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  • Detailed Multiplex Analysis of SARS-CoV-2 Specific Antibodies in COVID-19 Disease.

    Brynjolfsson, Siggeir F; Sigurgrimsdottir, Hildur; Einarsdottir, Elin D; Bjornsdottir, Gudrun A; Armannsdottir, Brynja; Baldvinsdottir, Gudrun E; Bjarnason, Agnar; Gudlaugsson, Olafur; Gudmundsson, Sveinn; Sigurdardottir, Sigurveig T; et al. (Frontiers Research Foundation, 2021-06-10)
    A detailed understanding of the antibody response against SARS-CoV-2 is of high importance, especially with the emergence of novel vaccines. A multiplex-based assay, analyzing IgG, IgM, and IgA antibodies against the receptor binding domain (RBD), spike 1 (S1), and nucleocapsid proteins of the SARS-CoV-2 virus was set up. The multiplex-based analysis was calibrated against the Elecsys® Anti-SARS-CoV-2 assay on a Roche Cobas® instrument, using positive and negative samples. The calibration of the multiplex based assay yielded a sensitivity of 100% and a specificity of 97.7%. SARS-CoV-2 specific antibody levels were analyzed by multiplex in 251 samples from 221 patients. A significant increase in all antibody types (IgM, IgG, and IgA) against RBD was observed between the first and the third weeks of disease. Additionally, the S1 IgG antibody response increased significantly between weeks 1, 2, and 3 of disease. Class switching appeared to occur earlier for IgA than for IgG. Patients requiring hospital admission and intensive care had higher levels of SARS-CoV-2 specific IgA levels than outpatients. These findings describe the initial antibody response during the first weeks of disease and demonstrate the importance of analyzing different antibody isotypes against multiple antigens and include IgA when examining the immunological response to COVID-19.
  • Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations.

    Boer, Cindy G; Hatzikotoulas, Konstantinos; Southam, Lorraine; Stefánsdóttir, Lilja; Zhang, Yanfei; Coutinho de Almeida, Rodrigo; Wu, Tian T; Zheng, Jie; Hartley, April; Teder-Laving, Maris; et al. (Cell Press, 2021-08-26)
    Osteoarthritis affects over 300 million people worldwide. Here, we conduct a genome-wide association study meta-analysis across 826,690 individuals (177,517 with osteoarthritis) and identify 100 independently associated risk variants across 11 osteoarthritis phenotypes, 52 of which have not been associated with the disease before. We report thumb and spine osteoarthritis risk variants and identify differences in genetic effects between weight-bearing and non-weight-bearing joints. We identify sex-specific and early age-at-onset osteoarthritis risk loci. We integrate functional genomics data from primary patient tissues (including articular cartilage, subchondral bone, and osteophytic cartilage) and identify high-confidence effector genes. We provide evidence for genetic correlation with phenotypes related to pain, the main disease symptom, and identify likely causal genes linked to neuronal processes. Our results provide insights into key molecular players in disease processes and highlight attractive drug targets to accelerate translation.
  • Clinical management of patients with drug‐induced liver injury (DILI)

    Björnsson, Einar S.; 1 Univ Iceland, Fac Med, Reykjavik, Iceland 2 Natl Univ Hosp Iceland, Dept Internal Med, Div Gastroenterol & Hepatol, Reykjavik, Iceland (Wiley, 2021-06-28)
    Drug-induced liver injury (DILI) should be considered in all patients with recent elevation of liver tests without obvious etiology and normal hepatobiliary imaging. There is currently no biomarker that is helpful in diagnosis which relies on clinical and laboratory findings. Diagnosis is dependent on temporal relationship with a recently started drug or herbal and dietary supplement and elevated liver tests with exclusion of competing etiologies. The implicated agent should be discontinued and the patient should be observed closely. This is particularly important in patients with jaundice who have approximately 10% risk of liver related mortality and/or need for liver transplantation. There is no specific therapy for DILI which is only symptomatic such as for itching. Patients with jaundice and coagulopathy usually require hospitalization.
  • Molecular Epidemiology and Evolutionary Trajectory of Emerging Echovirus 30, Europe.

    Benschop, Kimberley S M; Broberg, Eeva K; Hodcroft, Emma; Schmitz, Dennis; Albert, Jan; Baicus, Anda; Bailly, Jean-Luc; Baldvinsdottir, Gudrun; Berginc, Natasa; Blomqvist, Soile; et al. (Centers for Disease Control and Prevention (CDC), 2021-06)
    In 2018, an upsurge in echovirus 30 (E30) infections was reported in Europe. We conducted a large-scale epidemiologic and evolutionary study of 1,329 E30 strains collected in 22 countries in Europe during 2016-2018. Most E30 cases affected persons 0-4 years of age (29%) and 25-34 years of age (27%). Sequences were divided into 6 genetic clades (G1-G6). Most (53%) sequences belonged to G1, followed by G6 (23%), G2 (17%), G4 (4%), G3 (0.3%), and G5 (0.2%). Each clade encompassed unique individual recombinant forms; G1 and G4 displayed >2 unique recombinant forms. Rapid turnover of new clades and recombinant forms occurred over time. Clades G1 and G6 dominated in 2018, suggesting the E30 upsurge was caused by emergence of 2 distinct clades circulating in Europe. Investigation into the mechanisms behind the rapid turnover of E30 is crucial for clarifying the epidemiology and evolution of these enterovirus infections.
  • The Future of Sleep Measurements: A Review and Perspective.

