• Body mass index standard deviation score and obesity in children with type 1 diabetes in the Nordic countries. HbA and other predictors of increasing BMISDS.

      Birkebaek, N H; Kahlert, J; Bjarnason, R; Drivvoll, A K; Johansen, A; Konradsdottir, E; Pundziute-Lyckå, A; Samuelsson, U; Skrivarhaug, T; Svensson, J; [ 1 ] Aarhus Univ, Aarhus Univ Hosp, Dept Paediat, Aarhus, Denmark Show more [ 2 ] Aarhus Univ Hosp, Dept Clin Epidemiol, Aarhus, Denmark Show more [ 3 ] Landspitali Univ Hosp, Reykjavik, Iceland Show more [ 4 ] Univ Iceland, Fac Med, Reykjavik, Iceland Show more [ 5 ] Oslo Univ Hosp, Div Paediat & Adolescent Med, Oslo, Norway Show more [ 6 ] Rigshosp, Dept Growth & Reprod, Copenhagen, Denmark Show more [ 7 ] Univ Iceland, Sch Hlth Sci, Reykjavik, Iceland Show more [ 8 ] Queen Silvia Childrens Hosp, Gothenburg, Sweden [ 9 ] Linkobing Univ Hosp, Dept Pediat, Linkoping, Sweden Show more [ 10 ] Univ Copenhagen, Herlev Hosp, Dept Paediat, Copenhagen, Denmark (Wiley, 2018-11-01)
      Intensified insulin therapy may increase body weight and cause obesity. This study compared body mass index standard deviation score (BMISDS) and obesity rate in children with type 1 diabetes (T1D) in Denmark, Iceland, Norway and Sweden, and uncovered predictors for increasing BMISDS. Data registered in the Nordic national childhood diabetes databases during the period 2008-2012 on children below 15 years with T1D for more than 3 months were compiled, including information on gender, age, diabetes duration, hemoglobin A Totally, 11 025 children (48% females) (30 994 registrations) were included. Medians by the last recorded examination were: age, 13.5 years; diabetes duration, 4.3 years; HbA Obesity rate in children with T1D in the Nordic countries is high, however, with country differences. Low HbA
    • Use of venous-thrombotic-embolic prophylaxis in patients undergoing surgery for renal tumors: a questionnaire survey in the Nordic countries (The NORENCA-2 study)

      Lund, Lars; Nisen, Harry; Jarvinen, Petrus; Fovaeus, Magnus; Gudmundson, Eirikur; Kromann-Andersen, Bjarne; Ljungberg, Borje; Nilsen, Frode; Sundqvist, Pernilla; Clark, Peter E; Beisland, Christian; [ 1 ] Odense Univ Hosp, Dept Urol, JB Winsloew Vej 4,Entrance 20,Penthouse,2 Floor, DK-5000 Odense C, Denmark [ 2 ] Southern Univ Denmark, Clin Inst, Odense, Denmark Show more [ 3 ] Helsinki Univ Hosp, Dept Urol, Helsinki, Finland Show more [ 4 ] Sahlgrens Univ Hosp, Dept Urol, Gothenburg, Sweden Show more [ 5 ] Landspitali Univ Hosp, Dept Urol, Reykjavik, Iceland Show more [ 6 ] Herlev Univ Hosp, Dept Urol, Copenhagen, Denmark Show more [ 7 ] Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden Show more [ 8 ] Akershus Univ Hosp, Dept Urol, Lorenskog, Norway Show more [ 9 ] Orebro Univ, Fac Med & Hlth, Dept Urol, Orebro, Sweden [ 10 ] Atrium Hlth, Dept Urol, Charlotte, NC USA Show more [ 11 ] Haukeland Hosp, Dept Urol, Bergen, Norway Show more [ 12 ] Univ Bergen, Dept Clin Med, Bergen, Norway (Dove Medical Press, 2018-10-25)
      Purpose: To examine the variation in venous thromboembolism prophylactic treatment (VTEP) among renal cancer patients undergoing surgery. Materials and methods: An Internet-based questionnaire on renal tumor management before and after surgery was mailed to all Nordic departments of urology. The questions focused on the use of VTEP and were subdivided into different surgical modalities. Results: Questionnaires were mailed to 91 institutions (response rate 53%). None of the centers used VTEP before surgery, unless the patient had a vena caval tumor thrombus. Overall, the VTEP utilized during hospitalization for patients undergoing renal surgery included early mobilization (45%), compression stockings (52%) and low-molecular-weight heparin (89%). In patients undergoing open radical Nx, 80% of institutions used VTEP during their hospitalization (23% compression stockings and 94% low-molecular-weight heparin). After leaving the hospital, the proportion and type of VTEP received varied considerably across institutions. The most common interval, used in 60% of the institutions, was for a period of 4 weeks. The restriction to the Nordic countries was a limitation and, therefore, may not reflect the practice patterns elsewhere. It is a survey study and, therefore, cannot measure the behaviors of those institutions that did not participate. Conclusion: We found variation in the type and duration of VTEP use for each type of local intervention for renal cancer. These widely disparate variations in care strongly argue for the establishment of national and international guidelines regarding VTEP in renal surgery.
    • Impact of the 10-valent pneumococcal conjugate vaccine on antimicrobial prescriptions in young children: a whole population study.

      Eythorsson, Elias; Sigurdsson, Samuel; Hrafnkelsson, Birgir; Erlendsdóttir, Helga; Haraldsson, Ásgeir; Kristinsson, Karl G; 1 University of Iceland, Faculty of Medicine, 101, Reykjavík, Iceland. 2 Department of Mathematics, University of Iceland, Reykjavík, Iceland. 3 Department of Clinical Microbiology, Landspítali University Hospital, 101, Reykjavík, Iceland. 4 Children's Hospital Iceland, Landspítali University Hospital, Reykjavík, Iceland. 5 University of Iceland, Faculty of Medicine, 101, Reykjavík, Iceland. karl@landspitali.is. 6 Department of Clinical Microbiology, Landspítali University Hospital, 101, Reykjavík, Iceland. karl@landspitali.is. (BioMed Central, 2018-10-04)
      Antimicrobial resistance is a public-health threat and antimicrobial consumption is the main contributor. The ten-valent pneumococcal conjugate vaccine (PHiD-CV10) was introduced into the Icelandic vaccination program in 2011. The aim was to estimate the vaccine impact of PHiD-CV10 on outpatient antimicrobial prescriptions in children. Eleven Icelandic birth-cohorts (2005-2015) were followed from birth until three years of age or to the end of the study period (December 31, 2016). Birth-cohorts were grouped as vaccine non-eligible (VNEC, 2005-2010) or vaccine eligible (VEC, 2011-2015). Data on primary care visits for respiratory infections and antimicrobial prescriptions were extracted from two national registers. Using national identification numbers, prescriptions were linked to physician visits if filled within three days of the visit. Incidence rates and incidence rate ratios between VNEC and VEC were calculated. An Andersen-Gill model was used to model the individual level data, accounting for repeated events and censoring. Vaccine impact was calculated as (1 - Hazard Ratio) × 100%. Included were 53,510 children who contributed 151,992 person-years of follow-up and filled 231,660 antimicrobial prescriptions. The incidence rate was significantly lower in the VEC compared to the VNEC, 144.5 and 157.2 prescriptions per 100 person-years respectively (IRR 0.92, 95%CI 0.91-0.93). Children in VEC were more likely to have filled zero (IRR 1.16 (95%CI 1.10-1.23) and 1-4 (IRR 1.08 95%CI 1.06-1.11) prescriptions compared to children in VNEC. The vaccine impact of PHiD-CV10 against all-cause antimicrobial prescriptions was 5.8% (95%CI 1.6-9.8%).When only considering acute otitis media-associated prescriptions, the vaccine impact was 21.8% (95%CI 11.5-30.9%). The introduction of PHiD-CV10 lead to reduced antimicrobial use in children, mainly by reducing acute otitis media episodes. This intervention therefore reduces both disease burden and could slow the spread of antimicrobial resistance.
    • Mortality due to bleeding, myocardial infarction and stroke in dialysis patients.

