Recent Submissions

  • 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.
  • 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
  • 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.
  • 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. 6 Department of Clinical Microbiology, Landspítali University Hospital, 101, Reykjavík, Iceland. (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.
  • 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. 8 Department of Anesthesiology, Duke University Hospital, 2301 Erwin Road, Durham, NC, USA. (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
  • 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.
  • 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. 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.
  • Sex-Based Differences in Incidence of Inflammatory Bowel Diseases-Pooled Analysis of Population-Based Studies From Western Countries.

    Shah, Shailja C; Khalili, Hamed; Gower-Rousseau, Corinne; Olen, Ola; Benchimol, Eric I; Lynge, Elsebeth; Nielsen, Kári R; Brassard, Paul; Vutcovici, Maria; Bitton, Alain; Bernstein, Charles N; Leddin, Desmond; Tamim, Hala; Stefansson, Tryggvi; Loftus, Edward V; Moum, Bjørn; Tang, Whitney; Ng, Siew C; Gearry, Richard; Sincic, Brankica; Bell, Sally; Sands, Bruce E; Lakatos, Peter L; Végh, Zsuzsanna; Ott, Claudia; Kaplan, Gilaad G; Burisch, Johan; Colombel, Jean-Frederic; 1 Division of Gastroenterology, Mount Sinai Hospital, New York, New York; Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address: 2 Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. 3 Public Health Unit, Epimad Registre, Lille University Hospital, France; INSERM LIRIC, UMR 995, Lille University, France. 4 Department of Medicine, Karolinska Institutet, Stockholm, Sweden. 5 CHEO Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada; Department of Pediatrics and School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada. 6 Division of Gastroenterology, University of Copenhagen, Copenhagen, Denmark. 7 Division of Gastroenterology, National Hospital, Tórshavn, Faroe Islands. 8 Department of Medicine, McGill University, Montreal, Quebec, Canada. 9 Department of Gastroenterology, McGill University Health Center, Montreal, Quebec, Canada. 10 Division of Gastroenterology, University of Manitoba, Winnipeg, Manitoba, Canada. 11 Division of Gastroenterology, Dalhousie University, Halifax, Nova Scotia, Canada. 12 Division of Gastroenterology, National University Hospital of Iceland, Reykjavík, Iceland. 13 Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, New York. 14 Department of Gastroenterology, Oslo University Hospital and University of Oslo, Oslo, Norway. 15 Department of Medicine and Therapeutics, Institute of Digestive Disease, LKS Institute of Health Science, State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong. 16 Division of Gastroenterology, University of Otago, Christchurch, New Zealand. 17 Division of Gastroenterology, University of Rijeka, Rijeka, Croatia. 18 Division of Gastroenterology, St. Vincent's Hospital, Melbourne, Australia. 19 Division of Gastroenterology, Mount Sinai Hospital, New York, New York. 20 Division of Gastroenterology, Semmelweis University, Budapest, Hungary. 21 Division of Gastroenterology, University of Regensburg, Regensburg, Germany. 22 Department of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada. 23 Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark. (W.B. Saunders, 2018-01-01)
    Although the incidence of inflammatory bowel diseases (IBDs) varies with age, few studies have examined variations between the sexes. We therefore used population data from established cohorts to analyze sex differences in IBD incidence according to age at diagnosis. We identified population-based cohorts of patients with IBD for which incidence and age data were available (17 distinct cohorts from 16 regions of Europe, North America, Australia, and New Zealand). We collected data through December 2016 on 95,605 incident cases of Crohn's disease (CD) (42,831 male and 52,774 female) and 112,004 incident cases of ulcerative colitis (UC) (61,672 male and 50,332 female). We pooled incidence rate ratios of CD and UC for the combined cohort and compared differences according to sex using random effects meta-analysis. Female patients had a lower risk of CD during childhood, until the age range of 10-14 years (incidence rate ratio, 0.70; 95% CI, 0.53-0.93), but they had a higher risk of CD thereafter, which was statistically significant for the age groups of 25-29 years and older than 35 years. The incidence of UC did not differ significantly for female vs male patients (except for the age group of 5-9 years) until age 45 years; thereafter, men had a significantly higher incidence of ulcerative colitis than women. In a pooled analysis of population-based studies, we found age at IBD onset to vary with sex. Further studies are needed to investigate mechanisms of sex differences in IBD incidence.