    Arnardottir, Erna Sif; Islind, Anna Sigridur; Óskarsdóttir, María; 1Reykjavik University Sleep Institute, School of Technology, Reykjavik University, Menntavegi 1, 102 Reykjavik, Iceland; Internal Medicine Services, Landspitali University Hospital, E7 Fossvogi, 108 Reykjavik, Iceland. Electronic address: ernasifa@ru.is. 2Reykjavik University Sleep Institute, School of Technology, Reykjavik University, Menntavegi 1, 102 Reykjavik, Iceland; Department of Computer Science, Reykjavik University, Menntavegi 1, 102 Reykjavik, Iceland. (Elsevier, 2021-07-06)
    This article provides an overview of the current use, limitations, and future directions of the variety of subjective and objective sleep assessments available. This article argues for various ways and sources of collecting, combining, and using data to enlighten clinical practice and the sleep research of the future. It highlights the prospects of digital management platforms to store and present the data, and the importance of codesign when developing such platforms and other new instruments. It also discusses the abundance of opportunities that data science and machine learning open for the analysis of data. Keywords: Codesign; Data management platform; Data science; Machine learning; Objective data; Sleep diary; Sleep measurement; Subjective data.
  • Factor D Inhibition Blocks Complement Activation Induced by Mutant Factor B Associated With Atypical Hemolytic Uremic Syndrome and Membranoproliferative Glomerulonephritis.

    Aradottir, Sigridur Sunna; Kristoffersson, Ann-Charlotte; Roumenina, Lubka T; Bjerre, Anna; Kashioulis, Pavlos; Palsson, Runolfur; Karpman, Diana; 1Department of Pediatrics, Clinical Sciences Lund, Lund University, Lund, Sweden. 2Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Paris, France. 3Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway. 4Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 5Department of Molecular and Clinical Medicine/Nephrology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 6Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland. 7Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavík, Iceland. (Frontiers Research Foundation, 2021-06-10)
    Complement factor B (FB) mutant variants are associated with excessive complement activation in kidney diseases such as atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy and membranoproliferative glomerulonephritis (MPGN). Patients with aHUS are currently treated with eculizumab while there is no specific treatment for other complement-mediated renal diseases. In this study the phenotype of three FB missense variants, detected in patients with aHUS (D371G and E601K) and MPGN (I242L), was investigated. Patient sera with the D371G and I242L mutations induced hemolysis of sheep erythrocytes. Mutagenesis was performed to study the effect of factor D (FD) inhibition on C3 convertase-induced FB cleavage, complement-mediated hemolysis, and the release of soluble C5b-9 from glomerular endothelial cells. The FD inhibitor danicopan abrogated C3 convertase-associated FB cleavage to the Bb fragment in patient serum, and of the FB constructs, D371G, E601K, I242L, the gain-of-function mutation D279G, and the wild-type construct, in FB-depleted serum. Furthermore, the FD-inhibitor blocked hemolysis induced by the D371G and D279G gain-of-function mutants. In FB-depleted serum the D371G and D279G mutants induced release of C5b-9 from glomerular endothelial cells that was reduced by the FD-inhibitor. These results suggest that FD inhibition can effectively block complement overactivation induced by FB gain-of-function mutations. Keywords: C3 glomerulopathy; atypical hemolytic uremic syndrome; complement; danicopan; factor B; factor D.
  • Endothelial dysfunction and thromboembolism in children, adolescents, and young adults with acute lymphoblastic leukemia.

    Andrés-Jensen, Liv; Grell, Kathrine; Rank, Cecilie Utke; Albertsen, Birgitte Klug; Tuckuviene, Ruta; Linnemann Nielsen, Rikke; Lynggaard, Line Stensig; Jarvis, Kirsten Brunsvig; Quist-Paulsen, Petter; Trakymiene, Sonata Saulyte; et al. (Nature Publishing Group, 2021-08-13)
    Endothelial dysfunction has not previously been investigated as a thrombogenic risk factor among patients with acute lymphoblastic leukemia (ALL), known to be at high risk of thromboembolism. We retrospectively explored the association between three circulating biomarkers of endothelial dysfunction (thrombomodulin, syndecan-1, VEGFR-1) measured in prospectively collected blood samples and risk of thromboembolism in 55 cases and 165 time-matched controls, treated according to the NOPHO ALL2008 protocol. In age-, sex-, and risk group-adjusted analysis, increasing levels of thrombomodulin and VEGFR-1 were independently associated with increased odds of developing thromboembolism (OR 1.37 per 1 ng/mL [95% CI 1.20‒1.56, P < 0.0001] and OR 1.21 per 100 pg/mL [95% CI 1.02‒1.21, P = 0.005], respectively). These associations remained significant when including only samples drawn >30 days before thromboembolic diagnosis. Thrombomodulin levels were on average 3.2 ng/mL (95% CI 2.6-8.2 ng/mL) higher in samples with measurable asparaginase activity (P < 0.0001). Among single nucleotide variants located in or neighboring coding genes for the three biomarkers, none were significantly associated with odds of thromboembolism. If results are validated in another cohort, thrombomodulin and VEGFR-1 could serve as predictive biomarkers, identifying patients in need of preemptive antithrombotic prophylaxis.
  • Metformin is associated with decreased risk of basal cell carcinoma: A whole-population case-control study from Iceland.

