• 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.
    • Interactions between drugs and geriatric syndromes in nursing home and home care: results from Shelter and IBenC projects.

      Onder, Graziano; Giovannini, Silvia; Sganga, Federica; Manes-Gravina, Ester; Topinkova, Eva; Finne-Soveri, Harriet; Garms-Homolová, Vjenka; Declercq, Anja; van der Roest, Henriëtte G; Jónsson, Pálmi V; van Hout, Hein; Bernabei, Roberto; [ 1 ] Univ Cattolica Sacro Cuore, Dept Gerontol Neurosci & Orthoped, Ctr Med Invecchiamento, Largo F Vito 1, I-00168 Rome, Italy Show more [ 2 ] Charles Univ Prague, Dept Geriatr & Gerontol, Fac Med 1, Prague, Czech Republic Show more [ 3 ] Univ South Bohemia, Fac Hlth & Social Sci, Ceske Budejovice, Czech Republic Show more [ 4 ] Natl Inst Hlth & Welf, Helsinki, Finland [ 5 ] HTW Berlin Univ Appl Sci, Dept Econ & Law, Berlin, Germany Show more [ 6 ] Katholieke Univ Leuven, LUCAS, Leuven, Belgium Show more [ 7 ] Katholieke Univ Leuven, Ctr Sociol Res, Leuven, Belgium Show more [ 8 ] Vrije Univ Amsterdam Med Ctr, Amsterdam Publ Hlth Inst, Dept Gen Practice & Elderly Care Med, Amsterdam, Netherlands Show more [ 9 ] Univ Iceland, Dept Geriatr, Fac Med, Landspitali Univ Hosp, Reykjavik, Iceland (Springer, 2018-09-01)
      Drugs may interact with geriatric syndromes by playing a role in the continuation, recurrence or worsening of these conditions. Aim of this study is to assess the prevalence of interactions between drugs and three common geriatric syndromes (delirium, falls and urinary incontinence) among older adults in nursing home and home care in Europe. We performed a cross-sectional multicenter study among 4023 nursing home residents participating in the Services and Health for Elderly in Long-TERm care (Shelter) project and 1469 home care patients participating in the Identifying best practices for care-dependent elderly by Benchmarking Costs and outcomes of community care (IBenC) project. Exposure to interactions between drugs and geriatric syndromes was assessed by 2015 Beers criteria. 790/4023 (19.6%) residents in the Shelter Project and 179/1469 (12.2%) home care patients in the IBenC Project presented with one or more drug interactions with geriatric syndromes. In the Shelter project, 288/373 (77.2%) residents experiencing a fall, 429/659 (65.1%) presenting with delirium and 180/2765 (6.5%) with urinary incontinence were on one or more interacting drugs. In the IBenC project, 78/172 (45.3%) participants experiencing a fall, 80/182 (44.0%) presenting with delirium and 36/504 (7.1%) with urinary incontinence were on one or more interacting drugs. Drug-geriatric syndromes interactions are common in long-term care patients. Future studies and interventions aimed at improving pharmacological prescription in the long-term care setting should assess not only drug-drug and drug-disease interactions, but also interactions involving geriatric syndromes.
    • Sex differences in the spatial distribution of bone in relation to incident hip fracture: Findings from the AGES-Reykjavik study.

      Marques, Elisa A; Carballido-Gamio, Julio; Gudnason, Vilmundur; Sigurdsson, Gunnar; Sigurdsson, Sigurdur; Aspelund, Thor; Siggeirsdottir, Kristin; Launer, Lenore; Eiriksdottir, Gudny; Lang, Thomas; Harris, Tamara B; 1 National Institute on Aging, Intramural Research Program, Laboratory of Epidemiology and Population Sciences, Bethesda, MD, USA. Electronic address: emarques@ismai.pt. 2 Department of Radiology, School of Medicine, University of Colorado Denver, Denver, CO, USA. 3 Icelandic Heart Association Research Institute, Kópavogur, Iceland; University of Iceland, Reykjavik, Iceland. 4 Icelandic Heart Association Research Institute, Kópavogur, Iceland; University of Iceland, Reykjavik, Iceland; Landspitalinn University Hospital, Reykjavik, Iceland. 5 Icelandic Heart Association Research Institute, Kópavogur, Iceland. 6 Icelandic Heart Association Research Institute, Kópavogur, Iceland; Centre of Public Health Sciences, University of Iceland, Reykjavik, Iceland. 7 National Institute on Aging, Intramural Research Program, Laboratory of Epidemiology and Population Sciences, Bethesda, MD, USA. 8 Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA. (Elsevier Science, 2018-09-01)
      In this case-cohort study, we used data-driven computational anatomy approaches to assess within and between sex spatial differences in proximal femoral bone characteristics in relation to incident hip fracture. One hundred male and 234 female incident hip fracture cases, and 1047 randomly selected noncase subcohort participants (562 female) were chosen from the population-based AGES-Reykjavik study (mean age of 77 years). The baseline -i.e. before hip fracture- hip quantitative computed tomography scans of these subjects were analyzed using voxel-based morphometry, tensor-based morphometry, and surface-based statistical parametric mapping to assess the spatial distribution of volumetric bone mineral density (vBMD), internal structure, and cortical bone properties (thickness, vBMD and trabecular vBMD adjacent to the endosteal surface) of the proximal femur, respectively, in relation to incident hip fracture. Results showed that in both men and women: 1) the superior aspect of the femoral neck and the trochanteric region (except for cortical bone thickness) were consistently identified as being associated with incident hip fracture, and 2) differences in bone properties between noncases and incident hip fracture cases followed similar trends, were located at compatible regions, and manifested heterogeneity in the spatial distribution of their magnitude with focal regions showing larger differences. With respect to sex differences, most of the regions with a significant interaction between fracture group and sex showed: 1) differences of greater magnitude in men between noncases and incident hip fracture cases with different spatial distributions for all bone properties with the exception of cortical bone thickness, and 2) that while most of these regions showed better bone quality in male cases than in female cases, female cases showed higher vBMD in the principal compressive group and higher endotrabecular vBMD at several regions including the anterior, posterior, and lateral aspects of the proximal femur. These findings indicate the value of these image analysis techniques by providing unique information about the specific patterns of bone deterioration associated with incident hip fracture and their sex differences, highlighting the importance of looking to men and women separately in the assessment of hip fracture risk.
    • Low rate of reoperations after acute type A aortic dissection repair from The Nordic Consortium Registry.

      Pan, Emily; Gudbjartsson, Tomas; Ahlsson, Anders; Fuglsang, Simon; Geirsson, Arnar; Hansson, Emma C; Hjortdal, Vibeke; Jeppsson, Anders; Järvelä, Kati; Mennander, Ari; Nozohoor, Shahab; Olsson, Christian; Wickbom, Anders; Zindovic, Igor; Gunn, Jarmo; 1 Heart Center, Turku University Hospital, Turku, Finland; Department of Surgery, University of Turku, Turku, Finland. 2 Landspitali University Hospital and Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 3 Department of Cardiothoracic and Vascular Surgery, Örebro University Hospital, Orebro, Sweden; School of Health and Medicine, Orebro University, Orebro, Sweden. 4 Department of Thoracic and Cardiovascular Surgery, Aarhus University Hospital, Skejby, Denmark. 5 Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 6 Heart Center, Tampere University Hospital, Tampere, Finland; University of Tampere, Tampere, Finland. 7 Department of Cardiothoracic Surgery, Skane University Hospital, Lund, Sweden; Clinical Sciences, Lund University, Lund, Sweden. 8 Department of Thoracic and Cardiovascular Surgery, Karolinska University Hospital, Stockholm, Sweden. 9 Heart Center, Turku University Hospital, Turku, Finland; Department of Surgery, University of Turku, Turku, Finland. Electronic address: jarmo.gunn@tyks. (MOSBY-ELSEVIER, 2018-09-01)
      To describe the relationship between the extent of primary aortic repair and the incidence of reoperations after surgery for type A aortic dissection. A retrospective cohort of 1159 patients treated for type A aortic dissection at eight Nordic low- to medium-sized cardiothoracic centers from 2005 to 2014. Data were gathered from patient records and national registries. Patients were separately divided into 3 groups according to the distal anastomoses technique (ascending aorta [n = 791], hemiarch [n = 247], and total arch [n = 66]), and into 2 groups for proximal repair (aortic root replacement [n = 285] and supracoronary repair [n = 832]). Freedom from reoperation was estimated with cumulative incidence survival and Fine-Gray competing risk regression model was used to identify independent risk factors for reoperation. The median follow-up was 2.7 years (range, 0-10 years). Altogether 51 out of 911 patients underwent reoperation. Freedom from distal reoperation at 5 years was 96.9%, with no significant difference between the groups (P = .22). Freedom from proximal reoperation at 5 years was 97.8%, with no difference between the groups (P = .84). Neither DeBakey classification nor the extent of proximal or distal repair predicted freedom from a later reoperation. The only independent risk factor associated with a later proximal reoperation was a history of connective tissue disease. Type A aortic dissection repair in low- to medium-volume centers was associated with a low reoperation rate and satisfactory midterm survival. The extent of the primary repair had no significant influence on reoperation rate or midterm survival.
    • Associations between neutrophil recovery time, infections and relapse in pediatric acute myeloid leukemia

