for activities of daily living (OR, 3.55; 95% CI, 3.01-4.2), and metastatic cancer (OR, 4.34; 95% CI, 3.16-5.95). A high severity of illness predicted later decisions to limit LST. Diagnoses strongly associated with WHLS at admission were cardiac arrest, hepatic failure and chronic obstructive pulmonary disease. Later decisions were strongly associated with cardiac arrest, hepatic failure, non-traumatic intracranial hemorrhage, head trauma and stroke. Conclusion Early decisions to limit LST were typically associated with old age and chronic poor health whereas later decisions were related to the severity of illness. Limitations are common for certain diagnoses, particularly cardiac arrest and hepatic failure.

  • 13.
    Ahlström, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Center for Clinical Research Dalarna.
    The epidemiology of risk factors and short and long-term outcome in the Swedish intensive care cohort2021Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Dissertation presented at Uppsala University to be publicly examined on Zoom: https://uu-se.zoom.us/j/7214327760, Tuesday, 11 May 2021 at 13:00 for the degree of Licentiate of Philosophy (Faculty of Medicine). The examination will be conducted in English and Swedish. Chairman of the Examining committee: Professor Karl Michaëlsson (Medical epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala) 

    Abstract Ahlström, B. 2021. The epidemiology of risk factors and short- and long-term out-come in the Swedish intensive care cohort. 76 pp.  

    Severe sepsis and septic shock, linked to persistent organ dysfunctions, have poor short- and long-term mortality outcomes. These conditions also adversely affect health-related quality of life. After intensive care with severe sepsis and septic shock, memory and other cognitive functions have shown deterioration. In addition, there are indications of an increased risk of dementia. Yet, whether severe sepsis and septic shock are independently linked to dementia or dementia development is linked to more general severe illness remains unclear. In the Swedish intensive care cohort we compared 16 115 one-year sepsis survivors without previous dementia to 194 219 patients (controls) admitted to intensive care for other reasons using a Cox proportional hazards model. The crude risk of dementia was increased in the severe sepsis and septic shock group. However, after adjustment for demographics, comorbidities and factors reflecting the severity of acute illness, severe sepsis and septic shock was found not to be a significant risk factor of incident dementia with a haz-ard ratio of 1.01 (95% confidence interval 0.91-1.11). Thus, we concluded that although the incidence of dementia is high after intensive care, severe sepsis or septic shock is not causative.  

    Coronavirus disease 2019 (COVID-19) has put a tremendous strain on the healthcare system in general and intensive care, in particular, since its emergence in Wuhan, China, in late 2019. Risk factors of ICU admission and mortality from COVID-19 were reported early during the pandemic, but only as univariate variables. Under the hypothesis that there are several independent risk factors of critical COVID-19, we used statistical models to explore demographic characteristics and comorbidi-ties in the first 1 981 ICU-admitted patients with COVID-19 in Sweden. On the risk of ICU admission, we also included matched population controls in a 1:4 ratio. Hypertension, type 2 diabetes mellitus, chronic renal failure, asthma, obesity, solid organ transplant recipient and immunosuppressant medications were independent risk factors of ICU admission. Oral anticoagulants were associated with a protective effect. Stroke, asthma, chronic obstructive pulmonary disease and treatment with renin-angiotensin-aldosterone inhibitors were independent risk factors of ICU mortality. Treatment with statins was protective. Our findings suggest that there are several independent risk factors of ICU admission and ICU mortality in COVID-19.

    Björn Ahlström, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Uppsala University, SE-75185 Uppsala, Sweden  

    and  Centre of clinical research, Region Dalarna, SE-79182 Falun, Sweden. 

    List of papers
    1. A nationwide study of the long-term prevalence of dementia and its risk factors in the Swedish intensive care cohort
    Open this publication in new window or tab >>A nationwide study of the long-term prevalence of dementia and its risk factors in the Swedish intensive care cohort
    2020 (English)In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 24, no 1, article id 548Article in journal (Refereed) Published
    Abstract [en]