    Adalsteinsson, Jonas A; Muzumdar, Sonal; Waldman, Reid; Wu, Rong; Ratner, Désirée; Feng, Hao; Ungar, Jonathan; Silverberg, Jonathan I; Olafsdottir, Gudridur H; Kristjansson, Arni Kjalar; et al. (Elsevier, 2021-02-19)
    Background: Metformin has anticarcinogenic properties and is also known to inhibit the sonic hedgehog pathway, but population-based studies analyzing the potential protective effect for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are needed. Objectives: To delineate the association between metformin use and invasive SCC, SCC in situ (SCCis), and BCC. Methods: A population-based case-control study design was employed using all 6880 patients diagnosed in Iceland between 2003-2017 with first-time BCC, SCCis, or invasive SCC, and 69,620 population controls. Multivariate odds ratios (ORs) were calculated using conditional logistic regression. Results: Metformin was associated with a lower risk of developing BCC (OR, 0.71; 95% confidence interval [CI], 0.61-0.83), even at low doses. No increased risk of developing SCC was observed. SCCis risk was mildly elevated in the 501-1500 daily dose unit category (OR, 1.40; 95% CI, 1.00-1.96). Limitations: This study was retrospective in nature with the inability to adjust for ultraviolet exposure, Fitzpatrick skin type, and comorbidities. Conclusion: Metformin is associated with decreased risk of BCC development, even at low doses. Metformin might have potential as a chemoprotective agent for patients at high risk of BCC, although this will need confirmation in future studies. Keywords: basal cell carcinoma; keratinocyte carcinoma; metformin; squamous cell carcinoma; squamous cell carcinoma in situ.
  • Skimun fyrir krabbameinum í ristli og endaþarmi. Yfirlitsgrein um nýgengi, dánartíðni, kostnað og árangur.

    Helgi Birgisson; Elínborg J. Ólafsdóttir; Anna Sverrisdóttir; Sigurður Einarsson; Agnes Smáradóttir; Laufey Tryggvadóttir; 1 Rannsókna- og skráningarsetur Krabbameinsfélagsins. Ristil og endaþarmsskurðdeild, Akademiska sjúkrahúsið, Uppsölum, Svíþjóð, 2 Rannsóknaog skráningarsetur Krabbameinsfélagsins, 3 Miðstöð meltingarlækninga, Læknastöðin Glæsibæ. Fagráð Embættis landlæknis um skimun fyrir krabbameini í ristli og endaþarmi árin 2018-2020, 4 Meltingarlækningadeild Landspítalans. Meltingarsetrið, 5 Krabbameinslækningadeild Landspítalans, 6 Rannsókna- og skráningarsetur Krabbameinsfélagsins. Læknadeild og Lífvísindasetur Háskóla Íslands (Læknafélag Íslands, 2021-09)
    Nýgengi krabbameina í ristli og endaþarmi hefur aukist hjá bæði konum og körlum síðustu áratugina en dánartíðni hefur heldur lækkað frá sjötta áratugnum og lifun batnað vegna betri greiningar og meðferðar. Fjöldi þeirra sem látast úr ristil- og endaþarmskrabbameini er þó meiri en úr brjósta- og leghálskrabbameinum samanlagt. Viðfangsefni greinarinnar eru nýgengi og dánartíðni krabbameina í ristli og endaþarmi hérlendis. Fjallað er um tvær algengustu skimunaraðferðirnar, leit að blóði í hægðum og ristilspeglun. Þá er lagt mat á ætlaðan kostnað og ávinninning íslensks samfélags af því að skima fyrir krabbameinum í ristli og endaþarmi. Líklegt er að á Íslandi geti skipulögð lýðgrunduð skimun fyrir krabbameinum í ristli og endaþarmi komið í veg fyrir að minnsta kosti 6 dauðsföll af þeim 28 á ári sem verða úr sjúkdómnum meðal fólks á skimunaraldri, ef skimunaraldur verður 50-74 ára. Umframkostnaður fyrir samfélagið vegna skimunar fyrir krabbameinum í ristli og endaþarmi er talinn mjög ásættanlegur í ljósi þess að sparnaður verður vegna einfaldari meðferðar, lækkunar nýgengis og fækkunar dauðsfalla.
  • Einstaklingar sem nota vímuefni í æð á Íslandi: Bráðakomur og innlagnir á Landspítala og dánartíðni

