Welcome to Hirsla, Landspítali University Hospital research archive

Hirsla is an open access repository, designed as a place to store, index, preserve and redistribute in digital format scholarly work of Landspitali employees. (A/H1N1)

  • Biobank-driven genomic discovery yields new insight into atrial fibrillation biology.

    Nielsen, Jonas B; Thorolfsdottir, Rosa B; Fritsche, Lars G; Zhou, Wei; Skov, Morten W; Graham, Sarah E; Herron, Todd J; McCarthy, Shane; Schmidt, Ellen M; Sveinbjornsson, Gardar; Surakka, Ida; Mathis, Michael R; Yamazaki, Masatoshi; Crawford, Ryan D; Gabrielsen, Maiken E; Skogholt, Anne Heidi; Holmen, Oddgeir L; Lin, Maoxuan; Wolford, Brooke N; Dey, Rounak; Dalen, Håvard; Sulem, Patrick; Chung, Jonathan H; Backman, Joshua D; Arnar, David O; Thorsteinsdottir, Unnur; Baras, Aris; O'Dushlaine, Colm; Holst, Anders G; Wen, Xiaoquan; Hornsby, Whitney; Dewey, Frederick E; Boehnke, Michael; Kheterpal, Sachin; Mukherjee, Bhramar; Lee, Seunggeun; Kang, Hyun M; Holm, Hilma; Kitzman, Jacob; Shavit, Jordan A; Jalife, José; Brummett, Chad M; Teslovich, Tanya M; Carey, David J; Gudbjartsson, Daniel F; Stefansson, Kari; Abecasis, Gonçalo R; Hveem, Kristian; Willer, Cristen J; 1 Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA. 2 Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA. 3 deCODE genetics/Amgen, Inc., Reykjavik, Iceland. 4 Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 5 HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway. 6 K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway. 7 Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA. 8 Laboratory of Molecular Cardiology, Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. 9 Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI, USA. 10 Regeneron Genetics Center, Tarrytown, NY, USA. 11 Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA. 12 Department of Anesthesiology, University of Michigan, Ann Arbor, MI, USA. 13 Medical Device Development and Regulation Research Center, The University of Tokyo, Tokyo, Japan. 14 Department of Cardiology, St. Olav's University Hospital, Trondheim, Norway. 15 Department of Medicine, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway. 16 Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway. 17 Department of Cardiology, St. Olav's University Hospital, Trondheim University Hospital, Trondheim, Norway. 18 Department of Medicine, Landspitali - National University Hospital, Reykjavik, Iceland. 19 Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, USA. 20 Fundación Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain. 21 Geisinger Health System, Danville, PA, USA. 22 School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland. 23 K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway. goncalo@umich.edu. 24 Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA. goncalo@umich.edu. 25 HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway. kristian.hveem@ntnu.no. 26 K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway. kristian.hveem@ntnu.no. 27 Department of Medicine, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway. kristian.hveem@ntnu.no. 28 Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA. cristen@umich.edu. 29 Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA. cristen@umich.edu. 30 Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA. cristen@umich.edu. (Nature Pub. Co, 2018-09-01)
    To identify genetic variation underlying atrial fibrillation, the most common cardiac arrhythmia, we performed a genome-wide association study of >1,000,000 people, including 60,620 atrial fibrillation cases and 970,216 controls. We identified 142 independent risk variants at 111 loci and prioritized 151 functional candidate genes likely to be involved in atrial fibrillation. Many of the identified risk variants fall near genes where more deleterious mutations have been reported to cause serious heart defects in humans (GATA4, MYH6, NKX2-5, PITX2, TBX5)
  • Proton-pump inhibitors among adults: a nationwide drug-utilization study.