      Ocak, G; Noordzij, M; Rookmaaker, M B; Cases, A; Couchoud, C; Heaf, J G; Jarraya, F; De Meester, J; Groothoff, J W; Waldum-Grevbo, B E; Palsson, R; Resic, H; Remón, C; Finne, P; Stendahl, M; Verhaar, M C; Massy, Z A; Dekker, F W; Jager, K J; 1 Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, the Netherlands. 2 ERA-EDTA Registry, Department of Medical Informatics, Academic Medical Center, University of Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands. 3 Registre de Malalts Renals de Catalunya, Universitat de Barcelona, IDIBAPS, Barcelona, Spain. 4 REIN Registry, Agence de Biomedecine, Saint Denis La Plaine, France. 5 Department of Medicine, Zealand University Hospital, Roskilde, Denmark. 6 Department of Nephrology, Sfax University Hospital and Research Unit, Faculty of Medicine, Sfax University, Sfax, Tunisia. 7 Department of Nephrology, Dialysis and Hypertension, Dutch-Speaking Belgian Renal Registry, Sint-Niklaas, Belgium. 8 Department of Pediatric Nephrology, Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands. 9 Department of Nephrology, Oslo University Hospital Ullevål, Oslo, Norway. 10 Division of Nephrology, Internal Medicine Services, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland. 11 Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland. 12 Clinic for Hemodialysis, Clinical Center University of Sarajevo, Sarajevo, Bosnia and Herzegovina. 13 SICATA (The Information System of the Andalusian Transplant Autonomic Coordination Registry), Andalusia, Spain. 14 Finnish Registry for Kidney Diseases, Helsinki, Finland. 15 Swedish Renal Registry, Department of Internal Medicine, Ryhov County Hospital, Jönköping, Sweden. 16 Division of Nephrology, Ambroise Paré University Hospital, APHP, Boulogne Billancourt/Paris, France. 17 INSERM Unit 1018, CESP, Team 5, UVSQ, Villejuif, France. 18 Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands. (Wiley, 2018-10-01)
      Essentials Mortality due to bleeding vs. arterial thrombosis in dialysis patients is unknown. We compared death causes of 201 918 dialysis patients with the general population. Dialysis was associated with increased mortality risks of bleeding and arterial thrombosis. Clinicians should be aware of the increased bleeding and thrombosis risks. Background Dialysis has been associated with both bleeding and thrombotic events. However, there is limited information on bleeding as a cause of death versus arterial thrombosis as a cause of death. Objectives To investigate the occurrence of bleeding, myocardial infarction and stroke as causes of death in the dialysis population as compared with the general population. Methods We included 201 918 patients from 11 countries providing data to the ERA-EDTA Registry who started dialysis treatment between 1994 and 2011, and followed them for 3 years. Age-standardized and sex-standardized mortality rate ratios for bleeding, myocardial infarction and stroke as causes of death were calculated in dialysis patients as compared with the European general population. Associations between potential risk factors and these causes of death in dialysis patients were investigated by calculating hazard ratios (HRs) with 95% confidence intervals (CIs) by the use of Cox proportional-hazards regression. Results As compared with the general population, the age-standardized and sex-standardized mortality rate ratios in dialysis patients were 12.8 (95% CI 11.9-13.7) for bleeding as a cause of death (6.2 per 1000 person-years among dialysis patients versus 0.3 per 1000 person-years in the general population), 13.4 (95% CI 13.0-13.9) for myocardial infarction (22.5 versus 0.9 per 1000 person-years), and 12.4 (95% CI 11.9-12.9) for stroke (14.3 versus 0.7 per 1000 person-years). Conclusion Dialysis patients have highly increased risks of death caused by bleeding and arterial thrombosis as compared with the general population. Clinicians should be aware of the increased mortality risks caused by these conditions.
    • Acute kidney injury following coronary angiography: a nationwide study of incidence, risk factors and long-term outcomes.

      Helgason, Dadi; Long, Thorir E; Helgadottir, Solveig; Palsson, Runolfur; Sigurdsson, Gisli H; Gudbjartsson, Tomas; Indridason, Olafur S; Gudmundsdottir, Ingibjorg J; Sigurdsson, Martin I; 1 Internal Medicine Services, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. 2 Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 3 Division of Anaesthesia and Intensive Care Medicine, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. 4 Division of Nephrology, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. 5 Division of Cardiothoracic Surgery, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. 6 Division of Cardiology, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. 7 Division of Anaesthesia and Intensive Care Medicine, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. martiningi@gmail.com. 8 Department of Anesthesiology, Duke University Hospital, 2301 Erwin Road, Durham, NC, USA. martiningi@gmail.com. (Springer Heidelberg, 2018-10-01)
      We studied the incidence and risk factors of acute kidney injury (AKI) following coronary angiography (CA) and examined short- and long-term outcomes of patients who developed AKI, including progression of chronic kidney disease (CKD). This was a retrospective study of all patients undergoing CA in Iceland from 2008 to 2015, with or without percutaneous coronary intervention. All procedures were performed with iso-osmolar contrast. AKI was defined according to the SCr component of the KDIGO criteria. Patients without post-procedural SCr were assumed to be free of AKI. Incident CKD was defined as 90-day sustained estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m AKI was detected in 231 of 13,561 cases (1.7%). There was an interaction between contrast dose and preexisting kidney function, where the risk for AKI was only significant at a dose > 150 mL in patients with baseline eGFR < 45 mL/min/1.73 m For iso-osmolar contrast, the risk of AKI related to contrast dose was evident for higher amount of contrast in patients with baseline eGFR < 45 mL/min/1.73 m
    • Second malignancies in patients with myeloproliferative neoplasms: a population-based cohort study of 9379 patients.