      Løhmann, Ditte J. A.; Asdahl, Peter H.; Abrahamsson, Jonas; Ha, Shau-Yin; Jónsson, Ólafur G.; Kaspers, Gertjan J. L.; Koskenvuo, Minna; Lausen, Birgitte; De Moerloose, Barbara; Palle, Josefine; Zeller, Bernward; Hasle, Henrik; [ 1 ] Aarhus Univ Hosp, Dept Pediat & Adolescent Med, Palle Juul Jensens Blvd 99, DK-8200 Aarhus N, Denmark Show more [ 2 ] Aarhus Univ Hosp, Dept Hematol, Aarhus, Denmark [ 3 ] Queen Silvia Childrens Hosp, Inst Clin Sci, Dept Pediat, Gothenburg, Sweden Show more [ 4 ] Queen Mary Hosp, Dept Pediat, Hong Kong, Hong Kong, Peoples R China [ 5 ] HKPHOSG, Hong Kong, Hong Kong, Peoples R China Show more [ 6 ] Landspitali Univ Hosp, Dept Pediat, Reykjavik, Iceland [ 7 ] VU Univ Med Ctr Amsterdam, Dept Pediat, The Hague, Netherlands Show more [ 8 ] Dutch Childhood Oncol Grp, The Hague, Netherlands Show more [ 9 ] Univ Helsinki, Div Hematol Oncol & Stem Cell Transplantat, Childrens Hosp, Helsinki, Finland Show more [ 10 ] Univ Copenhagen, Dept Pediat & Adolescent Med, Rigshosp, Copenhagen, Denmark Show more [ 11 ] Ghent Univ Hosp, Dept Pediat, Ghent, Belgium Show more [ 12 ] Uppsala Univ, Dept Womans & Childrens Hlth, Uppsala, Sweden Show more [ 13 ] Oslo Univ Hosp, Div Pediat & Adolescent Med, Oslo, Norway; Department of Pediatrics and Adolescent Medicine; Aarhus University Hospital; Aarhus Denmark; Department of Hematology; Aarhus University Hospital; Aarhus Denmark; Institution for Clinical Sciences; Department of Pediatrics; Queen Silvia Children's Hospital; Gothenburg Sweden; Department of Pediatrics; Queen Mary Hospital and Hong Kong Pediatric Hematology and Oncology Study Group (HKPHOSG); Hong Kong China; Department of Pediatrics; Landspitali University Hospital; Reykjavik Iceland; Department of Pediatrics; VU University Medical Center Amsterdam, and Dutch Childhood Oncology Group; The Hague The Netherlands; Division of Hematology-Oncology and Stem Cell Transplantation; Children's Hospital; University of Helsinki; Helsinki Finland; Department of Pediatrics and Adolescent Medicine; Rigshospitalet; University of Copenhagen; Copenhagen Denmark; Department of Pediatrics; Ghent University Hospital; Ghent Belgium; Department of Woman´s and Children´s Health; Uppsala University; Uppsala Sweden; Division of Pediatric and Adolescent Medicine; Oslo University Hospital; Oslo Norway; Department of Pediatrics and Adolescent Medicine; Aarhus University Hospital; Aarhus Denmark (Wiley, 2018-09)
      BACKGROUND: Children with acute myeloid leukemia (AML) treated similarly show different toxicity and leukemic responses. We investigated associations between neutrophil recovery time after the first induction course, infection and relapse in children treated according to NOPHO-AML 2004 and DB AML-01. PROCEDURE: Newly diagnosed patients with AML with bone marrow blast <5% between day 15 after the start of the treatment and the start of second induction course, and in complete remission after the second induction course were included (n = 279). Neutrophil recovery time was defined as the time from the start of the course to the last day with absolute neutrophil count <0.5 × 109 /l. Linear and Cox regressions were used to investigate associations. RESULTS: Neutrophil recovery time after the first induction course was positively associated with neutrophil recovery time after the remaining courses, and longer neutrophil recovery time (≥25 days) was associated with increased risk of grade 3-4 infections (hazard ratio 1.4, 95% confidence interval [CI], 1.1-1.8). Longer neutrophil recovery time after the first induction (>30 days) was associated with the increased risk of relapse (5-year cumulative incidence: 48% vs. 42%, hazard ratio 1.7, 95% CI, 1.1-2.6) for cases not treated with hematopoietic stem cell transplantation in first complete remission. CONCLUSION: Longer neutrophil recovery time after the first induction course was associated with grade 3-4 infections and relapse. If confirmed, this knowledge could be incorporated into risk stratification strategies in pediatric AML.
    • MAP1B mutations cause intellectual disability and extensive white matter deficit.

      Walters, G Bragi; Gustafsson, Omar; Sveinbjornsson, Gardar; Eiriksdottir, Valgerdur K; Agustsdottir, Arna B; Jonsdottir, Gudrun A; Steinberg, Stacy; Gunnarsson, Arni F; Magnusson, Magnus I; Unnsteinsdottir, Unnur; Lee, Amy L; Jonasdottir, Adalbjorg; Sigurdsson, Asgeir; Jonasdottir, Aslaug; Skuladottir, Astros; Jonsson, Lina; Nawaz, Muhammad S; Sulem, Patrick; Frigge, Mike; Ingason, Andres; Love, Askell; Norddhal, Gudmundur L; Zervas, Mark; Gudbjartsson, Daniel F; Ulfarsson, Magnus O; Saemundsen, Evald; Stefansson, Hreinn; Stefansson, Kari; 1 deCODE genetics/Amgen, Reykjavik, 101, Iceland. 2 Faculty of Medicine, University of Iceland, Reykjavik, 101, Iceland. 3 Department of Pharmacology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 405 30, Sweden. 4 Department of Radiology, Landspitali University Hospital, Fossvogur, Reykjavik, 108, Iceland. 5 School of Engineering and Natural Sciences, University of Iceland, Reykjavik, 101, Iceland. 6 Faculty of Electrical and Computer Engineering, University of Iceland, Reykjavik, 101, Iceland. 7 The State Diagnostic and Counselling Centre, Kopavogur, 200, Iceland. 8 deCODE genetics/Amgen, Reykjavik, 101, Iceland. hreinn@decode.is. 9 deCODE genetics/Amgen, Reykjavik, 101, Iceland. kstefans@decode.is. 10 Faculty of Medicine, University of Iceland, Reykjavik, 101, Iceland. kstefans@decode.is. (Nature Publishing Group, 2018-08-27)
      Discovery of coding variants in genes that confer risk of neurodevelopmental disorders is an important step towards understanding the pathophysiology of these disorders. Whole-genome sequencing of 31,463 Icelanders uncovers a frameshift variant (E712KfsTer10) in microtubule-associated protein 1B (MAP1B) that associates with ID/low IQ in a large pedigree (genome-wide corrected P = 0.022). Additional stop-gain variants in MAP1B (E1032Ter and R1664Ter) validate the association with ID and IQ. Carriers have 24% less white matter (WM) volume (β = -2.1SD, P = 5.1 × 10
    • Safety of the Deferral of Coronary Revascularization on the Basis of Instantaneous Wave-Free Ratio and Fractional Flow Reserve Measurements in Stable Coronary Artery Disease and Acute Coronary Syndromes.

