Recent Submissions

  • Group B Streptococcal Neonatal and Early Infancy Infections in Iceland, 1976-2015.

    Björnsdóttir, Erla S; Martins, Elisabete R; Erlendsdóttir, Helga; Haraldsson, Gunnsteinn; Melo-Cristino, José; Ramirez, Mário; Kristinsson, Karl G; 1 From the Department of Clinical Microbiology, Landspitali University Hospital, Reykjavik, Iceland. 2 BioMedical Centre of the University of Iceland, Reykjavik, Iceland. 3 Instituto de Microbiologia, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal. (Lippincott Williams & Wilkins, 2019-06)
    BACKGROUND: Despite a risk-based peripartum chemoprophylaxis approach in Iceland since 1996, Streptococcus agalactiae [group B streptococci (GBS)] remains an important cause of early-onset [<7 days, early-onset disease (EOD)] and late-onset disease (LOD; 7 days to 3 months). METHODS: We studied GBS invasive disease in children <1 year in Iceland in 1976-2015. Bacteria (n = 98) were characterized by susceptibility to a panel of antimicrobials, capsular serotyping, resistance genes, surface protein and pilus-locus profiling and multilocus sequence typing. RESULTS: Both EOD and LOD increased during the early years, but while EOD subsequently decreased from 0.7/1000 live births in 1991-1995 to 0.2/1000 in 2011-2015, LOD showed a nonsignificant decrease from its peak value of 0.6/1000 in 2001-2005 to 0.4/1000 in 2006-2015. Serotype III was the most frequently found (n = 48), represented mostly by the hypervirulent lineage CC17/III/rib/PI-1+PI-2b (62%), but also by CC19/III/rib/PI-1+PI-2a (35%) frequently associated with colonization. Serotype Ia (n = 22) was represented by CC23/Ia/eps/PI-2a (68%) and CC7/Ia/bca/PI-1+PI-2b (23%) of possible zoonotic origin. Resistance to erythromycin and clindamycin was increasingly detected in the last years of the study (5 of the 9 cases were isolated after 2013), including representatives of a multiresistant CC17/III/rib/PI-2b sublineage described recently in other countries and expressing resistance to erythromycin, clindamycin and streptomycin. CONCLUSIONS: The risk-based chemoprophylaxis adopted in Iceland possibly contributed to the decline of EOD but has had limited effect on LOD. GBS causing neonatal and early infancy invasive infections in Iceland are genetically diverse, and the recent emergence of antimicrobial resistant lineages may reduce the choices for prophylaxis and therapy of these infections.
  • A worldwide perspective of sepsis epidemiology and survival according to age: Observational data from the ICON audit.

    Kotfis, Katarzyna; Wittebole, Xavier; Jaschinski, Ulrich; Solé-Violán, Jordi; Kashyap, Rahul; Leone, Marc; Nanchal, Rahul; Fontes, Luis E; Sakr, Yasser; Vincent, Jean-Louis; 1 Dept of Anaesthesiology, Intensive Therapy and Acute Intoxications, Pomeranian Medical University, Szczecin, Poland. 2 Dept of Critical Care, Cliniques Universitaires St Luc, UCL, Brussels, Belgium. 3 Klinik für Anästhesiologie und Operative Intensivmedizin, Klinikum Augsburg, Augsburg, Germany. 4 Dept of Intensive Care, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain. 5 Dept of Anesthesia & Perioperative Medicine, Mayo Clinic, Rochester, MN, USA. 6 Service d'Anesthésie et de Réanimation, Aix Marseille Université, APHM, Hôpital Nord, Marseille, France. 7 Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA. 8 Department of Intensive Care and Evidence-Based Medicine, Hospital Alcides Carneiro, Petrópolis Medical School, Petrópolis, Brazil. 9 Department of Anesthesiology and Intensive Care, Uniklinikum Jena, Jena, Germany. 10 Department of Intensive Care, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium. Electronic address: jlvincent@intensive.org. (W.B. Saunders, 2019-06)
    PURPOSE: To investigate age-related differences in outcomes of critically ill patients with sepsis around the world. METHODS: We performed a secondary analysis of data from the prospective ICON audit, in which all adult (>16 years) patients admitted to participating ICUs between May 8 and 18, 2012, were included, except admissions for routine postoperative observation. For this sub-analysis, the 10,012 patients with completed age data were included. They were divided into five age groups - ≤50, 51-60, 61-70, 71-80, >80 years. Sepsis was defined as infection plus at least one organ failure. RESULTS: A total of 2963 patients had sepsis, with similar proportions across the age groups (≤50 = 25.2%; 51-60 = 30.3%; 61-70 = 32.8%; 71-80 = 30.7%; >80 = 30.9%). Hospital mortality increased with age and in patients >80 years was almost twice that of patients ≤50 years (49.3% vs 25.2%, p < .05). The maximum rate of increase in mortality was about 0.75% per year, occurring between the ages of 71 and 77 years. In multilevel analysis, age > 70 years was independently associated with increased risk of dying. CONCLUSIONS: The odds for death in ICU patients with sepsis increased with age with the maximal rate of increase occurring between the ages of 71 and 77 years.
  • Effects of an intervention program for reducing severe perineal trauma during the second stage of labor.

    Sveinsdottir, Edda; Gottfredsdottir, Helga; Vernhardsdottir, Anna S; Tryggvadottir, Gudny B; Geirsson, Reynir T; 1 Midwifery Division, Faculty of Nursing, University of Iceland, Reykjavik, Iceland. 2 Department of Obstetrics and Gynecology, Women's Clinic, Landspítali University Hospital, Reykjavik, Iceland. 3 Department of Social Sciences, University of Iceland, Reykjavik, Iceland. 4 Faculty of Medicine, University of Iceland, Reykjavik, Iceland. (Wiley, 2019-06)
    BACKGROUND: Obstetric anal sphincter injuries lead frequently to short- and long-term consequences for the mother, including perineal pain, genital prolapse, and sexual problems. The aim of the study was to evaluate whether the implementation of an intervention program in the second stage of labor involving altered perineal support techniques reduced severe perineal trauma. METHODS: All women reaching the second stage of labor and giving birth vaginally to singleton babies at Landspítali University Hospital (comprising 76% of births in Iceland in 2013) were enrolled in a cohort study. Data were recorded retrospectively for 2008-2010 and prospectively in 2012-2014, for a total of 16 336 births. During 2011, an intervention program was implemented, involving all midwives and obstetricians working in the labor wards. Two professionals assessed and agreed on classification of every perineal tear. RESULTS: The prevalence of obstetric anal sphincter injuries decreased from 5.9% to 3.7% after the implementation (P < 0.001). Third-degree tears decreased by 40%, and fourth-degree tears decreased by 56% (P < 0.001). The prevalence of first-degree tears increased from 25.8% to 33.1%, whereas second-degree tears decreased from 44.7% to 36.6% between the before and after study periods. Severe perineal trauma was linked to birthweight, and this did not change despite the new intervention. CONCLUSIONS: Active intervention to reduce perineal trauma was associated with an overall significant decrease in obstetric anal sphincter injuries. Good perineal visualization, manual perineal support, and controlled delivery of the fetal head were essential components for reducing perineal trauma.
  • The Robson 10-group classification in Iceland: Obstetric interventions and outcomes.

