• Definition of excessive daytime sleepiness in the general population: Feeling sleepy relates better to sleep-related symptoms and quality of life than the Epworth Sleepiness Scale score. Results from an epidemiological study.

      Thorarinsdottir, Elin H; Bjornsdottir, Erla; Benediktsdottir, Bryndis; Janson, Christer; Gislason, Thorarinn; Aspelund, Thor; Kuna, Samuel T; Pack, Allan I; Arnardottir, Erna S; 1 Department of Medicine, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland. 2 Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 3 Sleep Department, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland. 4 School of Science and Engineering, Reykjavik University, Reykjavik, Iceland. 5 Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden. 6 Icelandic Heart Association, Kopavogur, Iceland. 7 Department of Medicine and Center for Sleep and Circadian Neurobiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. 8 Department of Medicine, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania, USA. 9 Internal Medicine Services, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland. (Wiley, 2019-12)
      Many different subjective tools are being used to measure excessive daytime sleepiness (EDS) but the most widely used is the Epworth Sleepiness Scale (ESS). However, it is unclear if using the ESS is adequate on its own when assessing EDS. The aim of this study was to estimate the characteristics and prevalence of EDS using the ESS and the Basic Nordic Sleep Questionnaire (BNSQ) in general population samples. Participants aged 40 years and older answered questions about sleepiness, health, sleep-related symptoms and quality of life. Two groups were defined as suffering from EDS: those who scored >10 on the ESS (with increased risk of dozing off) and those reporting feeling sleepy during the day ≥3 times per week on the BNSQ. In total, 1,338 subjects (53% male, 74.1% response rate) participated, 13.1% reported an increased risk of dozing off, 23.2% reported feeling sleepy and 6.4% reported both. The prevalence of restless leg syndrome, nocturnal gastroesophageal reflux, difficulties initiating and maintaining sleep and nocturnal sweating was higher among subjects reporting feeling sleepy compared to non-sleepy subjects. Also, subjects reporting feeling sleepy had poorer quality of life and reported more often feeling unrested during the day than non-sleepy subjects. However, subjects reporting increased risk of dozing off (ESS > 10) without feeling sleepy had a similar symptom profile as the non-sleepy subjects. Therefore, reporting only risk of dozing off without feeling sleepy may not reflect problematic sleepiness and more instruments in addition to ESS are needed when evaluating daytime sleepiness.
    • 2019 EACTS/EACTA/EBCP guidelines on cardiopulmonary bypass in adult cardiac surgery.

      Kunst, Gudrun; Milojevic, Milan; Boer, Christa; De Somer, Filip M J J; Gudbjartsson, Tomas; van den Goor, Jenny; Jones, Timothy J; Lomivorotov, Vladimir; Merkle, Frank; Ranucci, Marco; et al. (Elsevier Science, 2019-12)
      Disclaimer 2019: The EACTS/EACTA/EBCP Guidelines represent the views of the EACTS, the EACTA and EBCP and were produced after careful consideration of the scientific and medical knowledge and the evidence available at the time of their dating. The EACTS, EACTA and EBCP are not responsible in the event of any contradiction, discrepancy and/or ambiguity between the EACTS, EACTA and EBCP Guidelines and any other official recommendations or guidelines issued by the relevant public health authorities, in particular in relation to good use of healthcare or therapeutic strategies. Health professionals are encouraged to take the EACTS, EACTA and EBCP Guidelines fully into account when exercising their clinical judgement as well as in the determination and the implementation of preventive, diagnostic or therapeutic medical strategies; however, the EACTS, EACTA and EBCP Guidelines do not, in any way whatsoever, override the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient's health condition and, where appropriate and/or necessary, in consultation with that patient and the patient's care provider. Nor do the EACTS, EACTA and EBCP Guidelines exempt health professionals from giving full and careful consideration to the relevant official, updated recommendations or guidelines issued by the competent public health authorities, in order to manage each patient's case in light of the scientifically accepted data pursuant to their respective ethical and professional obligations. It is also the health professional's responsibility to verify the applicable rules and regulations relating to drugs and medical devices at the time of prescription. The article has been co-published with permission in the British Journal of Anaesthesia, the European Journal of Cardio-Thoracic Surgery and the Interactive CardioVascular and Thoracic Surgery. All rights reserved in respect of the European Journal of Cardio-Thoracic Surgery and the Interactive CardioVascular and Thoracic Surgery. (C) European Association for Cardio-Thoracic Surgery 2019, published by Oxford University Press, and in respect of the British Journal of Anaesthesia (C) 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.
    • Preterm births in Iceland 1997-2016: Preterm birth rates by gestational age groups and type of preterm birth.

