Recent Submissions

  • Higher Alkylresorcinol Concentrations, a Consequence of Whole-Grain Intake, are Inversely Associated with Gestational Diabetes Mellitus in Iceland.

    Tryggvadottir, Ellen A; Halldorsson, Thorhallur I; Landberg, Rikard; Hrolfsdottir, Laufey; Birgisdottir, Bryndis E; Magnusdottir, Ola K; Hreidarsdottir, Ingibjorg T; Hardardottir, Hildur; Gunnarsdottir, Ingibjorg; 1Unit for Nutrition Research, Landspitali University Hospital and Faculty of Food Science and Nutrition, University of Iceland, Reykjavik, Iceland. 2Centre for Fetal Programming, Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. 3Division of Food and Nutrition Science, Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden. 4Institution of Health Science Research, University of Akureyri and Akureyri Hospital, Akureyri, Iceland. 5Department of Obstetrics and Gynecology, Landspitali University Hospital, Reykjavík, Iceland. 6Faculty of Medicine, University of Iceland Reykjavík, Reykjavík, Iceland. 7Livio Reykjavík, Reproductive Center in Reykjavík, Reykjavík, Iceland. (Oxford University Press, 2021-05)
    Background: A diet rich in whole grains may provide benefits for pregnant women due to whole grains' high nutritional value and dietary fiber content. Objectives: To study the associations of whole-grain consumption, as well as the plasma alkylresorcinol concentration, a whole-grain consumption biomarker, in early pregnancy with gestational diabetes mellitus (GDM) diagnoses. Methods: Subjects were women from the prospective study Pregnant Women in Iceland II (PREWICE II; n = 853) who attended their ultrasound appointment in gestational weeks 11-14 during the period from October 2017 to March 2018. During that visit, whole-grain consumption was estimated using a diet screening questionnaire, and blood samples were collected for analysis of plasma alkylresorcinols (ARs). Information on GDM diagnoses was later extracted from medical records. Multivariate log-binomial regression was used to evaluate the association of dietary whole-grain and AR concentrations with GDM. Results: In total, 14.9% of the women adhered to the national food-based dietary guidelines (n = 127), which recommend 2 portions of whole grains daily. GDM was diagnosed in 127 women (14.9%). The frequency of whole-grain consumption was lower in women who were later diagnosed with GDM compared to the women without GDM (median, 5 times/week vs. 6 times/week, respectively; P = 0.02). This difference was reflected in the lower median concentration of total AR in women diagnosed with GDM (163 nmol/L vs. 209 nmol/L, respectively; P < 0.01). The quartile with the highest concentrations of AR had a RR of 0.50 (95% CI: 0.27-0.90) of being diagnosed with GDM, in comparison to the lowest quartile. There was a significant dose response in the GDM risk with higher AR levels. Conclusions: We found that a higher consumption of whole grains, reflected both by reported consumption according to the FFQ and AR biomarkers, was associated with a decreased risk of receiving a GDM diagnosis.
  • Testing soft tissue radiodensity parameters interplay with age and self-reported physical activity.

    Recenti, Marco; Ricciardi, Carlo; Edmunds, Kyle; Jacob, Deborah; Gambacorta, Monica; Gargiulo, Paolo; 1Institute for Biomedical and Neural Engineering, Reykjavík University, Reykjavík. 2Institute for Biomedical and Neural Engineering, Reykjavík University, Reykjavík, Iceland; Department of Electrical Engineering and Information Technology, University of Naples 'Federico II', Naples. 3Institute for Biomedical and Neural Engineering, Reykjavík University, Reykjavík. 4Institute for Biomedical and Neural Engineering, Reykjavík University, Reykjavík. 5Umberto I Hospital, ASL Salerno, Nocera Inferiore. 6Institute for Biomedical and Neural Engineering, Reykjavík University, Reykjavík, Iceland; Department of Science, Landspítali, Reykjavík. (PagePress, 2021-07-12)
    Aging well is directly associated to a healthy lifestyle. The focus of this paper is to relate individual wellness with medical image features. Non-linear trimodal regression analysis (NTRA) is a novel method that models the radiodensitometric distributions of x-ray computed tomography (CT) cross-sections. It generates 11 patient-specific parameters that describe the quality and quantity of muscle, fat, and connective tissues. In this research, the relationship of these 11 NTRA parameters with age, physical activity, and lifestyle is investigated in the 3,157 elderly volunteers AGES-I dataset. First, univariate statistical analyses were performed, and subjects were grouped by age and self-reported past (youth-midlife) and present (within 12 months of the survey) physical activity to ascertain which parameters were the most influential. Then, machine learning (ML) analyses were conducted to classify patients using NTRA parameters as input features for three ML algorithms. ML is also used to classify a Lifestyle index using the age groups. This classification analysis yielded robust results with the lifestyle index underlying the relevant differences of the soft tissues between age groups, especially in fat and connective tissue. Univariate statistical models suggested that NTRA parameters may be susceptible to age and differences between past and present physical activity levels. Moreover, for both age and physical activity, lean muscle parameters expressed more significant variation than fat and connective tissues.
  • Progression of traction bronchiectasis/bronchiolectasis in interstitial lung abnormalities is associated with increased all-cause mortality: Age Gene/Environment Susceptibility-Reykjavik Study.