      Escaned, Javier; Ryan, Nicola; Mejía-Rentería, Hernán; Cook, Christopher M; Dehbi, Hakim-Moulay; Alegria-Barrero, Eduardo; Alghamdi, Ali; Al-Lamee, Rasha; Altman, John; Ambrosia, Alphonse; Baptista, Sérgio B; Bertilsson, Maria; Bhindi, Ravinay; Birgander, Mats; Bojara, Waldemar; Brugaletta, Salvatore; Buller, Christopher; Calais, Fredrik; Silva, Pedro Canas; Carlsson, Jörg; Christiansen, Evald H; Danielewicz, Mikael; Di Mario, Carlo; Doh, Joon-Hyung; Erglis, Andrejs; Erlinge, David; Gerber, Robert T; Going, Olaf; Gudmundsdottir, Ingibjörg; Härle, Tobias; Hauer, Dario; Hellig, Farrel; Indolfi, Ciro; Jakobsen, Lars; Janssens, Luc; Jensen, Jens; Jeremias, Allen; Kåregren, Amra; Karlsson, Ann-Charlotte; Kharbanda, Rajesh K; Khashaba, Ahmed; Kikuta, Yuetsu; Krackhardt, Florian; Koo, Bon-Kwon; Koul, Sasha; Laine, Mika; Lehman, Sam J; Lindroos, Pontus; Malik, Iqbal S; Maeng, Michael; Matsuo, Hitoshi; Meuwissen, Martijn; Nam, Chang-Wook; Niccoli, Giampaolo; Nijjer, Sukhjinder S; Olsson, Hans; Olsson, Sven-Erik; Omerovic, Elmir; Panayi, Georgios; Petraco, Ricardo; Piek, Jan J; Ribichini, Flavo; Samady, Habib; Samuels, Bruce; Sandhall, Lennart; Sapontis, James; Sen, Sayan; Seto, Arnold H; Sezer, Murat; Sharp, Andrew S P; Shin, Eun-Seok; Singh, Jasvindar; Takashima, Hiroaki; Talwar, Suneel; Tanaka, Nobuhiro; Tang, Kare; Van Belle, Eric; van Royen, Niels; Varenhorst, Christoph; Vinhas, Hugo; Vrints, Christiaan J; Walters, Darren; Yokoi, Hiroyoshi; Fröbert, Ole; Patel, Manesh R; Serruys, Patrick; Davies, Justin E; Götberg, Matthias; 1 Hospital Clínico San Carlos, IDISSC, and Universidad Complutense de Madrid, Madrid, Spain. 2 Hammersmith Hospital, Imperial College London, London, United Kingdom. 3 CRUK & UCL Cancer Trials Centre, University College London, London, United Kingdom. 4 Hospital Universitario de Torrejón and Universidad Francisco de Vitoria, Madrid, Spain. 5 King Abdulaziz Medical City Cardiac Center, Riyadh, Saudi Arabia. 6 Colorado Heart and Vascular, Lakewood, Colorado. 7 Mesa, Arizona. 8 Hospital Prof. Doutor Fernando Fonseca, Amadora, Portugal. 9 Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden. 10 Royal North Shore Hospital, Sydney, Australia. 11 Department of Cardiology, Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden. 12 Gemeinschaftsklinikum Mittelrhein, Kemperhof Koblenz, Koblenz, Germany. 13 Cardiovascular Institute, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain. 14 St. Michaels Hospital, Toronto, Ontario, Canada. 15 Department of Cardiology, Faculty of Health, Örebro University, Örebro, Sweden. 16 Hospital Santa Maria, Lisbon, Portugal. 17 Kalmar County Hospital, and Linnaeus University, Faculty of Health and Life Sciences, Kalmar, Sweden. 18 Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark. 19 Department of Cardiology, Karlstad Hospital, Karlstad, Sweden. 20 Royal Brompton Hospital, Imperial College London, United Kingdom, and University of Florence, Florence, Italy. 21 Inje University Ilsan Paik Hospital, Daehwa-Dong, South Korea. 22 Pauls Stradins Clinical University Hospital, Riga, Latvia. 23 Conquest Hospital, St. Leonards-on-Sea, United Kingdom. 24 Sana Klinikum Lichtenberg, Lichtenberg, Germany. 25 Department of Cardiology, Reykjavik University Hospital, Reykjavik, Iceland. 26 Klinikum Oldenburg, European Medical School, Carl von Ossietzky University, Oldenburg, Germany. 27 Departments of Cardiology and Medical and Health Sciences, Linköping University, Linköping, Sweden. 28 Sunninghill Hospital, Johannesburg, South Africa. 29 University Magna Graecia, Catanzaro, Italy. 30 Imelda Hospital, Bonheiden, Belgium. 31 Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, and Unit of Cardiology, Capio S:t Görans Sjukhus, Stockholm, and Department of Medicine, Sundsvall Hospital, Sundsvall, Sweden. 32 Stony Brook University Medical Center, Stony Brook, New York. 33 Department of Internal Medicine, Västmanland Hospital Västerås, Västerås, Sweden. 34 Department of Cardiology, Halmstad Hospital, Halmstad, Sweden. 35 John Radcliffe Hospital, Oxford University Hospitals Foundation Trust, Oxford, United Kingdom. 36 Ain Shams University, Cairo, Egypt. 37 Fukuyama Cardiovascular Hospital, Fukuyama, Japan. 38 Charite Campus Virchow Klinikum, Universitaetsmedizin, Berlin, Germany. 39 Seoul National University Hospital, Seoul, South Korea. 40 Helsinki University Hospital, Helsinki, Finland. 41 Flinders University, Adelaide, Australia. 42 Department of Cardiology, St. Göran Hospital, Stockholm, Sweden. 43 Gifu Heart Center, Gifu, Japan. 44 Amphia Hospital, Breda, the Netherlands. 45 Keimyung University Dongsan Medical Center, Daegu, South Korea. 46 Catholic University of the Sacred Heart, Rome, Italy. 47 Departments of Cardiology and Radiology, Helsingborg Hospital, Helsingborg, Sweden. 48 Department of Cardiology, Sahlgrenska University Gothenburg, Sweden. 49 AMC Heart Center, Academic Medical Center, Amsterdam, the Netherlands. 50 University Hospital Verona, Verona, Italy. 51 Emory University, Atlanta, Georgia. 52 Cedars-Sinai Heart Institute, Los Angeles, California. 53 MonashHeart and Monash University, Melbourne, Australia. 54 Veterans Affairs Long Beach Healthcare System, Long Beach, California. 55 Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey. 56 Royal Devon and Exeter Hospital and University of Exeter, Exeter, United Kingdom. 57 Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea. 58 Washington University School of Medicine, St. Louis, Missouri. 59 Aichi Medical University Hospital, Aichi, Japan. 60 Royal Bournemouth General Hospital, Bournemouth, United Kingdom. 61 Tokyo Medical University, Tokyo, Japan. 62 Essex Cardiothoracic Centre, Basildon and Anglia Ruskin University, Chelmsford, United Kingdom. 63 Institut Coeur Poumon, Lille University Hospital, and INSERM Unité 1011, Lille, France. 64 VU University Medical Center, Amsterdam, the Netherlands. 65 Department of Medical Sciences, Uppsala University, Uppsala, Sweden. 66 Hospital Garcia de Horta, Lisbon, Portugal. 67 Antwerp University Hospital, Antwerp, Belgium. 68 Prince Charles Hospital, Brisbane, Australia. 69 Fukuoka Sannou Hospital, Fukuoka, Japan. 70 Duke University, Durham, North Carolina. 71 Department of Cardiology, Imperial College London, London, United Kingdom. 72 Hammersmith Hospital, Imperial College London, London, United Kingdom. Electronic address: justindavies@heart123.com. (Elsevier Science, 2018-08-13)
      The aim of this study was to investigate the clinical outcomes of patients deferred from coronary revascularization on the basis of instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) measurements in stable angina pectoris (SAP) and acute coronary syndromes (ACS). Assessment of coronary stenosis severity with pressure guidewires is recommended to determine the need for myocardial revascularization. The safety of deferral of coronary revascularization in the pooled per-protocol population (n = 4,486) of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) and iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome) randomized clinical trials was investigated. Patients were stratified according to revascularization decision making on the basis of iFR or FFR and to clinical presentation (SAP or ACS). The primary endpoint was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year. Coronary revascularization was deferred in 2,130 patients. Deferral was performed in 1,117 patients (50%) in the iFR group and 1,013 patients (45%) in the FFR group (p < 0.01). At 1 year, the MACE rate in the deferred population was similar between the iFR and FFR groups (4.12% vs. 4.05%; fully adjusted hazard ratio: 1.13; 95% confidence interval: 0.72 to 1.79; p = 0.60). A clinical presentation with ACS was associated with a higher MACE rate compared with SAP in deferred patients (5.91% vs. 3.64% in ACS and SAP, respectively; fully adjusted hazard ratio: 0.61 in favor of SAP; 95% confidence interval: 0.38 to 0.99; p = 0.04).
    • Reluctance of patients with chronic obstructive pulmonary disease in its early stages and their families to participate in a partnership-based self-management trial: A search for explanation.

      Jónsdóttir, Helga; Ingadóttir, Thorbjörg Sóley; [ 1 ] Univ Iceland, Sch Hlth Sci, Fac Nursing, Eiriksgata 34, IS-107 Reykjavik, Iceland Show more [ 2 ] Landspitali Univ Hosp, Dept Resp Med & Sleep, Reykjavik, Iceland (SAGE Publications, 2018-08-01)
      Recruitment, the process of accessing, screening, selecting and retaining participants for research remains a challenge. In a randomized controlled trial, partnership-based self-management intervention for patients who have chronic obstructive pulmonary disease (COPD) in its initial stages, and their families, a theoretical framework developed for patients with an advanced COPD and their families was modified and implemented in a primary care context. In contrast to recruitment to the original study where 4% decline participation, in this study 25% of the potential patients declined participation. Although participants were encouraged to bring a family member, only 25% of them did so. The main reason for not being accompanied by a family member was that patients did not want anybody accompany them. Those who had quit smoking were more often accompanied by a family member compared to those who smoked. Reviewing the literature, the most compelling explanations for non-participation are shame and self-blame due to smoking, and that potential participants may not have envisioned any benefits from participating since they might not have realized that they had COPD. An alternative recruitment process needs to embrace the situation that potential participants find themselves in and which takes account of the issues at stake.
    • Use of complementary therapies in nursing homes: Descriptive study.

      Gunnarsdottir, Thora Jenny; Vilhjalmsson, Runar; Hjaltadottir, Ingibjorg; 1 Faculty of Nursing, University of Iceland, Iceland. Electronic address: thoraj@hi.is. 2 Faculty of Nursing, University of Iceland, Iceland. Electronic address: runarv@hi.is. 3 Faculty of Nursing, University of Iceland, Iceland; National University Hospital, Reykjavik, Iceland. Electronic address: ingihj@hi.is. (Elsevier, 2018-08-01)
      Complementary therapies may have positive effect on residents in nursing homes. The aim of this research was to investigate what kind of complementary therapies are provided in Icelandic nursing homes and who are the providers. Also whether the nursing homes need assistance to support the use of such therapies. A questionnaire was mailed to all the nursing homes in Iceland (N = 59). Total of forty-five nursing homes replied or 76% response rate. Registered nurses and licenced practical did most of the planning and provision of complementary therapies. The most common therapies were: heat packs, physical exercise and massage. Managers would like to have more knowledge and support in providing complementary therapies. The use of some complementary therapies is common in Icelandic nursing homes. More knowledge is needed to support the use of CT in Icelandic nursing homes.
    • Two components of the new ESPEN diagnostic criteria for malnutrition are independent predictors of lung function in hospitalized patients with chronic obstructive pulmonary disease (COPD)

      Ingadottir, Arora Ros; Beck, Anne Marie; Baldwin, Christine; Weekes, C. Elizabeth; Geirsdottir, Olof Gudny; Ramel, Alfons; Gislason, Thorarinn; Gunnarsdottir, Ingibjorg; 1 ] Univ Iceland, Landspitali Univ Hosp, Unit Nutr Res, Reykjavik, Iceland Show more [ 2 ] Univ Iceland, Fac Food Sci & Nutr, Reykjavik, Iceland Show more [ 3 ] Landspitali Univ Hosp, Dept Clin Nutr, Reykjavik, Iceland [ 4 ] Metropolitan Univ Coll, Fac Hlth & Technol, Dept Nutr & Hlth, Copenhagen N, Denmark [ 5 ] Herlev & Gentofte Hosp, Res Unit Nutr, DK-2820 Gentofte, Denmark Show more [ 6 ] Kings Coll London, Div Diabet & Nutr Sci, London, England Show more [ 7 ] Landspitali Univ Hosp, Iceland Gerontol Res Ctr, Reykjavik, Iceland Show more [ 8 ] Univ Iceland, Reykjavik, Iceland Show more [ 9 ] Univ Iceland, Fac Med, Reykjavik, Iceland Show more [ 10 ] Landspitali Univ Hosp, Dept Resp Med & Sleep, Reykjavik, Icelan (Churchill Livingstone, 2018-08)
      INTRODUCTION: Low fat free mass index (FFMI) is a component of the ESPEN diagnosis criteria of malnutrition, that only when accompanied with weight loss is considered to be a determinant of malnutrition. Our aims were to assess the prevalence of malnutrition in patients with chronic obstructive pulmonary disease (COPD) applying the ESPEN criteria, and to examine the ability of different components of the criteria to predict COPD severity, length of stay (LOS), hospital readmissions within 30 days and mortality. METHODS: Subjects were COPD patients (n = 121) admitted to Landspitali University Hospital from March 2015 to March 2016. Patients were screened for nutritional risk using Icelandic screening tool (ISS) and NRS-2002. Body composition was measured by bioelectrical impedance analysis (BIA). Lung function was measured by spirometry. RESULTS: The prevalence of malnutrition according to the ESPEN criteria was 21%. The association between nutritional assessment, applying different components of the ESPEN criteria, and COPD severity was highly significant, with the highest risk being associated with low FFMI OR (95% CI) 4.77 (2.03, 11.20; p < 0.001). There was a trend towards higher risk of hospitalization for >7 days in subjects with low FFMI (OR 2.46 95% CI 0.92, 6.59; p = 0.074) and increased risk of 6 and 9 months' mortality (OR 2.72 95% CI 0.88, 8.39, P = 0.082 and OR 2.72 95% CI 0.94, 7.87, P = 0.065, respectively) in subjects diagnosed as malnourished by the ESPEN criteria. CONCLUSION: This study describes the prevalence of malnutrition in hospitalized COPD patients using the ESPEN criteria from 2015. Our findings suggest that FFMI could be used independently of weight loss for the diagnosis of malnutrition in COPD patients, although there remain some problems associated with its measurement in the clinical setting.
    • Incidence of kidney stone disease in Icelandic children and adolescents from 1985 to 2013: results of a nationwide study.