    Bjarni Össurarson Rafnar; Magnús Haraldsson; Guðrún Dóra Bjarnadóttir; Geðdeild Landspítala, Læknadeild Háskóla Íslands, Háskóli Íslands, heilbrigðisvísindasvið (Læknafélag Íslands, 2021-09)
    INNGANGUR Misnotkun vímuefna er stór áhrifaþáttur í ótímabærum veikindum og dauða í heiminum. Verst settir eru þeir sem nota vímuefni í æð. Hópurinn á erfitt með að nýta sér hefðbundna heilbrigðisþjónustu og leitar frekar á bráðamóttökur spítala með sín vandamál. Þessir einstaklingar leita sér oft seint aðstoðar og eiga erfitt með að fylgja ráðleggingum, með ærnum kostnaði fyrir einstaklinginn og samfélagið. MARKMIÐ Tilgangur rannsóknar var að kanna notkun einstaklinga sem nota vímuefni í æð á bráðamóttökum og innlagnardeildum Landspítala yfir tveggja ára tímabil og rannsaka dánartíðni þeirra 7 árum eftir komuviðtal. EFNIVIÐUR OG AÐFERÐIR Rannsóknin er afturskyggn og hluti af stærri rannsókn á 108 einstaklingum með sögu um að misnota vímuefni í æð. Inntökuviðtölin voru tekin á árunum 2012-2013 þegar rannsóknarhópurinn lagðist inn til fíknimeðferðar á einhverjum af þremur stöðum: Fíknigeðdeild Landspítala (45%), Vog (30%) eða Hlaðgerðarkot (25%). Til að meta þjónustuþunga voru komur, innlagnir og innlagnardagar taldir. Fjöldi koma á bráðamóttökur Landspítala var borinn saman við parað úrtak almennings. Komuástæður á bráðamóttökur voru greindar og gerður samanburður milli þeirra sem notuðu aðallega metylfenidat og annarra. Að lokum var dánartíðni rannsóknarhópsins skoðuð 7 árum eftir inntökuviðtal. NIÐURSTÖÐUR Rannsóknarhópurinn kom marktækt oftar á bráðamóttökur Landspítala en almenningur. Meðalfjöldi koma rannsóknarhópsins á ári var 4,8 og 43% komu fjórum sinnum eða oftar á ári. Meirihluti koma var vegna geðrænna einkenna (65%) og þar af var þriðjungur vegna alvarlegra geðrænna einkenna. Algengustu líkamlegu vandamálin voru húðsýkingar og slys/ofbeldi. Ekki reyndist marktækur munur á þeim hluta hópsins sem notaði aðallega metylfenidat og önnur vímuefni. Dánartíðni var marktækt hækkuð hjá rannsóknarhópnum og áhættuhlutfall fyrir andláti var 26,4 (vikmörk 16,7-41,5). ÁLYKTUN Einstaklingar sem nota vímuefni í æð tilheyra viðkvæmum hópi með flókin geðræn og líkamleg vandamál. Mikilvægt er að þessir einstaklingar hafi greiðan aðgang að gagnreyndri fíknimeðferð en ekki síður að almennri heilbrigðisþjónustu. Þá þjónustu þarf að laga að þörfum hópsins og hafa að markmiði að draga úr skaðsemi vímuefnanotkunar þannig að viðkomandi hafi heilsu og öðlist getu og áhugahvöt til að hætta vímuefnanotkun.
  • Accelerated decline in quadriceps area and Timed Up and Go test performance are associated with hip fracture risk in older adults with impaired kidney function.

    Marques, Elisa A; Elbejjani, Martine; Viana, João L; Gudnason, Vilmundur; Sigurdsson, Gunnar; Lang, Thomas; Sigurdsson, Sigurdur; Aspelund, Thor; Siggeirsdottir, Kristin; Launer, Lenore; et al. (Elsevier, 2021-03-16)
    Objective: This study aimed to examine whether an accelerated decline in quadriceps cross-sectional area (CSA), attenuation (a surrogate of quality), and strength, as well as lower limb muscular function, are associated with hip fractures in older adults with impaired kidney function. Design: Prospective population-based study. Setting: Community-dwelling old population in Reykjavik, Iceland. Subjects: A total of 875 older adults (mean baseline age 76 years) from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study with impaired kidney function. Methods: Quadriceps CSA and density were determined using computed tomography (CT), knee extension strength was measured with an isometric dynamometer chair, and muscular function was assessed using the Timed Up and Go (TUG) test. All muscle-related measurements were assessed twice over a mean follow-up of 5.2 years. Data on hip fracture incidence was obtained from medical records during a maximum of 8.4 years of follow-up time. Results: Fully adjusted cox-proportional hazard regression models showed that a faster decline in quadriceps CSA and TUG test performance were significantly associated with increased hip fracture risk (HR = 1.55, 95% CI = 1.02-2.36, and HR = 1.80, 95% CI = 1.19-2.72, respectively). A faster decrease in quadriceps density and isometric knee extension strength were not associated with fracture risk. Conclusions: Accelerated decline in CT-derived quadriceps CSA and muscular function, as measured by the TUG test's performance, are predictive of hip fracture risk in older adults with impaired kidney function. TUG test is a simple measure and easily included in routine medical examinations, compared to CT scans, which seems to be useful for identifying a subgroup of individuals with high risk of fracture. Keywords: Chronic kidney disease; Computed tomography; Estimated glomerular filtration rate; Fracture; Muscular function.
  • Computed tomography-based skeletal muscle and adipose tissue attenuation: Variations by age, sex, and muscle.

