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  • 251.
    Ajiko, Mary Margaret
    et al.
    Karolinska Inst, Sweden; Soroti Reg Referral Hosp, Uganda.
    Weidman, Viking
    Uppsala Univ, Sweden.
    Nordin, Pär
    Department of Surgery and Perioperative Sciences, University of Umeå, Umeå, Sweden.
    Wladis, Andreas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för kirurgi, ortopedi och onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Regionledningskontoret, Katastrofmedicinskt centrum.
    Löfgren, Jenny
    Karolinska Inst, Sweden.
    Prevalence of Paediatric Surgical Conditions in Eastern Uganda: A Cross-Sectional Study2022Ingår i: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 46, nr 3, s. 701-708Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background The role of surgery in global health has gained greater attention in recent years. Approximately 1.8 billion children below 15 years live in low- and middle-income countries (LMIC). Many surgical conditions affect children. Therefore, paediatric surgery requires specific emphasis. Left unattended, the consequences can be dire. Despite this, there is a paucity of data regarding prevalence of surgical conditions in children in LMIC. The present objective was to investigate the prevalence of paediatric surgical conditions in children in a defined geographical area in Eastern Uganda. Method A cross-sectional study was carried out in the Iganga-Mayuge Health and Demographic Surveillance Site located in Eastern Uganda. Through a two-stage, cluster-based sampling process, 490 households from 49 villages were randomly selected, generating a study population of 1581 children. The childrens caregivers were interviewed, and the children were physically examined by two medical doctors to identify any surgical conditions. Results The interview was performed with 1581 children, and 1054 were physically examined. Among these, the overall prevalence of any surgical condition was 16.0 per cent (n = 169). Of these, 39 per cent had an unmet surgical need (66 of 169). This is equivalent to a 6.3 per cent prevalence of current unmet surgical need. The most common groups of surgical condition were congenital anomalies and trauma-related conditions. Conclusion Surgical conditions in children are common in eastern Uganda. The unmet need for surgery is high. With a growing population, the need for paediatric surgical capacity will increase even further. The health care system must be reinforced to provide services for children with surgical conditions if United Nations Sustainability Development Goal 3 is to be achieved by 2030.

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  • 252.
    Ajileye, Adebisi
    et al.
    Birmingham Heartlands Hospital, England.
    Alvarez, Nataly
    Corp Invest Biol, Colombia; University of Pontificia Bolivariana, Colombia.
    Merker, Matthias
    Research Centre Borstel, Germany; German Centre Infect Research, Germany.
    Walker, Timothy M.
    University of Oxford, England.
    Akter, Suriya
    Institute Trop Med, Belgium.
    Brown, Kerstin
    Birmingham Heartlands Hospital, England.
    Moradigaravand, Danesh
    Wellcome Trust Sanger Institute, England.
    Schön, Thomas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten. Kalmar County Hospital, Sweden.
    Andres, Soenke
    Research Centre Borstel, Germany.
    Schleusener, Viola
    Research Centre Borstel, Germany.
    Omar, Shaheed V.
    Centre TB, South Africa.
    Coll, Francesc
    London School Hyg and Trop Med, England.
    Huang, Hairong
    Capital Medical University, Peoples R China.
    Diel, Roland
    University Hospital, Germany.
    Ismail, Nazir
    Centre TB, South Africa.
    Parkhill, Julian
    Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
    de Jong, Bouke C.
    Institute Trop Med, Belgium.
    Peto, Tim E. A.
    University of Oxford, England.
    Crook, Derrick W.
    University of Oxford, England; Public Health England Microbiol Serv, England.
    Niemann, Stefan
    Research Centre Borstel, Germany; German Centre Infect Research, Germany.
    Robledo, Jaime
    Corp Invest Biol, Colombia; University of Pontificia Bolivariana, Colombia.
    Grace Smith, E.
    Birmingham Heartlands Hospital, England.
    Peacock, Sharon J.
    Wellcome Trust Sanger Institute, England; London School Hyg and Trop Med, England; University of Cambridge, England.
    Koeser, Claudio U.
    University of Cambridge, England.
    Some Synonymous and Nonsynonymous gyrA Mutations in Mycobacterium tuberculosis Lead to Systematic False-Positive Fluoroquinolone Resistance Results with the Hain GenoType MTBDRsl Assays2017Ingår i: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 61, nr 4, artikel-id e02169-16Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In this study, using the Hain GenoType MTBDRsl assays (versions 1 and 2), we found that some nonsynonymous and synonymous mutations in gyrA in Mycobacterium tuberculosis result in systematic false-resistance results to fluoroquinolones by preventing the binding of wild-type probes. Moreover, such mutations can prevent the binding of mutant probes designed for the identification of specific resistance mutations. Although these mutations are likely rare globally, they occur in approximately 7% of multidrug-resistant tuberculosis strains in some settings.

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  • 253.
    Ajmera, Veeral H.
    et al.
    Univ Calif San Diego Hlth, CA USA.
    Cachay, Edward
    Univ Calif San Diego, CA 92103 USA.
    Ramers, Christian
    Family Hlth Ctr, CA USA.
    Vodkin, Irine
    Univ Calif San Diego Hlth, CA USA.
    Bassirian, Shirin
    Univ Calif San Diego Hlth, CA USA.
    Singh, Seema
    Univ Calif San Diego Hlth, CA USA.
    Mangla, Neeraj
    Univ Calif San Diego Hlth, CA USA.
    Bettencourt, Richele
    Univ Calif San Diego Hlth, CA USA.
    Aldous, Jeannette L.
    San Ysidro Hlth, CA USA.
    Park, Daniel
    San Ysidro Hlth, CA USA.
    Lee, Daniel
    Univ Calif San Diego, CA 92103 USA.
    Blanchard, Jennifer
    Univ Calif San Diego, CA 92103 USA.
    Mamidipalli, Adrija
    Univ Calif San Diego, CA 92093 USA.
    Boehringer, Andrew
    Univ Calif San Diego, CA 92093 USA.
    Aslam, Saima
    Univ Calif San Diego, CA 92103 USA.
    Dahlqvist Leinhard, Olof
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US. AMRA Med AB, Linkoping, Sweden.
    Richards, Lisa
    Univ Calif San Diego Hlth, CA USA.
    Sirlin, Claude B.
    Univ Calif San Diego, CA 92093 USA.
    Loomba, Rohit
    Univ Calif San Diego, CA 92093 USA.
    MRI Assessment of Treatment Response in HIV-associated NAFLD: A Randomized Trial of a Stearoyl-Coenzyme-A-Desaturase-1 Inhibitor (ARRIVE Trial)2019Ingår i: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 70, nr 5, s. 1531-1545Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aramchol, an oral stearoyl-coenzyme-A-desaturase-1 inhibitor, has been shown to reduce hepatic fat content in patients with primary nonalcoholic fatty liver disease (NAFLD); however, its effect in patients with human immunodeficiency virus (HIV)-associated NAFLD is unknown. The aramchol for HIV-associated NAFLD and lipodystrophy (ARRIVE) trial was a double-blind, randomized, investigator-initiated, placebo-controlled trial to test the efficacy of 12 weeks of treatment with aramchol versus placebo in HIV-associated NAFLD. Fifty patients with HIV-associated NAFLD, defined by magnetic resonance imaging (MRI)-proton density fat fraction (PDFF) amp;gt;= 5%, were randomized to receive either aramchol 600 mg daily (n = 25) or placebo (n = 25) for 12 weeks. The primary endpoint was a change in hepatic fat as measured by MRI-PDFF in colocalized regions of interest. Secondary endpoints included changes in liver stiffness using magnetic resonance elastography (MRE) and vibration-controlled transient elastography (VCTE), and exploratory endpoints included changes in total-body fat and muscle depots on dual-energy X-ray absorptiometry (DXA), whole-body MRI, and cardiac MRI. The mean (+/- standard deviation) of age and body mass index were 48.2 +/- 10.3 years and 30.7 +/- 4.6 kg/m(2), respectively. There was no difference in the reduction in mean MRI-PDFF between the aramchol group at -1.3% (baseline MRI-PDFF 15.6% versus end-of-treatment MRI-PDFF 14.4%, P = 0.24) and the placebo group at -1.4% (baseline MRI-PDFF 13.3% versus end-of-treatment MRI-PDFF 11.9%, P = 0.26). There was no difference in the relative decline in mean MRI-PDFF between the aramchol and placebo groups (6.8% versus 1.1%, P = 0.68). There were no differences in MRE-derived and VCTE-derived liver stiffness and whole-body (fat and muscle) composition analysis by MRI or DXA. Compared to baseline, end-of-treatment aminotransferases were lower in the aramchol group but not in the placebo arm. There were no significant adverse events. Conclusion: Aramchol, over a 12-week period, did not reduce hepatic fat or change body fat and muscle composition by using MRI-based assessment in patients with HIV-associated NAFLD (clinicaltrials.gov ID:NCT02684591).

  • 254.
    Akbar, Muhammad Usman
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik, Avdelningen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Larsson, Måns
    Eigenvision, Malmö, Sweden.
    Blystad, Ida
    Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Region Östergötland, Diagnostikcentrum, Röntgenkliniken i Linköping. Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin.
    Eklund, Anders
    Linköpings universitet, Institutionen för medicinsk teknik, Avdelningen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för datavetenskap, Statistik och maskininlärning.
    Brain tumor segmentation using synthetic MR images - A comparison of GANs and diffusion models2024Ingår i: Scientific Data, E-ISSN 2052-4463, Vol. 11, nr 1, artikel-id 259Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Large annotated datasets are required for training deep learning models, but in medical imaging data sharing is often complicated due to ethics, anonymization and data protection legislation. Generative AI models, such as generative adversarial networks (GANs) and diffusion models, can today produce very realistic synthetic images, and can potentially facilitate data sharing. However, in order to share synthetic medical images it must first be demonstrated that they can be used for training different networks with acceptable performance. Here, we therefore comprehensively evaluate four GANs (progressive GAN, StyleGAN 1–3) and a diffusion model for the task of brain tumor segmentation (using two segmentation networks, U-Net and a Swin transformer). Our results show that segmentation networks trained on synthetic images reach Dice scores that are 80%–90% of Dice scores when training with real images, but that memorization of the training images can be a problem for diffusion models if the original dataset is too small. Our conclusion is that sharing synthetic medical images is a viable option to sharing real images, but that further work is required. The trained generative models and the generated synthetic images are shared on AIDA data hub.

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  • 255.
    Akbari, Camilla
    et al.
    Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Dodd, Maja
    Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Stål, Per
    Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden; Karolinska University Hospital, Stockholm, Sweden.
    Nasr, Patrik
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Mag- tarmmedicinska kliniken. Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Ekstedt, Mattias
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Mag- tarmmedicinska kliniken.
    Kechagias, Stergios
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Mag- tarmmedicinska kliniken.
    Vessby, Johan
    Uppsala University Hospital, Uppsala, Sweden.
    Rorsman, Fredrik
    Uppsala University Hospital, Uppsala, Sweden.
    Zhang, Xiao
    Merck & Co., Inc., Rahway, NJ, USA.
    Wang, Tongtong
    Merck & Co., Inc., Rahway, NJ, USA.
    Jemielita, Thomas
    Merck & Co., Inc., Rahway, NJ, USA.
    Fernandes, Gail
    Merck & Co., Inc., Rahway, NJ, USA.
    Engel, Samuel S.
    Merck & Co., Inc., Rahway, NJ, USA.
    Hagström, Hannes
    Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden; Karolinska University Hospital, Stockholm, Sweden.
    Shang, Ying
    Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Long-term major adverse liver outcomes in 1,260 patients with non-cirrhotic NAFLD2024Ingår i: JHEP Reports, ISSN 2589-5559, Vol. 6, nr 2, artikel-id 100915Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background & aims: Long-term studies of the prognosis of NAFLD are scarce. Here, we investigated the risk of major adverse liver outcomes (MALO) in a large cohort of patients with NAFLD.

    Methods: We conducted a cohort study with data from Swedish university hospitals. Patients (n = 1,260) with NAFLD without cirrhosis were diagnosed through biopsy or radiology, and had fibrosis estimated through vibration-controlled transient elastography, biopsy, or FIB-4 score between 1974 and 2020 and followed up through 2020. Each patient was matched on age, sex, and municipality with up to 10 reference individuals from the general population (n = 12,529). MALO were ascertained from Swedish national registers. The rate of events was estimated by Cox regression.

    Results: MALO occurred in 111 (8.8%, incidence rate = 5.9/1,000 person-years) patients with NAFLD and 197 (1.6%, incidence rate = 1.0/1,000 person-years) reference individuals during a median follow up of 13 years. The rate of MALO was higher in patients with NAFLD (hazard ratio = 6.6; 95% CI = 5.2-8.5). The risk of MALO was highly associated with the stage of fibrosis at diagnosis. In the biopsy subcohort (72% of total sample), there was no difference in risk between patients with and without non-alcoholic steatohepatitis. The 20-year cumulative incidences of MALO were 2% for the reference population, 3% for patients with F0, and 35% for F3. Prognostic information from biopsy was comparable to FIB-4 (C-indices around 0.73 vs. 0.72 at 10 years).

    Conclusions: This study provides updated information on the natural history of NAFLD, showing a high rate of progression to cirrhosis in F3 and a similar prognostic capacity of non-invasive tests to liver biopsy.

    Impact and implications: Several implications for clinical care and future research may be noted based on these results. First, the risk estimates for cirrhosis development are important when communicating risk to patients and deciding on clinical monitoring and treatment. Estimates can also be used in updated health-economic evaluations, and for regulatory agencies. Second, our results again highlight the low predictive information obtained from ascertaining NASHstatus by histology and call for more objective means by which to define NASH. Such methods may include artificial intelligence-supported digital pathology. We highlight that NASH is most likely the causal factor for fibrosis progression in NAFLD, but the subjective definition makes the prognostic value of a histological NASH diagnosis of limited value. Third, the finding that prognostic information from biopsy and the very simple Fibrosis-4 score were comparable is important as it may lead to fewer biopsies and further move the field towards non-invasive means by which to define fibrosis and, importantly, use non-invasive tests as outcomes in clinical trials. However, all modalities had modest discriminatory capacity and new risk stratification systems are needed in NAFLD. Repeated measures of non-invasive scores may be a potential solution.

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  • 256.
    Akerblom, Sophia
    et al.
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Cervin, Matti
    Lund Univ, Sweden.
    Perrin, Sean
    Lund Univ, Sweden.
    Fischer, Marcelo Rivano
    Skane Univ Hosp, Sweden; Lund Univ, Sweden.
    Gerdle, Björn
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för prevention, rehabilitering och nära vård. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Smärt och rehabiliteringscentrum.
    McCracken, Lance M.
    Uppsala Univ, Sweden.
    A Network Analysis of Clinical Variables in Chronic Pain: A Study from the Swedish Quality Registry for Pain Rehabilitation (SQRP)2021Ingår i: Pain medicine, ISSN 1526-2375, E-ISSN 1526-4637, Vol. 22, nr 7, s. 1591-1602Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. Efforts to identify specific variables that impact most on outcomes from interdisciplinary pain rehabilitation are challenged by the complexity of chronic pain. Methods to manage this complexity are needed. The purpose of the study was to determine the network structure entailed in a set of self-reported variables, examine change, and look at potential predictors of outcome, from a network perspective. Methods. In this study we apply network analysis to a large sample of people seeking interdisciplinary pain treatment (N = 2,241). Variables analyzed include pain intensity, pain interference, extent of pain, depression, anxiety, insomnia, and psychological variables from cognitive behavioral models of chronic pain. Results. We found that Acceptance, Pain Interference, and Depression were key, "central," variables in the pretreatment network. Interestingly, there were few changes in the overall network configuration following treatment, specifically with respect to which variables appear most central relative to each other. On the other hand, Catastrophizing, Depression, Anxiety, and Pain Interference each became less central over time. Changes in Life Control, Acceptance, and Anxiety were most strongly related to changes in the remainder of the network as a whole. Finally, no network differences were found between treatment responders and non-responders. Conclusions. This study highlights potential future targets for pain treatment. Further application of a network approach to interdisciplinary pain rehabilitation data is recommended. Going forward, it may be better to next do this in a more comprehensive theoretically guided fashion, and ideographically, to detect unique individual differences in potential treatment processes.