      Edvardsson, Vidar O; Ingvarsdottir, Solborg E; Palsson, Runolfur; Indridason, Olafur S; 1 Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland. vidare@landspitali.is. 2 Children's Medical Center, Landspitali-The National University Hospital of Iceland, 101, Reykjavik, Iceland. vidare@landspitali.is. 3 Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland. 4 Children's Medical Center, Landspitali-The National University Hospital of Iceland, 101, Reykjavik, Iceland. 5 Division of Nephrology, Internal Medicine Services, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. (Springer, 2018-08)
      We found a significant increase in the incidence of childhood kidney stone disease, driven by a dramatic increase of stone frequency in teenage females which is poorly understood and warrants further study.
    • PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity

      van Setten, Jessica; Brody, Jennifer A.; Jamshidi, Yalda; Swenson, Brenton R.; Butler, Anne M.; Campbell, Harry; Del Greco, Fabiola M.; Evans, Daniel S.; Gibson, Quince; Gudbjartsson, Daniel F.; Kerr, Kathleen F.; Krijthe, Bouwe P.; Lyytikäinen, Leo-Pekka; Müller, Christian; Müller-Nurasyid, Martina; Nolte, Ilja M.; Padmanabhan, Sandosh; Ritchie, Marylyn D.; Robino, Antonietta; Smith, Albert V.; Steri, Maristella; Tanaka, Toshiko; Teumer, Alexander; Trompet, Stella; Ulivi, Sheila; Verweij, Niek; Yin, Xiaoyan; Arnar, David O.; Asselbergs, Folkert W.; Bader, Joel S.; Barnard, John; Bis, Josh; Blankenberg, Stefan; Boerwinkle, Eric; Bradford, Yuki; Buckley, Brendan M.; Chung, Mina K.; Crawford, Dana; den Hoed, Marcel; Denny, Josh C.; Dominiczak, Anna F.; Ehret, Georg B.; Eijgelsheim, Mark; Ellinor, Patrick T.; Felix, Stephan B.; Franco, Oscar H.; Franke, Lude; Harris, Tamara B.; Holm, Hilma; Ilaria, Gandin; Iorio, Annamaria; Kähönen, Mika; Kolcic, Ivana; Kors, Jan A.; Lakatta, Edward G.; Launer, Lenore J.; Lin, Honghuang; Lin, Henry J.; Loos, Ruth J. F.; Lubitz, Steven A.; Macfarlane, Peter W.; Magnani, Jared W.; Leach, Irene Mateo; Meitinger, Thomas; Mitchell, Braxton D.; Munzel, Thomas; Papanicolaou, George J.; Peters, Annette; Pfeufer, Arne; Pramstaller, Peter P.; Raitakari, Olli T.; Rotter, Jerome I.; Rudan, Igor; Samani, Nilesh J.; Schlessinger, David; Silva Aldana, Claudia T.; Sinner, Moritz F.; Smith, Jonathan D.; Snieder, Harold; Soliman, Elsayed Z.; Spector, Timothy D.; Stott, David J.; Strauch, Konstantin; Tarasov, Kirill V.; Thorsteinsdottir, Unnur; Uitterlinden, Andre G.; Van Wagoner, David R.; Völker, Uwe; Völzke, Henry; Waldenberger, Melanie; Jan Westra, Harm; Wild, Philipp S.; Zeller, Tanja; Alonso, Alvaro; Avery, Christy L.; Bandinelli, Stefania; Benjamin, Emelia J.; Cucca, Francesco; Dörr, Marcus; Ferrucci, Luigi; Gasparini, Paolo; Gudnason, Vilmundur; Hayward, Caroline; Heckbert, Susan R.; Hicks, Andrew A.; Jukema, J. Wouter; Kääb, Stefan; Lehtimäki, Terho; Liu, Yongmei; Munroe, Patricia B.; Parsa, Afshin; Polasek, Ozren; Psaty, Bruce M.; Roden, Dan M.; Schnabel, Renate B.; Sinagra, Gianfranco; Stefansson, Kari; Stricker, Bruno H.; van der Harst, Pim; van Duijn, Cornelia M.; Wilson, James F.; Gharib, Sina A.; de Bakker, Paul I. W.; Isaacs, Aaron; Arking, Dan E.; Sotoodehnia, Nona; Show more [ 1 ] Univ Utrecht, Univ Med Ctr Utrecht, Dept Cardiol, NL-3584 CX Utrecht, Netherlands Show more [ 2 ] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA Show more [ 3 ] St Georges Univ London, Cardiogenet Lab, Mol & Clin Sci Res Inst, London SW17 0RE, England Show more [ 4 ] Univ Washington, Inst Publ Hlth Genet, Sch Publ Hlth, Seattle, WA 98195 USA Show more [ 5 ] Washington Univ, Sch Med, Div Infect Dis, St Louis, MO 63110 USA Show more [ 6 ] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh EH8 9YL, Midlothian, Scotland Show more [ 7 ] Univ Lubeck, Inst Biomed, Affiliated Inst, Eurac Res, I-39100 Bolzano, Italy Show more [ 8 ] Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94107 USA Show more [ 9 ] Univ Alabama Birmingham Hosp, Dept Surg, Birmingham, AL 35233 USA [ 10 ] DeCODE Genet Amgen Inc, IS-101 Reykjavik, Iceland Show more [ 11 ] Univ Iceland, Sch Engn & Nat Sci, IS-101 Reykjavik, Iceland Show more [ 12 ] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA Show more [ 13 ] Erasmus MC, Dept Epidemiol, NL-3015 GD Rotterdam, Netherlands [ 14 ] Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland Show more [ 15 ] Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr Tampere, Dept Clin Chem, Tampere 33014, Finland Show more [ 16 ] Univ Heart Ctr Hamburg Eppendorf, Dept Gen & Intervent Cardiol, D-20251 Hamburg, Germany Show more [ 17 ] DZHK German Ctr Cardiovasc Res, Partner Site, Hamburg, Germany Show more [ 18 ] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, D-85764 Neuherberg, Germany Show more [ 19 ] Hosp Ludwig Maximilians Univ LMU Munich, Dept Internal Med Cardiol 1, D-81377 Munich, Germany Show more [ 20 ] DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, D-80802 Munich, Germany Show more [ 21 ] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-9713GZ Groningen, Netherlands Show more [ 22 ] Univ Glasgow, Coll Med Vet & Life Sci, Inst Cardiovasc & Med Sci, Glasgow G12 8TA, Lanark, Scotland Show more [ 23 ] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA Show more [ 24 ] IRCCS Burlo Garofolo, Inst Maternal & Child Health, I-34137 Trieste, Italy [ 25 ] Iceland Heart Assoc, IS-201 Kopavogur, Iceland Show more [ 26 ] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland Show more [ 27 ] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA Show more [ 28 ] CNR, Ist Ric Genet & Biomed, I-00185 Cagliari, Italy Show more [ 29 ] NIA, Translat Gerontol Branch, Bethesda, MD 20892 USA Show more [ 30 ] Univ Med Greifswald, Inst Community Med, D-17489 Greifswald, Germany Show more [ 31 ] DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, D-17475 Greifswald, Germany Show more [ 32 ] Leiden Univ, Med Ctr, Dept Cardiol, NL-2300 RC Leiden, Netherlands Show more [ 33 ] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, NL-2300 RC Leiden, Netherlands Show more [ 34 ] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, NL-7913GZ Groningen, Netherlands Show more [ 35 ] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA Show more [ 36 ] Landspitali Univ Hosp, Dept Med, IS-101 Reykjavik, Iceland [ 37 ] Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands Show more [ 38 ] UCL, Fac Populat Hlth Sci, Inst Cardiovasc Sci, London WC1E 6BT, England Show more [ 39 ] UCL, Farr Inst Hlth Informat Res, London WC1E 6BT, England Show more [ 40 ] UCL, Inst Hlth Informat, London WC1E 6BT, England Show more [ 41 ] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA Show more [ 42 ] Cleveland Clin, Lerner Res Inst, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA Show more [ 43 ] Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX 77030 USA Show more [ 44 ] Univ Coll Cork, Dept Pharmacol & Therapeut, Cork T12 K8AF, Ireland Show more [ 45 ] Cleveland Clin, Heart & Vasc Inst, Dept Cardiovasc Med, Cleveland, OH 44195 USA Show more [ 46 ] Cleveland Clin, Lerner Res Inst, Dept Mol Cardiol, Cleveland, OH 44195 USA Show more [ 47 ] Case Western Reserve Univ, Inst Computat Biol, Dept Populat & Quantitat Hlth Sci, Cleveland, OH 44106 USA Show more [ 48 ] Uppsala Univ, Dept Immunol Genet & Pathol, SE-75105 Uppsala, Sweden Show more [ 49 ] Uppsala Univ, Sci Life Lab, SE-75105 Uppsala, Sweden Show more [ 50 ] Vanderbilt Univ, Biomed Informat & Med, 221 Kirkland Hall, Nashville, TN 37235 USA Show more [ 51 ] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD 21287 USA Show more [ 52 ] Univ Med Ctr Groningen, Dept Nephrol, NL-7913GZ Groningen, Netherlands Show more [ 53 ] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA Show more [ 54 ] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA Show more [ 55 ] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA Show more [ 56 ] Univ Med Greifswald, Dept Internal Med B, D-17489 Greifswald, Germany Show more [ 57 ] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-7913GZ Groningen, Netherlands Show more [ 58 ] NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, Bethesda, MD 20892 USA Show more [ 59 ] Univ Trieste, Dept Med Sci, I-34127 Trieste, Italy [ 60 ] Osped Riuniti, Cardiovasc Dept, I-34124 Trieste, Italy Show more [ 61 ] Univ Trieste, I-34124 Trieste, Italy Show more [ 62 ] Tampere Univ Hosp, Dept Clin Physiol, Tampere 33521, Finland Show more [ 63 ] Univ Tampere, Finnish Cardiovasc Res Ctr Tampere, Fac Med & Life Sci, Dept Clin Physiol, Tampere 33014, Finland Show more [ 64 ] Univ Split, Fac Med, Split 21000, Croatia Show more [ 65 ] Erasmus Univ, Med Ctr, Dept Med Informat, NL-3015 GD Rotterdam, Netherlands Show more [ 66 ] NIA, Lab Cardiovasc Sci, NIH, Bethesda, MD 20892 USA Show more [ 67 ] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Dept Pediat, Torrance, CA 90502 USA Show more [ 68 ] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA Show more [ 69 ] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA Show more [ 70 ] Univ Glasgow, Inst Hlth & Wellbeing, Coll Med Vet & Life Sci, Glasgow G12 8QQ, Lanark, Scotland Show more [ 71 ] Univ Pittsburgh, Med Ctr, Heart & Vasc Inst, Dept Med,Div Cardiol, Pittsburgh, PA 15260 USA Show more [ 72 ] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, D-85764 Neuherberg, Germany Show more [ 73 ] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-81675 Munich, Germany Show more [ 74 ] Univ Maryland, Geriatr Res & Educ Clin Ctr, Baltimore VA Med Ctr, Dept Med,Sch Med, Baltimore, MD 21201 USA Show more [ 75 ] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Ctr Cardiol, D-55131 Mainz, Germany Show more [ 76 ] DZHK German Ctr Cardiovasc Res, Partner Site Rhine Main, D-55131 Mainz, Germany Show more [ 77 ] Johannes Gutenberg Univ Mainz, Univ Med Ctr, CTVB, D-55131 Mainz, Germany Show more [ 78 ] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA Show more [ 79 ] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, D-85764 Neuherberg, Germany [ 80 ] German Ctr Diabet Res, D-85764 Neuherberg, Germany [ 81 ] MVZ Molekulardiagnost, D-81543 Munich, Germany [ 82 ] Cent Hosp, Dept Neurol, I-39100 Bolzano, Italy Show more [ 83 ] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku 20521, Finland Show more [ 84 ] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku 20014, Finland Show more [ 85 ] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Dept Med, Torrance, CA 90502 USA Show more [ 86 ] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Dept Pediat, Torrance, CA 90502 USA Show more [ 87 ] Univ Leicester, Dept Cardiovasc Sci, Leicester LE1 7RH, Leics, England [ 88 ] NIHR Leicester Biomed Res Ctr, Leicester LE3 9QD, Leics, England Show more [ 89 ] NIA, Lab Genet & Gen, NIH, Baltimore, MD 20892 USA Show more [ 90 ] Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, NL-3015 GD Rotterdam, Netherlands Show more [ 91 ] Univ Rosario, Sch Med & Hlth Sci, Ctr Res Genet & Genom CIGGUR, GENIUROS Res Grp,Inst Translat Med IMT, Cl 12c 6-25, Bogota, Colombia Show more [ 92 ] Cleveland Clin, Lerner Res Inst, Dept Cellular & Mol Med Biol, Cleveland, OH 44195 USA Show more [ 93 ] Wake Forest Sch Med, Epidemiol Cardiol Res Ctr, Winston Salem, NC 27101 USA Show more [ 94 ] Kings Coll London, St Thomas Hosp, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England Show more [ 95 ] Ludwig Maximilians Univ Munchen, Fac Med, IBE, Chair Genet Epidemiol, D-81377 Munich, Germany Show more [ 96 ] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland Show more [ 97 ] Erasmus MC, Dept Internal Med, NL-3015 GD Rotterdam, Netherlands Show more [ 98 ] Univ Med Greifswald, Interfac Inst Genet & Funct Genom, D-17489 Greifswald, Germany Show more [ 99 ] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, D-85764 Neuherberg, Germany Show more [ 100 ] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Ctr Cardiol, Prevent Cardiol & Prevent Med, D-55131 Mainz, Germany Show more [ 101 ] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Ctr Thrombosis & Hemostasis, D-55131 Mainz, Germany Show more [ 102 ] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA Show more [ 103 ] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA Show more [ 104 ] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC 27514 USA [ 105 ] ASF, Geriatr Unit, I-50122 Florence, Italy Show more [ 106 ] Univ Edinburgh, Inst Genet & Mol Med, Med Res Council, Human Genet Unit, Edinburgh EH8 9YL, Midlothian, Scotland Show more [ 107 ] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA Show more [ 108 ] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA Show more [ 109 ] Leiden Univ, Med Ctr, Einthoven Lab Expt Vasc Med, NL-2300 RC Leiden, Netherlands Show more [ 110 ] Interuniv Cardiol Inst Netherlands, NL-3511EP Utrecht, Netherlands Show more [ 111 ] Wake Forest Univ, Div Publ Hlth Sci, Dept Epidemiol & Prevent, Winston Salem, NC 27101 USA Show more [ 112 ] Queen Mary Univ London, William Harvey Res Inst, Clin Pharmacol, London E1 4NS, England Show more [ 113 ] Barts Hlth NHS Trust & Queen Mary Univ London, NIHR Biomed Res Ctr, London E1 4NS, England Show more [ 114 ] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA Show more [ 115 ] Baltimore VA Med Ctr, Baltimore, MD 21201 USA [ 116 ] Psychiat Hosp Sveti Ivan, Zagreb 10000, Croatia [ 117 ] Gen Info Ltd, Zagreb 10000, Croatia Show more [ 118 ] Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA Show more [ 119 ] Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol & Hlth Serv, Seattle, WA 98195 USA [ 120 ] Kaiser Permanente Washington Hlth Res Inst, Seattle, WA 98101 USA Show more [ 121 ] Vanderbilt Univ, Med Pharmacol & Biomed Informat, Nashville, TN 37235 USA Show more [ 122 ] Erasmus MC, Dept Internal Med, NL-3015 GD Rotterdam, Netherlands [ 123 ] Inspectorate Hlth Care, NL-2511VX The Hague, Netherlands Show more [ 124 ] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-7913GZ Groningen, Netherlands [ 125 ] Netherlands Heart Inst, ICIN, Durrer Ctr Cardiogenet Res, NL-3511EP Utrecht, Netherlands Show more [ 126 ] Univ Washington, Div Pulm Crit Care & Sleep Med, Computat Med Core Ctr Lung Biol, Cardiovasc Hlth Res Unit,Dept Med, Seattle, WA 98195 USA Show more [ 127 ] Univ Med Ctr Utrecht, Ctr Mol Med, Dept Genet, NL-3584 CX Utrecht, Netherlands Show more [ 128 ] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, NL-3584 CX Utrecht, Netherlands [ 129 ] CARIM Sch Cardiovasc Dis, NL-6229ER Maastricht, Netherlands Show more [ 130 ] Maastricht Univ, Ctr Syst Biol MaCSBio, NL-6229ER Maastricht, Netherlands Show more [ 131 ] Maastricht Univ, Dept Biochem, NL-6229ER Maastricht, Netherlands Show more [ 132 ] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21287 USA Show more [ 133 ] Univ Washington, Cardiovasc Hlth Res Unit, Div Cardiol, Dept Med, Seattle, WA 98101 USA Show more [ 134 ] Univ Washington, Cardiovasc Hlth Res Unit, Div Cardiol, Dept Epidemiol, Seattle, WA 98101 USA (Nature Publishing Group, 2018-07-25)
      Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity. Genes in these loci are over-represented in cardiac disease processes including heart block and atrial fibrillation. Variants in over half of the 44 loci were associated with atrial or blood transcript expression levels, or were in high linkage disequilibrium with missense variants. Six additional loci were identified either by meta-analysis of ~105,000 African and European-descent individuals and/or by pleiotropic analyses combining PR interval with heart rate, QRS interval, and atrial fibrillation. These findings implicate developmental pathways, and identify transcription factors, ion-channel genes, and cell-junction/cell-signaling proteins in atrio-ventricular conduction, identifying potential targets for drug development.
    • EEG Theta Power Is an Early Marker of Cognitive Decline in Dementia due to Alzheimer’s Disease