      Grétarsdóttir, Áslaug Salka; Aspelund, Thor; Steingrímsdóttir, Þóra; Bjarnadóttir, Ragnheiður Ingibjörg; Einarsdóttir, Kristjana; 1 Centre of Public Health Sciences, Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 2 Faculty of Medicine, University of Iceland, Reykjavík, Iceland. 3 Department of Obstetrics and Gynaecology, Landspítali University Hospital, Reykjavík, Iceland. (Wiley, 2019-11-19)
      BACKGROUND: The frequency of preterm births has been increasing globally, mainly due to a rise in iatrogenic late preterm births. The aim of this study was to assess the prevalence of preterm births in Iceland during 1997-2016 by type of preterm birth. METHODS: This study included all live births in Iceland during 1997-2016 identified from the Icelandic Medical Birth Registry. Risk of preterm birth by time period was assessed with Poisson regression models adjusted for demographic variables and indications for iatrogenic births. RESULTS: The study population included 87 076 infants, of which 4986 (5.7%) were preterm. The preterm birth rate increased from 5.3% to 6.1% (adjusted rate ratio [ARR] = 1.16, confidence interval [CI] = 1.07-1.26) between 1997-2001 and 2012-2016 overall. The increase was only evident in multiples (ARR 1.41, 95% CI 1.21-1.65), not singletons (1.07, 0.97-1.19). The rate of late preterm births (34-36 weeks) increased significantly (1.24, 1.14-1.40), and the rate of iatrogenic preterm births more than doubled during this period even after adjustment for identified medical indications (2.40, 2.00-2.88). The rate of spontaneous preterm births decreased during the study period (0.63, 0.55-0.73), and the rate of PPROM increased (1.31, 1.09-1.57). The most common contributing indications for iatrogenic births were fetal distress (26.2%), hypertensive disorders (18.2%), and severe preeclampsia (16.9%). CONCLUSIONS: Preterm birth rates increased in multiples in Iceland between 1997 and 2016, and late and iatrogenic preterm births increased overall. The increase in iatrogenic preterm births remained significant after adjusting for medical indications, suggesting that other factors might be affecting the rise.
    • Effectiveness of cognitive behavioral therapy (CBT) for child and adolescent anxiety disorders across different CBT modalities and comparisons: a systematic review and meta-analysis.

      Sigurvinsdóttir, Anna Lilja; Jensínudóttir, Kolbrún Björk; Baldvinsdóttir, Karen Dögg; Smárason, Orri; Skarphedinsson, Gudmundur; 1 The Health Care Institution of North Iceland, Akureyri, Iceland. 2 Faculty of Psychology, University of Iceland, Reykjavik, Iceland. 3 Landspitali - the National University Hospital of Iceland, Reykjavik, Iceland. (Taylor & Francis, 2019-11-18)
      Aim: Pediatric Anxiety Disorders (AD) are common. Cognitive behavioral therapy (CBT) is one of two first-line treatments of youth AD and it has previously been shown to be superior to wait-list but not placebo therapy. This study consists of a systematic review and meta-analysis of the literature to assess the efficacy of CBT modalities in comparison to control contingencies for pediatric anxiety disorders.Methods: Studies were included if they were randomized controlled trials, and if CBT was manualized or modular, alone or in combination with medication. CBT was required to include behavioral treatment, exposure treatment, or cognitive elements. Eligible studies included participants aged 18 years or younger.Results: Eighty-one studies were included, with 3386 CBT participants and 2527 control participants. The overall results indicated that CBT is an effective treatment for childhood AD. The results showed that individual-based CBT is superior to wait-list and attention control. Group-based CBT is superior to wait-list control and treatment as usual. Remote-based CBT was superior to attention control and wait-list control. Family-based CBT was superior to treatment as usual, wait-list control, and attention control. Selective serotonin reuptake inhibitors were no more effective than individual-based CBT. Combination treatment was, however, more effective than individual-based CBT.Conclusion: To the best of our knowledge, no meta-analysis has thus far disentangled the effects of CBT modalities across various comparisons. This meta-analysis hence provides an important update to the literature on the efficacy of CBT for treating anxiety disorders in young people.
    • A standalone bioreactor system to deliver compressive load under perfusion flow to hBMSC-seeded 3D chitosan-graphene templates.