    BackgroundDeveloping dementia is feared by many for its detrimental effects on cognition and independence. Experimental and clinical evidence suggests that sepsis is a risk factor for the later development of dementia. We aimed to investigate whether intensive care-treated sepsis is an independent risk factor for a later diagnosis of dementia in a large cohort of intensive care unit (ICU) patients.MethodsWe identified adult patients admitted to an ICU in 2005 to 2015 and who survived without a dementia diagnosis 1year after intensive care admission using the Swedish Intensive Care Registry, collecting data from all Swedish general ICUs. Comorbidity, the diagnosis of dementia and mortality, was retrieved from the Swedish National Patient Registry, the Swedish Dementia Registry, and the Cause of Death Registry. Sepsis during intensive care served as a covariate in an extended Cox model together with age, sex, and variables describing comorbidities and acute disease severity.ResultsOne year after ICU admission 210,334 patients were alive and without a diagnosis of dementia; of these, 16,115 (7.7%) had a diagnosis of sepsis during intensive care. The median age of the cohort was 61years (interquartile range, IQR 43-72). The patients were followed for up to 11years (median 3.9years, IQR 1.7-6.6). During the follow-up, 6312 (3%) patients were diagnosed with dementia. Dementia was more common in individuals diagnosed with sepsis during their ICU stay (log-rank p<0.001), however diagnosis of sepsis during critical care was not an independent risk factor for a later dementia diagnosis in an extended Cox model: hazard ratio (HR) 1.01 (95% confidence interval 0.91-1.11, p=0.873). Renal replacement therapy and ventilator therapy during the ICU stay were protective. High age was a strong risk factor for later dementia, as was increasing severity of acute illness, although to a lesser extent. However, the severity of comorbidities and the length of ICU and hospital stay were not independent risk factors in the model.ConclusionAlthough dementia is more common among patients treated with sepsis in the ICU, sepsis was not an independent risk factor for later dementia in the Swedish national critical care cohort.Trial registrationThis study was registered a priori with the Australian and New Zeeland Clinical Trials Registry (registration no. ACTRN12618000533291).

    Place, publisher, year, edition, pages
    BMC, 2020
    Keywords
    Critical care, Sepsis, Dementia, Risk factors, Cohort studies
    National Category
    Anesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:uu:diva-422802 (URN)10.1186/s13054-020-03203-y (DOI)000569782600004 ()32887659 (PubMedID)
    Available from: 2020-10-16 Created: 2020-10-16 Last updated: 2024-01-10Bibliographically approved
    2. The swedish covid-19 intensive care cohort: Risk factors of ICU admission and ICU mortality
    Open this publication in new window or tab >>The swedish covid-19 intensive care cohort: Risk factors of ICU admission and ICU mortality
    Show others...
    2021 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 65, no 4, p. 525-533Article in journal (Refereed) Published
    Abstract [en]

    Background: Several studies have recently addressed factors associated with severe Coronavirus disease 2019 (COVID-19); however, some medications and comorbidities have yet to be evaluated in a large matched cohort. We therefore explored the role of relevant comorbidities and medications in relation to the risk of intensive care unit (ICU) admission and mortality.

    Methods: All ICU COVID-19 patients in Sweden until 27 May 2020 were matched to population controls on age and gender to assess the risk of ICU admission. Cases were identified, comorbidities and medications were retrieved from high-quality registries. Three conditional logistic regression models were used for risk of ICU admission and three Cox proportional hazards models for risk of ICU mortality, one with comorbidities, one with medications and finally with both models combined, respectively.

    Results: We included 1981 patients and 7924 controls. Hypertension, type 2 diabetes mellitus, chronic renal failure, asthma, obesity, being a solid organ transplant recipient and immunosuppressant medications were independent risk factors of ICU admission and oral anticoagulants were protective. Stroke, asthma, chronic obstructive pulmonary disease and treatment with renin-angiotensin-aldosterone inhibitors (RAASi) were independent risk factors of ICU mortality in the pre-specified primary analyses; treatment with statins was protective. However, after adjusting for the use of continuous renal replacement therapy, RAASi were no longer an independent risk factor.

    Conclusion: In our cohort oral anticoagulants were protective of ICU admission and statins was protective of ICU death. Several comorbidities and ongoing RAASi treatment were independent risk factors of ICU admission and ICU mortality.