    Hálfdánarson, Óskar Ö; Pottegård, Anton; Björnsson, Einar S; Lund, Sigrún H; Ogmundsdottir, Margret H; Steingrímsson, Eiríkur; Ogmundsdottir, Helga M; Zoega, Helga; 1 Centre of Public Health Sciences, Faculty of Medicine, University of Iceland, Sturlugata 8, 101 Reykjavík, Iceland. 2 Clinical Pharmacology and Pharmacy, University of Southern Denmark, Odense, Denmark. 3 Department of Internal Medicine, The National University Hospital of Iceland, Reykjavik, Iceland, and Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 4 Centre of Public Health Sciences, Faculty of Medicine, University of Iceland, Reykjavík, Iceland. 5 Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 6 Cancer Research Laboratory, Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 7 Centre of Public Health Sciences, Faculty of Medicine, University of Iceland, Reykjavík, Iceland, and Medicines Policy Research Unit, Centre for Big Data Research in Health, University of New South Wales, Sydney, New South Wales, Australia. (Sage Publications, 2018-01-01)
    The use of proton-pump inhibitors (PPIs) has grown worldwide, and there are concerns about increased unsubstantiated long-term use. The aim of the study was to describe the real-world use of PPIs over the past decade in an entire national population. This was a nationwide population-based drug-utilization study. Patterns of outpatient PPI use among adults in Iceland between 2003 and 2015 were investigated, including annual incidence and prevalence, duration of use, and dose of tablet used (lower We observed 1,372,790 prescription fills over the entire study period, of which 95% were for higher-dose PPIs. Annual incidence remained stable across time (3.3-4.1 per 100 persons per year), while the annual prevalence increased from 8.5 per 100 persons to 15.5 per 100 persons. Prevalence increased with patient age and was higher among women than men. Duration of treatment increased with patients' age (36% of users over 80 years remained on treatment after 1 year compared with 13% of users aged 19-39 years), and was longer among those initiating on a higher dose compared with a lower dose. The proportion of PPI users concurrently using nonsteroidal anti-inflammatory drugs decreased over the study period, while the proportion concurrently using acetylsalicylic acid, oral anticoagulants, or platelet inhibitors increased. In this nationwide study, a considerable increase in overall outpatient use of PPIs over a 13-year period was observed, particularly among older adults. Patients were increasingly treated for longer durations than recommended by clinical guidelines and mainly with higher doses.
  • Comparing osteonecrosis clinical phenotype, timing, and risk factors in children and young adults treated for acute lymphoblastic leukemia.

    Mogensen, Signe Sloth; Harila-Saari, Arja; Mäkitie, Outi; Myrberg, Ida Hed; Niinimäki, Riitta; Vestli, Anne; Hafsteinsdottir, Solveig; Griškevicius, Laimonas; Saks, Kadri; Hallböök, Helene; Retpen, Jens; Helt, Louise Rold; Toft, Nina; Schmiegelow, Kjeld; Frandsen, Thomas Leth; 1 Department of Pediatrics and Adolescent Medicine, the Juliane Marie Center, University Hospital Rigshospitalet, Copenhagen, Denmark. 2 Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden. 3 Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. 4 Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden. 5 Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland. 6 PEDEGO Research Unit, University of Oulu, Oulu, Finland. 7 Department of Pediatric Oncology and Hematology, Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway. 8 Children's Hospital, Landspitali University Hospital, Reykjavik, Iceland. 9 Department of Hematology, Oncology, and Transfusion Medicine Center, Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania. 10 Faculty of Medicine, Vilnius University, Vilnius, Lithuania. 11 Department of Hematology Oncology, Tallinn Children´s Hospital, Tallinn, Estonia. 12 Department of Medical Sciences, Uppsala University, Uppsala, Sweden. 13 Department of Orthopedic Surgery, University Hospital Herlev Gentofte, Copenhagen, Denmark. 14 Department of Hematology, University Hospital Rigshospitalet, Copenhagen, Denmark. 15 Institute of Clinical Medicine, Faculty of Medicine, University of Copenhagen, Copenhagen, Denmark. (Wiley, 2018-10-01)
    Treatment-related osteonecrosis (ON) is a serious complication of treatment of acute lymphoblastic leukemia (ALL). This study included 1,489 patients with ALL, aged 1-45 years, treated according to the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol, using alternate-week dexamethasone during delayed intensification, with prospective registration of symptomatic ON. We aimed at comparing risk factors, timing, and clinical characteristics of ON in children and young adults. ON was diagnosed in 67 patients, yielding a 5-year cumulative incidence of 6.3%, but 28% in female adolescents. Median age at ALL diagnosis was 12.1 years and 14.9 years for females and males, respectively. At ON diagnosis, 59 patients had bone pain (91%) and 30 (46%) had multiple-joint involvement. The median interval between ALL and ON diagnosis was significantly shorter in children aged 1.0-9.9 years (0.7 years [range: 0.2-2.1]) compared with adolescents (1.8 years [range: 0.3-3.7, P < 0.001]) and adults (2.1 years [range: 0.4-5.3, P = 0.001]). Female sex was a risk factor in adolescent patients (hazard ratio [HR] = 2.1, 95% confidence interval [CI]: 1.1-4.2) but not in children aged 1.1-9.9 years (HR = 2.4, 95% CI: 0.9-6.2, P = 0.08) or adults aged 19-45 years (HR = 1.1, 95% CI: 0.3-4.0). Age above 10 years at ALL diagnosis (odds ratio [OR] = 3.7, P = 0.026) and multiple joints affected at ON diagnosis (OR = 3.4, P = 0.027) were risk factors for developing severe ON. We provide a detailed phenotype of patients with ALL with symptomatic ON, including description of risk factors and timing of ON across age groups. This awareness is essential in exploring measures to prevent development of ON.
  • Following the genetic clues towards treatment of hand OA.