      Lovecchio, Joseph; Gargiulo, Paolo; Vargas Luna, Jose Luis; Giordano, Emanuele; Sigurjónsson, Ólafur Eysteinn; 1 Institute of Biomedical and Neural Engineering, Reykjavík University, Menntavegur 1, 101, Reykiavík, Iceland. joseph.lovecchio@unibo.it. 2 Laboratory of Cellular and Molecular Engineering "Silvio Cavalcanti" - Department of Electrical, Electronic and Information Engineering "Guglielmo Marconi" (DEI), University of Bologna, Via Cesare Pavese 50, 47522, Cesena, FC, Italy. joseph.lovecchio@unibo.it. 3 Advanced Research Center on Electronic Systems (ARCES), University of Bologna, Via Vincenzo Toffano 2/2, 40125, Bologna, Italy. joseph.lovecchio@unibo.it. 4 Institute of Biomedical and Neural Engineering, Reykjavík University, Menntavegur 1, 101, Reykiavík, Iceland. 5 Department of Science, Reykjavík University, Menntavegur 1, 101, Reykiavík, Iceland. 6 Center of Medical Physics and Biomedical Engineering, Medical University of Vienna, Waehringer Guertel 18-20/4L, 1090, Wien, Austria. 7 Laboratory of Cellular and Molecular Engineering "Silvio Cavalcanti" - Department of Electrical, Electronic and Information Engineering "Guglielmo Marconi" (DEI), University of Bologna, Via Cesare Pavese 50, 47522, Cesena, FC, Italy. 8 Advanced Research Center on Electronic Systems (ARCES), University of Bologna, Via Vincenzo Toffano 2/2, 40125, Bologna, Italy. 9 Health Sciences and Technologies - Interdepartmental Center for Industrial Research (HST-ICIR), University of Bologna, Via Tolara di Sopra 41/E, 40064, Ozzano dell'Emilia, BO, Italy. 10 The Blood Bank, The Landspitali University Hospital, Snorrabraut 60, 105, Reykjavík, Iceland. (Nature Publishing Group, 2019-11-14)
      The availability of engineered biological tissues holds great potential for both clinical applications and basic research in a life science laboratory. A prototype standalone perfusion/compression bioreactor system was proposed to address the osteogenic commitment of stem cells seeded onboard of 3D chitosan-graphene (CHT/G) templates. Testing involved the coordinated administration of a 1 mL/min medium flow rate together with dynamic compression (1% strain at 1 Hz; applied twice daily for 30 min) for one week. When compared to traditional static culture conditions, the application of perfusion and compression stimuli to human bone marrow stem cells using the 3D CHT/G template scaffold induced a sizable effect. After using the dynamic culture protocol, there was evidence of a larger number of viable cells within the inner core of the scaffold and of enhanced extracellular matrix mineralization. These observations show that our novel device would be suitable for addressing and investigating the osteogenic phenotype commitment of stem cells, for both potential clinical applications and basic research.
    • Geographical variation in the incidence of type 1 diabetes in the Nordic countries: A study within NordicDiabKids.

      Samuelsson, Ulf; Westerberg, Lars; Aakesson, Karin; Birkebaek, Niels H; Bjarnason, Ragnar; Drivvoll, Ann K; Skrivarhaug, Torild; Svensson, Jannet; Thorsson, Arni; Hanberger, Lena; et al. (Wiley, 2019-11-08)
      BACKGROUND: The incidence of type 1 diabetes (T1D) is high in the Nordic countries with geographic differences between as well as within countries. OBJECTIVE: To describe the geographical distribution of the incidence of T1D among children in four Nordic countries, an area where the population is considered genetically similar. METHODS: Data on children 0 to 14 years of age and diagnosed with T1D 2006 to 2011 was collected from four Nordic national pediatric quality diabetes registries. Data included year of diagnosis (2006-2011), sex, and age at diagnosis. Figures for number of children at risk during 2006 to 2011-as well as total population, proportion with foreign background and size of populated areas of geographic regions-were collected from official statistics. RESULTS: The total incidence during the study period for all four countries was 35.7/100 000 person years but differed between the countries (range 18.2-44.1; P < .001). The incidence difference between the countries was most obvious in the highest age group, 10 to 14 years of age, whereas there was no difference in the youngest age group 0 to 5 years of age. Iceland had similar incidence in the entire country, whereas the other countries had areas with different incidence. Densely populated areas, such as major cities, had the lowest incidence. CONCLUSION: The incidence of T1D differed between the Nordic countries and also between the neighboring countries and generally decreased with population density. This indicates that environmental factors may contribute to the level of incidence of T1D.
    • Decreasing and stabilising trends of antimicrobial consumption and resistance in and in segmented regression analysis, European Union/European Economic Area, 2001 to 2018.

      Penalva, German; Hogberg, Liselotte Diaz; Weist, Klaus; Vlahovic-Palcevski, Vera; Heuer, Ole; Monnet, Dominique L; Vandael, Eline; Ivanov, Ivan N.; Payerl-Pal, Marina; Skjold Selle Pedersen, Karoline; et al. (European Centre for Disease Prevention and Control (ECDC), 2019-11-01)
      Investments to reduce the spread of antimicrobial resistance (AMR) in the European Union have been made, including efforts to strengthen prudent antimicrobial use. Using segmented regression, we report decreasing and stabilising trends in data reported to the European Surveillance of Antimicrobial Consumption Network and stabilising trends in data reported to the European Antimicrobial Resistance Surveillance Network. Our results could be an early indication of the effect of prioritising AMR on the public health agenda.
    • Shared Genetic Risk Factors Across Carbamazepine-Induced Hypersensitivity Reactions.