    Place, publisher, year, edition, pages
    John Wiley & SonsWiley, 2021
    Keywords
    anticoagulants, cohort studies, coronavirus infections, critical care, renin angiotensin system, risk factors
    National Category
    Anesthesiology and Intensive Care
    Research subject
    Medical Science
    Identifiers
    urn:nbn:se:uu:diva-440109 (URN)10.1111/aas.13781 (DOI)000615874800001 ()33438198 (PubMedID)
    Available from: 2021-04-14 Created: 2021-04-14 Last updated: 2024-01-15Bibliographically approved
  • 14.
    Ahlström, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    The epidemiology of risk factors and short- and long-term outcome in the Swedish intensive care cohort2024Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The sepsis syndrome is present in ¼ to ⅓ of patients in intensive care units (ICUs) worldwide. The short-term prognosis is grim, with a 30-day mortality of 30–35%; however, the long- term outcomes are now being explored, as multi-professional follow-up after ICU care is increasingly being implemented. In 2020 the first and second waves of another severe infection, the Coronavirus disease 2019 (Covid-19) hit Sweden. The number of ICU beds were scaled up by several hundred percent while we simultaneously tried to understand the disease. Reports on risk factors for adverse outcomes in Covid-19 started to appear, but we needed to know more. Thus, we initiated this project aiming at assessing sepsis as an independent risk factor for later morbidity and mortality. Subsequently, with the onset of the pandemic, our focus shifted to identifying risk factors for adverse outcomes in Covid-19 and describing the functional recovery after severe Covid-19. We used the Swedish Intensive Care Registry and several governmental registries to this end.

    In Cox regression, we compared one-year ICU sepsis survivors without previous dementia with ICU patients without sepsis, finding no increased risk of dementia during follow- up. In a similar cohort, we assessed the impact of sepsis on long-term mortality and causes of death in a series of Cox and multinomial models. We found a surprisingly small overall association between sepsis and mortality and a persistently increased risk of infectious causes of death in sepsis patients. We compared the prevalence of several common comorbidities and medications as risk factors for ICU admission and mortality in ICU patients with Covid-19 with that of age- and sex-matched population controls and in patients discharged alive with those that were deceased at discharge. We found associations between several comorbidities and medications with these adverse outcomes. To better understand the meaning of these comorbidities as risk factors for short-term mortality, we compared them in logistic regression models on patients with Covid-19, sepsis and acute respiratory distress syndrome (ARDS). We found very similar impacts from the comorbidities; however, greater age was more associated with mortality in Covid-19 than in either sepsis or ARDS. Finally, we investigated the long-term functional recovery in ICU patients with Covid-19 compared to hospital-admitted patients with Covid-19 and population controls matched to the ICU group. The ICU patients had a markedly impeded recovery that was not explained by demographics or comorbidities in statistical models.

    List of papers
    1. A nationwide study of the long-term prevalence of dementia and its risk factors in the Swedish intensive care cohort
    Open this publication in new window or tab >>A nationwide study of the long-term prevalence of dementia and its risk factors in the Swedish intensive care cohort
    2020 (English)In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 24, no 1, article id 548Article in journal (Refereed) Published
    Abstract [en]

    BackgroundDeveloping dementia is feared by many for its detrimental effects on cognition and independence. Experimental and clinical evidence suggests that sepsis is a risk factor for the later development of dementia. We aimed to investigate whether intensive care-treated sepsis is an independent risk factor for a later diagnosis of dementia in a large cohort of intensive care unit (ICU) patients.MethodsWe identified adult patients admitted to an ICU in 2005 to 2015 and who survived without a dementia diagnosis 1year after intensive care admission using the Swedish Intensive Care Registry, collecting data from all Swedish general ICUs. Comorbidity, the diagnosis of dementia and mortality, was retrieved from the Swedish National Patient Registry, the Swedish Dementia Registry, and the Cause of Death Registry. Sepsis during intensive care served as a covariate in an extended Cox model together with age, sex, and variables describing comorbidities and acute disease severity.ResultsOne year after ICU admission 210,334 patients were alive and without a diagnosis of dementia; of these, 16,115 (7.7%) had a diagnosis of sepsis during intensive care. The median age of the cohort was 61years (interquartile range, IQR 43-72). The patients were followed for up to 11years (median 3.9years, IQR 1.7-6.6). During the follow-up, 6312 (3%) patients were diagnosed with dementia. Dementia was more common in individuals diagnosed with sepsis during their ICU stay (log-rank p<0.001), however diagnosis of sepsis during critical care was not an independent risk factor for a later dementia diagnosis in an extended Cox model: hazard ratio (HR) 1.01 (95% confidence interval 0.91-1.11, p=0.873). Renal replacement therapy and ventilator therapy during the ICU stay were protective. High age was a strong risk factor for later dementia, as was increasing severity of acute illness, although to a lesser extent. However, the severity of comorbidities and the length of ICU and hospital stay were not independent risk factors in the model.ConclusionAlthough dementia is more common among patients treated with sepsis in the ICU, sepsis was not an independent risk factor for later dementia in the Swedish national critical care cohort.Trial registrationThis study was registered a priori with the Australian and New Zeeland Clinical Trials Registry (registration no. ACTRN12618000533291).