    Einarsdóttir, Kristjana; Sigurðardóttir, Hekla; Ingibjörg Bjarnadóttir, Ragnheiður; Steingrímsdóttir, Þóra; Smárason, Alexander K; 1 Centre of Public Health Sciences, Faculty of Medicine, University of Iceland, Reykjavík, Iceland. 2 Faculty of Medicine, University of Iceland, Reykjavík, Iceland. 3 Centre of Development, Primary Health Care of the Capital Area, Reykjavík, Iceland. 4 Department of Obstetrics and Gynaecology, Landspítali University Hospital, Reykjavík, Iceland. 5 Institution of Health Science Research, University of Akureyri and Akureyri Hospital, Akureyri, Iceland. (Wiley, 2019-06)
    BACKGROUND: Rising cesarean rates call for studies on which subgroups of women contribute to the rising rates, both in countries with high and low rates. This study investigated the cesarean rates and contributing groups in Iceland using the Robson 10-group classification system. METHODS: This study included all births in Iceland from 1997 to 2015, identified from the Icelandic Medical Birth Registry (81 839). The Robson distribution, cesarean rate, and contribution of each Robson group were analyzed for each year, and the distribution of other outcomes was calculated for each Robson group. RESULTS: The overall cesarean rate in the population was 16.4%. Robson groups 1 (28.7%) and 3 (38.0%) (spontaneous term births) were the largest groups, and groups 2b (0.4%) and 4b (0.7%) (prelabor cesareans) were small. The cesarean rate in group 5 (prior cesarean) was 55.5%. Group 5 was the largest contributing group to the overall cesarean rate (31.2%), followed by groups 1 (17.1%) and 2a (11.0%). The size of groups 2a (RR 1.04 [95% CI 1.01-1.08]) and 4a (RR 1.04 [95% CI 1.01-1.07]) (induced labors) increased over time, whereas their cesarean rates were stable (group 2a: P = 0.08) or decreased (group 4a: RR 0.95 [95% CI 0.91-0.98]). CONCLUSIONS: In comparison with countries with high cesarean rates, the prelabor cesarean groups (singleton term pregnancies) in Iceland were small, and in women with a previous cesarean, the cesarean rate was low. The size of the labor induction group increased, yet the cesarean rate in this group did not increase.
  • Asthma and selective migration from farming environments in a three-generation cohort study.

    Timm, Signe; Frydenberg, Morten; Abramson, Michael J; Bertelsen, Randi J; Bråbäck, Lennart; Benediktsdottir, Bryndis; Gislason, Thorarinn; Holm, Mathias; Janson, Christer; Jogi, Rain; Johannessen, Ane; Kim, Jeong-Lim; Malinovschi, Andrei; Mishra, Gita; Moratalla, Jesús; Sigsgaard, Torben; Svanes, Cecilie; Schlünssen, Vivi; 1 Department of Public Health, Danish Ramazzini Centre, Aarhus University, Bartholins Alle 2, Building 1260, 8000, Aarhus C, Denmark. signe.timm@ph.au.dk. 2 Department of Public Health, Danish Ramazzini Centre, Aarhus University, Bartholins Alle 2, Building 1260, 8000, Aarhus C, Denmark. 3 School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. 4 Institute of Clinical Science, University of Bergen, Bergen, Norway. 5 Section of Sustainable Health, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden. 6 Medical Faculty, University of Iceland, Reykjavík, Iceland. 7 Primary Health Care Center, Gardabaer, Iceland. 8 Department of Sleep, Landspitali University Hospital, Reykjavík, Iceland. 9 Section of Occupational and Environmental Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden. 10 Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden. 11 Department of Pulmonology (ARKS), University of Tartu, Tartu, Estonia. 12 Department of Global Public Health and Primary Care, Centre for International Health, University of Bergen, Bergen, Norway. 13 Department of Occupational Medicine, Haukeland University Hospital, Bergen, Norway. 14 Section of Occupational and Environmental Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 15 Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden. 16 School of Public Health, The University of Queensland, Brisbane, QLD, 4006, Australia. 17 Department of Internal Medicine, Albacete University Hospital, Albacete, Spain. 18 National Research Centre for The Working Environment, Copenhagen, Denmark. (Springer, 2019-06)
    Individuals raised on a farm appear to have less asthma than individual raised elsewhere. However, selective migration might contribute to this as may also the suggested protection from farm environment. This study investigated if parents with asthma are less likely to raise their children on a farm. This study involved three generations: 6045 participants in ECRHS/RHINE cohorts (born 1945-1973, denoted G1), their 10,121 parents (denoted G0) and their 8260 offspring participating in RHINESSA (born 1963-1998, denoted G2). G2-offspring provided information on parents not participating in ECRHS/RHINE. Asthma status and place of upbringing for all three generations were reported in questionnaires by G1 in 2010-2012 and by G2 in 2013-2016. Binary regressions with farm upbringing as outcome were performed to explore associations between parental asthma and offspring farm upbringing in G0-G1 and G1-G2. Having at least one parent with asthma was not associated with offspring farm upbringing, either in G1-G2 (RR 1.11, 95% CI 0.81-1.52) or in G0-G1 (RR 0.99, 0.85-1.15). G1 parents with asthma born in a city tended to move and raise their G2 offspring on a farm (RR 2.00, 1.12-3.55), while G1 parents with asthma born on a farm were less likely to raise their G2 offspring on a farm (RR 0.34, 0.11-1.06). This pattern was not observed in analyses of G0-G1. This study suggests that the protective effect from farm upbringing on subsequent asthma development could not be explained by selective migration. Intriguingly, asthmatic parents appeared to change environment when having children.
  • Molecularly confirmed Kabuki (Niikawa-Kuroki) syndrome patients demonstrate a specific cognitive profile with extensive visuospatial abnormalities.

    Harris, J; Mahone, E M; Bjornsson, H T; 1 Department of Neurogenetics, Kennedy Krieger Institute, Baltimore, MD, USA. 2 McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD, USA. 3 Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 4 Department of Neuropsychology, Kennedy Krieger Institute, Baltimore, MD, USA. 5 Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 6 Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 7 Department of Genetics and Molecular Medicine, Landspitali University Hospital, Reykjavik, Iceland. (Wiley, 2019-06)
    BACKGROUND: Kabuki (Niikawa-Kuroki) syndrome (KS) is caused by disease-causing variants in either of two components (KMT2D and KDM6A) of the histone methylation machinery. Nearly all individuals with KS have cognitive difficulties, and most have intellectual disability. Recent studies on a mouse model of KS suggest disruption of normal adult neurogenesis in the granule cell layer of the dentate gyrus of the hippocampus. These mutant mice also demonstrate hippocampal memory defects compared with littermates, but this phenotype is rescued postnatally with agents that target the epigenetic machinery. If these findings are relevant to humans with KS, we would expect significant and disproportionate disruption of visuospatial functioning in these individuals. METHODS: To test this hypothesis, we have compiled a battery to robustly explore visuospatial function. We prospectively recruited 22 patients with molecularly confirmed KS and 22 IQ-matched patients with intellectual disability. RESULTS: We observed significant deficiencies in visual motor, visual perception and visual motor memory in the KS group compared with the IQ-matched group on several measures. In contrast, language function appeared to be marginally better in the KS group compared with the IQ-matched group in a sentence comprehension task. CONCLUSIONS: Together, our data suggest specific disruption of visuospatial function, likely linked to the dentate gyrus, in individuals with KS and provide the groundwork for a novel and specific outcome measure for a clinical trial in a KS population.
  • Development of a novel benchmark method to identify and characterize best practices in home care across six European countries: design, baseline, and rationale of the IBenC project.