  • 257.
    Akeroyd, Michael A.
    et al.
    MRC, England.
    Arlinger, Stig
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Bentler, Ruth A.
    University of Iowa, IA 52242 USA.
    Boothroyd, Arthur
    San Diego State University, CA 92182 USA.
    Dillier, Norbert
    University of Zurich, Switzerland.
    Dreschler, Wouter A.
    University of Amsterdam, Netherlands.
    Gagne, Jean-Pierre
    University of Montreal, Canada.
    Lutman, Mark
    University of Southampton, England.
    Wouters, Jan
    Katholieke University of Leuven, Belgium.
    Wong, Lena
    University of Hong Kong, Peoples R China.
    Kollmeier, Birger
    Carl von Ossietzky University of Oldenburg, Germany; Carl von Ossietzky University of Oldenburg, Germany; HorTechnical gGmbH, Germany.
    International Collegium of Rehabilitative Audiology (ICRA) recommendations for the construction of multilingual speech tests ICRA Working Group on Multilingual Speech Tests2015Ingår i: International Journal of Audiology, ISSN 1499-2027, E-ISSN 1708-8186, Vol. 54, s. 17-22Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To provide guidelines for the development of two types of closed-set speech-perception tests that can be applied and interpreted in the same way across languages. The guidelines cover the digit triplet and the matrix sentence tests that are most commonly used to test speech recognition in noise. They were developed by a working group on Multilingual Speech Tests of the International Collegium of Rehabilitative Audiology (ICRA). Design: The recommendations are based on reviews of existing evaluations of the digit triplet and matrix tests as well as on the research experience of members of the ICRA Working Group. They represent the results of a consensus process. Results: The resulting recommendations deal with: Test design and word selection; Talker characteristics; Audio recording and stimulus preparation; Masking noise; Test administration; and Test validation. Conclusions: By following these guidelines for the development of any new test of this kind, clinicians and researchers working in any language will be able to perform tests whose results can be compared and combined in cross-language studies.

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  • 258.
    Akerstrom, Finn
    et al.
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Hutter, Julie
    Kerckhoff Heart & Thorax Ctr, Germany.
    Charitakis, Emmanouil
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärtcentrum, Kardiologiska kliniken US.
    Tabrizi, Fariborz
    Arrhythm Ctr, Sweden.
    Asaad, Fahd
    Karolinska Univ Hosp, Sweden.
    Bastani, Hamid
    Karolinska Univ Hosp, Sweden.
    Bourke, Tara
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Braunschweig, Frieder
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Drca, Nikola
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Englund, Anders
    Arrhythm Ctr, Sweden.
    Friberg, Leif
    Karolinska Inst, Sweden.
    Insulander, Per
    Karolinska Inst, Sweden.
    Jonsson, Anders Hassel
    Linköpings universitet, Institutionen för hälsa, medicin och vård. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärtcentrum, Kardiologiska kliniken US.
    Kenneback, Goran
    Karolinska Univ Hosp, Sweden.
    Paul-Nordin, Astrid
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Sadigh, Bita
    Karolinska Univ Hosp, Sweden.
    Saluveer, Ott
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Saygi, Serkan
    Karolinska Univ Hosp, Sweden.
    Schwieler, Jonas
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Svennberg, Emma
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Tapanainen, Jari
    Danderyd Hosp, Sweden.
    Turkmen, Yusuf
    Karolinska Univ Hosp, Sweden.
    Jensen-Urstad, Mats
    Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Association between catheter ablation of atrial fibrillation and mortality or stroke2024Ingår i: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 110, s. 163-169Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective Catheter ablation of atrial fibrillation effectively reduces symptomatic burden. However, its long-term effect on mortality and stroke is unclear. We investigated if patients with atrial fibrillation who undergo catheter ablation have lower risk for all-cause mortality or stroke than patients who are managed medically. Methods We retrospectively included 5628 consecutive patients who underwent first-time catheter ablation for atrial fibrillation between 2008 and 2018 at three major Swedish electrophysiology units. Control individuals with an atrial fibrillation diagnosis but without previous stroke were selected from the Swedish National Patient Register, resulting in a control group of 48 676 patients. Propensity score matching was performed to produce two cohorts of equal size (n=3955) with similar baseline characteristics. The primary endpoint was a composite of all-cause mortality or stroke. Results Patients who underwent catheter ablation were healthier (mean CHA(2)DS(2)-VASc score 1.4 +/- 1.4 vs 1.6 +/- 1.5, p<0.001), had a higher median income (288 vs 212 1000 Swedish krona [KSEK]/year, p<0.001) and had more frequently received university education (45.1% vs 28.9%, p<0.001). Mean follow-up was 4.5 +/- 2.8 years. After propensity score matching, catheter ablation was associated with lower risk for the combined primary endpoint (HR 0.58, 95% CI 0.48 to 0.69). The result was mainly driven by a decrease in all-cause mortality (HR 0.51, 95% CI 0.41 to 0.63), with stroke reduction showing a trend in favour of catheter ablation (HR 0.75, 95% CI 0.53 to 1.07). Conclusions Catheter ablation of atrial fibrillation was associated with a reduction in the primary endpoint of all-cause mortality or stroke. This result was driven by a marked reduction in all-cause mortality.

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  • 259.
    Akesson, Karin
    et al.
    Ryhov County Hospital, Sweden; Jonköping County Council, Sweden; University of Jonköping, Sweden.
    Hanberger, Lena
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten.
    Samuelsson, Ulf
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    The influence of age, gender, insulin dose, BMI, and blood pressure on metabolic control in young patients with type 1 diabetes2015Ingår i: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 16, nr 8, s. 581-586Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    ObjectiveTo explore the relationship between certain clinical variables and metabolic HbA1c at diagnosis correlated to HbA1c at follow-up (p less than 0.001). There was a clear gender difference regarding HbA1c. Girls had higher values both at diagnosis and at follow-up (p less than 0.001). Girls also had lower BMI and pH at diagnosis than boys (p less than 0.001). In contrast, girls with the highest body mass index (BMI) at follow-up had higher mean HbA1c at follow-up in 2010 (p less than 0.001). Having a mother and/or a father with high BMI implied higher HbA1c at diagnosis (p less than 0.003). ConclusionsHbA1c at diagnosis seems to predict metabolic control years later. There is a gender difference at diagnosis as female patients have higher HbA1c than males at diagnosis as well as at follow up. As metabolic control is very much correlated to complications there is a need to early identify patients at risk of poor metabolic control. Even though we do not know whether a high HbA1c level is mainly due to severity of the disease or to behavioral patterns, new ways to treat and support these children, especially girls, are needed.

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  • 260.
    Akhtar, Zubair
    et al.
    Univ New South Wales, Australia; Icddr B, Bangladesh; Univ New South Wales, Australia.
    Gotberg, Matthias
    Lund Univ, Sweden.
    Erlinge, David
    Lund Univ, Sweden.
    Christiansen, Evald H.
    Aarhus Univ Hosp, Denmark.
    Oldroyd, Keith G.
    Univ Glasgow, Scotland.
    Motovska, Zuzana
    Charles Univ Prague, Czech Republic; Univ Hosp Kralovske Vinohrady, Czech Republic.
    Erglis, Andrejs
    Univ Latvia, Latvia.
    Hlinomaz, Ota
    St Anne Univ Hosp, Czech Republic; Masaryk Univ, Czech Republic.
    Jakobsen, Lars
    Aarhus Univ Hosp, Denmark.
    Engstrom, Thomas
    Univ Copenhagen, Denmark.
    Jensen, Lisette O.
    Odense Univ Hosp, Denmark.
    Fallesen, Christian O.
    Odense Univ Hosp, Denmark.
    Jensen, Svend E.
    Aalborg Univ Hosp, Denmark; Aalborg Univ, Denmark.
    Angeras, Oskar
    Sahlgrens Univ Hosp, Sweden; Gothenburg Univ, Sweden.
    Calais, Fredrik
    Orebro Univ, Sweden.
    Karegren, Amra
    Vastmanlands Sjukhus Vasteras, Sweden.
    Lauermann, Jörg
    Linköpings universitet, Institutionen för hälsa, medicin och vård. Linköpings universitet, Medicinska fakulteten. Reg Jonkoping Cty, Sweden.
    Mokhtari, Arash
    Lund Univ, Sweden.
    Nilsson, Johan
    Umea Univ, Sweden.
    Persson, Jonas
    Karolinska Inst, Sweden.
    Islam, Abu K. M. M.
    Natl Inst Cardiovasc Dis, Bangladesh.
    Rahman, Afzalur
    Natl Inst Cardiovasc Dis, Bangladesh.
    Malik, Fazila
    Natl Heart Fdn Hosp & Res Inst, Bangladesh.
    Choudhury, Sohel
    Natl Heart Fdn Hosp & Res Inst, Bangladesh.
    Collier, Timothy
    London Sch Hyg & Trop Med, England.
    Pocock, Stuart J.
    London Sch Hyg & Trop Med, England.
    Pernow, John
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Macintyre, Chandini R.
    Univ New South Wales, Australia; Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Frobert, Ole
    Orebro Univ, Sweden; Arizona State Univ, AZ USA; Aarhus Univ, Denmark; Aarhus Univ Hosp, Denmark; Aarhus Univ Hosp, Denmark.
    Optimal timing of influenza vaccination among patients with acute myocardial infarction - Findings from the IAMI trial2023Ingår i: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 41, nr 48, s. 7159-7165Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Influenza vaccination reduces the risk of adverse cardiovascular events. The IAMI trial randomly assigned 2571 patients with acute myocardial infarction (AMI) to receive influenza vaccine or saline placebo during their index hospital admission. It was conducted at 30 centers in 8 countries from October 1, 2016 to March 1, 2020. In this post-hoc exploratory sub-study, we compare the trial outcomes in patients receiving early season vaccination (n = 1188) and late season vaccination (n = 1344). The primary endpoint was the composite of all-cause death, myocardial infarction (MI), or stent thrombosis at 12 months. The cumulative incidence of the primary and key secondary endpoints by randomized treatment and early or late vaccination was estimated using the Kaplan-Meier method. In the early vaccinated group, the primary composite endpoint occurred in 36 participants (6.0%) assigned to influenza vaccine and 49 (8.4%) assigned to placebo (HR 0.69; 95% CI 0.45 to 1.07), compared to 31 participants (4.7%) assigned to influenza vaccine and 42 (6.2%) assigned to placebo (HR 0.74; 95% CI 0.47 to 1.18) in the late vaccinated group (P = 0.848 for interaction on HR scale at 1 year). We observed similar estimates for the key secondary endpoints of all-cause death and CV death. There was no statistically significant difference in vaccine effectiveness against adverse cardiovascular events by timing of vaccination. The effect of vaccination on all-cause death at one year was more pronounced in the group receiving early vaccination (HR 0.50; 95% CI, 0.29 to 0.86) compared late vaccination group (HR 0.75; 35% CI, 0.40 to 1.40) but there was no statistically significant difference between these groups (Interaction P = 0.335). In conclusion, there is insufficient evidence from the trial to establish whether there is a difference in efficacy between early and late vaccination but regardless of vaccination timing we strongly recommend influenza vaccination in all patients with cardiovascular diseases.

  • 261.
    Aksenova, Vasilisa
    et al.
    Institute of Cytology, Russian Academy of Sciences, Tikhoretsky av., 4, St. Petersburg, Russia; Laboratory of Molecular Pharmacology, Saint-Petersburg Technological Institute, 26 Moskovsky Prospect, St. Petersburg, Russia.
    Turoverova, Lidia
    Institute of Cytology, Russian Academy of Sciences, Tikhoretsky av., 4, St. Petersburg, Russia.
    Khotin, Mikhail
    Institute of Cytology, Russian Academy of Sciences, Tikhoretsky av., 4, St. Petersburg, Russia.
    Magnusson, Karl-Eric
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Medicinska fakulteten.
    Tulchinsky, Eugene
    Department of Cancer Studies and Molecular Medicine, University of Leicester, RKCSB, LRI, Leicester, UK.
    Melino, Gerry
    Laboratory of Molecular Pharmacology, Saint-Petersburg Technological Institute, 26 Moskovsky Prospect, St. Petersburg, Russia; MRC Toxicology Unit, Leicester, UK.
    Pinaev, George P
    Institute of Cytology, Russian Academy of Sciences, Tikhoretsky av., 4, St. Petersburg, Russia.
    Barlev, Nickolai
    Institute of Cytology, Russian Academy of Sciences, Tikhoretsky av., 4, St. Petersburg, Russia; Laboratory of Molecular Pharmacology, Saint-Petersburg Technological Institute, 26 Moskovsky Prospect, St. Petersburg, Russia; Department of Biochemistry, University of Leicester, Lancaster Road, Leicester, UK.
    Tentler, Dmitri
    Institute of Cytology, Russian Academy of Sciences, Tikhoretsky av., 4, St. Petersburg, Russia; Laboratory of Molecular Pharmacology, Saint-Petersburg Technological Institute, 26 Moskovsky Prospect, St. Petersburg, Russia.
    Correction: Actin-binding protein alpha-actinin 4 (ACTN4) is a transcriptional co-activator of RelA/p65 sub-unit of NF-kB (vol 4, pg 362, 2013)2018Ingår i: Oncotarget, E-ISSN 1949-2553, Vol. 9, nr 76, s. 34450-34450Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    [This corrects the article DOI: 10.18632/oncotarget.901.].