      Musaeus, Christian Sandøe; Engedal, Knut; Høgh, Peter; Jelic, Vesna; Mørup, Morten; Naik, Mala; Oeksengaard, Anne-Rita; Snaedal, Jon; Wahlund, Lars-Olof; Waldemar, Gunhild; Andersen, Birgitte Bo; 1 ] Univ Copenhagen, Rigshosp, DDRC, Dept Neurol, Copenhagen, Denmark [ 2 ] Vestfold Hosp Trust, Norwegian Natl Advisory Unit Ageing & Hlth Ageing, Oslo, Norway Show more [ 3 ] Oslo Univ Hosp, Oslo, Norway [ 4 ] Zealand Univ Hosp, Dept Neurol, Reg Dementia Res Ctr, Roskilde, Denmark Show more [ 5 ] Univ Copenhagen, Dept Clin Med, Copenhagen, Denmark Show more [ 6 ] Karolinska Institutet, Div Clin Geriatr Care Sci & Soc, Dept Neurobiol, Stockholm, Sweden Show more [ 7 ] Karolinska Univ Hosp Huddinge, Clin Cognit Disorders, Theme Aging, Huddinge, Sweden Show more [ 8 ] Tech Univ Denmark, Sect Cognit Syst, DTU Compute, Lyngby, Denmark [ 9 ] Haraldsplass Deaconess Hosp, Dept Geriatr Med, Bergen, Norway Show more [ 10 ] Landspitali Univ Hosp, Dept Geriatr Med, Reykjavik, Iceland; Department of Neurology, Danish Dementia Research Centre (DDRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Norwegian National Advisory Unit on Ageing and Health (Ageing and Health), Vestfold Hospital Trust and Oslo University Hospital, Ullevaal, Oslo, Norway; Regional Dementia Research Center, Department of Neurology, Zealand University Hospital, Roskilde, Denmark and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; Department of Neurobiology, Division of Clinical Geriatrics, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Section for Cognitive Systems, DTU Compute, Technical University of Denmark, Lyngby, Denmark; Department of Geriatric Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway; Department of Neurobiology, Division of Clinical Geriatrics, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Department of Geriatric Medicine, Landspítali University Hospital, Reykjavik, Iceland; Department of Neurobiology, Division of Clinical Geriatrics, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden; Department of Neurology, Danish Dementia Research Centre (DDRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Department of Neurology, Danish Dementia Research Centre (DDRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark (IOS Press, 2018-07-24)
      BACKGROUND: Quantitative EEG (qEEG) power could potentially be used as a diagnostic tool for Alzheimer's disease (AD) and may further our understanding of the pathophysiology. However, the early qEEG power changes of AD are not well understood. OBJECTIVE: To investigate the early changes in qEEG power and the possible correlation with memory function and cerebrospinal fluid biomarkers. In addition, whether qEEG power could discriminate between AD, mild cognitive impairment (MCI), and older healthy controls (HC) at the individual level. METHODS: Standard EEGs from 138 HC, 117 MCI, and 117 AD patients were included from six Nordic memory clinics. All EEGs were recorded consecutively before the diagnosis and were not used for the consensus diagnosis. Absolute and relative power was calculated for both eyes closed and open condition. RESULTS: At group level using relative power, we found significant increases globally in the theta band and decreases in high frequency power in the temporal regions for eyes closed for AD and, to a lesser extent, for MCI compared to HC. Relative theta power was significantly correlated with multiple neuropsychological measures and had the largest correlation coefficient with total tau. At the individual level, the classification rate for AD and HC was 72.9% for relative power with eyes closed. CONCLUSION: Our findings suggest that the increase in relative theta power may be the first change in patients with dementia due to AD. At the individual level, we found a moderate classification rate for AD and HC when using EEGs alone.
    • Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6

      Prins, Bram P.; Mead, Timothy J.; Brody, Jennifer A.; Sveinbjornsson, Gardar; Ntalla, Ioanna; Bihlmeyer, Nathan A.; van den Berg, Marten; Bork-Jensen, Jette; Cappellani, Stefania; Van Duijvenboden, Stefan; Klena, Nikolai T.; Gabriel, George C.; Liu, Xiaoqin; Gulec, Cagri; Grarup, Niels; Haessler, Jeffrey; Hall, Leanne M.; Iorio, Annamaria; Isaacs, Aaron; Li-Gao, Ruifang; Lin, Honghuang; Liu, Ching-Ti; Lyytikäinen, Leo-Pekka; Marten, Jonathan; Mei, Hao; Müller-Nurasyid, Martina; Orini, Michele; Padmanabhan, Sandosh; Radmanesh, Farid; Ramirez, Julia; Robino, Antonietta; Schwartz, Molly; van Setten, Jessica; Smith, Albert V.; Verweij, Niek; Warren, Helen R.; Weiss, Stefan; Alonso, Alvaro; Arnar, David O.; Bots, Michiel L.; de Boer, Rudolf A.; Dominiczak, Anna F.; Eijgelsheim, Mark; Ellinor, Patrick T.; Guo, Xiuqing; Felix, Stephan B.; Harris, Tamara B.; Hayward, Caroline; Heckbert, Susan R.; Huang, Paul L.; Jukema, J. W.; Kähönen, Mika; Kors, Jan A.; Lambiase, Pier D.; Launer, Lenore J.; Li, Man; Linneberg, Allan; Nelson, Christopher P.; Pedersen, Oluf; Perez, Marco; Peters, Annette; Polasek, Ozren; Psaty, Bruce M.; Raitakari, Olli T.; Rice, Kenneth M.; Rotter, Jerome I.; Sinner, Moritz F.; Soliman, Elsayed Z.; Spector, Tim D.; Strauch, Konstantin; Thorsteinsdottir, Unnur; Tinker, Andrew; Trompet, Stella; Uitterlinden, André; Vaartjes, Ilonca; van der Meer, Peter; Völker, Uwe; Völzke, Henry; Waldenberger, Melanie; Wilson, James G.; Xie, Zhijun; Asselbergs, Folkert W.; Dörr, Marcus; van Duijn, Cornelia M.; Gasparini, Paolo; Gudbjartsson, Daniel F.; Gudnason, Vilmundur; Hansen, Torben; Kääb, Stefan; Kanters, Jørgen K.; Kooperberg, Charles; Lehtimäki, Terho; Lin, Henry J.; Lubitz, Steven A.; Mook-Kanamori, Dennis O.; Conti, Francesco J.; Newton-Cheh, Christopher H.; Rosand, Jonathan; Rudan, Igor; Samani, Nilesh J.; Sinagra, Gianfranco; Smith, Blair H.; Holm, Hilma; Stricker, Bruno H.; Ulivi, Sheila; Sotoodehnia, Nona; Apte, Suneel S.; van der Harst, Pim; Stefansson, Kari; Munroe, Patricia B.; Arking, Dan E.; Lo, Cecilia W.; Jamshidi, Yalda; [ 1 ] St Georges Univ London, Genet Res Ctr, Mol & Clin Sci Inst, London SW17 0RE, England Show more [ 2 ] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Worts Causeway, Cambridge CB1 8RN, England Show more [ 3 ] Cleveland Clin, Dept Biomed Engn, Lerner Res Inst, Cleveland, OH 44195 USA Show more [ 4 ] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA [ 5 ] deCODE Genet Amgen Inc, IS-101 Reykjavik, Iceland Show more [ 6 ] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, Clin Pharmacol, London EC1M 6BQ, England Show more [ 7 ] Queen Mary Univ London, Barts & London Sch Med & Dent, NIHR Barts Cardiovasc Biomed Res Ctr, London EC1M 6BQ, England Show more [ 8 ] Johns Hopkins Univ, Sch Med, Predoctoral Training Program Human Genet, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA Show more [ 9 ] Erasmus MC Univ Med Ctr, Dept Med Informat, POB 2040, NL-3000 CA Rotterdam, Netherlands Show more [ 10 ] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark Show more [ 11 ] IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, I-34137 Trieste, Italy Show more [ 12 ] UCL, Inst Cardiovasc Sci, London WC1E 6BT, England Show more [ 13 ] Univ Pittsburgh, Sch Med, Dept Dev Biol, Pittsburgh, PA 15201 USA Show more [ 14 ] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA Show more [ 15 ] Univ Leicester, Glenfield Hosp, Cardiovasc Res Ctr, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England Show more [ 16 ] Leicester NIHR Biomed Res Ctr, Glenfield Hosp, Leicester LE3 9QP, Leics, England [ 17 ] Osped Riuniti, Cardiovasc Dept, I-34100 Trieste, Italy Show more [ 18 ] Univ Trieste, I-34100 Trieste, Italy Show more [ 19 ] Maastricht Univ, CARIM Sch Cardiovasc Dis, Maastricht Ctr Syst Biol MaCSBio, Univ Single 60, NL-6229 ER Maastricht, Netherlands Show more [ 20 ] Maastricht Univ, Dept Biochem, Univ Single 60, NL-6229 ER Maastricht, Netherlands Show more [ 21 ] Erasmus Univ, Med Ctr, Genet Epidemiol Unit, Dept Epidemiol, Rotterdam, Netherlands Show more [ 22 ] Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2300 RC Leiden, Netherlands Show more [ 23 ] Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, Boston, MA 02118 USA Show more [ 24 ] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA [ 25 ] Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland Show more [ 26 ] Univ Tampere, Fac Med & Life Sci, Dept Clin Chem, Tampere 33014, Finland Show more [ 27 ] Univ Edinburgh, Inst Genet & Mol Med, Med Res Council, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland Show more [ 28 ] Univ Mississippi, Med Ctr, Sch Populat Hlth, Dept Data Sci, Jackson, MS 39216 