  • 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.
  • 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.
  • 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.
  • Comparison of reports of missed nursing care: Registered Nurses vs. practical nurses in hospitals.

    Bragadóttir, Helga; Kalisch, Beatrice J; 1 Faculty of Nursing, University of Iceland and Landspitali University Hospital, Reykjavik, Iceland. 2 School of Nursing, University of Michigan, Ann Arbor, MI, USA. (Wiley, 2018-09-01)
    Missed nursing care is an error of omission defined as standard, required nursing care that is not completed or is seriously delayed. Study findings from around the world show that missed nursing care is a global concern. The purpose of this study was to compare reports of missed nursing care by two types of nurses - registered nurses and practical nurses - in acute care hospitals in Iceland. Former studies in the USA indicate a variance in reports of missed nursing care by staff with different roles. This was a cross-sectional descriptive study using the MISSCARE Survey-Icelandic questionnaire for data collection. The questionnaire asks about the amount of missed nursing care on the unit for 24 nursing elements (Part A) and 17 reasons of care being missed (Part B). Participants were nursing staff from medical, surgical and intensive care units in all hospitals in Iceland. A t-test for independent groups showed a significant difference for the overall missed nursing care score (Part A) between registered nurses (M = 2.09, SD = 0.51) and practical nurses (M = 1.82, SD = 0.59) [t(541) = 5.703, p < 0.001]. A comparison of the overall mean score for reasons of missed nursing care (Part B) between registered nurses (M = 2.32, SD = 0.38) and practical nurses (M = 2.21, SD = 0.62) indicated a significant difference in their reporting [t(299) = 2.210, p = 0.028]. In spite of the overall significant difference in ratings of the elements and reasons for missed nursing care by registered nurses and practical nurses, a pattern is evident in the ranking of the elements of nursing care being missed and reasons.
  • 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: (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.
  • Risk of Soft-Tissue Sarcoma Among 69 460 Five-Year Survivors of Childhood Cancer in Europe.

    Bright, Chloe J; Hawkins, Mike M; Winter, David L; Alessi, Daniela; Allodji, Rodrigue S; Bagnasco, Francesca; Bárdi, Edit; Bautz, Andrea; Byrne, Julianne; Feijen, Elizabeth A M; Fidler, Miranda M; Garwicz, Stanislaw; Grabow, Desiree; Gudmundsdottir, Thorgerdur; Guha, Joyeeta; Haddy, Nadia; Jankovic, Momcilo; Kaatsch, Peter; Kaiser, Melanie; Kuehni, Claudia E; Linge, Helena; Øfstaas, Hilde; Ronckers, Cecile M; Skinner, Roderick; Teepen, Jop C; Terenziani, Monica; Vu-Bezin, Giao; Wesenberg, Finn; Wiebe, Thomas; Sacerdote, Carlotta; Jakab, Zsuzsanna; Haupt, Riccardo; Lähteenmäki, Päivi; Zaletel, Lorna Zadravec; Kuonen, Rahel; Winther, Jeanette F; de Vathaire, Florent; Kremer, Leontien C; Hjorth, Lars; Reulen, Raoul C; 1 Center for Childhood Cancer Survivor Studies, Institute of Applied Health Research, Robert Aitken Building, University of Birmingham, Birmingham, UK. 2 Childhood Cancer Registry of Piedmont, Cancer Epidemiology Unit, Department of Medical Sciences, University of Turin and AOU Città della Salute e della Scienza di Torino, Torino, Italy. 3 Cancer and Radiation Team, U1018 INSERM, Gustave Roussy, Villejuif, France. 4 Epidemiology and Biostatistics Section, Gaslini Children Hospital, Genova, Italy. 5 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary. 6 Kepler Universitätsklinikum, Linz, Austria. 