      Landtblom, Anna Ravn; Bower, Hannah; Andersson, Therese M-L; Dickman, Paul W; Samuelsson, Jan; Björkholm, Magnus; Kristinsson, Sigurdur Yngvi; Hultcrantz, Malin; 1 Department of Medicine, Division of Hematology, Stockholm South Hospital and Karolinska Institutet, Stockholm, Sweden. anna.ravn-landtblom@sll.se. 2 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. 3 Department of Medicine, Division of Hematology, Stockholm South Hospital and Karolinska Institutet, Stockholm, Sweden. 4 Department of Medicine, Division of Hematology, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden. 5 Faculty of Medicine, University of Iceland and Department of Hematology, Landspitali National University Hospital, Reykjavik, Iceland. 6 Department of Medicine, Myeloma Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. (Nature Publishing Group, 2018-10-01)
      To determine the risk of a wide range of second malignancies in patients with myeloproliferative neoplasms (MPNs), we conducted a large population-based study and compared the results to matched controls. From national Swedish registers, 9379 patients with MPNs diagnosed between 1973 and 2009, and 35,682 matched controls were identified as well as information on second malignancies, with follow-up until 2010. Hazard ratios (HRs) with 95 % confidence intervals (CIs) were calculated using Cox regression and a flexible parametric model. There was a significantly increased risk of any non-hematologic cancer with HR of 1.6 (95% CI: 1.5-1.7). The HRs for non-melanoma skin cancer was 2.8 (2.4-3.3), kidney cancer 2.8 (2.0-4.0), brain cancer 2.8 (1.9-4.2), endocrine cancers 2.5 (1.6-3.8), malignant melanoma 1.9 (1.4-2.7), pancreas cancer 1.8 (1.2-2.6), lung cancer 1.7 (1.4-2.2), and head and neck cancer 1.7 (1.2-2.6). The HR of second malignancies was similar across all MPN subtypes, sex, and calendar periods of MPN diagnosis. The risk of developing a hematologic malignancy was also significantly increased; the HR for acute myeloid leukemia was 46.0 (32.6-64.9) and for lymphoma 2.6 (2.0-3.3). In conclusion, our study provides robust population-based support of an increased cancer risk in MPN patients.
    • 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.
    • Cervical cancer staging, pretreatment planning, and surgical treatment in the Nordic countries-Survey from the Surgical Subcommittee of the Nordic Society of Gynecological Oncology.

      Fuglsang, Katrine; Haldorsen, Ingfrid S; Avall-Lundqvist, Elisabeth; Lindahl, Gabriel; Roed, Henrik; Woie, Kathrine; Pakarinen, Päivi; Thoroddsen, Asgeir; Anttila, Maarit; Blaakaer, Jan; 1 Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, Denmark. 2 Department of Radiology, Haukeland University Hospital, Bergen, Norway. 3 Department of Oncology, Linköping University, Linköping, Sweden. 4 Department of Clinical and Experimental Medicine, Linköping, University, Linköping, Sweden. 5 Department of Oncology, Rigshospitalet University Hospital, Copenhagen, Denmark. 6 Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway. 7 Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland. 8 Department of Obstetrics and Gynecology, Reykjavik University Hospital, Reykjavik, Iceland. 9 Department of Gynecology, Kuopio University Hospital, Kuopio, Finland. 10 Department of Obstetrics and Gynecology, Odense University Hospital, Odense, Denmark. (Wiley, 2018-10-01)
      Women with cervical cancer in the Nordic countries are increasingly undergoing pretreatment imaging by ultrasound, magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT) or computed tomography, or sentinel lymph node procedure. The present survey reports the influence of pretreatment imaging findings on the recorded clinical International Federation of Gynecology and Obstetrics (FIGO) stage in Nordic countries and its impact on treatment planning and preferred surgical approach in cervical cancer. The Nordic Society of Gynecological Oncology Surgical Subcommittee developed a questionnaire-based survey that was conducted from 1 January to 31 March 2017. All the 22 Nordic Gynecological Oncology Centers (Denmark 5, Finland 5, Iceland 1, Norway 4, and Sweden 7) were invited to participate. The questionnaires were returned by 19 of 22 (86.3%) centers. The median number (range) of women with cervical cancer treated at each center annually was 32 (15-120). In 58% (11/19) of the centers, imaging findings were reported to influence the clinical staging. MRI in combination with PET-CT was the preferred imaging method and the results influenced treatment planning. Robotic-assisted radical hysterectomy was the preferred surgical method in 72% (13/18) of the centers. Sentinel lymph node procedure was not routinely implemented in the majority of the Nordic centers. More than half of the Nordic Gynecological Oncology Centers already report a clinical FIGO stage influenced by pretreatment imaging findings. The trend in preferred treatment is robotic-assisted radical hysterectomy and the sentinel lymph node procedure is gradually being introduced.
    • Composition of School Meals in Sweden, Finland, and Iceland: Official Guidelines and Comparison With Practice and Availability.

      Juniusdottir, Ragnheidur; Hörnell, Agneta; Gunnarsdottir, Ingibjorg; Lagstrom, Hanna; Waling, Maria; Olsson, Cecilia; Talvia, Sanna; Olafsdottir, Anna S; 1 School of Education, University of Iceland, v/Stakkahlid, 105 Reykjavik, Iceland. 2 Department of Food and Nutrition, Umeå University, SE-901 87 Umeå, Sweden. 3 Unit for Nutrition Research, Faculty of Food Science and Nutrition at the University of Iceland and Landspitali-National University Hospital, Eiriksgata 29, 101 Reykjavik, Iceland. 4 The Discipline of Public Health, University of Turku, Joukahaisenkatu 3-5 A, 20014 Turun yliopisto, Finland. 5 University of Eastern Finland, Kuopio campus, Institute of Public Health and Clinical Nutrition, P.O. Box 1627, FI-70211 Kuopio, Finland. (Wiley, 2018-10-01)
      Nutritious and attractive school meals can improve health equality and public health. Current official guidelines and recommendations on food and nutrient composition of school meals in 3 Nordic countries; Sweden, Finland, and Iceland, are described and compared with actual practice, ie, availability of foods and nutrients in served reference meals in 3 selected areas in each country. A country comparison was made between official guidelines, and actual practice was studied in participating schools. Reference portions of school meals (N = 170) provided in 24 compulsory schools were photographed and weighed. Food and nutrient availability were compared with official guidelines in each country. Emphasis of recommendations on whole-grain bread in Sweden, whole grains in Finland, and fish in Iceland were reflected in food availability. The energy content of the meals provided was lower than guidelines and there was a large variation in energy content between days. The guidelines regarding food availability were quite well followed, but the large variation in energy and nutrient content of provided school meals between days indicates a need for standardization.
    • Cerebrovascular Events in Systemic Lupus Erythematosus: Results From an International Inception Cohort Study.