USA Show more [ 29 ] German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany Show more [ 30 ] Ludwig Maximilians Univ Munchen, Univ Hosp Munich, Dept Med 1, Munich, Germany Show more [ 31 ] Munich Heart Alliance, Partner Site, German Ctr Cardiovasc Res DZHK, Munich, Germany Show more [ 32 ] UCL, Mech Engn Dept, London WC1E 6BT, England Show more [ 33 ] St Bartholomews Hosp, Barts Heart Ctr, London EC1A 7BE, England Show more [ 34 ] Univ Glasgow, Inst Cardiovasc & Med Sci, BHF GCRC, Glasgow G12 8TA, Lanark, Scotland Show more [ 35 ] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA Show more [ 36 ] Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA Show more [ 37 ] MIT, Cambridge, MA 02142 USA Show more [ 38 ] Univ Utrecht, Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands [ 39 ] Iceland Heart Assoc, IS-201 Kopavogur, Iceland Show more [ 40 ] Univ Iceland, Fac Med, Dept Cardiol, IS-101 Reykjavik, Iceland Show more [ 41 ] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands Show more [ 42 ] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA Show more [ 43 ] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA [ 44 ] Univ Med, Interfac Inst Genet & Funct Gen, D-17475 Greifswald, Germany Show more [ 45 ] Ernst Moritz Arndt Univ Greifswald, D-17475 Greifswald, Germany Show more [ 46 ] DZHK German Ctr Cardiovasc Res, Partner site Greifswald, D-17475 Greifswald, Germany Show more [ 47 ] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA Show more [ 48 ] Landspitali Univ Hosp, Dept Med, IS-101 Reykjavik, Iceland Show more [ 49 ] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands Show more [ 50 ] Univ Glasgow, Coll Med Vet & Life Sci, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland Show more [ 51 ] Erasmus MC Univ Med Ctr Rotterdam, POB 2040, NL-3000 CA Rotterdam, Netherlands Show more [ 52 ] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02114 USA Show more [ 53 ] Harbor UCLA Med Ctr, Translat Genom & Populat Sci, Torrance, CA 90509 USA Show more [ 54 ] Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA Show more [ 55 ] Harbor UCLA Med Ctr, Dept Pediat, Div Genom Outcomes, Torrance, CA 90502 USA Show more [ 56 ] Univ Med Greifswald, Dept Internal Med Cardiol Pneumol Infect Dis Inte, D-17475 Greifswald, Germany Show more [ 57 ] NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, Bethesda, MD 20892 USA Show more [ 58 ] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA Show more [ 59 ] Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA Show more [ 60 ] Leiden Univ, Dept Cardiol, Med Ctr, NL-2300 RC Leiden, Netherlands [ 61 ] Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands Show more [ 62 ] Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands Show more [ 63 ] Tampere Univ Hosp, Dept Clin Physiol, Tampere 33521, Finland Show more [ 64 ] Univ Tampere, Fac Med & Life Sci, Dept Clin Physiol, Tampere 33014, Finland Show more [ 65 ] Erasmus Univ, Med Ctr, Dept Med Informat, Rotterdam, Netherlands Show more [ 66 ] Univ Utah, Sch Med, Div Nephrol & Hypertens Internal Med, Salt Lake City, UT 84109 USA [ 67 ] Res Ctr Prevent & Hlth, DK-2600 Glostrup, Denmark Show more [ 68 ] Rigshosp, Dept Clin Expt Res, DK-2600 Glostrup, Denmark Show more [ 69 ] Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, DK-22000 Copenhagen, Denmark Show more [ 70 ] Stanford Univ, Div Cardiovasc Med, Stanford, CA 94305 USA Show more [ 71 ] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany [ 72 ] German Ctr Diabet Res, Neuherberg, Germany Show more [ 73 ] Univ Split, Fac Med, Split, Croatia Show more [ 74 ] Univ Washington, Dept Med Epidemiol & Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA [ 75 ] Kaiser Permanente Washington Hlth Res Inst, Seattle, WA 98101 USA Show more [ 76 ] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku 20521, Finland Show more [ 77 ] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku 20014, Finland Show more [ 78 ] Univ Washington, Dept Biostat, Seattle, WA 98195 USA Show more [ 79 ] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA Show more [ 80 ] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Dept Pediat, Torrance, CA 90502 USA Show more [ 81 ] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Dept Med, Torrance, CA 90502 USA Show more [ 82 ] Wake Forest Univ, Bowman Gray Sch Med, Epidemiol Cardiol Res Ctr EPICARE, 300 S Hawthorne Rd, Winston Salem, NC 27157 USA Show more [ 83 ] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England Show more [ 84 ] Ludwig Maximilians Univ Munchen, Fac Med, IBE, Chair Genet Epidemiol, Munich, Germany Show more [ 85 ] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland Show more [ 86 ] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, NL-2300 RC Leiden, Netherlands Show more [ 87 ] Erasmus MC Univ Med Ctr Rotterdam, Human Genotyping Facil, POB 2040, NL-3000 CA Rotterdam, Netherlands Show more [ 88 ] Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany Show more [ 89 ] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany Show more [ 90 ] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA Show more [ 91 ] Zhejiang Chinese Med Univ, TCM Clin Basis Inst, Hangzhou 310000, Zhejiang, Peoples R China [ 92 ] Netherlands Heart Inst, Durrer Ctr Cardiovasc Res, Utrecht, Netherlands Show more [ 93 ] UCL, Fac Populat Hlth Sci, Inst Cardiovasc Sci, London, England Show more [ 94 ] UCL, Farr Inst Hlth Informat Res, London, England Show more [ 95 ] UCL, Inst Hlth Informat, London, England Show more [ 96 ] Univ Trieste, Dept Med Surg & Hlth Sci, I-34100 Trieste, Italy Show more [ 97 ] Sidra Med & Res Ctr, Div Expt Genet, Doha, Qatar Show more [ 98 ] Univ Iceland, Sch Engn & Nat Sci, IS-101 Reykjavik, Iceland Show more [ 99 ] Univ Copenhagen, Lab Expt Cardiol, DK-2200 Copenhagen, Denmark Show more [ 100 ] Harbor UCLA Med Ctr, Dept Pediat, Div Med Genet, Torrance, CA 90502 USA Show more [ 101 ] Leiden Univ, Dept Publ Hlth & Primary Care, Med Ctr, NL-2300 RC Leiden, Netherlands Show more [ 102 ] UCL, Inst Child Hlth, Dubowitz Neuromuscular Ctr, 30 Guilford St, London WC1N 1EH, England Show more [ 103 ] Harvard Med Sch, Ctr Human Genet Res, Boston, MA 02114 USA Show more [ 104 ] Harvard Med Sch, Cardiovasc Res Ctr, Boston, MA 02114 USA Show more [ 105 ] Massachusetts Gen Hosp, Boston, MA 02114 USA Show more [ 106 ] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland Show more [ 107 ] Univ Dundee, Div Populat Hlth Sci, Ninewells Hosp, Dundee DD1 9SY, Scotland Show more [ 108 ] Univ Dundee, Med Sch, Dundee DD1 9SY, Scotland Show more [ 109 ] Erasmus MC Univ Med Ctr, Dept Epidemiol, POB 2040, NL-3000 CA Rotterdam, Netherlands Show more [ 110 ] Univ Washington, Div Cardiol, Dept Med, Seattle, WA 98101 USA Show more [ 111 ] Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA Show more [ 112 ] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands Show more [ 113 ] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA Show more [ 114 ] St Georges Univ London, Genet Res Ctr, Mol & Clin Sci Inst, London, England (BMC, 2018-07-17)
      BACKGROUND: Genome-wide association studies conducted on QRS duration, an electrocardiographic measurement associated with heart failure and sudden cardiac death, have led to novel biological insights into cardiac function. However, the variants identified fall predominantly in non-coding regions and their underlying mechanisms remain unclear. RESULTS: Here, we identify putative functional coding variation associated with changes in the QRS interval duration by combining Illumina HumanExome BeadChip genotype data from 77,898 participants of European ancestry and 7695 of African descent in our discovery cohort, followed by replication in 111,874 individuals of European ancestry from the UK Biobank and deCODE cohorts. We identify ten novel loci, seven within coding regions, including ADAMTS6, significantly associated with QRS duration in gene-based analyses. ADAMTS6 encodes a secreted metalloprotease of currently unknown function. In vitro validation analysis shows that the QRS-associated variants lead to impaired ADAMTS6 secretion and loss-of function analysis in mice demonstrates a previously unappreciated role for ADAMTS6 in connexin 43 gap junction expression, which is essential for myocardial conduction. CONCLUSIONS: Our approach identifies novel coding and non-coding variants underlying ventricular depolarization and provides a possible mechanism for the ADAMTS6-associated conduction changes.
    • Systems analysis of metabolism in platelet concentrates during storage in platelet additive solution.