    van der Roest, Henriëtte G; van Eenoo, Liza; van Lier, Lisanne I; Onder, Graziano; Garms-Homolová, Vjenka; Smit, Johannes H; Finne-Soveri, Harriet; Jónsson, Pálmi V; Draisma, Stasja; Declercq, Anja; Bosmans, Judith E; van Hout, Hein P J; 1 Department of General Practice and Elderly Care Medicine, Amsterdam Public Health research institute, Amsterdam UMC, VU University medical center, Van der Boechorststraat 7, 1081, BT, Amsterdam, The Netherlands. hg.vanderroest@gmail.com. 2 LUCAS Centre for Care Research and Consultancy, KU Leuven, Leuven, Belgium. 3 Department of General Practice and Elderly Care Medicine, Amsterdam Public Health research institute, Amsterdam UMC, VU University medical center, Van der Boechorststraat 7, 1081, BT, Amsterdam, The Netherlands. 4 Department of Geriatrics, Neuroscience and Orthopedics, Agostino Gemelli University Hospital, Università Cattolica del Sacro Cuore, Rome, Italy. 5 Department of Economics and Law, HTW Berlin, University of Applied Sciences, Berlin, Germany. 6 Department of Psychiatry, Amsterdam Public Health research institute, Amsterdam UMC, Vrije Universiteit Amsterdam, The Netherlands & GGZ inGeest Specialized Mental Health Care, Research and Innovation, Amsterdam, The Netherlands. 7 Department of Wellbeing, National Institute for Health and Welfare, Helsinki, Finland. 8 Department of Geriatrics, Landspitali University Hospital, and Faculty of Medicine, University of Iceland, Reykjavík, Iceland. 9 Department of Health Sciences, Faculty of Science, Amsterdam Public Health research institute, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. (BioMed Central, 2019-05-15)
    BACKGROUND: Europe's ageing society leads to an increased demand for long-term care, thereby putting a strain on the sustainability of health care systems. The 'Identifying best practices for care-dependent elderly by Benchmarking Costs and outcomes of Community Care' (IBenC) project aims to develop a new benchmark methodology based on quality of care and cost of care utilization to identify best practices in home care. The study's baseline data, methodology, and rationale are reported. METHODS: Home care organizations in Belgium, Finland, Germany, Iceland, Italy, and the Netherlands, home care clients of 65 years and over receiving home care, and professionals working in these organizations were included. Client data were collected according to a prospective longitudinal design with the interRAI Home Care instrument. Assessments were performed at baseline, after six and 12 months by trained (research) nurses. Characteristics of home care organizations and professionals were collected cross-sectionally with online surveys. RESULTS: Thirty-eight home care organizations, 2884 home care clients, and 1067 professionals were enrolled. Home care clients were mainly female (66.9%), on average 82.9 years (± 7.3). Extensive support in activities of daily living was needed for 41.6% of the sample, and 17.6% suffered cognitive decline. Care professionals were mainly female (93.4%), and over 45 years (52.8%). Considerable country differences were found. CONCLUSION: A unique, international, comprehensive database is established, containing in-depth information on home care organizations, their clients and staff members. The variety of data enables the development of a novel cost-quality benchmark method, based on interRAI-HC data. This benchmark can be used to explore relevant links between organizational efficiency and organizational and staff characteristics.
  • GBA and APOE ε4 associate with sporadic dementia with Lewy bodies in European genome wide association study.

    Rongve, Arvid; Witoelar, Aree; Ruiz, Agustín; Athanasiu, Lavinia; Abdelnour, Carla; Clarimon, Jordi; Heilmann-Heimbach, Stefanie; Hernández, Isabel; Moreno-Grau, Sonia; de Rojas, Itziar; Morenas-Rodríguez, Estrella; Fladby, Tormod; Sando, Sigrid B; Bråthen, Geir; Blanc, Frédéric; Bousiges, Olivier; Lemstra, Afina W; van Steenoven, Inger; Londos, Elisabet; Almdahl, Ina S; Pålhaugen, Lene; Eriksen, Jon A; Djurovic, Srdjan; Stordal, Eystein; Saltvedt, Ingvild; Ulstein, Ingun D; Bettella, Francesco; Desikan, Rahul S; Idland, Ane-Victoria; Toft, Mathias; Pihlstrøm, Lasse; Snaedal, Jon; Tárraga, Lluís; Boada, Mercè; Lleó, Alberto; Stefánsson, Hreinn; Stefánsson, Kári; Ramírez, Alfredo; Aarsland, Dag; Andreassen, Ole A; 1 Haugesund Hospital, Helse Fonna, Department of Research and Innovation, Haugesund, Norway. arvid.rongve@helse-fonna.no. 2 The University of Bergen, Department of Clinical Medicine (K1), Bergen, Norway. arvid.rongve@helse-fonna.no. 3 NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway. 4 Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 5 Memory Clinic and Research Center of Fundació ACE, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya (UIC), Barcelona, Spain. 6 Department of Neurology, IIB Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain. 7 Center for Networker Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid and Barcelona, Spain. 8 Institute of Human Genetics, University of Bonn, Bonn, Germany. 9 Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany. 10 Department of Neurology, Akershus University Hospital, Lørenskog, Norway. 11 University of Oslo, AHUS Campus, Oslo, Norway. 12 Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway. 13 Department of Neurology, St Olav's Hospital, Trondheim, Norway. 14 University Hospital of Strasbourg, CMRR (Memory Resources and Research Centre), Geriatrics Department, Strasbourg, France. 15 University of Strasbourg and CNRS, ICube laboratory and FMTS, team IMIS/Neurocrypto, Strasbourg, France. 16 University Hospital of Strasbourg, CMRR (Memory Resources and Research Centre), Laboratory of Biochemistry and Molecular Biology, Strasbourg, France. 17 University of Strasbourg and CNRS, Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), UMR7364, 67000, Strasbourg, France. 18 Alzheimercenter & Department of Neurology VU University Medical Center, Amsterdam, the Netherlands. 19 Lund University, Skane University Hospital, Institute of Clinical Sciences, Malmö, Sweden. 20 Department of Geriatric Psychiatry, Oslo University Hospital, Oslo, Norway. 21 Department of Medical Genetics, Oslo University Hospital, Oslo, Norway. 22 NORMENT, KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, Norway. 23 Department of Psychiatry, Namsos Hospital, Namsos, Norway. 24 Department of Mental Health, Norwegian University of Science and Technology, Trondheim, Norway. 25 Department of Geriatrics, St. Olav's Hospital, Trondheim, Norway. 26 Departments of Radiology and Biomedical Imaging, Neurology and Pediatrics, UCSF, San Francisco, USA. 27 Oslo Delirium Research Group, Department of Geriatric Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 28 Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway. 29 Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway. 30 Department of Neurology, Oslo University Hospital, Oslo, Norway. 31 Landspitali University Hospital, Reykjavik, Iceland. 32 DeCODE genetics, Reykjavik, Iceland. 33 Division for Neurogenetics and Molecular Psychiatry, Department of Psychiatry and Psychotherapy, Medical Faculty, University of Cologne, 50924, Cologne, Germany. 34 Department for Neurodegenerative Diseases and Geriatric Psychiatry, University of Bonn, 53127, Bonn, Germany. 35 Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. daarsland@gmail.com. 36 Center for Age-Related Diseases, Stavanger University Hospital, Stavanger, Norway. daarsland@gmail.com. 37 NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway. ole.andreassen@medisin.uio.no. 38 Institute of Clinical Medicine, University of Oslo, Oslo, Norway. ole.andreassen@medisin.uio.no. (Nature Publishing Group, 2019-05-07)
    Dementia with Lewy Bodies (DLB) is a common neurodegenerative disorder with poor prognosis and mainly unknown pathophysiology. Heritability estimates exceed 30% but few genetic risk variants have been identified. Here we investigated common genetic variants associated with DLB in a large European multisite sample. We performed a genome wide association study in Norwegian and European cohorts of 720 DLB cases and 6490 controls and included 19 top-associated single-nucleotide polymorphisms in an additional cohort of 108 DLB cases and 75545 controls from Iceland. Overall the study included 828 DLB cases and 82035 controls. Variants in the ASH1L/GBA (Chr1q22) and APOE ε4 (Chr19) loci were associated with DLB surpassing the genome-wide significance threshold (p < 5 × 10-8). One additional genetic locus previously linked to psychosis in Alzheimer's disease, ZFPM1 (Chr16q24.2), showed suggestive association with DLB at p-value < 1 × 10-6. We report two susceptibility loci for DLB at genome-wide significance, providing insight into etiological factors. These findings highlight the complex relationship between the genetic architecture of DLB and other neurodegenerative disorders.
  • Cardiovascular risk factors and incident giant cell arteritis: a population-based cohort study.