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  • 262.
    Aktaa, Suleman
    et al.
    Univ Leeds, England; Univ Leeds, England; Leeds Teaching Hosp NHS Trust, England.
    Gencer, Baris
    Geneva Univ Hosp, Switzerland; Univ Bern, Switzerland.
    Arbelo, Elena
    Univ Barcelona, Spain; Inst Invest August Pi i Sunyer IDIBAPS, Spain; Ctr Invest Biomed Enfermedades Cardiovasc CIBERCV, Spain.
    Davos, Constantinos H.
    Acad Athens, Greece.
    Desormais, Ileana
    Dupuytren Univ Hosp, France.
    Hollander, Monika
    Univ Utrecht, Netherlands.
    Abreu, Ana
    Ctr Hosp Univ Lisboa Norte CHULN Lisboa, Portugal.
    Ambrosetti, Marco
    Rivolta Dadda Hosp, Italy.
    Bäck, Maria
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för prevention, rehabilitering och nära vård. Linköpings universitet, Medicinska fakulteten. Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Carballo, David
    Univ Hosp Geneva, Switzerland.
    Crawford, Carolyn
    ESC Patient Forum, France.
    Deaton, Christi
    Univ Cambridge, England.
    Dendale, Paul
    Hasselt Univ, Belgium; Hasselt Univ, Belgium.
    Eijsvogels, Thijs M. H.
    Radboud Univ Nijmegen, Netherlands.
    Galbraith, Mary
    ESC Patient Forum, France.
    Piepoli, Massimo Francesco
    Guglielmo da Saliceto Hosp, Italy; Univ Pof Parma, Italy.
    Salzwedel, Annett
    Univ Potsdam, Germany.
    Smulders, Yvo
    Amsterdam UMC, Netherlands.
    Wilhelm, Matthias
    Univ Bern, Switzerland.
    Biondi-Zoccai, Giuseppe
    Sapienza Univ Rome, Italy; Mediterranea Cardioctr, Italy.
    Mach, Francois
    Geneva Univ Hosp, Switzerland.
    Visseren, Frank L. J.
    Univ Utrecht, Netherlands.
    Gale, Chris P.
    Univ Leeds, England; Univ Leeds, England; Leeds Teaching Hosp NHS Trust, England.
    European Society of Cardiology Quality Indicators for Cardiovascular Disease Prevention: developed by the Working Group for Cardiovascular Disease Prevention Quality Indicators in collaboration with the European Association for Preventive Cardiology of the European Society of Cardiology2022Ingår i: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 23, nr 7, s. 1060-1071Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims To develop a set of quality indicators (QIs) for the evaluation of the care and outcomes for atherosclerotic cardiovascular disease (ASCVD) prevention. Methods and results The Quality Indicator Committee of the European Society of Cardiology (ESC) formed the Working Group for Cardiovascular Disease Prevention Quality Indicators in collaboration with Task Force members of the 2021 ESC Guidelines on Cardiovascular Disease Prevention in Clinical Practice and the European Association of Preventive Cardiology (EAPC). We followed the ESC methodology for QI development, which involved (i) the identification of the key domains of care for ASCVD prevention by constructing a conceptual framework of care, (ii) the development of candidate QIs by conducting a systematic review of the literature, (iii) the selection of the final set of QIs using a modified Delphi method, and (iv) the evaluation of the feasibility of the developed QIs. In total, 17 main and 14 secondary QIs were selected across six domains of care for ASCVD prevention: (i) structural framework, (ii) risk assessment, (iii) care for people at risk for ASCVD, (iv) care for patients with established ASCVD, (v) patient education and experience, and (vi) outcomes. Conclusion We present the 2021 ESC QIs for Cardiovascular Disease Prevention, which have been co-constructed with EAPC using the ESC methodology for QI development. These indicators are supported by evidence from the literature, underpinned by expert consensus and aligned with the 2021 ESC Guidelines on Cardiovascular Disease Prevention in Clinical Practice to offer a mechanism for the evaluation of ASCVD prevention care and outcomes.

  • 263.
    Akyurek, Levent M.
    et al.
    Sahlgrens Univ Hosp, Sweden.
    Hussein, Aziz
    Sahlgrens Univ Hosp, Sweden.
    Nicholson, Andrew G.
    Imperial Coll, England; Imperial Coll, England.
    Mauritz, Nils-Johan
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten. Department of Nephrology, Jönköping, Region Jönköping County, Sweden.
    Molne, Johan
    Sahlgrens Univ Hosp, Sweden.
    Pulmonary manifestations of systemic karyomegaly2020Ingår i: RESPIRATORY MEDICINE CASE REPORTS, ISSN 2213-0071, Vol. 29, artikel-id 101032Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Over 40 years ago, abnormal enlargement of the nucleus of tubular epithelial cells was reported in a rare distinct hereditary chronic interstitial nephritis, karyomegalic interstitial nephritis (KIN). Here, we report the second case of systemic karyomegaly with pulmonary manifestations and present a detailed characterization of the karyomegalic cells in lung parenchyma. A 59-year-old woman who was diagnosed with KIN developed renal failure and eventually received a renal transplant later evaluated for chronic and progressive restrictive lung disease. The KIN diagnosis prompted us to carefully examine her lung parenchyma. Karyomegalic cells were identified in the alveolar epithelium, interstitium, as well as, in the vascular wall. Viral serological and biochemical blood analyses were negative. We consider that the pulmonary manifestations of karyomegaly expands the differential diagnosis of interstitial lung disease in patients with KIN.

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  • 264.
    Al Abri, Seif
    et al.
    Minist Hlth, Oman.
    Kasaeva, Thereza
    Who Global TB Programme, Switzerland.
    Migliori, Giovanni Battista
    Ist Clin Sci Maugeri IRCCS, Italy.
    Goletti, Delia
    Natl Inst Infect Dis Lazzaro Spallanzani IRCCS, Italy; ESCMID Study Grp Mycobacteria, Switzerland.
    Zenner, Dominik
    IOM, Belgium.
    Denholm, Justin
    Royal Melbourne Hosp, Australia; Victorian TB Programme, Australia.
    Al Maani, Amal
    Royal Hosp, Oman; Minist Hlth, Oman.
    Cirillo, Daniela Maria
    San Rafaele Sci Inst, Italy.
    Schön, Thomas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för inflammation och infektion. Linköpings universitet, Medicinska fakulteten. Kalmar Cty Hosp, Sweden.
    Lillebaek, Troels
    Univ Copenhagen, Denmark.
    Al-Jardani, Amina
    Minist Hlth, Oman.
    Go, Un-Yeong
    Int TB Res Ctr, South Korea.
    Dias, Hannah Monica
    WHO Global TB Programme Unit Policy Strategy and In, Switzerland.
    Tiberi, Simon
    Barts Hlth NHS Trust, England; Queen Mary Univ London, England.
    Al Yaquobi, Fatma
    Minist Hlth, Oman.
    Khamis, Faryal Ali
    Minist Hlth, Oman.
    Kurup, Padmamohan
    Muscat Governorate, Oman.
    Wilson, Michael
    Zero TB Initiat, South Africa.
    Memish, Ziad
    Alfaisal Univ, Saudi Arabia; Emory Univ, GA 30322 USA.
    Al Maqbali, Ali
    North Bathinah Governorate, Oman.
    Akhtar, Muhammad
    WHO MENA Reg TB Programme, Egypt.
    Wejse, Christian
    Univ Aarhus, Denmark; ESCMID Study Grp Travel and Migrat, Switzerland.
    Petersen, Eskild
    Minist Hlth, Oman; Univ Aarhus, Denmark; ESCMID Emerging Infect Task Force, Switzerland.
    Tools to implement the World Health Organization End TB Strategy: Addressing common challenges in high and low endemic countries2020Ingår i: International Journal of Infectious Diseases, ISSN 1201-9712, E-ISSN 1878-3511, Vol. 92, s. S60-S68Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim: The purpose of this viewpoint is to summarize the advantages and constraints of the tools and strategies available for reducing the annual incidence of tuberculosis (TB) by implementing the World Health Organization (WHO) End TB Strategy and the linked WHO TB Elimination Framework, with special reference to Oman. Methods: The case-study was built based on the presentations and discussions at an international workshop on TB elimination in low incidence countries organized by the Ministry of Health, Oman, which took place from September 5 to September 7, 2019, and supported by the WHO and European Society of Clinical Microbiology and Infectious Diseases (ESCMID). Results: Existing tools were reviewed, including the screening of migrants for latent TB infection (LTBI) with interferon-gamma release assays, clinical examination for active pulmonary TB (APTB) including chest X-rays, organization of laboratory services, and the existing centres for mandatory health examination of pre-arrival or arriving migrants, including examination for APTB. The need for public-private partnerships to handle the burden of screening arriving migrants for active TB was discussed at length and different models for financing were reviewed. Conclusions: In a country with a high proportion of migrants from high endemic countries, screening for LTBI is of high priority. Molecular typing and the development of public-private partnerships are needed. (C) 2020 Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

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  • 265.
    Alabas, Oras A.
    et al.
    University of Leeds, England.
    Gale, Chris P.
    University of Leeds, England; York Teaching Hospital NHS Fdn Trust, England.
    Hall, Marlous
    University of Leeds, England.
    Rutherford, Mark J.
    University of Leicester, England.
    Szummer, Karolina
    Department Med, Sweden.
    Sederholm Lawesson, Sofia
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US. Linköpings universitet, Medicinska fakulteten.
    Alfredsson, Joakim
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Lindahl, Bertil
    Uppsala University, Sweden; Uppsala University, Sweden.
    Jernberg, Tomas
    Karolinska Institute, Sweden.
    Sex Differences in Treatments, Relative Survival, and Excess Mortality Following Acute Myocardial Infarction: National Cohort Study Using the SWEDEHEART Registry2017Ingår i: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, nr 12, artikel-id e007123Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background-This study assessed sex differences in treatments, all-cause mortality, relative survival, and excess mortality following acute myocardial infarction. Methods and Results-A population-based cohort of all hospitals providing acute myocardial infarction care in Sweden (SWEDEHEART [Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies]) from 2003 to 2013 was included in the analysis. Excess mortality rate ratios (EMRRs), adjusted for clinical characteristics and guideline-indicated treatments after matching by age, sex, and year to background mortality data, were estimated. Although there were no sex differences in all-cause mortality adjusted for age, year of hospitalization, and comorbidities for ST-segment-elevation myocardial infarction (STEMI) and non-STEMI at 1 year (mortality rate ratio: 1.01 [95% confidence interval (CI), 0.96-1.05] and 0.97 [95% CI, 0.95-.99], respectively) and 5 years (mortality rate ratio: 1.03 [95% CI, 0.99-1.07] and 0.97 [95% CI, 0.95-.99], respectively), excess mortality was higher among women compared with men for STEMI and non-STEMI at 1 year (EMRR: 1.89 [95% CI, 1.66-2.16] and 1.20 [95% CI, 1.16-1.24], respectively) and 5 years (EMRR: 1.60 [95% CI, 1.48-1.72] and 1.26 [95% CI, 1.21-1.32], respectively). After further adjustment for the use of guideline-indicated treatments, excess mortality among women with non-STEMI was not significant at 1 year (EMRR: 1.01 [95% CI, 0.97-1.04]) and slightly higher at 5 years (EMRR: 1.07 [95% CI, 1.02-1.12]). For STEMI, adjustment for treatments attenuated the excess mortality for women at 1 year (EMRR: 1.43 [95% CI, 1.26-1.62]) and 5 years (EMRR: 1.31 [95% CI, 1.19-1.43]). Conclusions-Women with acute myocardial infarction did not have statistically different all-cause mortality, but had higher excess mortality compared with men that was attenuated after adjustment for the use of guideline-indicated treatments. This suggests that improved adherence to guideline recommendations for the treatment of acute myocardial infarction may reduce premature cardiovascular death among women.

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  • 266.
    Alalawi, Ahmed
    et al.
    Univ Birmingham, England; Umm Al Qura Univ, Saudi Arabia.
    Evans, David W.
    Univ Birmingham, England.
    Liew, Bernard
    Univ Essex, England.
    Peolsson, Anneli
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för prevention, rehabilitering och nära vård. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Medicincentrum, Arbets- och miljömedicin.
    Heneghan, Nicola
    Univ Birmingham, England.
    Rushton, Alison
    Univ Birmingham, England.
    Peterson, Gunnel
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för prevention, rehabilitering och nära vård. Linköpings universitet, Medicinska fakulteten. Uppsala Univ, Sweden.
    Barbero, Marco
    Univ Appl Sci & Arts Southern Switzerland, Switzerland.
    Falla, Deborah
    Univ Birmingham, England.
    Does Pain Extent Predict Ongoing Pain and Disability in Patients with Chronic Whiplash-Associated Disorders?2022Ingår i: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 11, nr 3, artikel-id 555Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This study investigates whether baseline pain extent, extracted from an electronic pain drawing, is an independent predictive factor of pain and disability measured 1 year and 2 years later in people with chronic WAD. Participants completed questionnaires assessing neck pain intensity, disability via the Neck Disability Index (NDI), psychological features, and work ability. Participants also completed electronic pain drawings from which their pain extent was extracted. A two-step modelling approach was undertaken to identify the crude and adjusted association between pain extent and NDI measured at 1-year and 2-year follow-ups. A total of 205 participants were included in the analysis. The univariate analysis showed that pain extent was significantly associated with the NDI score at the 1-year (p = 0.006, 95% CI: 0.159-0.909) and 2-year (p = 0.029, 0.057-0.914) follow-ups. These associations were not maintained when we introduced perceived disability, psychological health, and work ability into the model after 1 year (p = 0.56, 95%CI: -0.28-0.499) and 2 years (p = 0.401, -0.226-0.544). Pain extent, as an independent factor, was significantly associated with perceived pain and disability in patients with chronic WAD for up to 2 years. This association was masked by neck disability, psychological health, and work ability.

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  • 267.
    Al-Amiry, Bariq
    et al.
    Umea Univ, Sweden.
    Pantelakis, Georgios
    Umea Univ, Sweden.
    Mahmood, Sarwar
    Umea Univ, Sweden.
    Kadum, Bakir
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten.
    Brismar, Torkel B.
    Karolinska Inst, Sweden.
    Sayed-Noor, Arkan S.
    Umea Univ, Sweden.
    Does body mass index affect restoration of femoral offset, leg length and cup positioning after total hip arthroplasty?: A prospective cohort study2019Ingår i: BMC Musculoskeletal Disorders, E-ISSN 1471-2474, BMC MUSCULOSKELETAL DISORDERS, Vol. 20, nr 1, artikel-id 422Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    In obese patients, total hip arthroplasty (THA) can be technically demanding with increased perioperative risks. The aim of this prospective cohort study is to evaluate the effect of body mass index (BMI) on radiological restoration of femoral offset (FO) and leg length as well as acetabular cup positioning.

    Methods

    In this prospective study, patients with unilateral primary osteoarthritis (OA) treated with THA between September 2010 and December 2013 were considered for inclusion. The perioperative plain radiographs were standardised and used to measure the preoperative degree of hip osteoarthritis, postoperative FO, leg length discrepancy (LLD), acetabular component inclination and anteversion.

    Results

    We included 213 patients (74.5% of those considered for inclusion) with a mean BMI of 27.7 (SD 4.5) in the final analysis. The postoperative FO was improper in 55% and the LLD in 15%, while the cup inclination and anteversion were improper in 13 and 23% of patients respectively. A multivariable logistic regression model identified BMI as the only factor that affected LLD. Increased BMI increased the risk of LLD (OR 1.14, 95% CI 1.04 to 1.25). No other factors included in the model affected any of the primary or secondary outcomes.

    Conclusion

    Increased BMI showed a negative effect on restoration of post-THA leg length but not on restoration of FO or positioning of the acetabular cup. Age, gender, OA duration or radiological severity and surgeon’s experience showed no relation to post-THA restoration of FO, leg length or cup positioning.