      Jóhannsson, Freyr; Guðmundsson, Steinn; Paglia, Giuseppe; Guðmundsson, Sveinn; Palsson, Bernhard; Sigurjónsson, Ólafur E; Rolfsson, Óttar; [ 1 ] Univ Iceland, Ctr Syst Biol, Sturlugata 8, Reykjavik, Iceland Show more [ 2 ] Univ Iceland, Med Dept, Sturlugata 8, Reykjavik, Iceland Show more [ 3 ] European Acad Bolzano Bozen, Ctr Biomed, Via Galvani 31, Bolzano, Italy Show more [ 4 ] Landspitali Univ Hosp, Blood Bank, Snorrabraut 60, Reykjavik, Iceland Show more [ 5 ] Reykjavik Univ, Sch Sci & Engn, Menntavegur 1, Reykjavik, Iceland (Portland Press, 2018-07-17)
      Platelets (PLTs) deteriorate over time when stored within blood banks through a biological process known as PLT storage lesion (PSL). Here, we describe the refinement of the biochemical model of PLT metabolism, iAT-PLT-636, and its application to describe and investigate changes in metabolism during PLT storage. Changes in extracellular acetate and citrate were measured in buffy coat and apheresis PLT units over 10 days of storage in the PLT additive solution T-Sol. Metabolic network analysis of these data was performed alongside our prior metabolomics data to describe the metabolism of fresh (days 1-3), intermediate (days 4-6), and expired (days 7-10) PLTs. Changes in metabolism were studied by comparing metabolic model flux predictions of iAT-PLT-636 between stages and between collection methods. Extracellular acetate and glucose contribute most to central carbon metabolism in PLTs. The anticoagulant citrate is metabolized in apheresis-stored PLTs and is converted into aconitate and, to a lesser degree, malate. The consumption of nutrients changes during storage and reflects altered PLT activation profiles following their collection. Irrespective of the collection method, a slowdown in oxidative phosphorylation takes place, consistent with mitochondrial dysfunction during PSL. Finally, the main contributors to intracellular ammonium and NADPH are highlighted. Future optimization of flux through these pathways provides opportunities to address intracellular pH changes and reactive oxygen species, which are both of importance to PSL. The metabolic models provide descriptions of PLT metabolism at steady state and represent a platform for future PLT metabolic research.
    • Parent perspectives on home participation of high-functioning children with autism spectrum disorder compared with a matched group of children without autism spectrum disorder.