    Place, publisher, year, edition, pages
    BMC, 2020
    Keywords
    Critical care, Sepsis, Dementia, Risk factors, Cohort studies
    National Category
    Anesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:uu:diva-422802 (URN)10.1186/s13054-020-03203-y (DOI)000569782600004 ()32887659 (PubMedID)
    Available from: 2020-10-16 Created: 2020-10-16 Last updated: 2024-01-10Bibliographically approved
    2. Association of sepsis with long-term mortality and causes of death in the Swedish intensive care cohort
    Open this publication in new window or tab >>Association of sepsis with long-term mortality and causes of death in the Swedish intensive care cohort
    (English)Manuscript (preprint) (Other academic)
    National Category
    Anesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:uu:diva-519454 (URN)
    Available from: 2024-01-08 Created: 2024-01-08 Last updated: 2024-01-10
    3. The swedish covid-19 intensive care cohort: Risk factors of ICU admission and ICU mortality
    Open this publication in new window or tab >>The swedish covid-19 intensive care cohort: Risk factors of ICU admission and ICU mortality
    Show others...
    2021 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 65, no 4, p. 525-533Article in journal (Refereed) Published
    Abstract [en]

    Background: Several studies have recently addressed factors associated with severe Coronavirus disease 2019 (COVID-19); however, some medications and comorbidities have yet to be evaluated in a large matched cohort. We therefore explored the role of relevant comorbidities and medications in relation to the risk of intensive care unit (ICU) admission and mortality.

    Methods: All ICU COVID-19 patients in Sweden until 27 May 2020 were matched to population controls on age and gender to assess the risk of ICU admission. Cases were identified, comorbidities and medications were retrieved from high-quality registries. Three conditional logistic regression models were used for risk of ICU admission and three Cox proportional hazards models for risk of ICU mortality, one with comorbidities, one with medications and finally with both models combined, respectively.

    Results: We included 1981 patients and 7924 controls. Hypertension, type 2 diabetes mellitus, chronic renal failure, asthma, obesity, being a solid organ transplant recipient and immunosuppressant medications were independent risk factors of ICU admission and oral anticoagulants were protective. Stroke, asthma, chronic obstructive pulmonary disease and treatment with renin-angiotensin-aldosterone inhibitors (RAASi) were independent risk factors of ICU mortality in the pre-specified primary analyses; treatment with statins was protective. However, after adjusting for the use of continuous renal replacement therapy, RAASi were no longer an independent risk factor.

    Conclusion: In our cohort oral anticoagulants were protective of ICU admission and statins was protective of ICU death. Several comorbidities and ongoing RAASi treatment were independent risk factors of ICU admission and ICU mortality.

    Place, publisher, year, edition, pages
    John Wiley & SonsWiley, 2021
    Keywords
    anticoagulants, cohort studies, coronavirus infections, critical care, renin angiotensin system, risk factors
    National Category
    Anesthesiology and Intensive Care
    Research subject
    Medical Science
    Identifiers
    urn:nbn:se:uu:diva-440109 (URN)10.1111/aas.13781 (DOI)000615874800001 ()33438198 (PubMedID)
    Available from: 2021-04-14 Created: 2021-04-14 Last updated: 2024-01-15Bibliographically approved
    4. A comparison of impact of comorbidities and demographics on 60-day mortality in ICU patients with COVID-19, sepsis and acute respiratory distress syndrome
    Open this publication in new window or tab >>A comparison of impact of comorbidities and demographics on 60-day mortality in ICU patients with COVID-19, sepsis and acute respiratory distress syndrome
    Show others...
    2022 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 12, article id 15703Article in journal (Refereed) Published
    Abstract [en]