    Tomasson, G; Bjornsson, J; Zhang, Y; Gudnason, V; Merkel, P A; 1 a Department of Epidemiology and Biostatistics, Faculty of Medicine , University of Iceland , Reykjavik , Iceland. 2 b Department of Rheumatology , University Hospital , Reykjavik , Iceland. 3 c Centre for Rheumatology Research , University Hospital , Reykjavik , Iceland. 4 d Department of Pathology , Akureyri Regional Hospital , Akureyri , Iceland. 5 e Clinical Epidemiology Research and Training Unit , Boston University School of Medicine , Boston , MA , USA. 6 f Faculty of Medicine , University of Iceland , Reykjavik , Iceland. 7 g Icelandic Heart Association , Kopavogur , Iceland. 8 h Division of Rheumatology , University of Pennsylvania , Philadelphia , PA , USA. 9 i Department of Biostatistics, Epidemiology, and Informatics , University of Pennsylvania , Philadelphia , PA , USA. (Taylor & Francis, 2019-05)
    OBJECTIVE: To assess the strength of the effect of cardiovascular risk factors on the incidence of giant cell arteritis (GCA) in a general population context. METHOD: Data from the Reykjavik Study (RS), a population-based cohort study focusing on cardiovascular disease, were used. Everyone born in 1907-1935 living in Reykjavik, Iceland, or adjacent communities on 1 December 1967 were invited to participate. Subjects attended a study visit in 1967-1996 and information on cardiovascular risk factors [smoking habits, blood pressure, diabetes, body mass index (BMI), and serum cholesterol] was obtained. All temporal artery biopsies obtained from members of the RS cohort were re-examined by a single pathologist with expertise in vascular pathology. Effects of risk factors on GCA occurrence are expressed as incidence rate ratios (IRRs) with 95% confidence intervals (CIs). RESULTS: Altogether, 19 241 subjects contributed a median of 23.1 (interquartile range 17.6-29.4) years after the age of 50 to this analysis. During 444 126 person-years of follow-up, 194 subjects developed GCA, corresponding to an incidence rate of 43.6 (95% CI 37.8-50.2) per 100 000 person-years. Being overweight or obese were inversely associated with GCA, especially in women [IRRs 0.70 (0.48-1.02) and 0.31 (0.14-0.71), respectively]. There was a weaker association between BMI and incident GCA in men. Smoking was inversely associated with GCA in men [IRR 0.47 (0.27-0.81)], but not in women. CONCLUSIONS: The incidence of GCA in Iceland is very high. High BMI protects against the occurrence of GCA, and smoking may protect against GCA in men.
  • Publisher Correction: GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures.

    Styrkarsdottir, Unnur; Stefansson, Olafur A; Gunnarsdottir, Kristbjorg; Thorleifsson, Gudmar; Lund, Sigrun H; Stefansdottir, Lilja; Juliusson, Kristinn; Agustsdottir, Arna B; Zink, Florian; Halldorsson, Gisli H; Ivarsdottir, Erna V; Benonisdottir, Stefania; Jonsson, Hakon; Gylfason, Arnaldur; Norland, Kristjan; Trajanoska, Katerina; Boer, Cindy G; Southam, Lorraine; Leung, Jason C S; Tang, Nelson L S; Kwok, Timothy C Y; Lee, Jenny S W; Ho, Suzanne C; Byrjalsen, Inger; Center, Jacqueline R; Lee, Seung Hun; Koh, Jung-Min; Lohmander, L Stefan; Ho-Pham, Lan T; Nguyen, Tuan V; Eisman, John A; Woo, Jean; Leung, Ping-C; Loughlin, John; Zeggini, Eleftheria; Christiansen, Claus; Rivadeneira, Fernando; van Meurs, Joyce; Uitterlinden, Andre G; Mogensen, Brynjolfur; Jonsson, Helgi; Ingvarsson, Thorvaldur; Sigurdsson, Gunnar; Benediktsson, Rafn; Sulem, Patrick; Jonsdottir, Ingileif; Masson, Gisli; Holm, Hilma; Norddahl, Gudmundur L; Thorsteinsdottir, Unnur; Gudbjartsson, Daniel F; Stefansson, Kari; 1 deCODE genetics/Amgen Inc., Reykjavik, 101, Iceland. unnur.styrkarsdottir@decode.is. 2 deCODE genetics/Amgen Inc., Reykjavik, 101, Iceland. 3 Faculty of Medicine, University of Iceland, Reykjavik, 101, Iceland. 4 Department of Epidemiology, ErasmusMC, 3015 GD, Rotterdam, The Netherlands. 5 Department of Internal Medicine, ErasmusMC, 3015 GD, Rotterdam, The Netherlands. 6 Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK. 7 Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK. 8 Jockey Club Centre for Osteoporosis Care and Control, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. 9 Faculty of Medicine, Department of Chemical Pathology and Laboratory for Genetics of Disease Susceptibility, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China. 10 CUHK Shenzhen Research Institute, Shenzhen, 518000, China. 11 Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong, China. 12 Faculty of Medicine, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China. 13 Department of Medicine, Alice Ho Miu Ling Nethersole Hospital and Tai Po Hospital, Hong Kong, China. 14 JC School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. 15 Nordic Bioscience A/S, 2730, Herlev, Denmark. 16 Bone Biology Division, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia. 17 School of Medicine Sydney, University of Notre Dame Australia, Sydney, NSW, 2010, Australia. 18 St Vincent's Clinical School, University of New South Wales, Sydney, NSW, 2010, Australia. 19 Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea. 20 Orthopaedics, Department of Clinical Sciences Lund, Lund University, SE-22 100, Lund, Sweden. 21 Bone and Muscle Research Lab, Ton Duc Thang University, Ho Chi Minh City, 700000, Vietnam. 22 School of Biomedical Engineering, University of Technology Sydney, Sydney, NSW, 2007, Australia. 23 Clinical Translation and Advanced Education, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia. 24 Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China. 25 Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne, NE1 7RU, UK. 26 Institute of Translational Genomics, Helmholtz Zentrum München, 85764, München, Germany. 27 Department of Emergengy Medicine, Landspitali, The National University Hospital of Iceland, 101, Reykjavik, Iceland. 28 Research Institute in Emergency Medicine, Landspitali, The National University Hospital of Iceland, and University of Iceland, 101, Reykjavik, Iceland. 29 Department of Medicine, Landspitali-The National University Hospital of Iceland, 101, Reykjavik, Iceland. 30 Department of Orthopedic Surgery, Akureyri Hospital, 600, Akureyri, Iceland. 31 Institution of Health Science, University of Akureyri, 600, Akureyri, Iceland. 32 Research Service Center, Reykjavik, 201, Iceland. 33 Department of Endocrinology and Metabolism, Landspitali, The National University Hospital of Iceland, 101, Reykjavik, Iceland. 34 Department of Immunology, Landspitali-The National University Hospital of Iceland, 101, Reykjavik, Iceland. 35 School of Engineering and Natural Sciences, University of Iceland, Reykjavik, 107, Iceland. 36 deCODE genetics/Amgen Inc., Reykjavik, 101, Iceland. kstefans@decode.is. 37 Faculty of Medicine, University of Iceland, Reykjavik, 101, Iceland. kstefans@decode.is. (Nature Publishing Group, 2019-05-24)
    The original HTML version of this Article was updated shortly after publication to add links to the Peer Review file.In addition, affiliations 16 and 17 incorrectly read 'School of Medicine Sydney, University of Notre Dame Australia, Sydney, WA, 6160, Australia' and 'St Vincent's Clinical School, University of New South Wales Medicine, University of New South Wales, Sydney, NSW, 2052, Australia.' This has now been corrected in both the PDF and HTML versions of the Article.
  • GWAS of bone size yields twelve loci that also affect height, BMD, osteoarthritis or fractures.