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  • 268.
    Alarcon, E I
    et al.
    Bio-nanomaterials Chemistry and Engineering Laboratory, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Rm H5229, Ottawa, Canada.
    Vulesevic, B
    Bio-nanomaterials Chemistry and Engineering Laboratory, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Rm H5229, Ottawa, Canada.
    Argawal, A
    Bio-nanomaterials Chemistry and Engineering Laboratory, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Rm H5229, Ottawa, Canada.
    Ross, A
    Bio-nanomaterials Chemistry and Engineering Laboratory, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Rm H5229, Ottawa, Canada.
    Bejjani, P
    Bio-nanomaterials Chemistry and Engineering Laboratory, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Rm H5229, Ottawa, Canada.
    Podrebarac, J
    Bio-nanomaterials Chemistry and Engineering Laboratory, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Rm H5229, Ottawa, Canada.
    Ravichandran, Ranjithkumar
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Phopase, Jaywant
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär fysik. Linköpings universitet, Tekniska fakulteten.
    Suuronen, E J
    Bio-nanomaterials Chemistry and Engineering Laboratory, Division of Cardiac Surgery, University of Ottawa Heart Institute, 40 Ruskin Street, Rm H5229, Ottawa, Canada.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Coloured cornea replacements with anti-infective properties: expanding the safe use of silver nanoparticles in regenerative medicine.2016Ingår i: Nanoscale, ISSN 2040-3364, E-ISSN 2040-3372, Vol. 8, nr 12, s. 6484-6489Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Despite the broad anti-microbial and anti-inflammatory properties of silver nanoparticles (AgNPs), their use in bioengineered corneal replacements or bandage contact lenses has been hindered due to their intense yellow coloration. In this communication, we report the development of a new strategy to pre-stabilize and incorporate AgNPs with different colours into collagen matrices for fabrication of corneal implants and lenses, and assessed their in vitro and in vivo activity.

  • 269.
    Alarcon, Emilio I.
    et al.
    University of Ottawa, Canada; University of Ottawa, Canada; University of Ottawa, Canada.
    Udekwu, Klas I.
    Karolinska Institute, Sweden.
    Noel, Christopher W.
    University of Ottawa, Canada; .
    Gagnon, Luke B. -P.
    University of Ottawa, Canada.
    Taylor, Patrick K.
    University of Ottawa, Canada.
    Vulesevic, Branka
    University of Ottawa, Canada.
    Simpson, Madeline J.
    University of Ottawa, Canada.
    Gkotzis, Spyridon
    Karolinska Institute, Sweden.
    Islam, Mohammed Mirazul
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Karolinska Institute, Sweden.
    Lee, Chyan-Jang
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Sensorvetenskap och Molekylfysik. Linköpings universitet, Tekniska högskolan.
    Richter-Dahlfors, Agneta
    Karolinska Institute, Sweden.
    Mah, Thien-Fah
    University of Ottawa, Canada.
    Suuronen, Erik J.
    University of Ottawa, Canada.
    Scaiano, Juan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. University of Ottawa, Canada.
    Griffith, May
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Karolinska Institute, Sweden.
    Safety and efficacy of composite collagen-silver nanoparticle hydrogels as tissue engineering scaffolds2015Ingår i: Nanoscale, ISSN 2040-3364, E-ISSN 2040-3372, Vol. 7, nr 44, s. 18789-18798Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The increasing number of multidrug resistant bacteria has revitalized interest in seeking alternative sources for controlling bacterial infection. Silver nanoparticles (AgNPs), are amongst the most promising candidates due to their wide microbial spectrum of action. In this work, we report on the safety and efficacy of the incorporation of collagen coated AgNPs into collagen hydrogels for tissue engineering. The resulting hybrid materials at [AgNPs] less than0.4 mu M retained the mechanical properties and biocompatibility for primary human skin fibroblasts and keratinocytes of collagen hydrogels; they also displayed remarkable anti-infective properties against S. aureus, S. epidermidis, E. coli and P. aeruginosa at considerably lower concentrations than silver nitrate. Further, subcutaneous implants of materials containing 0.2 mu M AgNPs in mice showed a reduction in the levels of IL-6 and other inflammation markers (CCL24, sTNFR-2, and TIMP1). Finally, an analysis of silver contents in implanted mice showed that silver accumulation primarily occurred within the tissue surrounding the implant.

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  • 270.
    Albadri, Zeyad
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    AL Bayati, Doua
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Habel, Henrike
    Karolinska Inst, Sweden.
    Jerkovic Gulin, Sandra
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Div Dermatol & Venereol, Sweden.
    Groenhagen, Carina
    Lund Univ, Sweden.
    Seifert, Oliver
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Incidence of Dermatitis Herpetiformis in Sweden 2005 to 2018: A Nationwide Retrospective Cohort Study2023Ingår i: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 103, artikel-id adv13210Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Dermatitis herpetiformis has been investigated in the past; however, only a limited number of studies have reported its incidence based on validated nationwide population-based registries. To address this gap, the aims of this study are to estimate the incidence of dermatitis herpetiformis in Sweden and to validate the National Patient Register (NPR) for diagnosis of dermatitis herpetiformis. A population-based open cohort study was conducted, including all patients diagnosed with dermatitis herpetiformis (International Classification of Diseases 10th revision; ICD-10 code L13.0) in Sweden from 2005 to 2018 (n = 1,724), identified from the NPR. The diagnosis of dermatitis herpetiformis in the NPR was validated using medical records, histopathological and immunopathological data, yielding a positive predictive value (PPV) of 62.5%. The mean annual incidence of dermatitis herpetiformis was 0.93/100,000 (95% confidence interval 0.79-1.08), female to male ratio 1:1, and mean age at diagnosis 60.9 years. In conclusion, this large nationwide cohort study showed a low validity for diagnosis of dermatitis herpetiformis in the NPR, and the adjusted incidence rate of dermatitis herpetiformis in Sweden was estimated to be 0.93/100,000, which is lower than that in previous Swedish studies.

  • 271.
    Albadri, Zeyad
    et al.
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Thorslund, Kristofer
    Karolinska Inst, Sweden.
    Habel, Henrike
    Karolinska Inst, Sweden.
    Seifert, Oliver
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Div Dermatol & Venereol, Sweden.
    Gronhagen, Carina
    Lund Univ, Sweden.
    Increased Risk of Squamous Cell Carcinoma of the Skin and Lymphoma Among 5,739 Patients with Bullous Pemphigoid: A Swedish Nationwide Cohort Study2020Ingår i: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 100, artikel-id adv00289Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Evidence about the association of bullous pemphigoid and the risk of cancer is conflicting. Patients diagnosed with bullous pemphigoid (n = 5,739) between 2005 and 2016 were matched with a control cohort from the general population (n = 17,168) to estimate their overall and specific risk of cancer. The risk of squamous cell cancer of the skin (cSCC) was increased in patients with bullous pemphigoid (hazard ratio (HR) 1.3; 95% confidence interval (CI) 1.1-1.6). The risk of lymphoma within one year after bullous pemphigoid diagnosis was also increased (HR 3.1; 95% CI 1.3-7.6). While overall cancer risk prior to diagnosis of bullous pemphigoid was similar in cases and controls (prevalence odds ratio (POR) 1.0; 95% CI 0.9-1.0), the risk of male genital cancer within one year prior to diagnosis of bullous pemphigoid was lower in cases (POR 0.4; 95% CI 0.2-0.8). Clinicians must be aware of the increased risk of cSCC and lymphoma in patients with bullous pemphigoid.

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  • 272.
    Albanese-ONeill, Anastasia
    et al.
    Univ Florida, FL USA.
    Grimsmann, Julia M.
    Univ Ulm, Germany; German Ctr Diabet Res DZD, Germany.
    Svensson, Ann-Marie
    Ctr Registers Reg Vastra Gotaland, Sweden; Univ Gothenburg, Sweden.
    Miller, Kellee M.
    Jaeb Ctr Hlth Res, FL USA.
    Raile, Klemens
    Charite Univ Med Berlin, Germany.
    Åkesson, Karin
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Cty Hosp Ryhov, Sweden.
    Calhoun, Peter
    Jaeb Ctr Hlth Res, FL USA.
    Biesenbach, Beate
    Kepler Univ, Austria.
    Eeg-Olofsson, Katarina
    Univ Gothenburg, Sweden.
    Holl, Reinhard W.
    Univ Ulm, Germany; German Ctr Diabet Res DZD, Germany.
    Maahs, David M.
    Stanford Diabet Res Ctr, CA USA; Stanford Univ, CA USA.
    Hanas, Ragnar
    NU Hosp Grp, Sweden; Univ Gothenburg, Sweden.
    Changes in HbA1c Between 2011 and 2017 in Germany/Austria, Sweden, and the United States: A Lifespan Perspective2022Ingår i: Diabetes Technology & Therapeutics, ISSN 1520-9156, E-ISSN 1557-8593, Vol. 24, nr 1, s. 32-41Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims: This study assessed hemoglobin A1c (HbA1c) across the lifespan in people with type 1 diabetes (T1D) in Germany/Austria, Sweden, and the United States between 2011 and 2017 to ascertain temporal and age-related trends. Methods: Data from the Diabetes-Patienten-Verlaufsdokumentation (DPV) (n = 25,651 in 2011, n = 29,442 in 2017); Swedish Pediatric Diabetes Quality Registry (SWEDIABKIDS)/National Diabetes Register (NDR), (n = 44,474 in 2011, n = 53,690 in 2017); and T1D Exchange (n = 16,198 in 2011, n = 17,087 in 2017) registries were analyzed by linear regression to compare mean HbA1c overall and by age group. Results: Controlling for age, sex, and T1D duration, HbA1c increased in the United States between 2011 and 2017, decreased in Sweden, and did not change in Germany/Austria. Controlling for sex and T1D duration, mean HbA1c decreased between 2011 and 2017 in all age cohorts in Sweden (P < 0.001). In the United States, HbA1c stayed the same for participants <6 years and 45 to <65 years and increased in all other age groups (P < 0.05). In Germany/Austria, HbA1c stayed the same for participants <6 to <13 years and 18 to <25 years; decreased for participants ages 13 to <18 years (P < 0.01); and increased for participants >= 25 years (P < 0.05). Conclusions: The comparison of international trends in HbA1c makes it possible to identify differences, explore underlying causes, and share quality improvement processes. National quality improvement initiatives are well accepted in Europe but have yet to be implemented systematically in the United States. However, disparities created by the lack of universal access to health care coverage, unequal access to diabetes technologies (e.g., continuous glucose monitoring) regardless of insurance status, and high out-of-pocket cost for the underinsured ultimately limit the potential of quality improvement initiatives.

  • 273.
    Albers, Bianca
    et al.
    Univ Zurich, Switzerland.
    Rapley, Tim
    Northumbria Univ, England; NIHR ARC North East North Cumbria, England.
    Nilsen, Per
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för samhälle och hälsa. Linköpings universitet, Medicinska fakulteten.
    Clack, Lauren
    Univ Zurich, Switzerland; Univ Hosp Zurich, Switzerland.
    Tailoring in implementation science2023Ingår i: FRONTIERS IN HEALTH SERVICES, ISSN 2813-0146, Vol. 3, artikel-id 1233597Artikel i tidskrift (Övrigt vetenskapligt)
  • 274.
    Albertsson-Wikland, Kerstin
    et al.
    University of Gothenburg, Sweden.
    Mårtensson, Anton
    University of Gothenburg, Sweden; Stat Konsultgrp, Sweden.
    Savendahl, Lars
    Karolinska University Hospital, Sweden; Karolinska University Hospital, Sweden.
    Niklasson, Aimon
    University of Gothenburg, Sweden.
    Bang, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Dahlgren, Jovanna
    University of Gothenburg, Sweden.
    Gustafsson, Jan
    Uppsala University, Sweden.
    Kriström, Berit
    Umeå University, Sweden.
    Norgren, Svante
    Karolinska University Hospital, Sweden; Karolinska University Hospital, Sweden.
    Pehrsson, Nils-Gunnar
    Stat Konsultgrp, Sweden.
    Oden, Anders
    Stat Konsultgrp, Sweden; Chalmers, Sweden.
    Mortality Is Not Increased in Recombinant Human Growth Hormone-treated Patients When Adjusting for Birth Characteristics2016Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 101, nr 5, s. 2149-2159Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: This study aimed to investigate whether reported high mortality in childhood recombinant human GH (rhGH)-treated patients was related to birth-characteristics and/or rhGH treatment. Design and Setting: We sought to develop a mortality model of the Swedish general population born between 1973 and 2010, using continuous-hazard functions adjusting for birth characteristics, sex, age intervals, and calendar year to estimate standardized mortality ratio (SMR) and to apply this model to assess expected deaths in Swedish rhGH-treated patients with idiopathic isolated GH deficiency (IGHD), idiopathic short stature (155) or born small for gestational age (SGA). Participants:The general population: Swedish Medical Birth Register (1973-2010: 1 880 668 males; 1 781 131 females) and Cause of Death Register (1985-2010). Intervention Population: Three thousand eight hundred forty-seven patients starting rhGH treatment between 1985 and 2010 and followed in the National GH Register and/or in rhGH trials diagnosed with IGHD (n = 1890), ISS (n = 975), or SGA (n=982). Main Outcome Measures: Death. Results: Using conventional models adjusting for age, sex, and calendar-year, the SMR was 1.43 (95% confidence interval, 0.89-2.19), P = .14, observed/expected deaths 21/14.68. The rhGH population differed (P amp;lt; .001) from the general population regarding birth weight, birth length, and congenital malformations. Application of an Advanced Model: When applying the developed mortality model of the general population, the ratio of observed/expected deaths in rhGH-treated patients was 21/21.99; SMR = 0.955 (0.591-1.456)P = .95. Model Comparison: Expected number of deaths were 14.68 (14.35-14.96) using the conventional model, and 21.99 (21.24-22.81) using the advanced model, P amp;lt; .001, which had at all ages a higher gradient of risk per SD of the model, 24% (range, 18-42%; P amp;lt; .001). Conclusions: Compared with the general Swedish population, the ratio of observed/expected deaths (21/21.99) was not increased in childhood rhGH-treated IGHD, ISS, and SGA patients when applying an advanced sex-specific mortality model adjusting for birth characteristics.

  • 275.
    Albinsson-Stenholm, Erina
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten.
    Bergsen, Johannes
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten.
    Ingues, Simon
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten.
    Vilhelmsson, Nathalie
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten.
    Guldbrand, Hans
    Region Östergötland, Närsjukvården i västra Östergötland, Primärvården i västra länsdelen. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin.
    Nyström, Fredrik H
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen Cityhälsan Centrum, Norrköping.
    Subjects with high fasting insulin also have higher postprandial GLP-1 and glucagon levels than controls with lower insulin2019Ingår i: Nutrition Research, ISSN 0271-5317, E-ISSN 1879-0739, Vol. 72, s. 111-120Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Little is known about postprandial release of serum ghrelin, glucagon, and glucagon-like peptide-1 (GLP-1) in relation with differing fasting insulin levels. We hypothesized that these hormones are affected by insulin resistance, and hence, we compared different postprandial responses of GLP-1, glucagon, and ghrelin in subjects with relatively high (RHI) or relatively low (RLI) fasting insulin levels. The trial was a randomized crossover study with 4 different meal conditions. Fourteen nonobese or obese, healthy, men and 14 women were randomly assigned to the order of supervised intake of a 750 kcal drink with the same protein contents but with 20 energy-percent (E%) or 55 E% from carbohydrates, and the remaining energy from fat. Participants were also randomized to consume the drinks as 1 large beverage or as five 150-kcal portions every 30 minutes. The 28 subjects were divided into 2 equally sized groups based on fasting insulin levels. Statistics were done with general linear mixed model. Fasting insulin levels were 3-fold higher in the group with RHI compared with the RLI group (RHI: 1004 +/- 510 pg/mL, RLI: 324 +/- 123 pg/mL, P amp;lt; .0005). Serum GLP-1 was highest in the RHI group after both single meals and after 5 drinks and following high- and low-carbohydrate meals (both P amp;lt;= .002), and this was the case also for glucagon levels (both P amp;lt;= .018), whereas ghrelin levels did not differ between groups. Thus, subjects with RHI displayed both higher postprandial serum GLP-1 and glucagon than the participants with RLI, suggesting that glucagon could play a role in the advent of dysglycemia by insulin resistance. (C) 2019 Elsevier Inc. All rights reserved.