      Hanly, John G; Li, Qiuju; Su, Li; Urowitz, Murray B; Gordon, Caroline; Bae, Sang-Cheol; Romero-Diaz, Juanita; Sanchez-Guerrero, Jorge; Bernatsky, Sasha; Clarke, Ann E; Wallace, Daniel J; Isenberg, David A; Rahman, Anisur; Merrill, Joan T; Fortin, Paul; Gladman, Dafna D; Bruce, Ian N; Petri, Michelle; Ginzler, Ellen M; Dooley, M A; Steinsson, Kristjan; Ramsey-Goldman, Rosalind; Zoma, Asad A; Manzi, Susan; Nived, Ola; Jonsen, Andreas; Khamashta, Munther A; Alarcón, Graciela S; Chatham, Winn; van Vollenhoven, Ronald F; Aranow, Cynthia; Mackay, Meggan; Ruiz-Irastorza, Guillermo; Ramos-Casals, Manuel; Lim, S Sam; Inanc, Murat; Kalunian, Kenneth C; Jacobsen, Soren; Peschken, Christine A; Kamen, Diane L; Askanase, Anca; Theriault, Chris; Farewell, Vernon; 1 Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, Nova Scotia, Canada. 2 MRC Biostatistics Unit, Institute of Public Health, University of Cambridge, Cambridge, UK. 3 Toronto Western Hospital and University of Toronto, Ontario, Canada. 4 University of Birmingham, College of Medical and Dental Sciences, Birmingham, UK. 5 Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea. 6 Instituto Nacional de Ciencias Medicas y Nutrición, Mexico City, Mexico. 7 McGill University, Montreal, Quebec, Canada. 8 University of Calgary, Alberta, Canada. 9 Cedars-Sinai Medical Center and University of California at Los Angeles, David Geffen School of Medicine, Los Angeles. 10 University College London, London, UK. 11 Oklahoma Medical Research Foundation, Oklahoma City. 12 Centre Hospitalier Universitaire de Québec et Université Laval, Quebec City, Canada. 13 Manchester Academic Health Sciences Centre, University of Manchester, Manchester, UK, and Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK. 14 Johns Hopkins University School of Medicine, Baltimore, Maryland. 15 State University of New York Downstate Medical Center, Brooklyn. 16 University of North Carolina, Chapel Hill. 17 Landspitali University Hospital, Reykjavik, Iceland. 18 Northwestern University and Feinberg School of Medicine, Chicago, Illinois. 19 Lanarkshire Centre for Rheumatology and Hairmyres Hospital, East Kilbride, Scotland UK. 20 Lupus Center of Excellence, Allegheny Health Network, Pittsburgh, Pennsylvania. 21 Lund University, Lund, Sweden. 22 Lupus Research Unit, The Rayne Institute, St. Thomas' Hospital, King's College London School of Medicine, London, UK. 23 University of Alabama at Birmingham, Birmingham. 24 Karolinska Institute, Stockholm, Sweden. 25 Feinstein Institute for Medical Research, Manhasset, New York. 26 Hospital Universitario Cruces and University of the Basque Country, Barakaldo, Spain. 27 Institut d'Investigacions Biomèdiques August Pi I Sunyer, IDIBAPS, Hospital Clínic, Barcelona, Spain. 28 Emory University, Atlanta, Georgia. 29 Istanbul University, Istanbul, Turkey. 30 University of California at San Diego, La Jolla. 31 Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 32 University of Manitoba, Winnipeg, Manitoba, Canada. 33 Medical University of South Carolina, Charleston. 34 New York University, New York, New York. (Wiley, 2018-10-01)
      To determine the frequency, characteristics, and outcomes of cerebrovascular events (CerVEs), as well as clinical and autoantibody associations in a multiethnic/racial inception cohort of patients with systemic lupus erythematosus (SLE). A total of 1,826 patients were assessed annually for 19 neuropsychiatric (NP) events, including 5 types of CerVEs: 1) stroke, 2) transient ischemia, 3) chronic multifocal ischemia, 4) subarachnoid/intracranial hemorrhage, and 5) sinus thrombosis. Global disease activity (Systemic Lupus Erythematosus Disease [SLE] Activity Index 2000), damage scores (SLE International Collaborating Clinics/American College of Rheumatology Damage Index), and Short Form 36 (SF-36) scores were collected. Time to event, linear and logistic regressions, and multistate models were used as appropriate. CerVEs were the fourth most frequent NP event: 82 of 1,826 patients had 109 events; of these events, 103 were attributed to SLE, and 44 were identified at the time of enrollment. The predominant events were stroke (60 of 109 patients) and transient ischemia (28 of 109 patients). CerVEs were associated with other NP events attributed to SLE, non-SLE-attributed NP events, African ancestry (at US SLICC sites), and increased organ damage scores. Lupus anticoagulant increased the risk of first stroke and sinus thrombosis and transient ischemic attack. Physician assessment indicated resolution or improvement in the majority of patients, but patients reported sustained reduction in SF-36 summary and subscale scores following a CerVE. CerVEs, the fourth most frequent NP event in SLE, are usually attributable to lupus. In contrast to good physician-reported outcomes, patients reported a sustained reduction in health-related quality of life following a CerVE.
    • Patient-specific mobility assessment to monitor recovery after total hip arthroplasty.