    Figueiredo, Pedro; Marques, Elisa A; Gudnason, Vilmundur; Lang, Thomas; Sigurdsson, Sigurdur; Jonsson, Palmi V; Aspelund, Thor; Siggeirsdottir, Kristin; Launer, Lenore; Eiriksdottir, Gudny; et al. (Elsevier, 2021-03-10)
    Objective: This study aimed to investigate how skeletal muscle attenuation and adipose tissue (AT) attenuation of the quadriceps, hamstrings, paraspinal muscle groups and the psoas muscle vary according to the targeted muscles, sex, and age. Design: Population-based cross-sectional study. Setting: Community-dwelling old population in Reykjavik, Iceland. Subjects: A total of 5331 older adults (42.8% women), aged 66-96 years from the Age, Gene/Environment Susceptibility (AGES)- Reykjavik Study, who participated in the baseline visit (between 2002 and 2006) and had valid thigh and abdominal computed tomography (CT) scans were studied. Methods: Muscle attenuation and AT attenuation of the quadriceps, hamstrings, paraspinal muscle groups and the psoas muscle were determined using CT. Linear mixed model analysis of variance was performed for each sex, with skeletal muscle or AT attenuation as the dependent variable. Results: Muscle attenuation decreased, and AT attenuation increased with age in both sexes, and these differences were specific for each muscle, although not in all age groups. Age-related differences in muscle and AT attenuation varied with specific muscle. In general, for both sexes, skeletal muscle attenuation of the hamstrings declined more than average with age. Men and women displayed a different pattern in the age differences in AT attenuation for each muscle. Conclusions: Our data support the hypotheses that skeletal muscle attenuation decreases, and AT attenuation increases with aging. In addition, our data add new evidence, supporting that age-related differences in skeletal muscle and AT attenuation vary between muscles. Keywords: Computed tomography; Fat; Thigh muscles; Tissue density; Trunk muscles.
  • Cesarean birth, obstetric emergencies, and adverse neonatal outcomes in Iceland during a period of increasing labor induction.

    Gunnarsdóttir, Jóhanna; Swift, Emma M; Jakobsdóttir, Jóhanna; Smárason, Alexander; Thorkelsson, Thordur; Einarsdóttir, Kristjana; 1Centre of Public Health Sciences, Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 2Department of Obstetrics and Gynecology, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland. 3Faculty of Nursing - Department of Midwifery, University of Iceland, Reykjavik, Iceland. 4Institution of Health Science Research, University of Akureyri and Akureyri Hospital, Akureyri, Iceland. 5Division of Neonatal Intensive Care, Children's Medical Center, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland. (Wiley, 2021-06-16)
    Background: The rate of labor induction has risen steeply throughout the world. This project aimed to estimate changes in the rates of adverse maternal and neonatal outcomes in Iceland between 1997 and 2018, and to assess whether the changes can be explained by an increased rate of labor induction. Methods: Singleton live births, occurring between 1997 and 2018, that did not start by prelabor cesarean, were identified from the Icelandic Medical Birth Register (n = 85 971). Rates of intrapartum cesarean birth (CB), obstetric emergencies, and neonatal outcomes were calculated, and adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) were estimated with log-binomial regression (reference: 1997-2001). Adjustments were made for: (a) maternal characteristics, and (b) labor induction and gestational age. Results: The rate of labor induction increased from 13.6% in the period 1997-2001 to 28.1% in the period 2014-2018. The rate of intrapartum CB decreased between the periods of 1997-2001 and 2014-2018 for both primiparous (aRR 0.76, 95% CI: 0.69 to 0.84) and multiparous women (aRR 0.55, 95% CI: 0.49 to 0.63). The rate of obstetric emergencies and adverse neonatal outcomes also decreased between these time periods. Adjusting for labor induction did not attenuate these associations. Conclusions: The rates of adverse maternal outcomes and adverse neonatal outcomes decreased over the study period. However, there was no evidence that this decrease could be explained by the increased rate of labor induction. Keywords: cesarean; labor induction; neonatal outcome; obstetric emergencies.
  • Medication calculation skills of graduating nursing students within European context.

    Elonen, Imane; Salminen, Leena; Brasaitė-Abromė, Indrė; Fuster, Pilar; Kukkonen, Pia; Leino-Kilpi, Helena; Löyttyniemi, Eliisa; Noonan, Brendan; Stubner, Juliane; Svavarsdóttir, Margrét H; et al. (Wiley, 2021-06-08)
    Aim: The aim of this study is to evaluate the medication calculation skills of graduating nursing students in six European countries and analyse the associated factors. Background: Medication calculation skills are fundamental to medication safety, which is a substantial part of patient safety. Previous studies have raised concerns about the medication calculation skills of nurses and nursing students. Design: As part of a broader research project, this study applies a multinational cross-sectional survey design with three populations: graduating nursing students, nurse managers and patients. Methods: The students performed two calculations (tablet and fluid) testing medication calculation skills requiring different levels of conceptual understanding and arithmetic. The managers and patients answered one question about the students' medication kills. In total, 1,796 students, 538 managers and 1,327 patients participated the study. The data were analysed statistically. The STROBE guideline for cross-sectional studies was applied. Results: Almost all (99%) of the students performed the tablet calculation correctly, and the majority (71%) answered the fluid calculation correctly. Older age, a previous degree in health care and satisfaction with their current degree programme was positively associated with correct fluid calculations. The patients evaluated the students' medication skills higher than the nurse managers did and the evaluations were not systematically aligned with the calculation skills tested. Conclusions: Nursing students have the skills to perform simple medication calculations, but a significant number of students have difficulties with calculations involving multiple operations and a higher level of conceptual understanding. Due to the variation in students' medication calculation skills and the unalignment between the managers' and patients' evaluations and the calculation tests, further research is needed. Relevance to clinical practice: Graduating nursing students enter clinical field as qualified professionals, but there is still room for improvement in their medication calculation skills. This calls for attention in the fields of clinical nursing, education and research. Keywords: drug dosage calculations; graduating nursing students; medication calculation skills; nurse managers; patients.
  • Prevalence and early-life risk factors of school-age allergic multimorbidity: The EuroPrevall-iFAAM birth cohort.