    Severe Coronavirus disease 2019 (COVID-19) is associated with several pre-existing comorbidities and demographic factors. Similar factors are linked to critical sepsis and acute respiratory distress syndrome (ARDS). We hypothesized that age and comorbidities are more generically linked to critical illness mortality than a specific disease state. We used national databases to identify ICU patients and to retrieve comorbidities. The relative importance of risk factors for 60-day mortality was evaluated using the interaction with disease group (Sepsis, ARDS or COVID-19) in logistic regression models. We included 32,501 adult ICU patients. In the model on 60-day mortality in sepsis and COVID-19 there were significant interactions with disease group for age, sex and asthma. In the model on 60-day mortality in ARDS and COVID-19 significant interactions with cohort were found for acute disease severity, age and chronic renal failure. In conclusion, age and sex play particular roles in COVID-19 mortality during intensive care but the burden of comorbidity was similar between sepsis and COVID-19 and ARDS and COVID-19.

    Place, publisher, year, edition, pages
    Springer Nature, 2022
    National Category
    Public Health, Global Health, Social Medicine and Epidemiology
    Identifiers
    urn:nbn:se:uu:diva-486398 (URN)10.1038/s41598-022-19539-0 (DOI)000857187000001 ()36127433 (PubMedID)
    Available from: 2022-10-10 Created: 2022-10-10 Last updated: 2024-01-10Bibliographically approved
    5. One-year functional recovery from severe Covid-19 is severely affected in the Swedish intensive care and hospital admitted working age cohort
    Open this publication in new window or tab >>One-year functional recovery from severe Covid-19 is severely affected in the Swedish intensive care and hospital admitted working age cohort
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Anesthesiology and Intensive Care
    Identifiers
    urn:nbn:se:uu:diva-519456 (URN)
    Available from: 2024-01-08 Created: 2024-01-08 Last updated: 2024-01-10
    Download full text (pdf)
    UUThesis_B-Ahlström-2024
    Download (jpg)
    presentationsbild
  • 15.
    Ahlström, Björn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Center for Clinical Research Dalarna.
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Hedenstierna laboratory.
    Hultström, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Ing-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Strandberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Hedenstierna laboratory.
    One-year functional recovery from severe Covid-19 is severely affected in the Swedish intensive care and hospital admitted working age cohortManuscript (preprint) (Other academic)
  • 16.
    Ahlström, Björn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Center for Clinical Research Dalarna.
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hultström, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Ing-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Strandberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    The swedish covid-19 intensive care cohort: Risk factors of ICU admission and ICU mortality2021In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 65, no 4, p. 525-533Article in journal (Refereed)
    Abstract [en]

    Background: Several studies have recently addressed factors associated with severe Coronavirus disease 2019 (COVID-19); however, some medications and comorbidities have yet to be evaluated in a large matched cohort. We therefore explored the role of relevant comorbidities and medications in relation to the risk of intensive care unit (ICU) admission and mortality.

    Methods: All ICU COVID-19 patients in Sweden until 27 May 2020 were matched to population controls on age and gender to assess the risk of ICU admission. Cases were identified, comorbidities and medications were retrieved from high-quality registries. Three conditional logistic regression models were used for risk of ICU admission and three Cox proportional hazards models for risk of ICU mortality, one with comorbidities, one with medications and finally with both models combined, respectively.

    Results: We included 1981 patients and 7924 controls. Hypertension, type 2 diabetes mellitus, chronic renal failure, asthma, obesity, being a solid organ transplant recipient and immunosuppressant medications were independent risk factors of ICU admission and oral anticoagulants were protective. Stroke, asthma, chronic obstructive pulmonary disease and treatment with renin-angiotensin-aldosterone inhibitors (RAASi) were independent risk factors of ICU mortality in the pre-specified primary analyses; treatment with statins was protective. However, after adjusting for the use of continuous renal replacement therapy, RAASi were no longer an independent risk factor.

    Conclusion: In our cohort oral anticoagulants were protective of ICU admission and statins was protective of ICU death. Several comorbidities and ongoing RAASi treatment were independent risk factors of ICU admission and ICU mortality.