      Gargiulo, Paolo; Edmunds, Kyle Joseph; Gíslason, Magnús K; Latour, Chase; Hermannsson, Þröstur; Esposito, Luca; Bifulco, Paolo; Cesarelli, Mario; Fraldi, Massimiliano; Cristofolini, Luca; Jónsson, Halldór; 1 1 Institute for Biomedical and Neural Engineering, Reykjavík University, Reykjavík, Iceland. 2 2 Department of Science, Landspítali University Hospital, Reykjavík, Iceland. 3 3 Washington University in St. Louis, St. Louis, MO, USA. 4 4 Department of Structures for Engineering and Architecture, University of Naples Federico II, Naples, Italy. 5 5 Department of Electrical Engineering and Information Technologies, University of Naples Federico II, Naples, Italy. 6 6 Interdisciplinary Research Centre for Biomaterials, University of Naples Federico II, Naples, Italy. 7 7 Department of Industrial Engineering, University of Bologna, Bologna, Italy. 8 8 Faculty of Medicine, University of Iceland, Reykjavík, Iceland. 9 9 Orthopedic Clinic, Landspítali University Hospital, Reykjavík, Iceland. (Sage, 2018-10-01)
      Total hip arthroplasty is a ubiquitously successful orthopedic surgical procedure, whose prevalence is rising worldwide. While many investigations focus on characterizing periprosthetic pathophysiology, the objective of our research is to develop and describe multi-metric assemblies as a first step toward creating a patient-specific mobility index that rehabilitators and orthopedic surgeons can utilize for prescribing their respective procedures. In total, 48 total hip arthroplasty patients (both cemented and uncemented) undergoing unilateral, primary surgery went through computed tomographic scans and gait analysis measurements both before and 1 year following their surgery. Altogether, the reported quantitative metrics include 11 spatial and temporal gait parameters, muscle density, and electromyography signals from the rectus femoris, vastus lateralis, and vastus medialis, and bone mineral density values from bioimage analysis around the implant stem. We found that measured parameters from a subgroup were sensitive to changes observed during patient recovery, implicating the predictive sensitivity of these patient conditions. Most post-operative gait parameters changed significantly, while electromyography data indicated few significant differences. Moreover, results from bioimage analyses indicate a general reduction of periprosthetic bone mineral density after 1 year, in association with increasing density of the quadriceps muscles. Furthermore, this work identifies which quantitative metrics undergo the greatest variation after total hip arthroplasty and demonstrates the clinical feasibility of a multimodal approach to mobility assessment that may ultimately support decision-making for post-surgical rehabilitation protocols.
    • The prevalence of chronic airflow obstruction in three cities in the Nordic-Baltic region.

      Broström, Erika; Jõgi, Rain; Gislason, Thorarinn; Benediktsdottir, Bryndis; Burney, Peter G J; Janson, Christer; 1 Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Sweden. 2 Lung Clinic, Tartu University Hospital, Tartu, Estonia. 3 Department of Sleep, Landspitali University Hospital, Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Iceland. 4 Faculty of Medicine, University of Iceland, Iceland. 5 National Heart and Lung Institute, Imperial College, London, UK. 6 Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Sweden; National Heart and Lung Institute, Imperial College, London, UK. Electronic address: christer.janson@medsci.uu.se. (W.B. Saunders, 2018-10-01)
      Chronic airflow obstruction (CAO) is the primary characteristic of Chronic obstructive pulmonary disease (COPD) but is also seen in chronic asthma. To compare the prevalence of CAO and possible risk factors between Tartu in Estonia, Reykjavik in Iceland and Uppsala in Sweden. All participants underwent spirometry testing of forced expiratory volume in 1 s (FEV 1037 men and 956 women participated in the study. The prevalence of CAO was lower in women in Tartu compared to the other centres (4.9% vs. 13.4 and 8.7% in Reykjavik and Uppsala, respectively, p = 0.002) while no difference was found for men. A similar picture was seen for the proportion of participants that had smoked 10 pack years or more which was much lower in Tartu for women than in Reykjavik and Uppsala, respectively (13.2% vs. 33.7 and 29.2%, p < 0.001). (Fig. 1). Of the participants with CAO the majority (57-67%) did not have a previous diagnosis of asthma or COPD.
    • Reduction in All-Cause Acute Otitis Media in Children <3 Years of Age in Primary Care Following Vaccination With 10-Valent Pneumococcal Haemophilus influenzae Protein-D Conjugate Vaccine: A Whole-Population Study.

      Sigurdsson, Samuel; Eythorsson, Elias; Hrafnkelsson, Birgir; Erlendsdóttir, Helga; Kristinsson, Karl G; Haraldsson, Ásgeir; 1 Faculty of Medicine, University of Iceland. 2 Department of Mathematics, University of Iceland. 3 Department of Clinical Microbiology, Reykjavík. 4 Children's Hospital Iceland, Landspítali University Hospital, Reykjavík. (Oxford University Press, 2018-09-28)
      The 10-valent pneumococcal conjugate vaccine (PHiD-CV10) was introduced in Iceland in 2011, without catch-up. The aim of this study was to estimate vaccine impact (VI) on acute otitis media (AOM). In this whole-population study, all primary care visits due to AOM from 2005 to 2015 in children <3 years of age were included. Birth cohorts were grouped as vaccine noneligible (VNEC) or vaccine eligible (VEC). Crude incidence rates (IRs) were compared between the VNEC and VEC. A Cox regression model for repeated events was used to model the individual-level data. VI was calculated as (hazard ratio [HR] - 1) × 100%. Included were 53150 children, with 140912 person-years of follow-up and 58794 AOM episodes. Both IR and the mean number of episodes differed significantly between VNEC and VEC; 43 compared to 38 episodes per 100 person-years and 1.61 episodes per child compared to 1.37. IR was significantly reduced in all age brackets, with the largest reduction in children <4 months of age (40% [95% confidence interval {CI}, 31%-49%). The VI on all-cause AOM was 22% (95% CI, 12%-31%). The impact was mediated through its effect on the first (HR, 0.84 [95% CI, .82-.86]) and second (HR, 0.95 [95% CI, .93-.98]) episodes. The impact of PHiD-CV10 on all-cause AOM was considerable, mediated mainly by preventing the first two episodes of AOM. A decrease in the IR of AOM in children too young to receive direct vaccine protection was demonstrated, suggesting herd effect.
    • The clinical effect of an unloader brace on patients with osteoarthritis of the knee, a randomized placebo controlled trial with one year follow up.

      Hjartarson, Hjörtur F; Toksvig-Larsen, Sören; 1 Dept of Orthopedics, Landspitali University Hospital, E-4 Fossvogur, 101, Reykjavik, Iceland. hjorturfr@gmail.com. 2 Lund University, Lund, Sweden. hjorturfr@gmail.com. 3 Dept of Orthopedics, Hässleholm hospital, Esplanadgatan 19, 281 38, Hässleholm, Sweden. 4 Lund University, Lund, Sweden. (BioMed Central, 2018-09-22)
      Treatment of patients with knee osteoarthritis is challenging. Unloader braces have been developed with various success. Unloader One® Knee Brace is light, easily-fitted and shown to be effective by the unloading of the affected compartment. The aim of the study was to assess the clinical outcome of the brace vs. a placebo on patients with knee osteoarthritis. Initially 150 patients were randomized to receive either the Unloader brace or a control placebo group look-alike brace where the active strips had been removed. The patients were followed up at 6,12,26 and 52 weeks with Knee Society Score (KSS) and Knee injury and Osteoarthritis Outcome Score (KOOS). The reason for dropout was recorded. A total of 149 patients were included, 74 in the study and 75 in the control group. The mean age was 59.6 vs. 60.2, BMI was 27.5 vs. 26.9, 37% vs. 44% were women in the study vs. control group. Both groups showed improvement in KSS over 52 weeks, with the study group showing higher improvement in mean scores. KSS increased from 64.3 to 84.0 for the study group and from 64.0 to 74.6 for the control group (p = 0.009). The study group improved in KSS function from 67.0 to 78.6 (p < 0.001) and KOOS for knee related symptoms increased/improved from 64.3 to 72.4 (p < 0.001). Activity of daily living increased/improved from 65.3 to 75.2 and Sports/Recreation from 24.6 to 40.2 (p > 0.001) whereas the control group did not show significant improvements in any of the scores. The dropout was higher in the control group, 40 vs. 25. The brace seems to be more effective and better tolerated than the placebo.
    • The Effect of Maternal Age on Obstetric Interventions in a Low-Risk Population.