    Styrkarsdottir, Unnur; Stefansson, Olafur A; Gunnarsdottir, Kristbjorg; Thorleifsson, Gudmar; Lund, Sigrun H; Stefansdottir, Lilja; Juliusson, Kristinn; Agustsdottir, Arna B; Zink, Florian; Halldorsson, Gisli H; Ivarsdottir, Erna V; Benonisdottir, Stefania; Jonsson, Hakon; Gylfason, Arnaldur; Norland, Kristjan; Trajanoska, Katerina; Boer, Cindy G; Southam, Lorraine; Leung, Jason C S; Tang, Nelson L S; Kwok, Timothy C Y; Lee, Jenny S W; Ho, Suzanne C; Byrjalsen, Inger; Center, Jacqueline R; Lee, Seung Hun; Koh, Jung-Min; Lohmander, L Stefan; Ho-Pham, Lan T; Nguyen, Tuan V; Eisman, John A; Woo, Jean; Leung, Ping-C; Loughlin, John; Zeggini, Eleftheria; Christiansen, Claus; Rivadeneira, Fernando; van Meurs, Joyce; Uitterlinden, Andre G; Mogensen, Brynjolfur; Jonsson, Helgi; Ingvarsson, Thorvaldur; Sigurdsson, Gunnar; Benediktsson, Rafn; Sulem, Patrick; Jonsdottir, Ingileif; Masson, Gisli; Holm, Hilma; Norddahl, Gudmundur L; Thorsteinsdottir, Unnur; Gudbjartsson, Daniel F; Stefansson, Kari; 1 deCODE genetics/Amgen Inc., Reykjavik, 101, Iceland. unnur.styrkarsdottir@decode.is. 2 deCODE genetics/Amgen Inc., Reykjavik, 101, Iceland. 3 Faculty of Medicine, University of Iceland, Reykjavik, 101, Iceland. 4 Department of Epidemiology, ErasmusMC, 3015 GD, Rotterdam, The Netherlands. 5 Department of Internal Medicine, ErasmusMC, 3015 GD, Rotterdam, the Netherlands. 6 Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, UK. 7 Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK. 8 Jockey Club Centre for Osteoporosis Care and Control, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. 9 Faculty of Medicine, Department of Chemical Pathology and Laboratory for Genetics of Disease Susceptibility, Li Ka Shing Institute of Health Sciences,, The Chinese University of Hong Kong, Hong Kong, China. 10 CUHK Shenzhen Research Institute, Shenzhen, 518000, China. 11 Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong, China. 12 Faculty of Medicine, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China. 13 Department of Medicine, Alice Ho Miu Ling Nethersole Hospital and Tai Po Hospital, Hong Kong, China. 14 JC School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. 15 Nordic Bioscience A/S, 2730, Herlev, Denmark. 16 Bone Biology Division, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia. 17 School of Medicine Sydney, University of Notre Dame Australia, Sydney, NSW, 2010, Australia. 18 St Vincent's Clinical School, University of New South Wales, Sydney, NSW, 2010, Australia. 19 Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea. 20 Orthopaedics, Department of Clinical Sciences Lund, Lund University, SE-22 100, Lund, Sweden. 21 Bone and Muscle Research Lab, Ton Duc Thang University, Ho Chi Minh City, 700000, Vietnam. 22 School of Biomedical Engineering, University of Technology Sydney, Sydney, NSW, 2007, Australia. 23 Clinical Translation and Advanced Education, Garvan Institute of Medical Research, Sydney, NSW, 2010, Australia. 24 Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong, China. 25 Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne, NE1 7RU, UK. 26 Institute of Translational Genomics, Helmholtz Zentrum München, 85764, München, Germany. 27 Department of Emergengy Medicine, Landspitali, The National University Hospital of Iceland, 101, Reykjavik, Iceland. 28 Research Institute in Emergency Medicine, Landspitali, The National University Hospital of Iceland, and University of Iceland, 101, Reykjavik, Iceland. 29 Department of Medicine, Landspitali-The National University Hospital of Iceland, 101, Reykjavik, Iceland. 30 Department of Orthopedic Surgery, Akureyri Hospital, 600, Akureyri, Iceland. 31 Institution of Health Science, University of Akureyri, 600, Akureyri, Iceland. 32 Research Service Center, Reykjavik, 201, Iceland. 33 Department of Endocrinology and Metabolism, Landspitali, The National University Hospital of Iceland, 101, Reykjavik, Iceland. 34 Department of Immunology, Landspitali-The National University Hospital of Iceland, 101, Reykjavik, Iceland. 35 School of Engineering and Natural Sciences, University of Iceland, Reykjavik, 107, Iceland. 36 deCODE genetics/Amgen Inc., Reykjavik, 101, Iceland. kstefans@decode.is. 37 Faculty of Medicine, University of Iceland, Reykjavik, 101, Iceland. kstefans@decode.is. (Nature Publishing Group, 2019-05-03)
    Bone area is one measure of bone size that is easily derived from dual-energy X-ray absorptiometry (DXA) scans. In a GWA study of DXA bone area of the hip and lumbar spine (N ≥ 28,954), we find thirteen independent association signals at twelve loci that replicate in samples of European and East Asian descent (N = 13,608 - 21,277). Eight DXA area loci associate with osteoarthritis, including rs143384 in GDF5 and a missense variant in COL11A1 (rs3753841). The strongest DXA area association is with rs11614913[T] in the microRNA MIR196A2 gene that associates with lumbar spine area (P = 2.3 × 10-42, β = -0.090) and confers risk of hip fracture (P = 1.0 × 10-8, OR = 1.11). We demonstrate that the risk allele is less efficient in repressing miR-196a-5p target genes. We also show that the DXA area measure contributes to the risk of hip fracture independent of bone density.
  • A comparative brief on conducted electrical weapon safety.