      Nicoletti, Paola; Barrett, Sarah; McEvoy, Laurence; Daly, Ann K; Aithal, Guruprasad; Lucena, M Isabel; Andrade, Raul J; Wadelius, Mia; Hallberg, Pär; Stephens, Camilla; et al. (Wiley, 2019-11)
      Carbamazepine (CBZ) causes life-threating T-cell-mediated hypersensitivity reactions, including serious cutaneous adverse reactions (SCARs) and drug-induced liver injury (CBZ-DILI). In order to evaluate shared or phenotype-specific genetic predisposing factors for CBZ hypersensitivity reactions, we performed a meta-analysis of two genomewide association studies (GWAS) on a total of 43 well-phenotyped Northern and Southern European CBZ-SCAR cases and 10,701 population controls and a GWAS on 12 CBZ-DILI cases and 8,438 ethnically matched population controls. HLA-A*31:01 was identified as the strongest genetic predisposing factor for both CBZ-SCAR (odds ratio (OR) = 8.0; 95% CI 4.10-15.80; P = 1.2 × 10-9 ) and CBZ-DILI (OR = 7.3; 95% CI 2.47-23.67; P = 0.0004) in European populations. The association with HLA-A*31:01 in patients with SCAR was mainly driven by hypersensitivity syndrome (OR = 12.9; P = 2.1 × 10-9 ) rather than by Stevens-Johnson syndrome/toxic epidermal necrolysis cases, which showed an association with HLA-B*57:01. We also identified a novel risk locus mapping to ALK only for CBZ-SCAR cases, which needs replication in additional cohorts and functional evaluation.
    • Diffuse reflectance spectroscopy accurately identifies the pre-cortical zone to avoid impending pedicle screw breach in spinal fixation surgery

      Burstom, Gustav; Swamy, Akash; Spliethoff, Jarich W.; Reich, Christian; Babic, Drazenko; Hendriks, Benno H. W.; Skulason, Halldor; Persson, Oscar; Terander, Adrian Elmi; Edstrom, Erik; et al. (OSA Publishing, 2019-11)
      Pedicle screw placement accuracy during spinal fixation surgery varies greatly and severe misplacement has been reported in 1-6.5 % of screws. Diffuse reflectance (DR) spectroscopy has previously been shown to reliably discriminate between tissues in the human body. We postulate that it could be used to discriminate between cancellous and cortical bone. Therefore, the purpose of this study is to validate DR spectroscopy as a warning system to detect impending pedicle screw breach in a cadaveric surgical setting using typical clinical breach scenarios. DR spectroscopy was incorporated at the tip of an integrated pedicle screw and screw driver used for tissue probing during pedicle screw insertions on six cadavers. Measurements were collected in the wavelength range of 400-1600 nm and each insertion was planned to result in a breach. Measurements were labelled as cancellous, cortical or representing a pre-cortical zone (PCZ) in between, based on information from cone beam computed tomographies at corresponding positions. In addition, DR spectroscopy data was recorded after breach. Four typical pedicle breach types were performed, and a total of 45 pedicle breaches were recorded. For each breach direction, the technology was able to detect the transition of the screw tip from the cancellous bone to the PCZ (P < 0.001), to cortical bone (P < 0.001), and to a subsequent breach (P < 0.001). Using support vector machine (SVM) classification, breach could reliably be detected with a sensitivity of 98.3 % [94.3-100 %] and a specificity of 97.7 % [91.0-100%]. We conclude that DR spectroscopy reliably identifies the area of transition from cancellous to cortical bone in typical breach scenarios and can warn the surgeon of impending pedicle breach, thereby resulting in safer spinal fixation surgeries. (C) 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement
    • Patients with rheumatoid arthritis facing sick leave or work disability meet varying regulations: a study among rheumatologists and patients from 44 European countries.

      Putrik, Polina; Ramiro, Sofia; Guillemin, Francis; Péntek, Márta; Sivera, Francisca; Sokka, Tuulikki; de Wit, Maarten; Woolf, Anthony D; Zink, Angela; Andersone, Daina; et al. (BMJ Publishing Group, 2019-11)
      OBJECTIVES: To describe and explore differences in formal regulations around sick leave and work disability (WD) for patients with rheumatoid arthritis (RA), as well as perceptions by rheumatologists and patients on the system's performance, across European countries. METHODS: We conducted three cross-sectional surveys in 50 European countries: one on work (re-)integration and social security (SS) system arrangements in case of sick leave and long-term WD due to RA (one rheumatologist per country), and two among approximately 15 rheumatologists and 15 patients per country on perceptions regarding SS arrangements on work participation. Differences in regulations and perceptions were compared across categories defined by gross domestic product (GDP), type of social welfare regime, European Union (EU) membership and country RA WD rates. RESULTS: Forty-four (88%) countries provided data on regulations, 33 (75%) on perceptions of rheumatologists (n=539) and 34 (77%) on perceptions of patients (n=719). While large variation was observed across all regulations across countries, no relationship was found between most of regulations or income compensation and GDP, type of SS system or rates of WD. Regarding perceptions, rheumatologists in high GDP and EU-member countries felt less confident in their role in the decision process towards WD (β=-0.5 (95% CI -0.9 to -0.2) and β=-0.5 (95% CI -1.0 to -0.1), respectively). The Scandinavian and Bismarckian system scored best on patients' and rheumatologists' perceptions of regulations and system performance. CONCLUSIONS: There is large heterogeneity in rules and regulations of SS systems across Europe in relation to WD of patients with RA, and it cannot be explained by existing welfare regimes, EU membership or country's wealth.
    • Treatment response and drug retention rates in 24 195 biologic-naïve patients with axial spondyloarthritis initiating TNFi treatment: routine care data from 12 registries in the EuroSpA collaboration.