      Einarsdóttir, Kristjana; Bogadóttir, Hjördís Ýr; Bjarnadóttir, Ragnheiður Ingibjörg; Steingrímsdóttir, Þóra; [ 1 ] Univ Iceland, Fac Med, Ctr Publ Hlth Sci, Sturlugata 8, IS-101 Reykjavik, Iceland Show more [ 2 ] Univ Iceland, Fac Med, Reykjavik, Iceland Show more [ 3 ] Landspitali Univ Hosp, Ctr Dev Primary Hlth Care Capital Area, Reykjavik, Iceland Show more [ 4 ] Landspitali Univ Hosp, Dept Obstet & Gynaecol, Reykjavik, Iceland (Wiley, 2018-09-19)
      Obstetric interventions appear to increase with advancing maternal age, but limited supporting evidence exists, particularly for young women and specifically for prelabor and intrapartum cesarean birth. The aim of this study was to explore the association between obstetric interventions and maternal age in a low-risk population. The study was restricted to all low-risk, nulliparous women with singleton, vertex, term births who gave birth in Iceland from 1997 to 2015, identified in the Icelandic Medical Birth Registry. Logistic regression models were used to calculate adjusted odds ratios (aORs) and 95% CIs for the risks of labor induction, instrumental birth, and cesarean birth (prelabor and intrapartum), according to maternal age group. All models were adjusted for gestational age, year of birth, and demographic factors, and the models for intrapartum cesarean birth were also adjusted for dystocia and fetal distress. For women aged more than 40 years, the aOR for induction of labor was 4.69 (95% CI, 3.2-6.8) compared with women aged between 25 and 29 years. In women aged more than 40 years, the increased risks for prelabor cesarean birth and intrapartum cesarean birth were 7.4 (95% CI, 3.0-18.0) and 3.6 (95% CI, 2.1-6.0), respectively. The risk of instrumental birth was slightly increased for women aged between 35 and 39 years (aOR, 1.6; 95% CI, 1.3-2.0), compared with women aged between 25 and 29 years, but not for women aged at least 40 years (aOR, 1.1; 95% CI, 0.7-1.9). For women aged less than 20 years, the risk of induction of labor (aOR, 0.8; 95% CI, 0.7-0.9) and instrumental births (aOR, 0.6; 95% CI, 0.5-0.7) was reduced compared with women aged between 25 and 29 years. The risk of interventions generally increased with increasing maternal age, but the risk of instrumental births was not increased for women aged over 40 years. Also, young women were at a decreased risk of induction of labor and instrumental births.
    • Association between maternal gluten intake and type 1 diabetes in offspring: national prospective cohort study in Denmark.

      Antvorskov, Julie C; Halldorsson, Thorhallur I; Josefsen, Knud; Svensson, Jannet; Granström, Charlotta; Roep, Bart O; Olesen, Trine H; Hrolfsdottir, Laufey; Buschard, Karsten; Olsen, Sjudur F; 1 Bartholin Institute, Rigshospitalet, Ole Måløes Vej 5, 2200 Copenhagen K, Denmark. 2 Centre for Foetal Programming, Department of Epidemiology Research, Statens Serum Institute, Copenhagen, Denmark. 3 Unit for Nutrition Research, Landspitali University Hospital, Reykjavik, Iceland. 4 Faculty of Food Science and Nutrition, University of Iceland, Reykjavik, Iceland. 5 Copenhagen Diabetes Research Center (CPH-DIRECT), Department of Children and Adolescents, Copenhagen University Hospital Herlev, Herlev, Denmark. 6 Department of Diabetes Immunology, Diabetes and Metabolism Research Institute at the Beckman Diabetes Research Institute, City of Hope, Duarte, CA, USA. 7 Departments of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, Netherlands. 8 Department of Education, Science, and Quality, Akureyri Hospital, Akureyri, Iceland. 9 Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA. (British Medical Association, 2018-09-19)
      To examine the association between prenatal gluten exposure and offspring risk of type 1 diabetes in humans. National prospective cohort study. National health information registries in Denmark. Pregnant Danish women enrolled into the Danish National Birth Cohort, between January 1996 and October 2002, MAIN OUTCOME MEASURES: Maternal gluten intake, based on maternal consumption of gluten containing foods, was reported in a 360 item food frequency questionnaire at week 25 of pregnancy. Information on type 1 diabetes occurrence in the participants' children, from 1 January 1996 to 31 May 2016, were obtained through registry linkage to the Danish Registry of Childhood and Adolescent Diabetes.
    • A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk.