      Egilson, Snæfrídur T; Jakobsdóttir, Gunnhildur; Ólafsdóttir, Linda B; [ 1 ] Univ Iceland, Reykjavik, Iceland Show more [ 2 ] Natl Univ Hosp Iceland, Reykjavik, Iceland (SAGE PUBLICATIONS LTD, 2018-07-01)
      Few studies have focused on home participation of high-functioning children with autism spectrum disorder. We employed a mixed-methods design to explore and compare parent perspectives on (1) participation of children with and without autism spectrum disorder in activities at home, (2) the environmental features and resources that affect these children's home participation and (3) the strategies parents use to help their children participate at home. The Participation and Environment Measure for Children and Youth (PEM-CY) was used to gather online survey and qualitative data from parents of 99 high-functioning children with autism spectrum disorder and 241 children without autism spectrum disorder. Independent sample t-tests and χ
    • Acute myeloid leukemia (AML) with t(7;12)(q36;p13) is associated with infancy and trisomy 19: Data from Nordic Society for Pediatric Hematology and Oncology (NOPHO-AML) and review of the literature

      Espersen, Anne Dorte Lerche; Noren-Nyström, Ulrika; Abrahamsson, Jonas; Ha, Shau-Yin; Pronk, Cornelis Jan; Jahnukainen, Kirsi; Jónsson, Ólafur G.; Lausen, Birgitte; Palle, Josefine; Zeller, Bernward; Palmqvist, Lars; Hasle, Henrik; [ 1 ] Aarhus Univ Hosp Skejby, Dept Pediat, Aarhus, Denmark Show more [ 2 ] Umea Univ Hosp, Dept Pediat, Umea, Sweden [ 3 ] Queen Silvia Childrens Hosp, Dept Pediat, Inst Clin Sci, Gothenburg, Sweden Show more [ 4 ] Queen Mary Hosp, Dept Pediat, Hong Kong, Hong Kong, Peoples R China [ 5 ] HKPHOSG, Hong Kong, Hong Kong, Peoples R China Show more [ 6 ] Univ Hosp, Dept Pediat, Lund, Sweden Show more [ 7 ] Univ Helsinki, Childrens Hosp, Helsinki, Finland Show more [ 8 ] Univ Helsinki, Cent Hosp, Helsinki, Finland [ 9 ] Landspitalinn, Dept Pediat, Reykjavik, Iceland Show more [ 10 ] Univ Copenhagen, Rigshosp, Dept Pediat & Adolescent Med, Copenhagen, Denmark Show more [ 11 ] Uppsala Univ, Dept Womans & Childrens Hlth, Uppsala, Sweden Show more [ 12 ] Oslo Univ Hosp, Div Pediat & Adolescent Med, Oslo, Norway Show more [ 13 ] Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Clin Chem & Transfus Med, Gothenburg, Sweden; Department of Pediatrics; Aarhus University Hospital Skejby; Denmark; Department of Pediatrics; Umeå University Hospital; Umeå Sweden; Institution for Clinical Sciences, Department of Pediatrics; Queen Silvia Children's Hospital; Gothenburg Sweden; Department of Pediatrics; Queen Mary Hospital and Hong Kong Pediatric Hematology & Oncology Study Group (HKPHOSG); Hong Kong China; Department of Pediatrics; University Hospital; Lund Sweden; Children's Hospital, University of Helsinki and Helsinki University Central Hospital; Helsinki Finland; Department of Pediatrics; Landspitalinn; Reykjavik Iceland; Department of Pediatrics and Adolescent Medicine; Rigshospitalet, University of Copenhagen; Copenhagen Denmark; Department of Woman's and Children's Health; Uppsala University; Uppsala Sweden; Division of Pediatric and Adolescent Medicine; Oslo University Hospital; Oslo Norway; Department of Clinical Chemistry and Transfusion Medicine; Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg; Gothenburg Sweden; Department of Pediatrics; Aarhus University Hospital Skejby; Denmark (Wiley, 2018-07)
      The t(7;12)(q36;p13) (MNX1/ETV6) is not included in the WHO classification but has been described in up to 30% of acute myeloid leukemia (AML) in children <2 years and associated with a poor prognosis. We present the clinical and cytogenetics characteristics of AML cases with t(7;12)(p36;p13). A literature review identified 35 patients with this translocation, published between 2000 and 2015. Outcome data were available in 22 cases. The NOPHO-AML (Nordic Society for Pediatric Hematology and Oncology) database contained 651 patients with AML from 1993 to 2014 and seven (1.1%) had the translocation. The t(7;12) was only present in patients <2 years of age (median age 6 months) but none was diagnosed as newborn. These patients constituted 4.3% of the patients <2 years of age. There was a strong association with trisomy 19 (literature: 86%, NOPHO: 100%) and +8 (literature: 19%, NOPHO: 14%). Seventeen of 22 patients from the literature with t(7;12) and four of seven patients from the NOPHO database suffered from relapse. The patients with t(7;12) had a 3-year event free survival of 24% (literature) vs. 43% (NOPHO) and a 3-year overall survival of 42% (literature) vs. 100% (NOPHO). None of the NOPHO patients was treated with hematopoietic stem cell transplantation (HSCT) in first complete remission. Relapse was frequent but the salvage rate using HSCT was high. We conclude that t(7;12)(q36;13) is a unique subgroup of childhood AML with presentation before 2 years of age with most cases being associated with +19.
    • "You stop thinking about yourself as a woman". An interpretive phenomenological study of the meaning of sexuality for Icelandic women during pregnancy and after birth.

      Bender, Sóley S; Sveinsdóttir, Edda; Fridfinnsdóttir, Hilda; [ 1 ] Univ Iceland, Fac Nursing, Eiriksgata 34, IS-101 Reykjavik, Iceland [ 2 ] Landspitali Natl Univ Hosp Iceland, Dept Obstet & Gynecol, IS-101 Reykjavik, Iceland (Elsevier Science Ltd., 2018-07)
      Health care professionals, especially midwives and nurses, could contribute to the balance in the relationship through the provision of evidence-based information about normal changes in sexual behaviour during the childbearing process and by discussing intimacy issues. The partner may need this information as much as the woman.
    • Critical age windows in the impact of lifetime smoking exposure on respiratory symptoms and disease among ever smokers

      Erbas, Bircan; Knudsen, Toril Mørkve; Janson, Christer; Nilsen, Roy M.; Accordini, Simone; Benediktdottir, Bryndis; Dratva, Julia; Heinrich, Joachim; Jarvis, Debbie; Leynaert, Benedcite; Matheson, Melanie C.; Norbäck, Dan; Real, Francisco G.; Raherison-Semjen, Chantal; Villani, Simona; Dharmage, S.C.; Svanes, C.; 1 ] La Trobe Univ, Dept Publ Hlth, Melbourne, Vic, Australia Show more [ 2 ] Univ Bergen, Dept Clin Sci, Bergen, Norway [ 3 ] Uppsala Univ, Dept Med Sci Resp Allergy & Sleep Res, Uppsala, Sweden Show more [ 4 ] Haukeland Hosp, Ctr Clin Res, Bergen, Norway Show more [ 5 ] Univ Verona, Dept Publ Hlth & Community Med, Unit Epidemiol & Med Stat, Verona, Italy Show more [ 6 ] Univ Iceland, Landspitali Univ Hosp, Fac Med, Dept Resp Med & Sleep, Reykjavik, Iceland Show more [ 7 ] Swiss Trop & Publ Hlth Inst, Dept Publ Hlth & Epidemiol, Basel, Switzerland Show more [ 8 ] Helmholtz Zentrum, Inst Epidemiol 1, Munich, Germany Show more [ 9 ] Imperial Coll, Natl Heart & Lung Inst, Dept Resp Epidemiol Occupat Med & Publ Hlth, London, England Show more [ 10 ] INSERM, UMR1152, Team Epidemiol, Paris, France Show more [ 11 ] Univ Melbourne, Allergy & Lung Hlth Unit, Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia Show more [ 12 ] Uppsala Univ, Dept Med Sci, Uppsala, Sweden Show more [ 13 ] Bordeaux Univ, Inst Publ Hlth & Epidemiol, INSERM, U897, Bordeaux, France Show more [ 14 ] Univ Pavia, Dept Publ Hlth Expt & Forens Med, Unit Biostat & Clin Epidemiol, Pavia, Italy Show more [ 15 ] Univ Bergen, Ctr Int Hlth, Bergen, Norway Show more [ 16 ] Haukeland Hosp, Dept Occupat Med, Bergen, Norway Show more [ 17 ] Univ Basel, Basel, Switzerland Show more [ 18 ] Ludwig Maximilian Univ Munich, Univ Hosp Munich, Inst & Outpatient Clin Occupat Social & Environm, Inner City Clin, Munich, Germany Show more [ 19 ] Haukeland Hosp, Dept Gynecol & Obstet, Bergen, Norway (Academic Press Inc Elsevier Science, 2018-07)
      BACKGROUND: Despite extensive knowledge of smoking effects on respiratory disease, there is no study including all age windows of exposure among ever smokers. The objective of this study was to assess the effects from smoking exposure in utero, early childhood, adolescence and adulthood on respiratory health outcomes in adult male and female ever smokers. METHODS: Respiratory health outcomes were assessed in 10,610 participants of the European Community Respiratory Health Survey (ECRHS) I who reported a history of ever smoking by questionnaire. The associations of maternal smoking in utero, maternal smoking during childhood, age of smoking debut and pack-years of smoking with respiratory symptoms, obstructive diseases and bronchial hyperreactivity were analysed using generalized linear regression, non-linearity between age of smoking debut and outcomes were assessed by Generalized additive mixed models. RESULTS: Respiratory symptoms and asthma were more frequent in adults if their mother smoked during pregnancy, and, in men, also if mother smoked in childhood. Wheeze and ≥3 respiratory symptoms declined with later smoking debut among women [≤10 years: OR = 3.51, 95% CI 1.26, 9.73; 11-12 years: 1.57[1.01-2.44]; 13-15 years: 1.11[0.94-1.32] and ≤10 years: 3.74[1.56-8.83]; 11-12 years: 1.76[1.19-2.56]; 13-15 years: 1.12[0.94-1.35], respectively]. Effects of increasing number of packyears were pronounced in women (Chronic Obstructive Pulmonary Disease (COPD): OR/10 packyears women: 1.33 [1.18, 1.50], men: 1.14 [1.04, 1.26] pinteraction = 0.01). CONCLUSIONS: Among ever smokers, smoking exposure in each stage of the lifespan show persistent harmful effects for adult respiratory health, while women appeared to be more vulnerable to an early age of smoking debut and amount of smoking in adulthood.