    Kunz, Sebastian N; Adamec, Jiri; 1 Department of Forensic Pathology, Landspítali University Hospital Reykjavik, v/Barónsstíg 101, Reykjavik, Iceland. sebastian@landspitali.is. 2 Institute of Forensic Medicine, Ludwigs-Maximilians University Munich, Munich, Germany. (Springer Verlag, 2019-05)
    The variety and high number of published research articles on conducted electrical weapons (CEW) provides a detailed, yet in some parts inconclusive overview of medical aspects of CEW. Due to different research approaches and the use of dissimilar test subjects, an assessment of possible health risks of CEW is limited. The present work provides a brief on CEW safety based on currently available animal, computer and human research data. Using the medical database PubMed, articles published on this topic are critically evaluated and compared with each other. Special focuses are the differences and similarities of human and animal research as well as computer simulation programs. The authors explain why some studies are more reliable than others and give their expert opinion on the safety of CEW. The body of data that have been reviewed provides reasonable support for the safety of CEW.
  • Oral anticoagulant monitoring: Are we on the right track?

    Onundarson, Pall T; Flygenring, Bjorn; 1 Landspitali/The National University Hospital of Iceland, Reykjavik, Iceland. 2 Faculty of Medicine, University of Iceland, Reykjavik, Iceland. (Wiley, 2019-05-01)
    Vitamin K antagonists (VKAs) cannot be administered without regular monitoring in order to assure their efficacy and safety. Indeed, if well managed, the VKAs appear to be no less efficacious or safe than the newer direct oral anticoagulants (DOACs). Although it is claimed that no regular monitoring of the DOACs is needed, their levels are increasingly being measured under a variety of circumstances, for example, prior to surgery, in suspected overdose, to confirm effective reversal, in patients with malabsorption and to assess patient compliance. Although no therapeutic range has been identified for the DOACs, it has been demonstrated for dabigatran and edoxaban that their antithrombotic effect increases gradually with increasing concentrations and that the risk of major bleeding also gradually increases. Furthermore, it has been determined that almost all dabigatran-related thrombotic events occur in patients with the lowest quartile concentration of the drug. This suggests that to assure an ideal effect of DOACs in all patients taking them, some form of regular monitoring and dose tailoring should be performed. For the vitamin K antagonists, the best outcome is obtained using formal algorithms and centralized management. Furthermore, data suggest that replacing the standard prothrombin time as a monitoring test may increase the stability of VKA anticoagulation with consequent reduction in thromboembolism without an increase in bleeding. Thus, it is likely that the outcome of all current oral anticoagulants can be improved in the coming years by improving monitoring and tailoring their effect.
  • High-density Bacterial Nasal Carriage in Children Is Transient and Associated With Respiratory Viral Infections-Implications for Transmission Dynamics.

    Thors, Valtyr; Christensen, Hannah; Morales-Aza, Begonia; Oliver, Elizabeth; Sikora, Paulina; Vipond, Ian; Muir, Peter; Finn, Adam; 1 From the School of Cellular and Molecular Medicine, University of Bristol, Education Centre, Bristol, United Kingdom. 2 Children's Hospital, Landspitali University Hospital Iceland, Reykjavik, Iceland. 3 School of Population Health Sciences, University of Bristol. 4 Public Health Laboratory Bristol, Public Health England, Southmead Hospital, Bristol, United Kingdom. (Lippincott Williams & Wilkins, 2019-05)
    BACKGROUND: This longitudinal study describes the associations between respiratory viral infections, rhinitis and the prevalence and density of the common nasopharyngeal bacterial colonizers, Streptococcus pneumoniae (Sp), Moraxella catarrhalis (Mc), Haemophilus influenzae (Hi) and Staphylococcus aureus. METHODS: In an observational cohort study, 161 children attending day care centers in Bristol, United Kingdom, were recruited. Monthly nasopharyngeal swabs were taken and stored frozen in Skim-milk, tryptone, glucose and glycerin broth (STGG) broth. Quantitative polymerase chain reaction was used for detection of respiratory viruses and 4 bacterial species. t tests and logistic regression models were used for analysis. RESULTS: The frequent colonisers, Sp, Mc and Hi were more frequently found at high density in contrast to Staphylococcus aureus although temporally, high-density carriage was short lived. Respiratory viral infections and symptoms of rhinitis were both independently and consistently associated with higher bacterial density with an observed 2-fold increase in density for Sp, Mc and Hi (P = 0.004-0.017). CONCLUSIONS: For Sp and Hi, the association between young age and higher bacterial DNA density was explained by more frequent viral infection and increased nasal discharge, while the associations between some viral specie's and some bacterial species' density appear to be stronger than others. Increased colonization density and rhinitis may promote transmission of these commonly carried organisms.
  • Signs of Inequality? Variations in Providing Home Health Care Across Care Organizations and Across European Countries in the IBenC Study.

    van Hout, Hein Pj; van Lier, Lisanne; Draisma, Stasja; Smit, Jan; Finne-Soveri, Harriet; Garms-Homolová, Vjenka; Bosmans, Judith E; Declercq, Anja; Jónsson, Pálmi; Onder, Graziano; van der Roest, Henriëtte G; 1 Department of General Practice and Elderly Care Medicine, Amsterdam UMC, Vrije Universiteit, Amsterdam Public Health, Amsterdam, The Netherlands. 2 GGZ InGeest Mental Health Organization, Amsterdam, The Netherlands. 3 National Institute for Health and Welfare, Helsinki, Finland. 4 Department of Economics and Law, HTW Berlin University of Applied Sciences, Berlin, Germany. 5 Department of Health Sciences, Faculty Science, Vrije Universiteit Amsterdam, Amsterdam Public Health, Amsterdam, The Netherlands. 6 Centre for Sociological Research, LUCAS-KU Leuven, Leuven, Belgium. 7 Department of Geriatrics, Landspitali University Hospital, University of Iceland, Reykjavík, Iceland. 8 Department of Gerontology, Neuroscience and Orthopedics, Università Cattolica del Sacro Cuore, Rome, Italy. (SAGE Publications, 2019-04-18)
    Most countries aim to allocate home health care to those in need in a fair and equal way. Equal allocation implies that the amount of home care a person receives would reflect the level of health impairment and the need for resources. It is not clear whether countries succeed in attaining this. Our objective was to explore signs of (un)equal home health care provisioning across care organizations and across European health countries. We used data of the IBenC study collected from 2718 older community care recipients from 33 organizations in 6 Western European countries (www.ibenc.eu). We benchmarked differences of provided and expected formal care time across organizations and countries. Expected formal care hours were estimated by multiplying the overall sample's mean formal hours with recipients' case mix weights from interRAI's resources utilization group profiles. We found substantial variations in provided formal care time among organizations both within and across countries that could not be explained by the case mix differences of recipients. This implied presence of inequality of home care provisioning. These findings may alert professionals and policy makers striving for equal home health care provisioning for dependent older persons.
  • Pedicle Screw Placement Using Augmented Reality Surgical Navigation With Intraoperative 3D Imaging: A First In-Human Prospective Cohort Study.