    Download full text (pdf)
    fulltext
  • 17.
    Ahlström, Björn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Falun Cent Hosp, Ctr Clin Res Dalarna, Reg Dalarna, Nissers V6g 3, S-79182 Falun, Sweden..
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Ing-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Strandberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Hedenstierna laboratory.
    Hultström, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    A comparison of impact of comorbidities and demographics on 60-day mortality in ICU patients with COVID-19, sepsis and acute respiratory distress syndrome2022In: Scientific Reports, E-ISSN 2045-2322, Vol. 12, article id 15703Article in journal (Refereed)
    Abstract [en]

    Severe Coronavirus disease 2019 (COVID-19) is associated with several pre-existing comorbidities and demographic factors. Similar factors are linked to critical sepsis and acute respiratory distress syndrome (ARDS). We hypothesized that age and comorbidities are more generically linked to critical illness mortality than a specific disease state. We used national databases to identify ICU patients and to retrieve comorbidities. The relative importance of risk factors for 60-day mortality was evaluated using the interaction with disease group (Sepsis, ARDS or COVID-19) in logistic regression models. We included 32,501 adult ICU patients. In the model on 60-day mortality in sepsis and COVID-19 there were significant interactions with disease group for age, sex and asthma. In the model on 60-day mortality in ARDS and COVID-19 significant interactions with cohort were found for acute disease severity, age and chronic renal failure. In conclusion, age and sex play particular roles in COVID-19 mortality during intensive care but the burden of comorbidity was similar between sepsis and COVID-19 and ARDS and COVID-19.

    Download full text (pdf)
    FULLTEXT01
  • 18.
    Ahlström, Björn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Centre for Clinical Research Dalarna, Healthcare Region Dalarna, Falun, Sweden..
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Ing-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Strandberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Hedenstierna laboratory.
    Hultström, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Integrative Physiology, Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden..
    Comorbid burden at ICU admission in COVID-19 compared to sepsis and acute respiratory distress syndrome.2024In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 68, no 10, p. 1417-1425Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Comorbidities are similarly associated with short-term mortality for COVID-19, acute respiratory distress syndrome (ARDS) and sepsis in intensive care unit (ICU) patients, but their adjusted frequencies at admission are unknown. Thus, we aimed to evaluate the adjusted distribution, reported as odds ratios, of known risk factors (i.e., age, sex and comorbidities) for ICU admission between COVID-19, sepsis and ARDS patients in this nationwide registry-based study.

    METHODS: In this cohort study, we included adult patients admitted to Swedish ICUs with COVID-19 (n = 7382) during the pandemic and compared them to patients admitted to ICU with sepsis (n = 22,354) or ARDS (n = 2776) during a pre-COVID-19 period. The main outcomes were the adjusted odds for comorbidities, sex, and age in multivariable logistic regression on diagnostic categories in patients admitted to ICU, COVID-19 or sepsis and COVID-19 or ARDS.

    RESULTS: We found that most comorbidities, as well as age, had a stronger association with sepsis admission than COVID-19 admission with the exception of male sex, type 2 diabetes mellitus, and asthma that were more strongly associated with COVID-19 admission, while no difference was seen for chronic renal failure and obesity. For COVID-19 and ARDS admission most risk factors were more strongly associated with ARDS admission except for male sex, type 2 diabetes mellitus, chronic renal failure, and obesity which were more strongly associated with COVID-19 admission, whereas hypertension, chronic obstructive pulmonary disease and asthma were not different.

    CONCLUSIONS: Patients admitted to ICU with sepsis or ARDS carry a heavier burden of comorbidity and high age than patients admitted with COVID-19. This is likely caused by a combination of: (1) respiratory failure in COVID-19 being less dependent on comorbidities than in other forms of ARDS, and the cause of critical illness in other infections causing sepsis and (2) COVID-19 patients being deferred admission in situations where patients with the other syndromes were admitted.