      Ørnbjerg, Lykke Midtbøll; Brahe, Cecilie Heegaard; Askling, Johan; Ciurea, Adrian; Mann, Herman; Onen, Fatos; Kristianslund, Eirik Klami; Nordström, Dan; Santos, Maria Jose; Codreanu, Catalin; et al. (BMJ Publishing Group, 2019-11)
      OBJECTIVE: To study drug retention and response rates in patients with axial spondyloarthritis (axSpA) initiating a first tumour necrosis factor inhibitor (TNFi). METHODS: Data from 12 European registries, prospectively collected in routine care, were pooled. TNFi retention rates (Kaplan-Meier statistics), Ankylosing Spondylitis Disease Activity Score (ASDAS) Inactive disease (<1.3), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) <40 mm and Assessment of SpondyloArthritis International Society responses (ASAS 20/40) were assessed at 6, 12 and 24 months. RESULTS: A first TNFi was initiated in 24 195 axSpA patients. Heterogeneity of baseline characteristics between registries was observed. Twelve-month retention was 80% (95% CI 79% to 80%), ranging from 71% to 94% across registries. At 6 months, ASDAS Inactive disease/BASDAI<40 rates were 33%/72% (LUNDEX-adjusted: 27%/59%), ASAS 20/40 response rates 64%/49% (LUNDEX-adjusted 52%/40%). In patients initiating first TNFi after 2009, 6097 patients was registered to fulfil ASAS criteria for axSpA, 2935 was registered to fulfil modified New York Criteria for Ankylosing Spondylitis and 1178 patients was registered as having non-radiographic axSpA. In nr-axSpA patients, we observed lower 12-month retention rates (73% (70%-76%)) and lower 6-month LUNDEX adjusted response rates (ASDAS Inactive disease/BASDAI40 20%/50%, ASAS 20/40 45%/33%). For patients initiating first TNFi after 2014, 12-month retention rate, but not 6-month response rate, was numerically higher compared with patients initiating TNFi in 2009-2014. CONCLUSION: A large European database of patients with axSpA initiating a first TNFi treatment in routine care, demonstrated that 27% of patients achieved ASDAS inactive disease after 6 months, while 59% achieved BASDAI <40. Four of five patients continued treatment after 1 year.
    • Outcome after type A aortic dissection repair in patients with preoperative cardiac arrest.

      Pan, Emily; Wallinder, Andreas; Peterström, Eric; Geirsson, Arnar; Olsson, Christian; Ahlsson, Anders; Fuglsang, Simon; Gunn, Jarmo; Hansson, Emma C; Hjortdal, Vibeke; et al. (ELSEVIER IRELAND, 2019-11)
      AIM OF THE STUDY: Patients presenting with acute type A aortic dissection (ATAAD) and cardiac arrest before surgery are considered to have very poor prognosis, but limited data is available. We used a large database to evaluate the outcome of ATAAD patients with a cardiac arrest before surgery. METHODS: We evaluated 1154 surgically treated ATAAD patients from the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) database between 2005 and 2014. Patients with (n = 44, 3.8%) and without preoperative cardiac arrest were compared and variables univariably associated with mortality in the cardiac arrest group were identified. Median follow-up time was 2.7 years (interquartile range 0.5-5.5). RESULTS: Thirty-day mortality in the arrest and non-arrest group was 43.2% and 16.6%, respectively (odds ratio [OR] 3.83, CI 2.06-7.09; P < 0.001). In the nine patients with ongoing cardiopulmonary resuscitation when cardiopulmonary bypass was initiated, five died intraoperatively and one died after 65 days. In patients surviving the operation, stroke was significantly more common in the arrest group (48.4% vs 18.2%; OR 4.21, CI 2.05-8.67; P < 0.001). In total, 50.0% (22/44) of the arrest patients survived to the end of follow-up. Non-survivors in the arrest group more often had DeBakey type I dissection, cardiac tamponade, cardiac malperfusion and higher preoperative serum lactate (all P < 0.05). CONCLUSIONS: Early mortality and complications after ATAAD surgery in patients with a preoperative cardiac arrest are high, but mid-term outcome after surviving the initial period is acceptable. Preoperative cardiac arrest should not be considered an absolute contraindication for a surgical ATAAD repair.
    • Improved long-term outcome of surgical AVR for AS: Results from a population-based cohort.