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  • 276.
    Albonico, Andrea
    et al.
    Human Vision and Eye Movement Laboratory, Departments of Medicine (Neurology), Ophthalmology and Visual Sciences, Psychology, University of British Columbia, Vancouver, Canada.
    Furubacke, Amanda
    Linköpings universitet, Medicinska fakulteten. Human Vision and Eye Movement Laboratory, Departments of Medicine (Neurology), Ophthalmology and Visual Sciences, Psychology, University of British Columbia, Vancouver, Canada.
    Barton, Jason J. S.
    Human Vision and Eye Movement Laboratory, Departments of Medicine (Neurology), Ophthalmology and Visual Sciences, Psychology, University of British Columbia, Vancouver, Canada.
    Oruc, Ipek
    Department of Ophthalmology and Visual Sciences, University of British Columbia, Canada; Program in Neuroscience, University of British Columbia, Canada.
    Perceptual efficiency and the inversion effect for faces, words and houses2018Ingår i: Vision Research, ISSN 0042-6989, E-ISSN 1878-5646, Vol. 153, s. 91-97Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Face and visual word recognition are two key forms of expert visual processing. In the domain of object recognition, it has been suggested that expert processing is characterized by the use of different mechanisms from the ones involved in general object recognition. It has been suggested that one traditional marker of expert processing is the inversion effect. To investigate whether face and word recognition differ from general object recognition, we compared the effect of inversion on the perceptual efficiency of face and visual word recognition as well as on the recognition of a third, non-expert object category, houses. From the comparison of identification contrast thresholds to an ideal observer, we derived the efficiency and equivalent input noise of stimulus processing in both upright and inverted orientations. While efficiency reflects the efficacy in sampling the available information, equivalent input noise is associated with the degradation of the stimulus signal within the visual system. We hypothesized that large inversion effects for efficiency and/or equivalent input noise should characterize expert high-level processes, and asked whether this would be true for both faces and words, but not houses. However, we found that while face recognition efficiency was profoundly reduced by inversion, the efficiency of word and house recognition was minimally influenced by the orientation manipulation. Inversion did not affect equivalent input noise. These results suggest that even though faces and words are both considered expert processes, only the efficiency of the mechanism involved in face recognition is sensitive to orientation.

  • 277.
    Albrecht, Inka
    et al.
    Karolinska Institute, Sweden.
    Wick, Cecilia
    Karolinska Institute, Sweden.
    Hallgren, Asa
    Karolinska Institute, Sweden.
    Tjarnlund, Anna
    Karolinska Institute, Sweden.
    Nagaraju, Kanneboyina
    Childrens National Medical Centre, DC 20010 USA.
    Andrade, Felipe
    Johns Hopkins University, MD 21205 USA.
    Thompson, Kathryn
    Childrens National Medical Centre, DC 20010 USA.
    Coley, William
    Childrens National Medical Centre, DC 20010 USA.
    Phadke, Aditi
    Childrens National Medical Centre, DC 20010 USA.
    Diaz-Gallo, Lina-Marcela
    Karolinska Institute, Sweden.
    Bottai, Matteo
    Karolinska Institute, Sweden.
    Nennesmo, Inger
    Karolinska Institute, Sweden.
    Chemin, Karine
    Karolinska Institute, Sweden.
    Herrath, Jessica
    Karolinska Institute, Sweden.
    Johansson, Karin
    Karolinska Institute, Sweden.
    Wikberg, Anders
    Karolinska Institute, Sweden.
    Jimmy Ytterberg, A.
    Karolinska Institute, Sweden; Karolinska Institute, Sweden.
    Zubarev, Roman A.
    Karolinska Institute, Sweden.
    Danielsson, Olof
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Krystufkova, Olga
    Charles University of Prague, Czech Republic; Charles University of Prague, Czech Republic.
    Vencovsky, Jiri
    Charles University of Prague, Czech Republic; Charles University of Prague, Czech Republic.
    Landegren, Nils
    Karolinska Institute, Sweden; Uppsala University, Sweden.
    Wahren-Herlenius, Marie
    Karolinska Institute, Sweden.
    Padyukov, Leonid
    Karolinska Institute, Sweden.
    Kampe, Olle
    Karolinska Institute, Sweden; Uppsala University, Sweden.
    Lundberg, Ingrid E.
    Karolinska Institute, Sweden.
    Development of autoantibodies against muscle-specific FHL1 in severe inflammatory myopathies2015Ingår i: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, Vol. 125, nr 12, s. 4612-4624Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mutations of the gene encoding four-and-a-half LIM domain 1 (FHL1) are the causative factor of several X-linked hereditary myopathies that are collectively termed FHL1-related myopathies. These disorders are characterized by severe muscle dysfunction and damage. Here, we have shown that patients with idiopathic inflammatory myopathies (IIMs) develop autoimmunity to FHL1, which is a muscle-specific protein. Anti-FHL1 autoantibodies were detected in 25% of IIM patients, while patients with other autoimmune diseases or muscular dystrophies were largely anti-FHL1 negative. Anti-FHL1 reactivity was predictive for muscle atrophy, dysphagia, pronounced muscle fiber damage, and vasculitis. FHL1 showed an altered expression pattern, with focal accumulation in the muscle fibers of autoantibody-positive patients compared with a homogeneous expression in anti-FHL1-negative patients and healthy controls. We determined that FHL1 is a target of the cytotoxic protease granzyme B, indicating that the generation of FHL1 fragments may initiate FHL1 autoimmunity. Moreover, immunization of myositis-prone mice with FHL1 aggravated muscle weakness and increased mortality, suggesting a direct link between anti-FHL1 responses and muscle damage. Together, our findings provide evidence that FHL1 may be involved in the pathogenesis not only of genetic FHL1-related myopathies but also of autoimmune IIM. Importantly, these results indicate that anti-FHL1 autoantibodies in peripheral blood have promising potential as a biomarker to identify a subset of severe IIM.

  • 278.
    Al-Chalabi, Ammar
    et al.
    Kings Coll London, England.
    Andersen, Peter M.
    Umeå University, Sweden.
    Chandran, Siddharthan
    University of Edinburgh, Scotland.
    Chio, Adriano
    University of Torino, Italy.
    Corcia, Philippe
    CHU Tours, France.
    Couratier, Philippe
    CHU Limoges, France.
    Danielsson, Olof
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    de Carvalho, Mamede
    University of Lisbon, Portugal; H Santa Maria CHLN, Portugal.
    Desnuelle, Claude
    CHU Nice, France.
    Grehl, Torsten
    Alfried Krupp Hospital, Germany.
    Grosskreutz, Julian
    Jena University Hospital, Germany.
    Holmoy, Trygve
    Kershus University of Lorenskog, Norway.
    Ingre, Caroline
    Karolinska Institute, Sweden.
    Karlsborg, Merete
    Bispebjerg Hospital, Denmark.
    Kleveland, Grethe
    Sykehuset Innlandet, Norway.
    Christoph Koch, Jan
    University of Medical Gottingen, Germany.
    Koritnik, Blaz
    University of Medical Centre Ljubljana, Slovenia.
    KuzmaKozakiewicz, Magdalena
    Medical University of Warsaw, Poland.
    Laaksovirta, Hannu
    University of Helsinki, Finland.
    Ludolph, Albert
    University of Ulm, Germany.
    McDermott, Christopher
    University of Sheffield, England.
    Meyer, Thomas
    University of Medical Berlin, Germany.
    Mitre Ropero, Bernardo
    Sahlgrens University Hospital, Sweden.
    Mora Pardina, Jesus
    Hospital San Rafael, Spain.
    Nygren, Ingela
    Uppsala University, Sweden.
    Petri, Susanne
    Hannover Medical Sch, Germany.
    Povedano Panades, Monica
    University of Bellvitge, Spain.
    Salachas, Francois
    Hop Salptriere, France.
    Shaw, Pamela
    University of Sheffield, England.
    Silani, Vincenzo
    University of Milan, Italy; University of Milan, Italy.
    Staaf, Gert
    Lund University, Sweden.
    Svenstrup, Kirsten
    Bispebjerg Hospital, Denmark.
    Talbot, Kevin
    University of Oxford, England.
    Tysnes, Ole-Bjorn
    Haukeland University of Sjukehus, Norway.
    Van Damme, Philip
    University of Leuven, Belgium; VIB Centre Brain and Disease Research, Belgium; University Hospital Leuven, Belgium.
    van der Kooi, Anneke
    University of Amsterdam Centre, Netherlands.
    Weber, Markus
    Kantonssp St Gallen, Switzerland.
    Weydt, Patrick
    University of Bonn, Germany.
    Wolf, Joachim
    Diakonissen Hospital, Germany.
    Hardiman, Orla
    Trinity Coll Dublin, Ireland.
    van den Berg, Leonard H.
    University of Medical Centre Utrecht, Netherlands.
    July 2017 ENCALS statement on edaravone2017Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, ISSN 2167-8421, E-ISSN 2167-9223, Vol. 18, nr 7-8, s. 471-474Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    n/a

  • 279.
    Al-Dury, Nooraldeen
    et al.
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden.
    Rawshani, Araz
    University of Gothenburg, Sweden.
    Israelsson, Johan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten. Kalmar County Hospital, Sweden; Linnaeus University, Sweden.
    Stromsoe, Anneli
    School Health Care and Social Welf, Sweden.
    Aune, Solveig
    Sahlgrens University Hospital, Sweden.
    Agerstrom, Jens
    Linnaeus University, Sweden.
    Karlsson, Thomas
    University of Gothenburg, Sweden.
    Ravn-Fischer, Annica
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden.
    Herlitz, Johan
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden; University of Boras, Sweden.
    Characteristics and outcome among 14,933 adult cases of in-hospital cardiac arrest: A nationwide study with the emphasis on gender and age2017Ingår i: American Journal of Emergency Medicine, ISSN 0735-6757, E-ISSN 1532-8171, Vol. 35, nr 12, s. 1839-1844Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim: To investigate characteristics and outcome among patients suffering in-hospital cardiac arrest (IHCA) with the emphasis on gender and age. Methods: Using the Swedish Register of Cardiopulmonary Resuscitation, we analyzed associations between gender, age and co-morbidities, etiology, management, 30-day survival and cerebral function among survivors in 14,933 cases of IHCA. Age was divided into three ordered categories: young (18-49 years), middle-aged (5064 years) and older (65 years and above). Comparisons between men and women were age adjusted. Results: The mean age was 72.7 years and women were significantly older than men. Renal dysfunction was the most prevalent co-morbidity. Myocardial infarction/ischemia was the most common condition preceding IHCA, with men having 27% higher odds of having MI as the underlying etiology. A shockable rhythm was found in 31.8% of patients, with men having 52% higher odds of being found in VT/VF. After adjusting for various confounders, it was found that men had a 10% lower chance than women of surviving to 30 days. Older individuals were managed less aggressively than younger patients. Increasing age was associated with lower 30-day survival but not with poorer cerebral function among survivors. Conclusion: When adjusting for various confounders, it was found that men had a 10% lower chance than women of surviving to 30 days after in-hospital cardiac arrest. Older individuals were managed less aggressively than younger patients, despite a lower chance of survival. Higher age was, however, not associated with poorer cerebral function among survivors. (C) 2017 Elsevier Inc. All rights reserved.

  • 280.
    Alegroth, Emil
    et al.
    Blekinge Inst Technol, Sweden.
    Borch Petersen, Eline
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Logopedi, Audiologi och Otorhinolaryngologi. Linköpings universitet, Medicinska fakulteten.
    Tinnerholm, John
    Linköpings universitet, Institutionen för datavetenskap, Programvara och system. Linköpings universitet, Tekniska fakulteten.
    A Failed attempt at creating Guidelines for Visual GUI Testing: An industrial case study2021Ingår i: 2021 14TH IEEE CONFERENCE ON SOFTWARE TESTING, VERIFICATION AND VALIDATION (ICST 2021), IEEE COMPUTER SOC , 2021, s. 340-350Konferensbidrag (Refereegranskat)
    Abstract [en]

    Software development is governed by guidelines that aim to improve the codes qualities, such as maintainability. However, whilst coding guidelines are commonplace for software, guidelines for testware are much less common. In particular, for GUI-based tests driven with image recognition, also referred to as Visual GUI Testing (VGT), explicit coding guidelines are missing. In this industrial case study, performed at the Swedish defence contractor Saab AB, we propose a set of coding guidelines for VGT and evaluate their impact on test scripts for an industrial, safety-critical system. To study the guidelines effect on maintenance costs, five representative manual test cases are each translated with and without the proposed guidelines in the two VGT tools SikuliX and EyeAutomate. As such, 20 test scripts were developed, with a combined development cost of more than 100 man-hours. Three of the tests are then maintained by one researcher and two practitioners for another version of the system and costs measured to evaluate return on investment. This analysis is complemented with observations and interviews to elicit practitioners perceptions and experiences with VGT. Results show that scripts developed with the guidelines had higher maintenance costs than scripts developed without guide-lines. This is supported by qualitative results that many of the guidelines are considered inappropriate, superfluous or unnecessary due to the inherent properties of the scripts, e.g. their natural small size, linear flows, natural separation of concerns, and more. We conclude that there are differences between VGT scripts and software that prohibit direct translation of guidelines between the two. As such, we consider our study as a failure but argue that several lessons can be drawn from our results to guide future research into guidelines for VGT and GUI-based test automation.

  • 281.
    Alehagen, Urban
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten.
    Aaseth, Jan
    Innlandet Hosp Trust, Norway.
    Alexander, Jan
    Norwegian Inst Publ Hlth, Norway.
    Brismar, Kerstin
    Karolinska Univ Hosp, Sweden.
    Larsson, Anders
    Uppsala Univ, Sweden.
    Selenium and Coenzyme Q10 Supplementation Improves Renal Function in Elderly Deficient in Selenium: Observational Results and Results from a Subgroup Analysis of a Prospective Randomised Double-Blind Placebo-Controlled Trial2020Ingår i: Nutrients, E-ISSN 2072-6643, Vol. 12, nr 12, artikel-id 3780Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A low selenium intake is found in European countries, and is associated with increased cardiovascular mortality. There is an association between selenium level and the severity of kidney disease. An association between inflammation and selenium intake is also reported. The coenzyme Q10 level is decreased in kidney disease. The aim of this study was to examine a possible association between selenium and renal function in an elderly population low in selenium and coenzyme Q(10), and the impact of intervention with selenium and coenzyme Q(10) on the renal function. The association between selenium status and creatinine was studied in 589 elderly persons. In 215 of these (mean age 71 years) a randomised double-blind placebo-controlled prospective trial with selenium yeast (200 mu g/day) and coenzyme Q(10) (200 mg/day) (n = 117) or placebo (n = 98) was conducted. Renal function was determined using measures of glomerular function at the start and after 48 months. The follow-up time was 5.1 years. All individuals were low on selenium (mean 67 mu g/L (SD 16.8)). The changes in renal function were evaluated by measurement of creatinine, cystatin-C, and the use of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) algorithm, and by the use of T-tests, repeated measures of variance and ANCOVA analyses. An association between low selenium status and impaired renal function was observed. Intervention causes a significantly lower serum creatinine, and cystatin-C concentration in the active treatment group compared with those on placebo (p = 0.0002 and p = 0.001 resp.). The evaluation with CKD-EPI based on both creatinine and cystatin-C showed a corresponding significant difference (p < 0.0001). All validations showed corresponding significant differences. In individuals with a deficiency of selenium and coenzyme Q(10,) low selenium status is related to impaired renal function, and thus supplementation with selenium and coenzyme Q10 results in significantly improved renal function as seen from creatinine and cystatin-C and through the CKD-EPI algorithm. The explanation could be related to positive effects on inflammation and oxidative stress as a result of the supplementation.