    Elmi-Terander, Adrian; Burström, Gustav; Nachabe, Rami; Skulason, Halldor; Pedersen, Kyrre; Fagerlund, Michael; Ståhl, Fredrik; Charalampidis, Anastasios; Söderman, Michael; Holmin, Staffan; Babic, Drazenko; Jenniskens, Inge; Edström, Erik; Gerdhem, Paul; [ 1 ] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden Show more [ 2 ] Karolinska Univ Hosp, Dept Neurosurg, Stockholm, Sweden Show more [ 3 ] Philips Healthcare, Dept Image Guided Therapy Syst, Veenpluis 6, NL-5684 PC Best, Netherlands Show more [ 4 ] Landspitali Univ Hosp, Dept Neurosurg, Reykjavik, Iceland Show more [ 5 ] Karolinska Univ Hosp, Dept Neuroradiol, Stockholm, Sweden Show more [ 6 ] Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden Show more [ 7 ] Karolinska Univ Hosp, Dept Reconstruct Orthopaed, Stockholm, Sweden (Lippincott Williams & Wilkins, 2019-04-01)
    STUDY DESIGN: Prospective observational study. OBJECTIVE: The aim of this study was to evaluate the accuracy of pedicle screw placement using augmented reality surgical navigation (ARSN) in a clinical trial. SUMMARY OF BACKGROUND DATA: Recent cadaveric studies have shown improved accuracy for pedicle screw placement in the thoracic spine using ARSN with intraoperative 3D imaging, without the need for periprocedural x-ray. In this clinical study, we used the same system to place pedicle screws in the thoracic and lumbosacral spine of 20 patients. METHODS: The study was performed in a hybrid operating room with an integrated ARSN system encompassing a surgical table, a motorized flat detector C-arm with intraoperative 2D/3D capabilities, integrated optical cameras for augmented reality navigation, and noninvasive patient motion tracking. Three independent reviewers assessed screw placement accuracy using the Gertzbein grading on 3D scans obtained before wound closure. In addition, the navigation time per screw placement was measured. RESULTS: One orthopedic spinal surgeon placed 253 lumbosacral and thoracic pedicle screws on 20 consenting patients scheduled for spinal fixation surgery. An overall accuracy of 94.1% of primarily thoracic pedicle screws was achieved. No screws were deemed severely misplaced (Gertzbein grade 3). Fifteen (5.9%) screws had 2 to 4 mm breach (Gertzbein grade 2), occurring in scoliosis patients only. Thirteen of those 15 screws were larger than the pedicle in which they were placed. Two medial breaches were observed and 13 were lateral. Thirteen of the grade 2 breaches were in the thoracic spine. The average screw placement time was 5.2 ± 4.1 minutes. During the study, no device-related adverse event occurred. CONCLUSION: ARSN can be clinically used to place thoracic and lumbosacral pedicle screws with high accuracy and with acceptable navigation time. Consequently, the risk for revision surgery and complications could be minimized.
  • Cell Internalization in Fluidic Culture Conditions Is Improved When Microparticles Are Specifically Targeted to the Human Epidermal Growth Factor Receptor 2 (HER2).

    Mora-Espí, Inmaculada; Ibáñez, Elena; Soriano, Jorge; Nogués, Carme; Gudjonsson, Thorarinn; Barrios, Leonardo; 1 Unitat de Biologia Cel·lular, Departament de Biologia Cel·lular, Fisiologia i Immunologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain. xapaxin@gmail.com. 2 Unitat de Biologia Cel·lular, Departament de Biologia Cel·lular, Fisiologia i Immunologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain. Elena.ibanez@uab.cat. 3 Unitat de Biologia Cel·lular, Departament de Biologia Cel·lular, Fisiologia i Immunologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain. jorge.soriano@uab.cat. 4 Unitat de Biologia Cel·lular, Departament de Biologia Cel·lular, Fisiologia i Immunologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain. carme.nogues@uab.cat. 5 Biomedical Center, University of Iceland, 101 Reykjavík, Iceland. tgudjons@hi.is. 6 Department of Anatomy, Faculty of Medicine, and Department of Laboratory Hematology, University Hospital, 101 Reykjavik, Iceland. tgudjons@hi.is. 7 Unitat de Biologia Cel·lular, Departament de Biologia Cel·lular, Fisiologia i Immunologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain. lleonard.barrios@uab.cat. (MDPI, 2019-04-11)
    PURPOSE: To determine if the specific targeting of microparticles improves their internalization by cells under fluidic conditions. METHODS: Two isogenic breast epithelial cell lines, one overexpressing the Human Epidermal Growth Factor Receptor 2 (HER2) oncogene (D492HER2) and highly tumorigenic and the other expressing HER2 at much lower levels and non-tumorigenic (D492), were cultured in the presence of polystyrene microparticles of 1 µm in diameter, biofunctionalized with either a specific anti-HER2 antibody or a non-specific secondary antibody. Mono- and cocultures of both cell lines in static and fluidic conditions were performed, and the cells with internalized microparticles were scored. RESULTS: Globally, the D492 cell line showed a higher endocytic capacity than the D492HER2 cell line. Microparticles that were functionalized with the anti-HER2 antibody were internalized by a higher percentage of cells than microparticles functionalized with the non-specific secondary antibody. Although internalization was reduced in fluidic culture conditions in comparison with static conditions, the increase in the internalization of microparticles biofunctionalized with the anti-HER2 antibody was higher for the cell line overexpressing HER2. CONCLUSION: The biofunctionalization of microparticles with a specific targeting molecule remarkably increases their internalization by cells in fluidic culture conditions (simulating the blood stream). This result emphasizes the importance of targeting for future in vivo delivery of drugs and bioactive molecules through microparticles.
  • Assessing the Nationwide Impact of a Registry-Based Randomized Clinical Trial on Cardiovascular Practice.

    Buccheri, Sergio; Sarno, Giovanna; Fröbert, Ole; Gudnason, Thorarinn; Lagerqvist, Bo; Lindholm, Daniel; Maeng, Michael; Olivecrona, Göran; James, Stefan; 1 ] Uppsala Univ, Dept Med Sci, Cardiol, Dag Hammarskjolds Vag 38, S-75185 Uppsala, Sweden Show more [ 2 ] Uppsala Univ, Uppsala Clin Res Ctr, Dag Hammarskjolds Vag 38, S-75185 Uppsala, Sweden Show more [ 3 ] Orebro Univ Hosp, Dept Cardiol, Orebro, Sweden Show more [ 4 ] Landspitali Univ Hosp, Reykjavik, Iceland Show more [ 5 ] Univ Iceland, Dept Cardiol, Reykjavik, Iceland Show more [ 6 ] Univ Iceland, Cardiovasc Res Ctr, Reykjavik, Iceland Show more [ 7 ] Aarhus Univ Hosp, Dept Cardiol, Aarhus, Denmark Show more [ 8 ] Lund Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden (Lippincott Williams & Wilkins, 2019-03)
    BACKGROUND: Registry-based randomized clinical trials have emerged as useful tools to provide evidence on the comparative efficacy and safety of different therapeutic strategies. However, it remains unknown whether the results of registry-based randomized clinical trials have a sizable impact on daily clinical practice. We sought, therefore, to describe the temporal trends in thrombus aspiration (TA) use in Sweden before, during, and after dissemination of the TASTE trial (Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia) results. METHODS AND RESULTS: From January 1, 2006, to December 31, 2017, we included all consecutive patients with ST-segment-elevation myocardial infarction undergoing percutaneous revascularization in Sweden. All patients were registered in the Swedish Coronary Angiography and Angioplasty Registry. A total of 55 809 ST-segment-elevation myocardial infarction patients were included. TA use in Sweden substantially decreased after dissemination of TASTE results (from 39.8% to 11.8% during and after TASTE, respectively). Substantial variability in TA use across treating centers was observed before TASTE (TA use ranging from 0% to 70%), but after TASTE both the interhospital variability and the frequency of TA use were markedly reduced. A constant shift in medical practice was seen about 4 months after dissemination of the TASTE trial results. Time trends for all-cause mortality and definite stent thrombosis at 30 days were not associated with variations in TA use ( P values >0.05 using the Granger test). CONCLUSIONS: In Sweden, the results of the TASTE trial were impactful in daily clinical practice and led to a relevant decrease in TA use in ST-segment-elevation myocardial infarction patients undergoing percutaneous revascularization.
  • Kabuki syndrome: international consensus diagnostic criteria.