    Sigurdardottir, Sigurveig T; Jonasson, Kristjan; Clausen, Michael; Lilja Bjornsdottir, Kristin; Sigurdardottir, Sigridur Erla; Roberts, Graham; Grimshaw, Kate; Papadopoulos, Nikolaos G; Xepapadaki, Paraskevi; Fiandor, Ana; et al. (Wiley, 2021-06-08)
    Background: Coexistence of childhood asthma, eczema and allergic rhinitis is higher than can be expected by chance, suggesting a common mechanism. Data on allergic multimorbidity from a pan-European, population-based birth cohort study have been lacking. This study compares the prevalence and early-life risk factors of these diseases in European primary school children. Methods: In the prospective multicentre observational EuroPrevall-iFAAM birth cohort study, we used standardized questionnaires on sociodemographics, medical history, parental allergies and lifestyle, and environmental exposures at birth, 12 and 24 months. At primary school age, parents answered ISAAC-based questions on current asthma, rhinitis and eczema. Allergic multimorbidity was defined as the coexistence of at least two of these. Results: From 10,563 children recruited at birth in 8 study centres, we included data from 5,572 children (mean age 8.2 years; 51.8% boys). Prevalence estimates were as follows: asthma, 8.1%; allergic rhinitis, 13.3%; and eczema, 12.0%. Allergic multimorbidity was seen in 7.0% of the whole cohort, ranging from 1.2% (Athens, Greece) to 10.9% (Madrid, Spain). Risk factors for allergic multimorbidity, identified with AICc, included family-allergy-score, odds ratio (OR) 1.50 (95% CI 1.32-1.70) per standard deviation; early-life allergy symptoms, OR 2.72 (2.34-3.16) for each symptom; and caesarean birth, OR 1.35 (1.04-1.76). Female gender, OR 0.72 (0.58-0.90); older siblings, OR 0.79 (0.63-0.99); and day care, OR 0.81 (0.63-1.06) were protective factors. Conclusion: Allergic multimorbidity should be regarded as an important chronic childhood disease in Europe. Some of the associated early-life factors are modifiable and may be considered for prevention strategies. Keywords: allergic multimorbidity; allergic rhinitis; asthma; children; eczema.
  • The Impact of Histological Subtype on the Incidence, Timing, and Patterns of Recurrence in Patients with Renal Cell Carcinoma After Surgery-Results from RECUR Consortium.

    Abu-Ghanem, Yasmin; Powles, Thomas; Capitanio, Umberto; Beisland, Christian; Järvinen, Petrus; Stewart, Grant D; Gudmundsson, Eiríkur Orri; Lam, Thomas B; Marconi, Lorenzo; Fernandéz-Pello, Sergio; et al. (Elsevier, 2020-10-24)
    Background: Current follow-up strategies for patients with renal cell carcinoma (RCC) after curative surgery rely mainly on risk models and the treatment delivered, regardless of the histological subtype. Objective: To determine the impact of RCC histological subtype on recurrence and to examine the incidence, pattern, and timing of recurrences to improve follow-up recommendations. Design, setting, and participants: This study included consecutive patients treated surgically with curative intention (ie, radical and partial nephrectomy) for nonmetastatic RCC (cT1-4, M0) between January 2006 and December 2011 across 15 centres from 10 countries, as part of the euRopEan association of urology renal cell carcinoma guidelines panel Collaborative multicenter consortium for the studies of follow-Up and recurrence patterns in Radically treated renal cell carcinoma patients (RECUR) database project. Outcome measurements and statistical analysis: The impact of histological subtype (ie, clear cell RCC [ccRCC], papillary RCC [pRCC], and chromophobe RCC [chRCC]) on recurrence-free survival (RFS) was assessed via univariate and multivariate analyses, adjusting for potential interactions with important variables (stage, grade, risk score, etc.) Patterns of recurrence for all histological subtypes were compared according to recurrence site and risk criteria. Results and limitations: Of the 3331 patients, 62.2% underwent radical nephrectomy and 37.8% partial nephrectomy. A total of 2565 patients (77.0%) had ccRCC, 535 (16.1%) had pRCC, and 231 (6.9%) had chRCC. The median postoperative follow-up period was 61.7 (interquartile range: 47-83) mo. Patients with ccRCC had significantly poorer 5-yr RFS than patients with pRCC and chRCC (78% vs 86% vs 91%, p = 0.001). The most common sites of recurrence for ccRCC were the lung and bone. Intermediate-/high-risk pRCC patients had an increased rate of lymphatic recurrence, both mediastinal and retroperitoneal, while recurrence in chRCC was rare (8.2%), associated with higher stage and positive margins, and predominantly in the liver and bone. Limitations include the retrospective nature of the study. Conclusions: The main histological subtypes of RCC exhibit a distinct pattern and dynamics of recurrence. Results suggest that intermediate- to high-risk pRCC may benefit from cross-sectional abdominal imaging every 6 mo until 2 yr after surgery, while routine imaging might be abandoned for chRCC except for abdominal computed tomography in patients with advanced tumour stage or positive margins. Patient summary: In this analysis of a large database from 15 countries around Europe, we found that the main histological subtypes of renal cell carcinoma have a distinct pattern and dynamics of recurrence. Patients should be followed differently according to subtype and risk score. Keywords: Chromophobe; Clear cell; Follow-up; Papillary; RECUR database; Recurrence-free survival; Renal cell carcinoma.
  • A nationwide population-based prospective study of cirrhosis in Iceland.