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  • 282.
    Alehagen, Urban
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Aaseth, Jan
    Innlandet Hosp Trust, Norway; Inland Norway Univ Appl Sci, Norway.
    Alexander, Jan
    Norwegian Inst Publ Hlth, Norway.
    Johansson, Peter
    Linköpings universitet, Institutionen för samhälls- och välfärdsstudier, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i östra Östergötland, Medicinkliniken ViN. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin.
    Still reduced cardiovascular mortality 12 years after supplementation with selenium and coenzyme Q10 for four years: A validation of previous 10-year follow-up results of a prospective randomized double-blind placebo-controlled trial in elderly2018Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 13, nr 4, artikel-id e0193120Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Selenium and coenzyme Q10 are both necessary for optimal cell function in the body. The intake of selenium is low in Europe, and the endogenous production of coenzyme Q10 decreases as age increases. Therefore, an intervention trial using selenium and coenzyme Q10 for four years as a dietary supplement was performed. The main publication reported reduced cardiovascular mortality as a result of the intervention. In the present sub-study the objective was to determine whether reduced cardiovascular (CV) mortality persisted after 12 years, in the supplemented population or in subgroups with diabetes, hypertension, ischemic heart disease or reduced functional capacity due to impaired cardiac function. Methods From a rural municipality in Sweden, four hundred forty-three healthy elderly individuals were included. All cardiovascular mortality was registered, and no participant was lost to the follow-up. Based on death certificates and autopsy results, mortality was registered. Findings After 12 years a significantly reduced CV mortality could be seen in those supplemented with selenium and coenzyme Q10, with a CV mortality of 28.1% in the active treatment group, and 38.7% in the placebo group. A multivariate Cox regression analysis demonstrated a reduced CV mortality risk in the active treatment group (HR: 0.59; 95% CI 0.42-0.81; P = 0.001). In those with ischemic heart disease, diabetes, hypertension and impaired functional capacity we demonstrated a significantly reduced CV mortality risk. Conclusions This is a 12-year follow-up of a group of healthy elderly participants that were supplemented with selenium and coenzyme Q10 for four years. Even after twelve years we observed a significantly reduced risk for CV mortality in this group, as well as in subgroups of patients with diabetes, hypertension, ischemic heart disease or impaired functional capacity. The results thus validate the results obtained in the 10-year evaluation. The protective action was not confined to the intervention period, but persisted during the follow-up period. The mechanisms behind this effect remain to be fully elucidated, although various effects on cardiac function, oxidative stress, fibrosis and inflammation have previously been identified. Since this was a small study, the observations should be regarded as hypothesis-generating.

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  • 283.
    Alehagen, Urban
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten.
    Aaseth, Jan
    Innlandet Hosp Trust, Norway.
    Alexander, Jan
    Norwegian Inst Publ Hlth, Norway.
    Johansson, Peter
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för omvårdnad och reproduktiv hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i östra Östergötland, Medicinkliniken ViN.
    Larsson, Anders
    Uppsala Univ, Sweden.
    Supplemental selenium and coenzyme Q10 reduce glycation along with cardiovascular mortality in an elderly population with low selenium status - A four-year, prospective, randomised, double-blind placebo-controlled trial2020Ingår i: Journal of Trace Elements in Medicine and Biology, ISSN 0946-672X, E-ISSN 1878-3252, Vol. 61, artikel-id UNSP 126541Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: A low intake of selenium has been shown to increase the risk of cardiovascular mortality, and supplementation of selenium and coenzyme Q10 influences this. The mechanism behind is unclear although effects on inflammation, oxidative stress and microRNA expression have been reported. Fructosamine, a marker of long-term glycaemic control, is also a marker of increased risk of heart disease and death, even in non-diabetics. Objective: To analyse the impact of selenium and coenzyme Q10 supplementation on the concentration of fructosamine. Also, the relation between pre-intervention serum selenium concentration and the effect on fructosamine of the intervention was studied. Methods: Fructosamine plasma concentration was determined in 219 participants after six and 42 months of intervention with selenium yeast (200 mu g/day) and coenzyme Q10 (200 mg/ day) (n = 118 of which 20 had diabetes at inclusion), or placebo (n = 101 of which 18 had diabetes at inclusion). Pre-intervention, the serum selenium levels were 67 mu g/L (active treatment group: 66.6 mu g/L; placebo group: 67.4 mu g/L), corresponding to an estimated intake of 35 mu g/day. Changes in concentrations of fructosamine following intervention were assessed by the use of T-tests, repeated measures of variance, and ANCOVA analyses. Results: Post-intervention selenium concentrations were 210 mu g/L in the active group and 72 mu g/L in the placebo group. A lower concentration of fructosamine could be seen as a result of the intervention in the total population (P = 0.001) in both the males (P = 0.04) and in the females (P = 0.01) in the non-diabetic population (P = 0.002), and in both the younger ( < 76 years) (P = 0.01) and the older (>= 6 years) participants (P = 0.03). No difference could be demonstrated in fructosamine concentration in the diabetic patients, but the total sample was small (n = 38). In subjects with a low pre-intervention level of serum selenium the intervention gave a more pronounced decrease in fructosamine compared with those with a higher baseline selenium level. Conclusion: A significantly lower concentration of fructosamine was observed in the elderly community-living participants supplemented with selenium and coenzyme Q10 for 42 months compared to those on the placebo. As oxidative mechanisms are involved in the glycation of proteins, less glycoxidation could be a result of the supplementation of selenium and coenzyme Q10, which could have contributed to lower cardiac mortality and less inflammation, as has earlier been reported.

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  • 284.
    Alehagen, Urban
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Aaseth, Jan
    Innlandet Hosp, Norway; Hedmark Univ Coll, Norway.
    Alexander, Jan
    Norwegian Inst Publ Hlth, Norway.
    Svensson, Erland
    Swedish Def Res Agcy, Linkoping, Sweden.
    Johansson, Peter
    Linköpings universitet, Institutionen för samhälls- och välfärdsstudier, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i östra Östergötland, Medicinkliniken ViN.
    Larsson, Anders
    Uppsala Univ, Sweden.
    Less fibrosis in elderly subjects supplemented with selenium and coenzyme Q10A mechanism behind reduced cardiovascular mortality?2018Ingår i: Biofactors, ISSN 0951-6433, E-ISSN 1872-8081, Vol. 44, nr 2, s. 137-147Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: In an intervention study where 221 healthy elderly persons received selenium and coenzyme Q10 as a dietary supplement, and 222 received placebo for 4 years we observed improved cardiac function and reduced cardiovascular mortality. As fibrosis is central in the aging process, we investigated the effect of the intervention on biomarkers of fibrogenic activity in a subanalysis of this intervention study. Material and Methods: In the present subanalysis 122 actively treated individuals and 101 controls, the effect of the treatment on eight biomarkers of fibrogenic activity were assessed. These biomarkers were: Cathepsin S, Endostatin, Galectin 3, Growth Differentiation Factor-15 (GDF-15), Matrix Metalloproteinases 1 and 9, Tissue Inhibitor of Metalloproteinases 1 (TIMP 1) and Suppression of Tumorigenicity 2 (ST-2). Blood concentrations of these biomarkers after 6 and 42 months were analyzed by the use of T-tests, repeated measures of variance, and factor analyses. Results: Compared with placebo, in those receiving supplementation with selenium and coenzyme Q10, all biomarkers except ST2 showed significant decreased concentrations in blood. The changes in concentrations, that is, effects sizes as given by partial eta(2) caused by the intervention were considered small to medium. Conclusion: The significantly decreased biomarker concentrations in those on active treatment with selenium and coenzyme Q10 compared with those on placebo after 36 months of intervention presumably reflect less fibrogenic activity as a result of the intervention. These observations might indicate that reduced fibrosis precedes the reported improvement in cardiac function, thereby explaining some of the positive clinical effects caused by the intervention. (c) 2017 BioFactors, 44(2):137-147, 2018

  • 285.
    Alehagen, Urban
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Aaseth, Jan
    Research Department, Innlandet Hospital Trust and Hedmark University College, Norway.
    Johansson, Peter
    Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten.
    Less increase of copeptin and MR-proADM due to intervention with selenium and coenzyme Q10 combined: Results from a 4-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens.2015Ingår i: Biofactors, ISSN 0951-6433, E-ISSN 1872-8081, Vol. 41, nr 6, s. 443-452Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Intervention with selenium and coenzyme Q10 have recently been found to reduce mortality and increase cardiac function. The mechanisms behind these effects are unclear. As selenium and coenzyme Q10 is involved in the anti-oxidative defence, the present study aimed to evaluate effects of selenium and coenzyme Q10 on copeptin and adrenomedullin as oxidative stress biomarkers. Therefore 437 elderly individuals were included and given intervention for 4 years. Clinical examination and blood samples were undertaken at start and after 18 and 48 months. Evaluations of copeptin and MR-proADM changes were performed using repeated measures of variance. Cardiovascular mortality was evaluated using a 10-year-period of follow-up, and presented in Kaplan-Meier plots. A significant increase in copeptin level could be seen in the placebo group during the intervention period (from 9.4 pmol/L to 15.3 pmol/L), compared to the active treatment group. The difference between the groups was confirmed in the repeated measurement of variance analyses (P = 0.031) with less copeptin increase in the active treatment group. Furthermore, active treatment appeared to protect against cardiovascular death both in those with high and with low copeptin levels at inclusion. Less increase of MR-proADM could also be seen during the intervention in the active treatment group compared to controls (P=0.026). Both in those having an MR-proADM level above or below median level, significantly less cardiovascular mortality could be seen in the active treatment group (P=0.0001, and P=0.04 respectively). In conclusion supplementation with selenium and coenzyme Q10 during four years resulted in less concentration of both copeptin and MR-proADM. A cardioprotective effect of the supplementation was registered, irrespective of the initial levels of these biomarkers, and this protection was recognized also after 10 years of observation. © 2015 BioFactors, 41(6):443-452, 2015.

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  • 286.
    Alehagen, Urban
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Aaseth, Jan
    Innlandet Hospital Trust, Norway; Hedmark University of Coll, Norway.
    Johansson, Peter
    Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten.
    Reduced Cardiovascular Mortality 10 Years after Supplementation with Selenium and Coenzyme Q10 for Four Years: Follow-Up Results of a Prospective Randomized Double-Blind Placebo-Controlled Trial in Elderly Citizens2015Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 10, nr 12, s. e0141641-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Selenium and coenzyme Q10 are important antioxidants in the body. As the intake of selenium is low in Europe, and the endogenous production of coenzyme Q10 decreases as age increases, an intervention trial using selenium and coenzyme Q10 for four years was performed. As previously reported, the intervention was accompanied by reduced cardiovascular mortality. The objective of the present study was to analyze cardiovascular mortality for up to 10 years after intervention, to evaluate if mortality differed in subgroups differentiated by gender, diabetes, ischemic heart disease (IHD), and functional class. Methods Four-hundred forty-three healthy elderly individuals were included from a rural municipality in Sweden. All cardiovascular mortality was registered, and no participant was lost to the follow-up. Based on death certificates and autopsy results mortality was registered. Findings Significantly reduced cardiovascular mortality could be seen in those on selenium and coenzyme Q10 intervention. A multivariate Cox regression analysis demonstrated a reduced cardiovascular mortality risk in the active treatment group (HR: 0.51; 95% CI 0.36-0.74; P = 0.0003). The reduced mortality could be seen to persist during the 10-year period. Subgroup analysis showed positive effects in both genders. An equally positive risk reduction could be seen in those with ischemic heart disease (HR: 0.51; 95% CI 0.27-0.97; P = 0.04), but also in the different functional classes. Conclusions In a 10-year follow-up of a group of healthy elderly participants given four years of intervention with selenium and coenzyme Q10, significantly reduced cardiovascular mortality was observed. The protective action was not confined to the intervention period, but persisted during the follow-up period. The mechanism explaining the persistency remains to be elucidated. Since this was a small study, the observations should be regarded as hypothesis-generating.

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  • 287.
    Alehagen, Urban
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten.
    Aaseth, Jan
    Innlandet Hosp Trust, Norway.
    Larsson, Anders
    Uppsala Univ, Sweden.
    Alexander, Jan
    Norwegian Inst Publ Hlth, Norway.
    Decreased Concentration of Fibroblast Growth Factor 23 (FGF-23) as a Result of Supplementation with Selenium and Coenzyme Q(10) in an Elderly Swedish Population: A Sub-Analysis2022Ingår i: Cells, E-ISSN 2073-4409, Vol. 11, nr 3, artikel-id 509Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There is a reduced intake of selenium in many countries due to low levels of selenium in the soil. This results in an increased cardiovascular risk. Fibroblast growth factor 23 (FGF-23) is active mainly in the metabolism of vitamin D and phosphorus. However, there are indications that FGF-23 may also provide information both on cardiovascular function and prognosis. The aim of the study was to evaluate the effect of supplementation with selenium and coenzyme Q(10) on the FGF-23 concentration in an elderly population with low concentrations of both selenium and coenzyme Q(10) and in which the supplementation improved cardiac function and mortality. In a randomised double-blind placebo-controlled trial, FGF-23 was measured in 219 individuals at the start and after 48 months. Selenium yeast (200 mu g/day) and coenzyme Q(10) (200 mg/day) (n = 118) or placebo (n = 101) were given as a dietary supplement. The intervention time was 48 months. t-Tests, repeated measures of variance, and ANCOVA analyses were used to evaluate the differences in FGF-23 concentration. Following supplementation with selenium and coenzyme Q(10), a significantly lower level of FGF-23 could be seen (p = 0.01). Applying 10 years of follow-up, those who later died a cardiovascular death had a significantly higher FGF-23 concentration after 48 months compared with those who survived (p = 0.036), and a significantly lower FGF-23 concentration could be seen in those with a normal renal function compared to those with an impaired renal function (p = 0.027). Supplementation with selenium and coenzyme Q(10) to an elderly community-living population low in both substances prevented an increase of FGF-23 and also provided a reduced cardiovascular risk.