7 Danish Cancer Society Research Center, Survivorship Unit, Copenhagen, Denmark. 8 Boyne Research Institute, Drogheda, Ireland. 9 Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, the Netherlands. 10 Lund University, Skane University Hospital, Department of Clinical Sciences Lund, Pediatrics, Lund, Sweden. 11 German Childhood Cancer Registry (GCCR), Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center, Mainz, Germany. 12 Childreńs Hospital, Landspitali University Hospital, Reykjavik, Iceland. 13 Foundation MBBM, Hemato-Oncology Center, University of Milano-Bicocca, Monza, Italy. 14 Swiss Childhood Cancer Registry, Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland. 15 Department of Paediatrics, University Children's Hospital of Bern, University of Bern, Bern, Switzerland. 16 Norwegian National Advisory Unit on Solid Tumors in Children, Oslo, Norway. 17 Great North Children's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, and Northern Institute of Cancer Research, Newcastle University, Newcastle upon Tyne, UK. 18 Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. 19 Norwegian Cancer Registry and Department of Pediatric Medicine, Oslo University Hospital and Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway. 20 Hungarian Childhood Cancer Registry, Semmelweis University, Budapest, Hungary. 21 Department of Pediatric and Adolescent Medicine, Turku University and Turku University Hospital, Turku, Finland. 22 Institute of Oncology, Ljubljana, Slovenia. 23 Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark. 24 Department of Pediatric Oncology, Princess Maxima Center for Pediatric Oncology, Utrecht, the Netherlands. (Oxford University Press, 2018-06-01)
    Childhood cancer survivors are at risk of subsequent primary soft-tissue sarcomas (STS), but the risks of specific STS histological subtypes are unknown. We quantified the risk of STS histological subtypes after specific types of childhood cancer. We pooled data from 13 European cohorts, yielding a cohort of 69 460 five-year survivors of childhood cancer. Standardized incidence ratios (SIRs) and absolute excess risks (AERs) were calculated. Overall, 301 STS developed compared with 19 expected (SIR = 15.7, 95% confidence interval [CI] = 14.0 to 17.6). The highest standardized incidence ratios were for malignant peripheral nerve sheath tumors (MPNST; SIR = 40.6, 95% CI = 29.6 to 54.3), leiomyosarcomas (SIR = 29.9, 95% CI = 23.7 to 37.2), and fibromatous neoplasms (SIR = 12.3, 95% CI = 9.3 to 16.0). SIRs for MPNST were highest following central nervous system tumors (SIR = 80.5, 95% CI = 48.4 to 125.7), Hodgkin lymphoma (SIR = 81.3, 95% CI = 35.1 to 160.1), and Wilms tumor (SIR = 76.0, 95% CI = 27.9 to 165.4). Standardized incidence ratios for leiomyosarcoma were highest following retinoblastoma (SIR = 342.9, 95% CI = 245.0 to 466.9) and Wilms tumor (SIR = 74.2, 95% CI = 37.1 to 132.8). AERs for all STS subtypes were generally low at all years from diagnosis (AER < 1 per 10 000 person-years), except for leiomyosarcoma following retinoblastoma, for which the AER reached 52.7 (95% CI = 20.0 to 85.5) per 10 000 person-years among patients who had survived at least 45 years from diagnosis of retinoblastoma. For the first time, we provide risk estimates of specific STS subtypes following childhood cancers and give evidence that risks of MPNSTs, leiomyosarcomas, and fibromatous neoplasms are particularly increased. While the multiplicative excess risks relative to the general population are substantial, the absolute excess risk of developing any STS subtype is low, except for leiomyosarcoma after retinoblastoma. These results are likely to be informative for both survivors and health care providers.