      Lu, Yingchang; Beeghly-Fadiel, Alicia; Wu, Lang; Guo, Xingyi; Li, Bingshan; Schildkraut, Joellen M; Im, Hae Kyung; Chen, Yian A; Permuth, Jennifer B; Reid, Brett M; Teer, Jamie K; Moysich, Kirsten B; Andrulis, Irene L; Anton-Culver, Hoda; Arun, Banu K; Bandera, Elisa V; Barkardottir, Rosa B; Barnes, Daniel R; Benitez, Javier; Bjorge, Line; Brenton, James; Butzow, Ralf; Caldes, Trinidad; Caligo, Maria A; Campbell, Ian; Chang-Claude, Jenny; Claes, Kathleen B M; Couch, Fergus J; Cramer, Daniel W; Daly, Mary B; deFazio, Anna; Dennis, Joe; Diez, Orland; Domchek, Susan M; Dörk, Thilo; Easton, Douglas F; Eccles, Diana M; Fasching, Peter A; Fortner, Renée T; Fountzilas, George; Friedman, Eitan; Ganz, Patricia A; Garber, Judy; Giles, Graham G; Godwin, Andrew K; Goldgar, David E; Goodman, Marc T; Greene, Mark H; Gronwald, Jacek; Hamann, Ute; Heitz, Florian; Hildebrandt, Michelle A T; Høgdall, Claus K; Hollestelle, Antoinette; Hulick, Peter J; Huntsman, David G; Imyanitov, Evgeny N; Isaacs, Claudine; Jakubowska, Anna; James, Paul; Karlan, Beth Y; Kelemen, Linda E; Kiemeney, Lambertus A; Kjaer, Susanne K; Kwong, Ava; Le, Nhu D; Leslie, Goska; Lesueur, Fabienne; Levine, Douglas A; Mattiello, Amalia; May, Taymaa; McGuffog, Lesley; McNeish, Iain A; Merritt, Melissa A; Modugno, Francesmary; Montagna, Marco; Neuhausen, Susan L; Nevanlinna, Heli; Nielsen, Finn C; Nikitina-Zake, Liene; Nussbaum, Robert L; Offit, Kenneth; Olah, Edith; Olopade, Olufunmilayo I; Olson, Sara H; Olsson, Håkan; Osorio, Ana; Park, Sue K; Parsons, Michael T; Peeters, Petra H M; Pejovic, Tanja; Peterlongo, Paolo; Phelan, Catherine M; Pujana, Miquel Angel; Ramus, Susan J; Rennert, Gad; Risch, Harvey; Rodriguez, Gustavo C; Rodríguez-Antona, Cristina; Romieu, Isabelle; Rookus, Matti A; Rossing, Mary Anne; Rzepecka, Iwona K; Sandler, Dale P; Schmutzler, Rita K; Setiawan, Veronica W; Sharma, Priyanka; Sieh, Weiva; Simard, Jacques; Singer, Christian F; Song, Honglin; Southey, Melissa C; Spurdle, Amanda B; Sutphen, Rebecca; Swerdlow, Anthony J; Teixeira, Manuel R; Teo, Soo H; Thomassen, Mads; Tischkowitz, Marc; Toland, Amanda E; Trichopoulou, Antonia; Tung, Nadine; Tworoger, Shelley S; van Rensburg, Elizabeth J; Vanderstichele, Adriaan; Vega, Ana; Edwards, Digna Velez; Webb, Penelope M; Weitzel, Jeffrey N; Wentzensen, Nicolas; White, Emily; Wolk, Alicja; Wu, Anna H; Yannoukakos, Drakoulis; Zorn, Kristin K; Gayther, Simon A; Antoniou, Antonis C; Berchuck, Andrew; Goode, Ellen L; Chenevix-Trench, Georgia; Sellers, Thomas A; Pharoah, Paul D P; Zheng, Wei; Long, Jirong; 1 Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee. 2 Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee. 3 Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia. 4 Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, Illinois. 5 Department of Biostatistics, Moffitt Cancer Center, Tampa, Florida. 6 Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida. 7 Division of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York. 8 Fred A. Litwin Center for Cancer Genetics, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada. 9 Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. 10 Department of Epidemiology, Genetic Epidemiology Research Institute, University of California Irvine, Irvine, California. 11 Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas. 12 Cancer Prevention and Control Program, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey. 13 Department of Pathology, Landspitali University Hospital, Reykjavik, Iceland....... (American Association for Cancer Research, 2018-09-15)
      Large-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci. We used RNA sequencing data (68 normal ovarian tissue samples from 68 individuals and 6,124 cross-tissue samples from 369 individuals) and high-density genotyping data from European descendants of the Genotype-Tissue Expression (GTEx V6) project to build ovarian and cross-tissue models of genetically regulated expression using elastic net methods. We evaluated 17,121 genes for their
    • Change in the prevalence asthma, rhinitis and respiratory symptom over a 20 year period: associations to year of birth, life style and sleep related symptoms.

      Janson, Christer; Johannessen, Ane; Franklin, Karl; Svanes, Cecilie; Schiöler, Linus; Malinovschi, Andrei; Gislason, Thorarinn; Benediktsdottir, Bryndis; Schlünssen, Vivi; Jõgi, Rain; Jarvis, Deborah; Lindberg, Eva; 1 Department of Medical Sciences, Respiratory, Allergy and Sleep Medicine, Uppsala University, Uppsala, Sweden. christer.janson@medsci.uu.se. 2 Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway. 3 Dept. of Surgical and Perioperative Sciences, Surgery, Umea University, Umea, Sweden. 4 Institute of Clinical Science, University of Bergen, Bergen, Norway. 5 Department of Occupational and Environmental Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden. 6 Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden. 7 Department of Respiratory Medicine and Sleep, the National University Hospital of Iceland, Reykjavik, Iceland. 8 Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 9 Department of Public Health, Section for Environment, Occupation and Health, Aarhus University, Aarhus, Denmark. 10 National Research Center for the Working Environment, Copenhagen, Denmark. 11 Lung Clinic, Tartu University Clinics, Tartu, Estonia. 12 Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College, London, UK. 13 Department of Medical Sciences, Respiratory, Allergy and Sleep Medicine, Uppsala University, Uppsala, Sweden. (BioMed Central, 2018-09-12)
      The aim of this investigation was to study change in adults over a 20 year period in the prevalence of respiratory symptoms and disorders and its association to year of birth, life style and sleep related variables. Adults 20-44 years of age, 6085 women and 5184 men, were randomly selected from seven centres in Northern Europe and followed for 20 years. The number of participants in the first survey was 21,595 and 11,269 participated in all three surveys. The participants were divided into three birth cohorts: 1944-1955, 1956-1965 and 1966-1975. During the 20 year period the prevalence of wheeze decreased (- 2%) and the prevalence of asthma (+ 4%) and allergic rhinitis (+ 5%) increased, whereas the prevalence of nocturnal respiratory symptoms was relatively unchanged. The increase in allergic rhinitis was largest in those born 1966 to 1975 except in Estonia. There was large decrease in smoking (- 20%), increase in obesity (+ 7%) and snoring (+ 6%) during the study period. Smoking, obesity, snoring and nocturnal gastroesophageal reflux (nGER) were related to a higher risk of all symptoms. Obesity, snoring and nGER were also independently related to asthma. We conclude that as our participants got older there was a decrease in wheeze, no change in nocturnal symptoms and an increase in reported asthma and allergic rhinitis. These changes in prevalence are probably related to a decrease in smoking being counteracted by an increase in allergy, obesity and sleep related disorders.
    • Variants associating with uterine leiomyoma highlight genetic background shared by various cancers and hormone-related traits.