    Olafsson, Sigurdur; Rögnvaldsson, Sigurjon; Bergmann, Ottar M; Jonasson, Jon G; Benitez Hernandez, Ubaldo; Björnsson, Einar S; 1Department of Internal Medicine, Division of Gastroenterology and Hepatology, Landspitali-National University Hospital of Iceland, Reykjavik, Iceland. 2Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 3Department of Surgery, Landspitali-National University Hospital of Iceland, Reykjavik, Iceland. 4Department of Pathology, Landspitali-National University Hospital of Iceland, Reykjavik, Iceland. 5Department of Science/Biostatistics, Landspitali-National University Hospital of Iceland, Reykjavik, Iceland. (Elsevier, 2021-03-31)
    Background & aims: The incidence of cirrhosis in Iceland has been the lowest in the world with only 3 cases per 100,000 inhabitants. Alcohol consumption has almost doubled in Iceland from 1980 to 2016. Obesity has also risen and hepatitis C virus has spread among people who inject drugs in Iceland. The aim of this study was to evaluate the effects of these risk factors on the incidence and aetiology of cirrhosis in Iceland. Methods: The study included all patients diagnosed with cirrhosis for the first time during 2010-2015. Diagnosis was based on liver histology or 2 of 4 criteria: cirrhosis on imaging, ascites, varices, and/or elevated INR. Results: Overall, 157 patients were diagnosed, 105 (67%) males, mean age 61 years. The overall incidence was 9.7 cases per 100,000 inhabitants annually. Alcohol was the only underlying cause in 48/157 (31%), non-alcoholic fatty liver disease (NAFLD) in 34/157(22%), and alcohol and hepatitis C together in 23/157(15%) were the most common causes. Only 6% of patients had an unknown cause of cirrhosis. Upon diagnosis, the median model for end-stage liver disease score was 11 (IQR 8-15), 53% were of Child-Pugh class A whereas 61 (39%) had ascites, 11% encephalopathy, and 8% variceal bleeding. In all, 25% of deaths were from HCC and 25% from liver failure. Conclusion: A major increase in incidence of cirrhosis has occurred in Iceland associated with increases in alcohol consumption, obesity, and hepatitis C. In a high proportion NAFLD was the aetiology and very few had unknown cause of cirrhosis. The highest death rate was from HCC. Lay summary: In a nationwide population-based study from Iceland, including all patients diagnosed with cirrhosis of the liver over a period of 5 years, we found the incidence of new cases had increased 3-fold compared with a previous study 20 years ago. The increase is attributable to increased alcohol consumption, an epidemic of diabetes and obesity, and infection with the hepatitis C virus. Furthermore, we found that with thorough investigations, a specific cause for cirrhosis could be found in 94% of patients. Patients with cirrhosis frequently die of liver cancer and other complications related to their liver disease. Keywords: AIH, autoimmune hepatitis; ALD, alcoholic liver disease; Aetiology of cirrhosis; Alcohol; CIF, cumulative incidence function; CRR, competing-risks regression; Cirrhosis; HCC, hepatocellular carcinoma; Hepatitis C; Incidence of cirrhosis; MELD, model for end-stage liver disease; NAFLD; NAFLD, non-alcoholic fatty liver disease; NALD, non-alcoholic liver disease; NASH, non-alcoholic steatohepatitis; PBC, primary biliary cirrhosis; PSC, primary sclerosing cholangitis; SHRs, subhazard ratios.
  • Changes in the incidence of invasive disease due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis during the COVID-19 pandemic in 26 countries and territories in the Invasive Respiratory Infection Surveillance Initiative: a prospective analysis of surveillance data.

    Brueggemann, Angela B; Jansen van Rensburg, Melissa J; Shaw, David; McCarthy, Noel D; Jolley, Keith A; Maiden, Martin C J; van der Linden, Mark P G; Amin-Chowdhury, Zahin; Bennett, Désirée E; Borrow, Ray; et al. (Elsevier, 2021-06)
    Background Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, which are typically transmitted via respiratory droplets, are leading causes of invasive diseases, including bacteraemic pneumonia and meningitis, and of secondary infections subsequent to post-viral respiratory disease. The aim of this study was to investigate the incidence of invasive disease due to these pathogens during the early months of the COVID-19 pandemic. Methods In this prospective analysis of surveillance data, laboratories in 26 countries and territories across six continents submitted data on cases of invasive disease due to S pneumoniae, H influenzae, and N meningitidis from Jan 1, 2018, to May, 31, 2020, as part of the Invasive Respiratory Infection Surveillance (IRIS) Initiative. Numbers of weekly cases in 2020 were compared with corresponding data for 2018 and 2019. Data for invasive disease due to Streptococcus agalactiae, a non-respiratory pathogen, were collected from nine laboratories for comparison. The stringency of COVID-19 containment measures was quantified using the Oxford COVID-19 Government Response Tracker. Changes in population movements were assessed using Google COVID-19 Community Mobility Reports. Interrupted time-series modelling quantified changes in the incidence of invasive disease due to S pneumoniae, H influenzae, and N meningitidis in 2020 relative to when containment measures were imposed. Findings 27 laboratories from 26 countries and territories submitted data to the IRIS Initiative for S pneumoniae (62 837 total cases), 24 laboratories from 24 countries submitted data for H influenzae (7796 total cases), and 21 laboratories from 21 countries submitted data for N meningitidis (5877 total cases). All countries and territories had experienced a significant and sustained reduction in invasive diseases due to S pneumoniae, H influenzae, and N meningitidis in early 2020 (Jan 1 to May 31, 2020), coinciding with the introduction of COVID-19 containment measures in each country. By contrast, no significant changes in the incidence of invasive S agalactiae infections were observed. Similar trends were observed across most countries and territories despite differing stringency in COVID-19 control policies. The incidence of reported S pneumoniae infections decreased by 68% at 4 weeks (incidence rate ratio 0.32 [95% CI 0.27-0.37]) and 82% at 8 weeks (0.18 [0.14-0.23]) following the week in which significant changes in population movements were recorded. Interpretation The introduction of COVID-19 containment policies and public information campaigns likely reduced transmission of S pneumoniae, H influenzae, and N meningitidis, leading to a significant reduction in life-threatening invasive diseases in many countries worldwide.
  • Reliability and Validity of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): Portuguese Version.