      Viktorsson, Sindri Aron; Vidisson, Kristjan Orri; Gunnarsdottir, Anna Gudlaug; Helgason, Dadi; Johnsen, Arni; Ingvarsdottir, Inga Lara; Sigurdsson, Martin Ingi; Geirsson, Arnar; Gudbjartsson, Tomas; [ 1 ] Landspitali Univ Hosp, Div Cardiothorac Surg, Hringbraut 101, Reykjavik, Iceland Show more [ 2 ] Landspitali Univ Hosp, Div Internal Med, Reykjavik, Iceland Show more [ 3 ] Landspitali Univ Hosp, Div Anesthesia & Intens Care, Reykjavik, Iceland Show more [ 4 ] Yale Sch Med, Sect Cardiac Surg, New Haven, CT USA Show more [ 5 ] Univ Iceland, Fac Med, Reykjavik, Iceland (Wiley, 2019-11)
      Mean age was 71 years, 65.1% were males, and mean EuroSCORE II was 3.9. Mean preoperative aortic valve area increased significantly (0.013 cm2 /year; P < .001) and mean aortic cross-clamp time declined (108 minutes, 2.8 min/year; P < .001). The rate of complications decreased, including new-onset atrial fibrillation (60.9% overall, decreased by 3.1%/year, P = .02), acute kidney injury (17.1%, 7.6%/year, P < .001), and reoperation for bleeding (12.5%, 6.3%/year, P = .02). Operative mortality did not change (5.4%); nor did 1- and 5-year overall survival (92.5% and 81.6%, respectively). Notable long-term events were chronic heart failure (27.7 admissions/100 patient-years), embolic event (15.9/100 patient-years), and bleeding (13.0/100 patient-years).
    • The need for an adapted initiation nomogram during Fiix prothrombin time monitoring of warfarin.

      Onundarson, Pall T; Gudmundsdottir, Brynja R; 1 Landspitali National University Hospital of Iceland, Reykjavík, Iceland. pallt@landspitali.is. 2 Faculty of Medicine, University of Iceland, Reykjavík, Iceland. pallt@landspitali.is. 3 Landspitali National University Hospital of Iceland, Reykjavík, Iceland. (Springer, 2019-11)
      The new Fiix prothrombin time (Fiix-PT) and its derived Fiix-normalized ratio (Fiix-NR) is affected only by reductions in coagulation factors (F) II and X, the two factors responsible for the antithrombotic effect of vitamin K antagonists (VKA). Due to insensitivity to reductions in the short half-life FVII, the Fiix-NR rises later than standard PT-INR during warfarin initiation. To describe a warfarin initiation nomogram adapted for monitoring with Fiix-NR, anticoagulation development was assessed during use of standard PT-INR based initiation nomogram and after adapting the initiation nomogram for Fiix-NR monitoring. Normalized ratios were retrospectively assessed in consecutive warfarin naïve patients during their first 60 days of warfarin intake for one year prior to (PT-INR period) and for one year after replacing the PT-INR with the Fiix-NR (Fiix-NR period). The INR target was NR 2.0-3.0. We evaluated 160 patients monitored with PT-INR and dosed with the PT-nomogram, 57 monitored with Fiix-INR but dosed with PT-nomogram, and 163 Fiix-NR monitored patients dosed using a new Fiix nomogram. Mean PT-INR over 2.0 was reached on day 7 during the PT-period and remained around 2.5 thereafter. When the PT-nomogram continued in use during Fiix-monitoring significantly more patients became overanticoagulated during days 11-29. After the nomogram was modified to respond to rising Fiix-NR with larger initial dose reduction, the mean Fiix-NR reached over 2 on day 8-9 and remained around 2.5 thereafter. When warfarin is monitored with Fiix-NR, an adjusted dosing nomogram should be used during initiation to prevent early overanticoagulation.
    • Epigenetic inactivation of the splicing RNA-binding protein CELF2 in human breast cancer.

      Piqué, Laia; Martinez de Paz, Alexia; Piñeyro, David; Martínez-Cardús, Anna; Castro de Moura, Manuel; Llinàs-Arias, Pere; Setien, Fernando; Gomez-Miragaya, Jorge; Gonzalez-Suarez, Eva; Sigurdsson, Stefan; et al. (Nature Publishing Group, 2019-11)
      Human tumors show altered patterns of protein isoforms that can be related to the dysregulation of messenger RNA alternative splicing also observed in transformed cells. Although somatic mutations in core spliceosome components and their associated factors have been described in some cases, almost nothing is known about the contribution of distorted epigenetic patterns to aberrant splicing. Herein, we show that the splicing RNA-binding protein CELF2 is targeted by promoter hypermethylation-associated transcriptional silencing in human cancer. Focusing on the context of breast cancer, we also demonstrate that CELF2 restoration has growth-inhibitory effects and that its epigenetic loss induces an aberrant downstream pattern of alternative splicing, affecting key genes in breast cancer biology such as the autophagy factor ULK1 and the apoptotic protein CARD10. Furthermore, the presence of CELF2 hypermethylation in the clinical setting is associated with shorter overall survival of the breast cancer patients carrying this epigenetic lesion.
    • Bullying and Pain in School-Aged Children and Adolescents: A Cross-Sectional Study