    Jonsson, Helgi; Landspitali University Hospital, University of Iceland, Reykjavik, Iceland. helgi@hi.is. (Nature Pub. Group, 2018-09-01)
  • Accidental injuries among older adults: An incidence study.

    Gudnadottir, Maria; Thorsteinsdottir, Thordis Katrin; Mogensen, Brynjolfur; Aspelund, Thor; Thordardottir, Edda Bjork; 1 Centre of Public Health Sciences, University of Iceland, Reykjavik, Iceland. Electronic address: maria.gudnadottir@gmail.com. 2 Research Institute in Emergency Care, Landspitali, The National University Hospital of Iceland, Iceland; Faculty of Nursing, University of Iceland, Reykjavik, Iceland. Electronic address: thordith@landspitali.is. 3 Research Institute in Emergency Care, Landspitali, The National University Hospital of Iceland, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland. Electronic address: brynmog@landspitali.is. 4 Centre of Public Health Sciences, University of Iceland, Reykjavik, Iceland; Icelandic Heart Association, Iceland. Electronic address: thor@hi.is. 5 Centre of Public Health Sciences, University of Iceland, Reykjavik, Iceland. Electronic address: eddat@hi.is. (Elsevier, 2018-01-01)
    To date, the majority of studies assessing accidental injuries among the elderly have focused on fall injuries, while studies of other mechanisms of injuries have been lacking. Therefore, the main objective of this study was to investigate all injury-related visits among older adults to an emergency department and risk factors for injuries. Data were collected on all registered visits of adults, ≥67 years old, living in the capital of Iceland, to the emergency department of Landspitali, the National University Hospital, in 2011 and 2012. The yearly incidence rate for injuries was 106 per 1000 adults, ≥67 years old. Of all injuries (n = 4,469), falls were the most common mechanism of injury (78 per 1000), followed by being struck or hit (12 per 1000) and being crushed, cut or pierced (8 per 1000). Other mechanisms of injury, such as acute overexertion, foreign body in natural orifice, injuries caused by thermal and chemical effect and other and unspecified mechanism were less common (8 per 1000). Fractures were the most common consequences of injuries (36 per 1000). The most frequent place of injury was in or around homes (77 per 1000), with men being more likely than women to be injured outside of the home (60 per 1000 vs. 36 per 1000). Results indicate that falls are the main cause of accidental injuries, followed by being struck and hit injuries but other causes contributed to the rest. Falls constitute a major public health problem and fall-related injuries can have a substantial impact on the lives of older adults. As life expectancy continues to increase, fall risk is expected to increase. Since falls constitute a major impact on the lives of older adults and can lead to not only declines in physical activity and functional status, but to considerable health care costs, the health care system needs to intervene.

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