    Adam, Margaret P; Banka, Siddharth; Bjornsson, Hans T; Bodamer, Olaf; Chudley, Albert E; Harris, Jaqueline; Kawame, Hiroshi; Lanpher, Brendan C; Lindsley, Andrew W; Merla, Giuseppe; Miyake, Noriko; Okamoto, Nobuhiko; Stumpel, Constanze T; Niikawa, Norio; [ 1 ] Univ Washington, Sch Med, Dept Pediat, Div Med Genet, Seattle, WA 98195 USA Show more [ 2 ] Univ Manchester, Manchester Ctr Genom Med, Div Evolut & Genom Sci, Sch Biol Sci,Fac Biol Med & Hlth, Manchester, Lancs, England Show more [ 3 ] Manchester Univ NHS Fdn Trust, Hlth Innovat Manchester, St Marys Hosp, Manchester Ctr Genom Med, Manchester, Lancs, England Show more [ 4 ] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA Show more [ 5 ] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA Show more [ 6 ] Univ Iceland, Fac Med, Reykjavik, Iceland Show more [ 7 ] Landspitali Univ Hosp, Dept Genet & Mol Med, Reykjavik, Iceland Show more [ 8 ] Harvard Med Sch, Boston Childrens Hosp, Div Genet & Genom, Dept Med, Boston, MA 02115 USA Show more [ 9 ] Broad Inst & Harvard Univ, Div Genet & Genom, Cambridge, MA USA Show more [ 10 ] Univ Manitoba, Max Rady Coll Med, Rady Fac Hlth Sci, Dept Pediat & Child Hlth, Winnipeg, MB, Canada Show more [ 11 ] Univ Manitoba, Rady Fac Hlth Sci, Max Rady Coll Med, Dept Biochem & Med Genet, Winnipeg, MB, Canada Show more [ 12 ] Kennedy Krieger Inst, Dept Neurol, Baltimore, MD USA Show more [ 13 ] Kennedy Krieger Inst, Dept Pediat, Baltimore, MD USA Show more [ 14 ] Tohoku Univ, Sch Med, Dept Educ & Training, Sendai, Miyagi, Japan Show more [ 15 ] Mayo Clin, Hlth Sci Res, Ctr Individualized Med, Rochester, MN USA Show more [ 16 ] Mayo Clin, Dept Clin Genom, Rochester, MN USA Show more [ 17 ] Cincinnati Childrens Hosp Med Ctr, Div Allergy & Immunol, Cincinnati, OH 45229 USA Show more [ 18 ] Univ Cincinnati, Dept Pediat, Cincinnati, OH USA Show more [ 19 ] IRCCS Casa Sollievo Sofferenza, Div Med Genet, San Giovanni Rotondo, Italy Show more [ 20 ] Yokohama City Univ, Grad Sch Med, Dept Human Genet, Yokohama, Kanagawa, Japan [ 21 ] Osaka Womens & Childrens Hosp, Dept Med Genet, Izumi, Japan Show more [ 22 ] Maastricht Univ, Med Ctr, Dept Clin Genet, Maastricht, Netherlands Show more [ 23 ] Maastricht Univ, Med Ctr, GROW Sch Oncol & Dev Biol, Maastricht, Netherlands Show more [ 24 ] Hlth Sci Univ Hokkaido, Res Inst Personalized Hlth Sci, Tobetsu, Hokkaido, Japan (BMJ Publishing Group, 2019-02)
    BACKGROUND: Kabuki syndrome (KS) is a clinically recognisable syndrome in which 70% of patients have a pathogenic variant in KMT2D or KDM6A. Understanding the function of these genes opens the door to targeted therapies. The purpose of this report is to propose diagnostic criteria for KS, particularly when molecular genetic testing is equivocal. METHODS: An international group of experts created consensus diagnostic criteria for KS. Systematic PubMed searches returned 70 peer-reviewed publications in which at least one individual with molecularly confirmed KS was reported. The clinical features of individuals with known mutations were reviewed. RESULTS: The authors propose that a definitive diagnosis can be made in an individual of any age with a history of infantile hypotonia, developmental delay and/or intellectual disability, and one or both of the following major criteria: (1) a pathogenic or likely pathogenic variant in KMT2D or KDM6A; and (2) typical dysmorphic features (defined below) at some point of life. Typical dysmorphic features include long palpebral fissures with eversion of the lateral third of the lower eyelid and two or more of the following: (1) arched and broad eyebrows with the lateral third displaying notching or sparseness; (2) short columella with depressed nasal tip; (3) large, prominent or cupped ears; and (4) persistent fingertip pads. Further criteria for a probable and possible diagnosis, including a table of suggestive clinical features, are presented. CONCLUSION: As targeted therapies for KS are being developed, it is important to be able to make the correct diagnosis, either with or without molecular genetic confirmation.
  • COPD patients' experiences, self-reported needs, and needs-driven strategies to cope with self-management

    Sigurgeirsdottir, Jonina; Halldorsdottir, Sigridur; Arnardottir, Ragnheidur Harpa; Gudmundsson, Gunnar; Bjornsson, Eythor Hreinn; [ 1 ] Univ Iceland, Fac Med, Reykjavik, Iceland [ 2 ] Reykjalundur Rehabil Ctr, Mosfellsbaer, Iceland [ 3 ] Univ Akureyri, Sch Hlth Sci, Akureyri, Iceland [ 4 ] Akureyri Hosp, Dept Rehabil, Akureyri, Iceland [ 5 ] Uppsala Univ, Dept Med Sci Resp Allergy & Sleep Res, Uppsala, Sweden Show more [ 6 ] Landspitali Univ Hosp, Dept Resp Med, Reykjavik, Iceland (DOVE Medical Press, 2019-05)
    Background: COPD is a common cause of morbidity and mortality. The aim of this study was to explore patients' experiences, self-reported needs, and needs-driven strategies to cope with self-management of COPD. Patients and methods: In this phenomenological study, 10 participants with mild to severe COPD were interviewed 1-2 times, until data saturation was reached. In total, 15 in-depth interviews were conducted, recorded, transcribed, and analyzed. Results: COPD negatively affected participants' physical and psychosocial well-being, their family relationships, and social life. They described their experiences of COPD like fighting a war without weapons in an ever-shrinking world with a loss of freedom at most levels, always fearing possible breathlessness. Fourteen needs were identified and eight clusters of needs-driven strategies that participants used to cope with self-management of COPD. Coping with the reality of COPD, a life-threatening disease, meant coping with dyspnea, feelings of suffocation, indescribable smoking addiction, anxiety, and lack of knowledge about the disease. Reduced participation in family and social life meant loss of ability to perform usual and treasured activities. Having a positive mindset, accepting help and assuming healthy lifestyle was important, as well as receiving continuous professional health care services. The participants' needs-driven strategies comprised conducting financial arrangements, maintaining hope, and fighting their smoking addiction, seeking knowledge about COPD, thinking differently, facing the broken chain of health care, and struggling with accepting support. Procrastination and avoidance were also evident. Finally, the study also found that participants experienced a perpetuating cycle of dyspnea, anxiety, and fear of breathlessness due to COPD which could lead to more severe dyspnea and even panic attacks. Conclusion: COPD negatively affects patients' physical and psychosocial well-being, family relationships and, social life. Identifying patients' self-reported needs and needs-driven strategies can enable clinicians to empower patients by educating them to improve their self-management.

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