      Garmy, Pernilla; Hansson, Erika; Vilhjálmsson, Rúnar; Kristjánsdóttir, Gudrún; 1 ] Kristianstad Univ, Fac Hlth Sci, S-29188 Kristianstad, Sweden Show more [ 2 ] Lund Univ, Fac Med, Clin Hlth Promot Ctr, Lund, Sweden Show more [ 3 ] Kristianstad Univ, Fac Educ, Kristianstad, Sweden Show more [ 4 ] Univ Iceland, Fac Nursing, Reykjavik, Iceland Show more [ 5 ] Landspitali Univ Hosp, Reykjavik, Iceland (SAGE Publications, 2019-11)
      Bullying is defined as repeated and unwanted aggressive behavior involving a power imbalance and hurt children and adolescents' socioemotional functioning. The aim is to investigate associations between pain (headache, stomach pain, backache, and neck/shoulder pain) and bullying among school-aged children and adolescents. This cross-sectional school-based survey comes from the Icelandic data set in the international research network Health Behaviour in School-Aged Children. The study population included all Icelandic students in Grades 6, 8, and 10 (ages 11, 13, and 15years, respectively; participation rate, 84%; n=10,626). An anonymous standardized questionnaire was distributed and completed by students in their classrooms. About every 8 in 10 bullied students reported weekly pain (79%), compared with little over half of nonbullied students (57%). The prevalence of pain was significantly higher among bullied students compared with their nonbullied peers. Being a bullying victim was associated with an increased frequency of experiencing headaches, stomachaches, and back pain, in addition to neck or shoulder pain. It is important for mental health nurses and health professionals to ask about pain when meeting with children and adolescents as well as to inquire about their peer relationships.
    • Pathogen inactivation with amotosalen plus UVA illumination minimally impacts microRNA expression in platelets during storage under standard blood banking conditions.

      Arnason, Niels Arni; Johannson, Freyr; Landrö, Ragna; Hardarsson, Björn; Irsch, Johannes; Gudmundsson, Sveinn; Rolfsson, Ottar; Sigurjonsson, Olafur E; 1 The Blood Bank, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland. 2 Department of Medicine, University of Iceland, Reykjavik, Iceland. 3 Cerus B.V., Amersfoort, The Netherlands. 4 School of Science and Engineering, Reykjavik University, Reykjavik, Iceland. (Wiley, 2019-10-31)
      BACKGROUND: To reduce the risk of transfusion transmission infection, nucleic acid targeted methods have been developed to inactivate pathogens in PCs. miRNAs have been shown to play an important role in platelet function, and changes in the abundance of specific miRNAs during storage have been observed, as have perturbation effects related to pathogen inactivation (PI) methods. The aim of this work was to investigate the effects of PI on selected miRNAs during storage. STUDY DESIGN AND METHODS: Using a pool and split strategy, 3 identical buffy coat PC units were generated from a pool of 24 whole blood donors. Each unit received a different treatment: 1) Untreated platelet control in platelet additive solution (C-PAS); 2) Amotosalen-UVA-treated platelets in PAS (PI-PAS); and 3) untreated platelets in donor plasma (U-PL). PCs were stored for 7 days under standard blood banking conditions. Standard platelet quality control (QC) parameters and 25 selected miRNAs were analyzed. RESULTS: During the 7-day storage period, differences were found in several QC parameters relating to PI treatment and storage in plasma, but overall the three treatments were comparable. Out of 25 miRNA tested changes in regulation of 5 miRNA in PI-PAS and 3 miRNA U-PL where detected compared to C-PAS. A statistically significant difference was observed in down regulations miR-96-5p on Days 2 and 4, 61.9% and 61.8%, respectively, in the PI-PAS treatment. CONCLUSION: Amotosalen-UVA treatment does not significantly alter the miRNA profile of platelet concentrates generated and stored using standard blood banking conditions.
    • The microphthalmia-associated transcription factor (Mitf) gene and its role in regulating eye function.