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  • 288.
    Alehagen, Urban
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten.
    Aaseth, Jan
    Innlandet Hosp Trust, Norway.
    Lindahl, Tomas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi och farmakologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Larsson, Anders
    Uppsala Univ, Sweden.
    Alexander, Jan
    Norwegian Inst Publ Hlth, Norway.
    Dietary Supplementation with Selenium and Coenzyme Q(10) Prevents Increase in Plasma D-Dimer While Lowering Cardiovascular Mortality in an Elderly Swedish Population2021Ingår i: Nutrients, E-ISSN 2072-6643, Vol. 13, nr 4, artikel-id 1344Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A low intake of selenium is associated with increased cardiovascular mortality. This could be reduced by supplementation with selenium and coenzyme Q(10). D-dimer, a fragment of fibrin mirroring fibrinolysis, is a biomarker of thromboembolism, increased inflammation, endothelial dysfunction and is associated with cardiovascular mortality in ischemic heart disease. The objective was to examine the impact of selenium and coenzyme Q(10) on the level of D-dimer, and its relationship to cardiovascular mortality. D-dimer was measured in 213 individuals at the start and after 48 months of a randomised double-blind placebo-controlled trial with selenium yeast (200 mu g/day) and coenzyme Q(10) (200 mg/day) (n = 106) or placebo (n = 107). The follow-up time was 4.9 years. All included individuals were low in selenium (mean 67 mu g/L, SD 16.8). The differences in D-dimer concentration were evaluated by the use of T-tests, repeated measures of variance and ANCOVA analyses. At the end, a significantly lower D-dimer concentration was observed in the active treatment group in comparison with those on placebo (p = 0.006). Although D-dimer values at baseline were weakly associated with high-sensitive CRP, while being more strongly associated with soluble tumour necrosis factor receptor 1 and sP-selectin, controlling for these in the analysis there was an independent effect on D-dimer. In participants with a D-dimer level above median at baseline, the supplementation resulted in significantly lower cardiovascular mortality compared to those on placebo (p = 0.014). All results were validated with a persisting significant difference between the two groups. Therefore, supplementation with selenium and coenzyme Q(10) in a group of elderly low in selenium and coenzyme Q(10) prevented an increase in D-dimer and reduced the risk of cardiovascular mortality in comparison with the placebo group. The obtained results also illustrate important associations between inflammation, endothelial function and cardiovascular risk.

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  • 289.
    Alehagen, Urban
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten.
    Alexander, J.
    Norwegian Inst Publ Hlth, Norway.
    Aaseth, J.
    Innlandet Hosp Trust, Norway.
    Larsson, A.
    Uppsala Univ, Sweden.
    Lindahl, Tomas
    Linköpings universitet, Institutionen för biomedicinska och kliniska vetenskaper, Avdelningen för klinisk kemi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk kemi.
    Significant decrease of von Willebrand factor and plasminogen activator inhibitor-1 by providing supplementation with selenium and coenzyme Q10 to an elderly population with a low selenium status2020Ingår i: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215, Vol. 59, s. 3581-3590Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose Endothelial dysfunction and inflammation are conditions which fuel atherosclerosis and ischaemic heart disease. We have previously reported reduced cardiovascular (CV) mortality following supplementation with selenium and coenzyme Q10 to 443 elderly individuals with low selenium status (mean 67 mu g/L) for 4 years. Here, we wanted to evaluate a possible association between the supplementation and the plasma concentrations of the von Willebrand factor (vWf), and the plasminogen activator inhibitor-1 (PAI-1), as they, besides other functions, are also strongly associated with endothelial function. Methods In this sub-study, 308 individuals (active substance: 157, placebo: 151) were included. Blood samples were drawn after 6 and 36 months and vWf and PAI-1 were determined in plasma by ELISA. Changes in concentrations of the biomarkers were evaluated by the use of T tests, repeated measures of variance, and ANCOVA analyses. Results The active treatment group presented a lower level of vWf after 36 months compared with the placebo group (1.08 U/mL vs. 5.10 U/mL; p = 0.0007). The results were validated through the repeated measures of variance evaluation. The PAI-1 levels showed an equally significant decrease in the active group (26.2 ng/mL vs. 49.2 ng/mL; p = 0.0002) and were also validated through repeated measures of variance evaluation. Conclusion In this sub-study on elderly receiving selenium and coenzyme Q10, or placebo we found significantly lower levels of vWf and PAI-1 in the active treatment group as compared to the placebo group. We interpret this as a better endothelial function because of the intervention, which accords with a previous finding of reduced CV mortality.

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  • 290.
    Alehagen, Urban
    et al.
    Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin.
    Alexander, Jan
    Norwegian Institute Public Heatlh, Norway; Norwegian University of Life Science NMBU, Norway.
    Aaseth, Jan
    Innlandet Hospital Trust, Norway; Hedmark University of Coll, Norway.
    Supplementation with Selenium and Coenzyme Q10 Reduces Cardiovascular Mortality in Elderly with Low Selenium Status. A Secondary Analysis of a Randomised Clinical Trial2016Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 11, nr 7, artikel-id e0157541Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Selenium is needed by all living cells in order to ensure the optimal function of several enzyme systems. However, the selenium content in the soil in Europe is generally low. Previous reports indicate that a dietary supplement of selenium could reduce cardiovascular disease but mainly in populations in low selenium areas. The objective of this secondary analysis of a previous randomised double-blind placebo-controlled trial from our group was to determine whether the effects on cardiovascular mortality of supplementation with a fixed dose of selenium and coenzyme Q10 combined during a four-year intervention were dependent on the basal level of selenium. Methods In 668 healthy elderly individuals from a municipality in Sweden, serum selenium concentration was measured. Of these, 219 individuals received daily supplementation with selenium (200 mu g Se as selenized yeast) and coenzyme Q10 (200 mg) combined for four years. The remaining participants (n = 449) received either placebo (n = 222) or no treatment (n = 227). All cardiovascular mortality was registered. No participant was lost during a median follow-up of 5.2 years. Based on death certificates and autopsy results, all mortality was registered. Findings The mean serum selenium concentration among participants at baseline was low, 67.1 mu g/L. Based on the distribution of selenium concentration at baseline, the supplemented group was divided into three groups; amp;lt;65 mu g/L, 65-85 mu g/L, and amp;gt;85 mu g/L (45 and 90 percentiles) and the remaining participants were distributed accordingly. Among the non-treated participants, lower cardiovascular mortality was found in the high selenium group as compared with the low selenium group (13.0% vs. 24.1%; P = 0.04). In the group with the lowest selenium basal concentration, those receiving placebo or no supplementation had a mortality of 24.1%, while mortality was 12.1% in the group receiving the active substance, which was an absolute risk reduction of 12%. In the middle selenium concentration group a mortality of 14.0% in the non-treated group, and 6.0% in the actively treated group could be demonstrated; thus, there was an absolute risk reduction of 8.0%. In the group with a serum concentration of amp;gt;85 mu g/L, a cardiovascular mortality of 17.5% in the non-treated group, and 13.0% in the actively treated group was observed. No significant risk reduction by supplementation could thus be found in this group. Conclusions In this evaluation of healthy elderly Swedish municipality members, two important results could be reported. Firstly, a low mean serum selenium concentration, 67 mu g/L, was found among the participants, and the cardiovascular mortality was higher in the subgroup with the lower selenium concentrations amp;lt; 65 mu g/L in comparison with those having a selenium concentration amp;gt; 85 mu g/L. Secondly, supplementation was cardio-protective in those with a low selenium concentration, amp;lt;= 85 at inclusion. In those with serum seleniumamp;gt; 85 mu g/L and no apparent deficiency, there was no effect of supplementation. This is a small study, but it presents interesting data, and more research on the impact of lower selenium intake than recommended is therefore warranted.

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  • 291.
    Alehagen, Urban
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Alexander, Jan
    Norwegian Inst Publ Hlth, Norway.
    Aaseth, Jan
    Innlandet Hosp Trust, Norway; Inland Norway Univ Appl Sci, Norway.
    Larsson, Anders
    Uppsala Univ, Sweden.
    Decrease in inflammatory biomarker concentration by intervention with selenium and coenzyme Q10: a subanalysis of osteopontin, osteoprotergerin, TNFr1, TNFr2 and TWEAK2019Ingår i: Journal of Inflammation, E-ISSN 1476-9255, Vol. 16, artikel-id 5Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Inflammation is central to the pathogenesis of many diseases. Supplementation with selenium and coenzyme Q10 has been shown to reduce cardiovascular mortality, and increase cardiac function in elderly persons with a low intake of selenium. There are indications that one of the mechanisms of this positive effect is a decrease in inflammation. Methods: Osteopontin, osteoprotegerin, sTNF receptor 1, sTNF receptor 2 and the tumor necrosis factor-like weak inducer of apoptosis called TWEAK, were determined in plasma after 6 months and 42months in 219 community-living elderly persons, of whom 119 received supplements of selenium (200g/day) and coenzyme Q10 (200mg/day), and 101 received a placebo. Repeated measures of variance were used to evaluate the levels, and the results were validated through ANCOVA analyses with adjustments for important covariates. Results: Significantly lower concentrations of four of the five biomarkers for inflammation were observed as a result of the intervention with the supplements. Only TWEAK did not show significant differences. Conclusion: In this sub-analysis of the intervention with selenium and coenzyme Q10 or placebo in an elderly community-living population, biomarkers for inflammation were evaluated. A significantly lower concentration in four of the five biomarkers tested could be demonstrated as a result of the supplementation, indicating a robust effect on the inflammatory system. The decrease in inflammation could be one of the mechanisms behind the positive clinical results on reduced cardiovascular morbidity and mortality reported earlier as a result of the intervention. The study is small and should be regarded as hypothesis-generating, but nonetheless adds important data about mechanisms presently known to increase the risk of clinical effects such as reduced cardiovascular mortality, increased cardiac function and better health-related quality of life scoring, as previously demonstrated in the active treatment group.

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  • 292.
    Alehagen, Urban
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten.
    Alexander, Jan
    Norwegian Inst Publ Hlth, Norway.
    Aaseth, Jan O.
    Innlandet Hosp Trust, Norway; Inland Norway Univ Appl Sci, Norway.
    Larsson, Anders
    Uppsala Univ, Sweden.
    Opstad, Trine B.
    Oslo Univ Hosp Ulleval, Norway; Univ Oslo, Norway.
    Supplementation with selenium and coenzyme Q<sub>10</sub> in an elderly Swedish population low in selenium - positive effects on thyroid hormones, cardiovascular mortality, and quality of life2024Ingår i: BMC Medicine, E-ISSN 1741-7015, Vol. 22, nr 1, artikel-id 191Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Selenium-dependent deiodinases play a central role in thyroid hormone regulation and metabolism. In many European countries, insufficient selenium intake may consequently lead to adverse effects on thyroid function. In this randomised placebo-controlled double-blind study, we examined the effect of supplementation with selenium and coenzyme Q(10) on thyroid hormonal status, cardiovascular (CV) mortality and health-related quality of life (Hr-QoL). Methods Free T3, free T4, reverse T3, and TSH were determined in 414 individuals at baseline, and the effect of selenium yeast (200 mu g/day) and coenzyme Q(10) (200 mg/day) supplementation on hormone concentrations, CV mortality and Hr-QoL was evaluated after 48 months using Short Form 36 (SF-36). Pre-intervention plasma selenium was low, mean 67 mu g/L, corresponding to an estimated intake of 35 mu g/day. Changes in concentrations of thyroid hormones following the intervention were assessed using T-tests, repeated measures of variance, and ANCOVA analyses. Results In the total population, the group with the lowest selenium concentration at baseline presented with significantly higher levels of TSH and lower levels of fT3 as compared to subjects with the highest selenium concentration. Supplementation with selenium and coenzyme Q(10) for 4 years significantly increased fT3 and rT3, decreased fT4, and diminished the increase in TSH levels compared with placebo treatment (p = 0.03, all). In the placebo group, TSH and fT4 values above the median were associated with an increase in 10-year CV mortality, as compared with the mortality rate among those with TSH and fT4 below the median (p &lt; 0.04, both), with no difference in mortality rate according to TSH and fT4 levels in the active intervention group. Similarly, TSH &gt; median and fT3 &lt; median were associated with a decline in mental Hr-QoL measures vs. TSH &lt; and fT3 &gt; median in the placebo group during 4 years of follow-up, but this was wiped out in the active group. Conclusions Supplementation with selenium and coenzyme Q(10) had a beneficial effect on thyroid hormones with respect to CV mortality and Hr-QoL outcomes. The initial deficient selenium status was associated with an impaired thyroid function and the changes in thyroid hormone levels can be explained by increased activity of deiodinases. We conclude that a substantial part of the elderly study population might suffer from suboptimal thyroidal function with adverse clinical implications due to selenium deficiency. Trial registration This study was registered at ClinicalTrials.gov and has the identifier NCT01443780. Since it was not mandatory to register at the time the study began, the study has been registered retrospectively.

  • 293.
    Alehagen, Urban
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten.
    Alexander, Jan
    Norwegian Inst Publ Hlth, Norway.
    Aaseth, Jan O.
    Innlandet Hosp Trust, Norway; Inland Norway Univ Appl Sci, Norway.
    Larsson, Anders
    Uppsala Univ, Sweden.
    Svensson, Erland
    Swedish Def Res Agcy, Sweden.
    Opstad, Trine B.
    Oslo Univ Hosp Ulleval, Norway; Univ Oslo, Norway.
    Effects of an Intervention with Selenium and Coenzyme Q(10) on Five Selected Age-Related Biomarkers in Elderly Swedes Low in Selenium: Results That Point to an Anti-Ageing Effect-A Sub-Analysis of a Previous Prospective Double-Blind Placebo-Controlled Randomised Clinical Trial2023Ingår i: Cells, E-ISSN 2073-4409, Vol. 12, nr 13, artikel-id 1773Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Ageing is associated with cardiovascular disease (CVD). As no single biomarker reflects the full ageing process, we aimed to investigate five CVD- and age-related markers and the effects of selenium and coenzyme Q10 intervention to elucidate the mechanisms that may influence the course of ageing. Methods: This is a sub-study of a previous prospective double-blind placebo-controlled randomized clinical trial that included 441 subjects low in selenium (mean age 77, 49% women). The active treatment group (n = 220) received 200 & mu;g/day of selenium and 200 mg/day of coenzyme Q10, combined. Blood samples were collected at inclusion and after 48 months for measurements of the intercellular adhesion molecule (ICAM-1), adiponectin, leptin, stem cell factor (SCF) and osteoprotegerin (OPG), using ELISAs. Repeated measures of variance and ANCOVA evaluations were used to compare the two groups. In order to better understand and reduce the complexity of the relationship between the biomarkers and age, factor analyses and structural equation modelling (SEM) were performed, and a structural model is presented. Results: Correlation analyses of biomarker values at inclusion in relation to age, and relevant markers related to inflammation, endothelial dysfunction and fibrosis, demonstrated the biomarkers association with these pathological processes; however, only ICAM1 and adiponectin were directly correlated with age. SEM analyses showed, however, that the biomarkers ICAM-1, adiponectin, SCF and OPG, but not leptin, all had significant associations with age and formed two independent structural factors, both significantly related to age. While no difference was observed at inclusion, the biomarkers were differently changed in the active treatment and placebo groups (decreasing and increasing levels, respectively) at 48 months (p & LE; 0.02 in all, adjusted), and in the SEM model, they showed an anti-ageing impact. Conclusions: Supplementation with selenium/Q10 influenced the analysed biomarkers in ways indicating an anti-ageing effect, and by applying SEM methodology, the interrelationships between two independent structural factors and age were validated.