  • 19.
    Ahlström, Björn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Ctr Clin Res Dalarna, Reg Dalarna, Nissers Vag 3, S-79182 Falun, Sweden..
    Larsson, Ing-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Strandberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala Univ, Dept Surg Sci, Uppsala, Sweden.;Uppsala Univ, CIRRUS, Dept Surg Sci, Hedenstierna Lab,Anesthesiol & Intens Care, Uppsala, Sweden..
    A nationwide study of the long-term prevalence of dementia and its risk factors in the Swedish intensive care cohort2020In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 24, no 1, article id 548Article in journal (Refereed)
    Abstract [en]

    BackgroundDeveloping dementia is feared by many for its detrimental effects on cognition and independence. Experimental and clinical evidence suggests that sepsis is a risk factor for the later development of dementia. We aimed to investigate whether intensive care-treated sepsis is an independent risk factor for a later diagnosis of dementia in a large cohort of intensive care unit (ICU) patients.MethodsWe identified adult patients admitted to an ICU in 2005 to 2015 and who survived without a dementia diagnosis 1year after intensive care admission using the Swedish Intensive Care Registry, collecting data from all Swedish general ICUs. Comorbidity, the diagnosis of dementia and mortality, was retrieved from the Swedish National Patient Registry, the Swedish Dementia Registry, and the Cause of Death Registry. Sepsis during intensive care served as a covariate in an extended Cox model together with age, sex, and variables describing comorbidities and acute disease severity.ResultsOne year after ICU admission 210,334 patients were alive and without a diagnosis of dementia; of these, 16,115 (7.7%) had a diagnosis of sepsis during intensive care. The median age of the cohort was 61years (interquartile range, IQR 43-72). The patients were followed for up to 11years (median 3.9years, IQR 1.7-6.6). During the follow-up, 6312 (3%) patients were diagnosed with dementia. Dementia was more common in individuals diagnosed with sepsis during their ICU stay (log-rank p<0.001), however diagnosis of sepsis during critical care was not an independent risk factor for a later dementia diagnosis in an extended Cox model: hazard ratio (HR) 1.01 (95% confidence interval 0.91-1.11, p=0.873). Renal replacement therapy and ventilator therapy during the ICU stay were protective. High age was a strong risk factor for later dementia, as was increasing severity of acute illness, although to a lesser extent. However, the severity of comorbidities and the length of ICU and hospital stay were not independent risk factors in the model.ConclusionAlthough dementia is more common among patients treated with sepsis in the ICU, sepsis was not an independent risk factor for later dementia in the Swedish national critical care cohort.Trial registrationThis study was registered a priori with the Australian and New Zeeland Clinical Trials Registry (registration no. ACTRN12618000533291).

    Download full text (pdf)
    FULLTEXT01
  • 20.
    Ahlström, Björn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Center for Clinical Research Dalarna.
    Larsson, Ing-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Strandberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Hedenstierna laboratory.
    Association of sepsis with long-term mortality and causes of death in the Swedish intensive care cohortManuscript (preprint) (Other academic)
  • 21.
    Ahlström, Björn
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Centre for Clinical Research Dalarna, Healthcare Region Dalarna, Falun, Sweden.
    Larsson, Ing-Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Nursing Research.
    Strandberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Hedenstierna laboratory.
    Association of sepsis with long-term mortality and causes of death in the Swedish intensive care cohort.2024In: Intensive Care Medicine, ISSN 0342-4642, E-ISSN 1432-1238, Vol. 50, no 4, p. 605-607Article in journal (Refereed)
  • 22.
    Ahlström, J. Zebialowicz
    et al.
    Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Massaro, F.
    Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden.
    Mikolka, P.
    Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden;Comenius Univ, Jessenius Fac Med Martin, Biomed Ctr Martin, Martin, TN USA;Comenius Univ, Jessenius Fac Med Martin, Dept Physiol, Martin, TN USA.
    Feinstein, R.
    Swedish Natl Vet Inst, Dept Pathol, Uppsala, Sweden.
    Perchiazzi, Gaetano
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala Univ, Dept Surg Sci, Hedenstierna Lab, Uppsala, Sweden.
    Basabe-Burgos, O.
    Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Curstedt, T.
    Karolinska Inst, Karolinska Univ Hosp, Dept Mol Med & Surg, Stockholm, Sweden.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Johansson, J.
    Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
    Rising, A.
    Karolinska Inst, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden;Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden.
    Synthetic surfactant with a recombinant surfactant protein C analogue improves lung function and attenuates inflammation in a model of acute respiratory distress syndrome in adult rabbits2019In: Respiratory Research, ISSN 1465-9921, E-ISSN 1465-993X, Vol. 20, article id 245Article in journal (Refereed)
    Abstract [en]