      García-Llorca, Andrea; Aspelund, Snaefridur Gudmundsdottir; Ogmundsdottir, Margret Helga; Steingrimsson, Eiríkur; Eysteinsson, Thor; 1 Department of Physiology, Biomedical Center, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101, Reykjavík, Iceland. 2 Department of Ophthalmology, Landspitali National University Hospital, Eiriksgata 37, 101, Reykjavik, Iceland. 3 Department of Anatomy, Biomedical Center, Faculty of Medicine, University of Iceland, Sturlugata 8, Reykjavík, Iceland. 4 Department of Biochemistry and Molecular Biology, Biomedical Center, Faculty of Medicine, University of Iceland, Sturlugata 8, Reykjavík, Iceland. 5 Department of Physiology, Biomedical Center, Faculty of Medicine, University of Iceland, Vatnsmyrarvegur 16, 101, Reykjavík, Iceland. thoreys@hi.is. 6 Department of Ophthalmology, Landspitali National University Hospital, Eiriksgata 37, 101, Reykjavik, Iceland. thoreys@hi.is. (Nature Publishing Group, 2019-10-28)
      Mutations in the microphthalmia-associated transcription factor (Mitf) gene can cause retinal pigment epithelium (RPE) and retinal dysfunction and degeneration. We examined retinal and RPE structure and function in 3 month old mice homo- or heterozygous or compound heterozygous for different Mitf mutations (Mitfmi-vga9/+, Mitfmi-enu22(398)/Mitfmi-enu22(398), MitfMi-Wh/+ and MitfMi-Wh/Mitfmi) which all have normal eye size with apparently normal eye pigmentation. Here we show that their vision and retinal structures are differentially affected. Hypopigmentation was evident in all the mutants while bright-field fundus images showed yellow spots with non-pigmented areas in the Mitfmi-vga9/+ mice. MitfMi-Wh/+ and MitfMi-Wh/Mitfmi mice showed large non-pigmented areas. Fluorescent angiography (FA) of all mutants except Mitfmi-vga9/+ mice showed hyperfluorescent areas, whereas FA from both Mitf-Mi-Wh/+ and MitfMi-Wh/Mitfmi mice showed reduced capillary network as well as hyperfluorescent areas. Electroretinogram (ERG) recordings show that MitfMi-Wh/+ and MitfMi-Wh/Mitfmi mice are severely impaired functionally whereas the scotopic and photopic ERG responses of Mitfmi-vga9/+ and Mitfmi-enu22(398)/Mitfmi-enu22(398) mice were not significantly different from wild type mice. Histological sections demonstrated that the outer retinal layers were absent from the MitfMi-Wh/+ and MitfMi-Wh/Mitfmi blind mutants. Our results show that Mitf mutations affect eye function, even in the heterozygous condition and that the alleles studied can be arranged in an allelic series in this respect.
    • The demographics of persistent opioid consumption following limb amputation.

      Steen, Talora; Lirk, Philipp B; Sigurdsson, Martin I; 1 Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 2 Division of Anesthesia and Intensive Care Medicine, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. 3 Faculty of Medicine, University of Iceland, Reykjavik, Iceland. (Wiley, 2019-10-24)
      BACKGROUND: Patients who have limb amputation are at risk of chronic pain, including phantom limb pain that can be challenging to treat. The aim of this study was to describe the incidence of pre-operative opioid usage and the incidence and risk factors for new persistent post-operative opioid usage in opioid-naïve patients after limb amputation. METHODS: A retrospective study of all patients 18 years and older underwent upper or lower extremity amputations in Landspitali University Hospital between 2005 and 2015. Patients were considered to use opioids pre-operatively if they filled an opioid prescription 1-6 months prior to amputation and were considered to have persistent opioid use if opioid prescriptions were filled between post-operative months four to twenty-four. In addition to incidence estimate, uni- and multivariate analysis was performed to identify risk factors for persistent post-operative opioid usage. RESULTS: Of 328 total patients, 216 (66%) were opioid naïve and 112 (34%) were chronic opioid users. Of the opioid-naïve patients surviving more than 3 months 40 (20%) developed persistent post-operative opioid usage. In multivariate analysis, factors independently associated with persistent post-operative opioid usage were younger age, male gender, pre-operative use of neuropathic medications or benzodiazepines and lower (opposed to upper) extremity amputation. CONCLUSION: Opioid naïve patients undergoing major amputation had a 20% chance of having a persistent opioid requirement following surgery. This could represent new-onset phantom limb pain or other chronic pain. Our findings should encourage perioperative multimodal efforts to reduce the burden of chronic pain after limb amputations.
    • ABO blood group does not impact incidence or outcomes of surgery for acute type A aortic dissection.

      Nozohoor, Shahab; Ahmad, Khalil; Bjurbom, Markus; Hansson, Emma C; Heimisdottir, Alexandra; Jeppsson, Anders; Mennander, Ari; Olsson, Christian; Pan, Emily; Ragnarsson, Sigurdur; et al. (Taylor & Francis, 2019-10-23)
      Objectives. To evaluate the distribution and impact of ABO blood groups on postoperative outcomes in patients undergoing surgery for acute type A aortic dissection (ATAAD). Design. A total of 1144 surgical ATAAD patients from eight Nordic centres constituting the Nordic consortium for acute type A aortic dissection (NORCAAD) were analysed. Blood group O patients were compared to non-O subjects. The relative frequency of blood groups was assessed with t-distribution, modified for weighted proportions. Multivariable logistic regression was performed to identify independent predictors of 30-day mortality. Cox regression analyses were performed for assessing independent predictors of late mortality. Results. There was no significant difference in the proportions of blood group O between the study populations in the NORCAAD registry and the background population (40.6 (95% CI 37.7-43.4)% vs 39.0 (95% CI 39.0-39.0)%). ABO blood group was not associated with any significant change in risk of 30-day or late mortality, with the exception of blood group A being an independent predictor of late mortality. Prevalence of postoperative complications was similar between the ABO blood groups. Conclusions. In this large cohort of Nordic ATAAD patients, there were no associations between ABO blood group and surgical incidence or outcomes, including postoperative complications and survival.