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  • 294.
    Alehagen, Urban
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Benson, Lina
    Karolinska Institute, Sweden.
    Edner, Magnus
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Dahlström, Ulf
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Lund, Lars H.
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Association Between Use of Statins and Mortality in Patients With Heart Failure and Ejection Fraction of greater than= 50%2015Ingår i: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 8, nr 5, s. 862-870Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background The pathophysiology of heart failure with preserved ejection fraction is poorly understood, but may involve a systemic proinflammatory state. Therefore, statins might improve outcomes in patients with heart failure with preserved ejection fraction defined as 50%. Methods and Results Of 46 959 unique patients in the prospective Swedish Heart Failure Registry, 9140 patients had heart failure and ejection fraction 50% (age 7711 years, 54.0% women), and of these, 3427 (37.5%) were treated with statins. Propensity scores for statin treatment were derived from 40 baseline variables. The association between statin use and primary (all-cause mortality) and secondary (separately, cardiovascular mortality, and combined all-cause mortality or cardiovascular hospitalization) end points was assessed with Cox regressions in a population matched 1:1 based on age and propensity score. In the matched population, 1-year survival was 85.1% for statin-treated versus 80.9% for untreated patients (hazard ratio, 0.80; 95% confidence interval, 0.72-0.89; Pless than0.001). Statins were also associated with reduced cardiovascular death (hazard ratio, 0.86; 95% confidence interval, 0.75-0.98; P=0.026) and composite all-cause mortality or cardiovascular hospitalization (hazard ratio, 0.89; 95% confidence interval, 0.82-0.96; P=0.003). Conclusions In heart failure with ejection fraction 50%, the use of statins was associated with improved outcomes. The mechanisms should be evaluated and the effects tested in a randomized trial.

  • 295.
    Alehagen, Urban
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Benson, Lina
    Karolinska Institute, Sweden.
    Edner, Magnus
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Dahlström, Ulf
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Lund, Lars H.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Association Between Use of Statins and Outcomes in Heart Failure With Reduced Ejection Fraction Prospective Propensity Score Matched Cohort Study of 21 864 Patients in the Swedish Heart Failure Registry2015Ingår i: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 8, nr 2, s. 252-260Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background-In heart failure (HF) with reduced ejection fraction, randomized trials of statins did not demonstrate improved outcomes. However, randomized trials may not always be generalizable. The aim was to determine whether statins are associated with improved outcomes in an unselected nationwide population of patients with HF with reduced ejection fraction overall and in relation to ischemic heart disease (IHD). Methods and Results-In the Swedish Heart Failure Registry, 21 864 patients with HF with reduced ejection fraction (age +/- SD, 72+/-12 years; 29% women), of whom 10 345 (47%) were treated with statins, were studied. Propensity scores for statin use were derived from 42 baseline variables. The associations between statin use and outcomes were assessed with Cox regressions in a population matched 1: 1 based on propensity score and age and in the overall population with adjustment for propensity score and age. The primary outcome was all-cause mortality; secondary outcomes were cardiovascular mortality; HF hospitalization; and combined all-cause mortality or cardiovascular hospitalization. Survival at 1 year in the matched population was 83% for statin-treated versus 79% for untreated patients (hazard ratio, 0.81; 95% confidence interval, 0.76-0.86; Pless than0.001). In the unmatched population, 1-year survival was 85% for statin-treated versus 79% for untreated patients, hazard ratio after adjustment for propensity score and age was 0.84 (95% confidence interval, 0.80-0.89; Pless than0.001). No examined baseline variables interacted with statin use except for IHD (P=0.001), with a hazard ratio of 0.76 (95% confidence interval, 0.70-0.82, Pless than0.001) with IHD and 0.95 (95% confidence interval, 0.85-1.07; P=0.430 without IHD. Statin use was also associated with reduced risk for all 3 secondary outcomes. Conclusions-In an unselected nationwide population of patients with HF with reduced ejection fraction, statins were associated with improved outcomes, specifically in the presence of IHD. This contrasts with previous randomized controlled trials. Additional randomized controlled trials with more generalized inclusion or focused on IHD may be warranted.

  • 296.
    Alehagen, Urban
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Johansson, Peter
    Linköpings universitet, Institutionen för samhälls- och välfärdsstudier, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin.
    Aaseth, Jan
    Innlandet Hospital Trust, Norway; Hedmark University of Appl Science, Norway.
    Alexander, Jan
    Norwegian Institute Public Heatlh, Norway; Norwegian University of Life Science NMBU, Norway.
    Brismar, Kerstin
    Karolinska University Hospital, Sweden.
    Increase in insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 1 after supplementation with selenium and coenzyme Q10. A prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens2017Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 12, nr 6, artikel-id e0178614Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Insulin-like growth factor-1(IGF-1) has a multitude of effects besides cell growth and metabolism. Reports also indicate anti-inflammatory and antioxidative effects. The concentrations of IGF-1 decrease with age and during inflammation. As selenium and coenzyme Q10 are involved in both the antioxidative defense and the inflammatory response, the present study aimed to examine the effects of supplementation with selenium and coenzyme Q10 on concentrations of IGF-1 and its binding protein IGFBP-1 in a population showing reduced cardiovascular mortality following such supplementation. Methods 215 elderly individuals were included and given the intervention for four years. A clinical examination was performed and blood samples were taken at the start and after 48 months. Evaluations of IGF-1, the age adjusted IGF-1 SD score and IGFBP-1 were performed using group mean values, and repeated measures of variance. Findings After supplementation with selenium and coenzyme Q10, applying group mean evaluations, significantly higher IGF-1 and IGF-1 SD scores could be seen in the active treatment group, whereas a decrease in concentration could be seen of the same biomarkers in the placebo group. Applying the repeated measures of variance evaluations, the same significant increase in concentrations of IGF-1 (F = 68; P amp;gt; 0.0001), IGF-1 SD score (F = 29; P amp;lt; 0.0001) and of IGFBP-1 (F = 6.88; P = 0.009) could be seen, indicating the effect of selenium and coenzyme Q10 also on the expression of IGF-1 as one of the mechanistic effects of the intervention. Conclusion Supplementation with selenium and coenzyme Q10 over four years resulted in increased levels of IGF-1 and the postprandial IGFBP-1, and an increase in the age-corrected IGF-1 SD score, compared with placebo. The effects could be part of the mechanistic explanation behind the surprisingly positive clinical effects on cardiovascular morbidity and mortality reported earlier. However, as the effects of IGF-1 are complex, more research on the result of intervention with selenium and coenzyme Q10 is needed.

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  • 297.
    Alehagen, Urban
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Johansson, Peter
    Linköpings universitet, Institutionen för samhälls- och välfärdsstudier, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i östra Östergötland, Medicinkliniken ViN.
    Aaseth, Jan
    Innlandet Hosp Trust, Norway.
    Alexander, Jan
    Norwegian Inst Publ Hlth, Norway.
    Surowiec, Izabella
    AcureOmics AB, Sweden.
    Lundstedt-Enkel, Katrin
    AcureOmics AB, Sweden.
    Lundstedt, Torbjorn
    AcureOmics AB, Sweden.
    Significant Changes in Metabolic Profiles after Intervention with Selenium and Coenzyme Q10 in an Elderly Population2019Ingår i: BIOMOLECULES, ISSN 2218-273X, Vol. 9, nr 10, artikel-id 553Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Selenium and coenzyme Q10 (SeQ10) are important for normal cellular function. Low selenium intake leads to increased cardiovascular mortality. Intervention with these substances with healthy elderly persons over a period of four years in a double-blind, randomised placebo-controlled prospective study showed reduced cardiovascular mortality, increased cardiac function, and a lower level of NT-proBNP. Therefore, we wanted to evaluate changes in biochemical pathways as a result of the intervention with SeQ10 using metabolic profiling. From a population of 443 healthy elderly individuals that were given 200 µg selenium and 200 mg coenzyme Q10, or placebo daily for four years, we selected nine males on active intervention and nine males on placebo for metabolic profiling in the main study. To confirm the results, two validation studies (study 1 n = 60 males, study 2 n = 37 males) were conducted. Principal component analyses were used on clinical and demographic data to select representative sets of samples for analysis and to divide the samples into batches for analysis. Gas chromatography time-of-flight mass spectrometry-based metabolomics was applied. The metabolite data were evaluated using univariate and multivariate approaches, mainly T-tests and orthogonal projections to latent structures (OPLS) analyses. Out of 95 identified metabolites, 19 were significantly decreased due to the intervention after 18 months of intervention. Significant changes could be seen in the pentose phosphate, the mevalonate, the beta-oxidation and the xanthine oxidase pathways. The intervention also resulted in changes in the urea cycle, and increases in the levels of the precursors to neurotransmitters of the brain. This adds information to previous published results reporting decreased oxidative stress and inflammation. This is the first-time metabolic profiling has been applied to elucidate the mechanisms behind an intervention with SeQ10. The study is small and should be regarded as hypothesis-generating; however, the results are interesting and, therefore, further research in the area is needed.

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  • 298.
    Alehagen, Urban
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Johansson, Peter
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US.
    Aaseth, Jan
    Innlandet Hospital Trust, Norway; Hedmark University of Coll, Norway.
    Alexander, Jan
    Norwegian Institute Public Heatlh, Norway; Norwegian University of Life Science NMBU, Norway.
    Wågsäter, Dick
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten.
    Significant changes in circulating microRNA by dietary supplementation of selenium and coenzyme Q10 in healthy elderly males. A subgroup analysis of a prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens2017Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 12, nr 4, artikel-id e0174880Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Selenium and coenzyme Q10 is essential for important cellular functions. A low selenium intake is reported from many European countries, and the endogenous coenzyme Q10 production is decreasing in the body with increasing age. Supplementation with selenium and coenzyme Q10 in elderly have shown reduced cardiovascular mortality and reduced levels of markers of inflammation. However, microRNA analyses could give important information on the mechanisms behind the clinical effects of supplementation. Methods Out of the 443 healthy elderly participants that were given supplementation with 200 mu g Se/ day as organic selenium yeast tablets, and 200 mg/day of coenzyme Q10 capsules, or placebo for 4 years, 25 participants from each group were randomized and evaluated regarding levels of microRNA. Isolation of RNA from plasma samples and quantitative PCR analysis were performed. Volcano- and principal component analyses (PCA)-plots were used to illustrate the differences in microRNA expression between the intervention, and the placebo groups. Serum selenium concentrations were measured before intervention. Findings On average 145 different microRNAs out of 172 were detected per sample. In the PCA plots two clusters could be identified indicating significant difference in microRNA expression between the two groups. The pre-treatment expression of the microRNAs did not differ between active treatment and the placebo groups. When comparing the post- treatment microRNAs in the active and the placebo groups, 70 microRNAs exhibited significant differences in expression, also after adjustment for multiple measurements. For the 20 microRNAs with the greatest difference in expression the difference was up to more than 4 fold and with a P-value that were less than 4.4e(-8). Conclusions Significant differences were found in expression of more than 100 different microRNAs with up to 4 fold differences as a result of the intervention of selenium and coenzyme Q10 combined. The changes in microRNA could be a part of mechanisms underlying the clinical effects earlier reported that reduced cardiovascular mortality, gave better cardiac function, and showed less signs of inflammation and oxdative stress following the intervention. However, more research is needed to understand biological mechanisms of the protective effects of selenium and Q10 supplementation.

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  • 299.
    Alehagen, Urban
    et al.
    Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US. Linköpings universitet, Medicinska fakulteten. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin.
    Johansson, Peter
    Region Östergötland, Hjärt- och Medicincentrum, Kardiologiska kliniken US. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten.
    Björnstedt, Mikael
    Division of Pathology F42, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Rosén, Anders
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Post, Claes
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Aaseth, Jan
    Research Department, Innlandet Hospital Trust and Hedmark University College, Norway.
    Relatively high mortality risk in elderly Swedish subjects with low selenium status2016Ingår i: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 70, nr 1, s. 91-96Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background/Objectives: 

    The daily dietary intake of selenium (Se), an essential trace element, is still low in Sweden in spite of decades of nutritional information campaigns and the effect of this on the public health is presently not well known. The objective of this study was to determine the serum Se levels in an elderly Swedish population and to analyze whether a low Se status had any influence on mortality.

    Subjects/Methods: 

    Six-hundred sixty-eight (n=668) elderly participants were invited from a municipality and evaluated in an observational study. Individuals were followed for 6.8 years and Se levels were re-evaluated in 98 individuals after 48 months. Clinical examination of all individuals included functional classification, echocardiography, electrocardiogram and serum Se measurement. All mortality was registered and endpoints of mortality were assessed by Kaplan–Meier plots, and Cox proportional hazard ratios adjusted for potential confounding factors were calculated.

    Results: 

    The mean serum Se level of the study population (n=668) was 67.1 μg/l, corresponding to relatively low Se intake. After adjustment for male gender, smoking, ischemic heart disease, diabetes, chronic obstructive pulmonary disease and impaired heart function, persons with serum Se in the lowest quartile had 43% (95% confidence interval (CI): 1.02–2.00) and 56% (95% CI: 1.03–2.36) increased risk for all-cause and cardiovascular mortality, respectively. The result was not driven by inflammatory effects on Se concentration in serum.

    Conclusion: 

    The mean serum Se concentration in an elderly Swedish population was 67.1 μg/l, which is below the physiological saturation level for several selenoprotein enzymes. This result may suggest the value of modest Se supplementation in order to improve the health of the Swedish population.

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  • 300.
    Alehagen, Urban
    et al.
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för diagnostik och specialistmedicin. Linköpings universitet, Medicinska fakulteten.
    Johansson, Peter
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för omvårdnad och reproduktiv hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i östra Östergötland, Medicinkliniken ViN.
    Svensson, Erland
    Swedish Def Res Agcy, Sweden.
    Aaseth, Jan
    Innlandet Hosp Trust, Norway; Inland Norway Univ Appl Sci, Norway.
    Alexander, Jan
    Norwegian Inst Publ Hlth, Norway.
    Improved cardiovascular health by supplementation with selenium and coenzyme Q10: applying structural equation modelling (SEM) to clinical outcomes and biomarkers to explore underlying mechanisms in a prospective randomized double-blind placebo-controlled intervention project in Sweden2022Ingår i: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215, Vol. 61, nr 6, s. 3135-3148Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose Selenium and coenzyme Q10 have synergistic antioxidant functions. In a four-year supplemental trial in elderly Swedes with a low selenium status, we found improved cardiac function, less cardiac wall tension and reduced cardiovascular mortality up to 12 years of follow-up. Here we briefly review the main results, including those from studies on biomarkers related to cardiovascular risk that were subsequently conducted. In an effort, to explain underlying mechanisms, we conducted a structured analysis of the inter-relationship between biomarkers. Methods Selenium yeast (200 mu g/day) and coenzyme Q10 (200 mg/ day), or placebo was given to 443 elderly community-living persons, for 48 months. Structural Equation Modelling (SEM) was used to investigate the statistical inter-relationships between biomarkers related to inflammation, oxidative stress, insulin-like growth factor 1, expression of microRNA, fibrosis, and endothelial dysfunction and their impact on the clinical effects. The main study was registered at Clinicaltrials.gov at 30th of September 2011, and has the identifier NCT01443780. Results In addition to positive clinical effects, the intervention with selenium and coenzyme Q10 was also associated with favourable effects on biomarkers of cardiovascular risk. Using these results in the SEM model, we showed that the weights of the first-order factors inflammation and oxidative stress were high, together forming a second-order factor inflammation/oxidative stress influencing the factors, fibrosis (beta = 0.74; p &lt; 0.001) and myocardium (beta = 0.65; p &lt; 0.001). According to the model, the intervention impacted fibrosis and myocardium through these factors, resulting in improved cardiac function and reduced CV mortality. Conclusion Selenium reduced inflammation and oxidative stress. According to the SEM analysis, these effects reduced fibrosis and improved myocardial function pointing to the importance of supplementation in those low on selenium and coenzyme Q10.

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