    AimIn acute respiratory distress syndrome (ARDS) damaged alveolar epithelium, leakage of plasma proteins into the alveolar space and inactivation of pulmonary surfactant lead to respiratory dysfunction. Lung function could potentially be restored with exogenous surfactant therapy, but clinical trials have so far been disappointing. These negative results may be explained by inactivation and/or too low doses of the administered surfactant. Surfactant based on a recombinant surfactant protein C analogue (rSP-C33Leu) is easy to produce and in this study we compared its effects on lung function and inflammation with a commercial surfactant preparation in an adult rabbit model of ARDS.MethodsARDS was induced in adult New Zealand rabbits by mild lung-lavages followed by injurious ventilation (V-T 20m/kg body weight) until P/F ratio<26.7kPa. The animals were treated with two intratracheal boluses of 2.5mL/kg of 2% rSP-C33Leu in DPPC/egg PC/POPG, 50:40:10 or poractant alfa (Curosurf (R)), both surfactants containing 80mg phospholipids/mL, or air as control. The animals were subsequently ventilated (V-T 8-9m/kg body weight) for an additional 3h and lung function parameters were recorded. Histological appearance of the lungs, degree of lung oedema and levels of the cytokines TNF alpha IL-6 and IL-8 in lung homogenates were evaluated.ResultsBoth surfactant preparations improved lung function vs. the control group and also reduced inflammation scores, production of pro-inflammatory cytokines, and formation of lung oedema to similar degrees. Poractant alfa improved compliance at 1h, P/F ratio and PaO2 at 1.5h compared to rSP-C33Leu surfactant.ConclusionThis study indicates that treatment of experimental ARDS with synthetic lung surfactant based on rSP-C33Leu improves lung function and attenuates inflammation.

    Download full text (pdf)
    FULLTEXT01
  • 23.
    Akerman, Sara
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala Ctr Paediat Anaesthes & Intens Care Res, Uppsala, Sweden..
    Axelin, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Univ Turku, Dept Nursing Sci, Turku, Finland..
    Traube, Chani
    Weill Cornell Med Ctr, Dept Pediat, New York, NY USA..
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala Ctr Paediat Anaesthes & Intens Care Res, Uppsala, Sweden..
    Thernström Blomqvist, Ylva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Perinatal, Neonatal and Pediatric Cardiology Research.
    Adapting the Cornell assessment of pediatric delirium for Swedish context: translation, cultural validation and inter-rater reliability2024In: BMC Pediatrics, E-ISSN 1471-2431, Vol. 24, no 1, article id 413Article in journal (Refereed)
    Abstract [en]

    Background: Pediatric delirium causes prolonged hospital stays, increased costs, and distress for children and caregivers. Currently, there is no delirium screening tool available in Sweden that has been translated, culturally validated, and tested for reliability. This study aimed to translate, culturally adapt, and assess the suitability of the Cornell Assessment of Pediatric Delirium (CAPD) for implementation in Swedish healthcare settings.

    Methods: The CAPD was translated and culturally adapted to Swedish context following the ten-step process recommended by the International Society for Pharmacoeconomics and Outcomes Task Force for Translation and Cultural Adaptation. The Swedish CAPD was tested in the pediatric intensive care unit of Uppsala University Hospital, a tertiary hospital in Sweden. Inter-rater reliability was tested using intraclass correlation coefficient (ICC), with both Registered Nurses (RNs) and Assistant Nurses (ANs) conducting parallel measurements using the Swedish CAPD. A reliability score of ICC > 0.75 was considered indicative of good reliability.

    Results: After translation of the CAPD into Swedish, 10 RNs participated in the cultural adaptation process. Issues related to word choice, education, and instructions were addressed. Wording improvements were made to ensure accurate interpretation. Supplementary training sessions were organized to strengthen users' proficiency with the Swedish CAPD. Additional instructions were provided to enhance clarity and usability. Inter-rater reliability testing resulted in an ICC of 0.857 (95% CI: 0.708-0.930), indicating good reliability.

    Conclusion: This study successfully translated and culturally adapted the CAPD to align with Swedish contextual parameters. The resulting Swedish CAPD demonstrated good inter-rater reliability, establishing its viability as a tool for measuring delirium among pediatric patients in Swedish pediatric intensive care units. Trail registration Not applicable.