  • 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. 2 Lund University, Lund, Sweden. 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.
  • Influenza infection directly alters innate IL-23 and IL-12p70 and subsequent IL-17A and IFN-γ responses to pneumococcus in vitro in human monocytes.

    Loughran, Sinead T; Power, Patrick A; Maguire, Paula T; McQuaid, Samantha L; Buchanan, Paul J; Jonsdottir, Ingileif; Newman, Robert W; Harvey, Ruth; Johnson, Patricia A; 1 Viral Immunology Laboratory, School of Nursing and Human Sciences, Dublin City University, Dublin, Ireland. 2 Translational Cancer Physiology Laboratory, School of Nursing and Human Sciences, Dublin City University, Dublin, Ireland. 3 Department of Immunology, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland. 4 National Institute for Biological Standards and Controls, Potters Bar, Herts, United Kingdom. (Public Library of Science, 2018-01-01)
    Influenza virus is highly contagious and poses substantial public health problems due to its strong association with morbidity and mortality. Approximately 250,000-500,000 deaths are caused by seasonal influenza virus annually, and this figure increases during periods of pandemic infections. Most of these deaths are due to secondary bacterial pneumonia. Influenza-bacterial superinfection can result in hospitalisation and/or death of both patients with pre-existing lung disease or previously healthy individuals. The importance of our research is in determining that influenza and its component haemagglutinin has a direct effect on the classic pneumococcus induced pathways to IL-17A in our human ex vivo model. Our understanding of the mechanism which leaves people exposed to influenza infection during superinfection remain unresolved. This paper demonstrates that early infection of monocytes inhibits an arm of immunity crucial to bacterial clearance. Understanding this mechanism may provide alternative interventions in the case of superinfection with antimicrobial resistant strains of bacteria.
  • Association of BRCA2 K3326* With Small Cell Lung Cancer and Squamous Cell Cancer of the Skin.

    Rafnar, Thorunn; Sigurjonsdottir, Gudbjorg R; Stacey, Simon N; Halldorsson, Gisli; Sulem, Patrick; Pardo, Luba M; Helgason, Hannes; Sigurdsson, Stefan T; Gudjonsson, Thorkell; Tryggvadottir, Laufey; Olafsdottir, Gudridur H; Jonasson, Jon G; Alexiusdottir, Kristin; Sigurdsson, Asgeir; Gudmundsson, Julius; Saemundsdottir, Jona; Sigurdsson, Jon K; Johannsdottir, Hrefna; Uitterlinden, Andre; Vermeulen, Sita H; Galesloot, Tessel E; Allain, Dawn C; Lacko, Martin; Sigurgeirsson, Bardur; Thorisdottir, Kristin; Johannsson, Oskar T; Sigurdsson, Fridbjorn; Ragnarsson, Gunnar B; Isaksson, Helgi; Hardardottir, Hronn; Gudbjartsson, Tomas; Gudbjartsson, Daniel F; Masson, Gisli; Kiemeney, Lambertus A M L; Ewart Toland, Amanda; Nijsten, Tamar; Peters, Wilbert H M; Olafsson, Jon H; Jonsson, Steinn; Thorsteinsdottir, Unnur; Thorleifsson, Gudmar; Stefansson, Kari; 1 deCODE Genetics/Amgen, Reykjavik, Iceland. 2 Department of Oncology, Landspitali-University Hospital, Reykjavik, Iceland. 3 Department of Dermatology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands. 4 Faculty of Electrical and Computer Engineering, University of Iceland, Reykjavik, Iceland. 5 Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 6 Icelandic Cancer Registry, Reykjavik, Iceland. 7 Department of Pathology, Landspitali-University Hospital, Reykjavik, Iceland. 8 Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands. 9 Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, the Netherlands. 10 Department of Internal Medicine. 11 The Ohio State University, Columbus, OH. 12 Department of Otorhinolaryngology, Head and Neck Surgery, Maastricht University Medical Center, Maastricht, the Netherlands. 13 Department of Dermatology, Landspitali-University Hospital, Reykjavik, Iceland. 14 Department of Medicine, Landspitali-University Hospital, Reykjavik, Iceland. 15 Department of Surgery, Landspitali-University Hospital, Reykjavik, Iceland. 16 School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland. 17 Department of Cancer Biology. 18 Department of Genetics and Internal Medicine. 19 Division of Human Genetics, and The Comprehensive Cancer Center. 20 Department of Gastroenterology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands. (Oxford University Press, 2018-09-01)