    Marques, Cristiana Campos; Matos, Ana Paula; do Céu Salvador, Maria; Arnarson, Eiríkur Örn; Craighead, W Edward; 1Center for Research in Neuropsychology and Cognitive Behavioural Intervention (CINEICC), Faculty of Psychology and Educational Sciences, University of Coimbra, Rua do Colégio Novo, 3000-115, Coimbra, Portugal. cristiana.marques@uc.pt. 2Center for Research in Neuropsychology and Cognitive Behavioural Intervention (CINEICC), Faculty of Psychology and Educational Sciences, University of Coimbra, Rua do Colégio Novo, 3000-115, Coimbra, Portugal. 3School of Health Sciences, Faculty of Medicine, University of Iceland, Landspítali -University Hospital, 101, Reykjavik, Iceland. 4Department of Psychiatry and Behavioral Sciences, Department of Psychology, Emory University, Atlanta, GA, USA. (Springer, 2021-05-28)
    This study examined the test-retest reliability, consensual, convergent and divergent validities, sensitivity, specificity, positive and negative predictive values, and accuracy of the Portuguese version of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K-SADS-PL). Eighty-nine children/adolescents (65 psychiatric outpatients and 24 healthy controls) were interviewed with K-SADS-PL and completed measures of depressive and anxiety symptoms. The child's parent/caretaker completed the Child Behavior Checklist. Good to excellent values were obtained for test-retest reliability and consensual validity. For the convergent validity, moderate correlations between the K-SADS-PL and the corresponding self-report measures were observed. Divergent validity was acceptable for the K-SADS-PL diagnoses. The lowest values of sensitivity, specificity, and accuracy of the K-SADS-PL were 88, 88, and 91, respectively. The Portuguese version of K-SADS-PL proved to be a valid and reliable assessment instrument for children and adolescents, and was sensitive, specific and accurate when diagnosing mood, anxiety, adjustment, and attention-deficit/hyperactivity disorders. Keywords: Children/adolescents; K-SADS-PL; Portuguese version; Reliability; Validity.
  • Detection mode of childhood acute lymphoblastic leukaemia relapse and its effect on survival: a Nordic population-based cohort study.

    Jensen, Karen S; Oskarsson, Trausti; Lähteenmäki, Päivi M; Flaegstad, Trond; Schmiegelow, Kjeld; Vedsted, Peter; Albertsen, Birgitte K; Schrøder, Henrik; 1Department of Paediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark. 2Department of Paediatric Oncology, Karolinska University Hospital, Stockholm, Sweden. 3Childhood Cancer Research Unit, Department of Women´s and Children´s Health, Karolinska Institutet, Stockholm, Sweden. 4Children's Hospital, Landspitali University Hospital, Reykjavik, Iceland. 5Department of Paediatric and Adolescent Haematology/Oncology, Turku University Hospital, FICAN-West, Turku University, Turku, Finland. 6Department of Paediatrics, University of Tromsø and University Hospital of North Norway, Tromsø, Norway. 7Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Copenhagen, Denmark. 8Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 9Research Unit for General Practice, Department of Public Health, Aarhus University, Aarhus, Denmark. (Wiley, 2021-05-27)
    Relapse constitutes the greatest threat to event-free survival after completion of treatment for childhood acute lymphoblastic leukaemia (ALL). However, evidence on optimal follow-up schedules is limited. The aims of the present population-based cohort study were to assess the value of current follow-up schedules after completion of Nordic Society of Paediatric Haematology and Oncology ALL protocol treatment and to estimate the impact of relapse detection mode on overall survival (OS). Among 3262 patients diagnosed between 1992 and 2014 and who completed treatment, 338 developed a relapse. Relapse detection was equally distributed between extra visits (50·8%) and scheduled follow-up visits (49·2%). All cases detected at an extra visit and 64·3% of cases detected at a scheduled visit presented with symptoms or objective findings. Neither the mode of detection {adjusted hazard ratio 0·95, [95% confidence interval (CI) 0·61-1·48] for scheduled visits} nor the duration of symptoms was an independent risk factor for OS after relapse. The estimated number of scheduled blood samples needed to diagnose one subclinical relapse during the first 5 years after treatment cessation was 1269 (95% CI 902-1637). In conclusion, based on OS data, scheduled visits after cessation of therapy seem to yield no extra benefit. These results should frame future follow-up strategies. Keywords: acute lymphoblastic leukaemia; cancer survivors; childhood leukaemia; recurrence; surveillance.

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