      Rafnar, Thorunn; Gunnarsson, Bjarni; Stefansson, Olafur A; Sulem, Patrick; Ingason, Andres; Frigge, Michael L; Stefansdottir, Lilja; Sigurdsson, Jon K; Tragante, Vinicius; Steinthorsdottir, Valgerdur; Styrkarsdottir, Unnur; Stacey, Simon N; Gudmundsson, Julius; Arnadottir, Gudny A; Oddsson, Asmundur; Zink, Florian; Halldorsson, Gisli; Sveinbjornsson, Gardar; Kristjansson, Ragnar P; Davidsson, Olafur B; Salvarsdottir, Anna; Thoroddsen, Asgeir; Helgadottir, Elisabet A; Kristjansdottir, Katrin; Ingthorsson, Orri; Gudmundsson, Valur; Geirsson, Reynir T; Arnadottir, Ragnheidur; Gudbjartsson, Daniel F; Masson, Gisli; Asselbergs, Folkert W; Jonasson, Jon G; Olafsson, Karl; Thorsteinsdottir, Unnur; Halldorsson, Bjarni V; Thorleifsson, Gudmar; Stefansson, Kari; 1 deCODE Genetics/Amgen, Sturlugata 8, 101, Reykjavik, Iceland. thorunn.rafnar@decode.is. 2 deCODE Genetics/Amgen, Sturlugata 8, 101, Reykjavik, Iceland. 3 Department of Cardiology, Division Heart & Lungs, University Medical Center Utrecht, University of Utrecht, 3584 CX, Utrecht, The Netherlands. 4 Department of Obstetrics and Gynecology, Landspitali University Hospital, 101, Reykjavik, Iceland. 5 Department of Obstetrics and Gynecology, Akureyri Hospital, 600, Akureyri, Iceland. 6 Faculty of Medicine, School of Health Sciences, University of Iceland, 101, Reykjavik, Iceland. 7 School of Engineering and Natural Sciences, University of Iceland, 101, Reykjavik, Iceland. 8 Durrer Center for Cardiovascular Research, Netherlands Heart Institute, 3501 DG, Utrecht, The Netherlands. 9 Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, WC1E 6HX, UK. 10 Farr Institute of Health Informatics Research and Institute of Health Informatics, University College London, London, NW1 2DA, UK. 11 Department of Pathology, Landspitali University Hospital, 101, Reykjavik, Iceland. 12 School of Science and Engineering, Reykjavik University, 101, Reykjavik, Iceland. 13 deCODE Genetics/Amgen, Sturlugata 8, 101, Reykjavik, Iceland. kstefans@decode.is. 14 Faculty of Medicine, School of Health Sciences, University of Iceland, 101, Reykjavik, Iceland. kstefans@decode.is. (Nature Publishing Group, 2018-09-07)
      Uterine leiomyomas are common benign tumors of the myometrium. We performed a meta-analysis of two genome-wide association studies of leiomyoma in European women (16,595 cases and 523,330 controls), uncovering 21 variants at 16 loci that associate with the disease. Five variants were previously reported to confer risk of various malignant or benign tumors (rs78378222 in TP53, rs10069690 in TERT, rs1800057 and rs1801516 in ATM, and rs7907606 at OBFC1) and four signals are located at established risk loci for hormone-related traits (endometriosis and breast cancer) at 1q36.12 (CDC42/WNT4), 2p25.1 (GREB1), 20p12.3 (MCM8), and 6q26.2 (SYNE1/ESR1). Polygenic score for leiomyoma, computed using UKB data, is significantly correlated with risk of cancer in the Icelandic population. Functional annotation suggests that the non-coding risk variants affect multiple genes, including ESR1. Our results provide insights into the genetic background of leiomyoma that are shared by other benign and malignant tumors and highlight the role of hormones in leiomyoma growth.
    • A rare missense mutation in MYH6 associates with non-syndromic coarctation of the aorta.

      Bjornsson, Thorsteinn; Thorolfsdottir, Rosa B; Sveinbjornsson, Gardar; Sulem, Patrick; Norddahl, Gudmundur L; Helgadottir, Anna; Gretarsdottir, Solveig; Magnusdottir, Audur; Danielsen, Ragnar; Sigurdsson, Emil L; Adalsteinsdottir, Berglind; Gunnarsson, Sverrir I; Jonsdottir, Ingileif; Arnar, David O; Helgason, Hrodmar; Gudbjartsson, Tomas; Gudbjartsson, Daniel F; Thorsteinsdottir, Unnur; Holm, Hilma; Stefansson, Kari; 1 deCODE genetics/Amgen, Inc., Sturlugata 8, Reykjavik, Iceland. 2 Department of Medicine, Landspitali-The National University Hospital of Iceland, Hringbraut, Reykjavik, Iceland. 3 Department of Family Medicine, University of Iceland, Vatnsmyrarvegur 16, Reykjavik, Iceland. 4 Department of Development, Primary Health Care of the Capital Area, Alfabakki 16, Reykjavik, Iceland. 5 Department of Cardiology, Haukeland University Hospital, Jonas Lies vei 83, Bergen, Norway. 6 Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, Reykjavik, Iceland. 7 Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin, 600 Highland Ave, Madison, WI, USA. 8 Department of Immunology, Landspitali-The National University Hospital of Iceland, Hringbraut, Reykjavik, Iceland. 9 Children's Hospital, Landspitali-The National University Hospital of Iceland, Hringbraut, Reykjavik, Iceland. 10 Department of Cardiothoracic Surgery, Landspitali-The National University Hospital of Iceland, Hringbraut, Reykjavik, Iceland. 11 School of Engineering and Natural Sciences, University of Iceland, Hjardarhagi 4, Reykjavik, Iceland. (Oxford University Press, 2018-09-07)
      Coarctation of the aorta (CoA) accounts for 4-8% of congenital heart defects (CHDs) and confers substantial morbidity despite treatment. It is increasingly recognized as a highly heritable condition. The aim of the study was to search for sequence variants that affect the risk of CoA. We performed a genome-wide association study of CoA among Icelanders (120 cases and 355 166 controls) based on imputed variants identified through whole-genome sequencing. We found association with a rare (frequency = 0.34%) missense mutation p.Arg721Trp in MYH6 (odds ratio = 44.2, P = 5.0 × 10-22), encoding the alpha-heavy chain subunit of cardiac myosin, an essential sarcomere protein. Approximately 20% of individuals with CoA in Iceland carry this mutation. We show that p.Arg721Trp also associates with other CHDs, in particular bicuspid aortic valve. We have previously reported broad effects of p.Arg721Trp on cardiac electrical function and strong association with sick sinus syndrome and atrial fibrillation. Through a population approach, we found that a rare missense mutation p.Arg721Trp in the sarcomere gene MYH6 has a strong effect on the risk of CoA and explains a substantial fraction of the Icelanders with CoA. This is the first mutation associated with non-familial or sporadic form of CoA at a population level. The p.Arg721Trp in MYH6 causes a cardiac syndrome with highly variable expressivity and emphasizes the importance of sarcomere integrity for cardiac development and function.