    Most pathogenic mutations in the BRCA2 gene carry a high risk of hereditary breast and ovarian cancer (HBOC). However, a stop-gain mutation, K3326* (rs11571833), confers risk of lung cancer and cancers of the upper-aero-digestive tract but only a modest risk of breast or ovarian cancer. The Icelandic population provides an opportunity for comprehensive characterization of the cancer risk profiles of K3326* and HBOC mutations because a single mutation, BRCA2 999del5, is responsible for almost all BRCA2-related HBOC in the population. Genotype information on 43 641 cancer patients and 370 971 control subjects from Iceland, the Netherlands, and the United States was used to assess the cancer risk profiles of K3326* and BRCA2 999del5. BRCA2 expression was assessed using RNAseq data from blood (n = 2233), as well as 52 tissues reported in the GTEx database. The cancer risks associated with K3326* are fundamentally different from those associated with 999del5. We report for the first time an association between K3326* and small cell lung cancer (odds ratio [OR] = 2.06, 95% confidence interval [CI] = 1.35 to 3.16) and squamous cell carcinoma of the skin (OR = 1.69, 95% CI = 1.26 to 2.26). Individuals homozygous for K3326* reach old age and have children. Unlike BRCA2 999del5, the K3326* allele does not affect the level of BRCA2 transcripts, and the allele is expressed to the same extent as the wild-type allele. K3326* associates primarily with cancers that have strong environmental genotoxic risk factors. Expression of the K3326* allele suggests that a variant protein may be made that retains the DNA repair capabilities important to hormone-responsive tissues but may be less efficient in responding to genotoxic stress.
  • Interstitial lung abnormalities and self-reported health and functional status.

    Axelsson, Gisli Thor; Putman, Rachel K; Araki, Tetsuro; Sigurdsson, Sigurdur; Gudmundsson, Elias Freyr; Eiriksdottir, Gudny; Aspelund, Thor; Miller, Ezra R; Launer, Lenore J; Harris, Tamara B; Hatabu, Hiroto; Gudnason, Vilmundur; Hunninghake, Gary Matt; Gudmundsson, Gunnar; 1 Icelandic Heart Association, Kopavogur, Iceland. 2 Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 3 Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. 4 Department of Radiology, Brigham and Women's Hospital, Boston, Massachusetts, USA. 5 Center for Pulmonary Functional Imaging, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. 6 Intramural Research Program, National Institute on Aging, Bethesda, Maryland, USA. 7 Department of Respiratory Medicine, Landspitali University Hospital, Reykjavik, Iceland. # Contributed equally (British Medical Association, 2018-09-01)
    We investigated the association between interstitial lung abnormalities (ILA) and self-reported measures of health and functional status in 5764 participants from the Age, Gene/Environment Susceptibility-Reykjavik study. The associations of ILA to activities of daily living (ADLs), general health status and physical activity were explored using logistic regression models. Participants with ILA were less likely to be independent in ADLs (OR 0.70; 95% CI 0.55 to 0.90) to have good or better self-reported health (OR 0.66; 95% CI 0.52 to 0.82) and to participate in physical activity (OR 0.72; CI 0.56 to 0.91). The results demonstrate ILA's association with worsening self-reported health and functional status.
  • 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

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