    Hino, Takuya; Hida, Tomoyuki; Nishino, Mizuki; Lu, Junwei; Putman, Rachel K; Gudmundsson, Elias F; Hata, Akinori; Araki, Tetsuro; Valtchinov, Vladimir I; Honda, Osamu; et al. (Elsevier, 2021-03-10)
    Purpose: The aim of this study is to assess the role of traction bronchiectasis/bronchiolectasis and its progression as a predictor for early fibrosis in interstitial lung abnormalities (ILA). Methods: Three hundred twenty-seven ILA participants out of 5764 in the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study who had undergone chest CT twice with an interval of approximately five-years were enrolled in this study. Traction bronchiectasis/bronchiolectasis index (TBI) was classified on a four-point scale: 0, ILA without traction bronchiectasis/bronchiolectasis; 1, ILA with bronchiolectasis but without bronchiectasis or architectural distortion; 2, ILA with mild to moderate traction bronchiectasis; 3, ILA and severe traction bronchiectasis and/or honeycombing. Traction bronchiectasis (TB) progression was classified on a five-point scale: 1, Improved; 2, Probably improved; 3, No change; 4, Probably progressed; 5, Progressed. Overall survival (OS) among participants with different TB Progression Score and between the TB progression group and No TB progression group was also investigated. Hazard radio (HR) was estimated with Cox proportional hazards model. Results: The higher the TBI at baseline, the higher TB Progression Score (P < 0.001). All five participants with TBI = 3 at baseline progressed; 46 (90 %) of 51 participants with TBI = 2 progressed. TB progression was also associated with shorter OS with statistically significant difference (adjusted HR = 1.68, P < 0.001). Conclusion: TB progression was visualized on chest CT frequently and clearly. It has the potential to be the predictor for poorer prognosis of ILA.
  • Group B streptococcal infections in infants in Iceland: clinical and microbiological factors.

    Baeringsdottir, Birta; Erlendsdottir, Helga; Bjornsdottir, Erla Soffia; Martins, Elisabete R; Ramirez, Mário; Haraldsson, Asgeir; Thorkelsson, Thordur; 1Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 2Department of Clinical Microbiology, Landspitali University Hospital, Reykjavik, Iceland. 3Instituto de Microbiologia, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal. 4The Children's Hospital, Landspitali University Hospital, Reykjavik, Iceland. (Microbiology Society, 2021-09)
    Introduction. Group B streptococcus (GBS) is a leading cause of invasive neonatal infections. These have been divided into early-onset disease (EOD; <7 days) and late-onset disease (LOD; 7-89 days), with different GBS clonal complexes (CCs) associated with different disease presentations.Hypothesis. Different GBS CCs are associated with timing of infection (EOD or LOD) and clinical presentation (sepsis, meningitis or pneumonia).Aim. To study infant GBS infections in Iceland from 1975 to 2019. Are specific GBS CCs related to disease presentation? Is CC17 overrepresented in infant GBS infections in Iceland?Methodology. All culture-confirmed invasive GBS infections in infants (<90 days) in Iceland from 1975 to 2019 were included. Clinical information was gathered from medical records.Results. A total of 127 invasive GBS infections in infants were diagnosed, but 105 infants were included in the study. Of these, 56 had EOD and 49 had LOD. The incidence of GBS infections declined from 2000 onwards but increased again at the end of the study period. Furthermore, there was a significant increase in LOD over the study period (P=0.0001). The most common presenting symptoms were respiratory difficulties and fever and the most common presentation was sepsis alone. Approximately one-third of the cases were caused by GBS CC17 of serotype III with surface protein RIB and pili PI-1+PI-2b or PI-2b. CC17 was significantly associated with LOD (P<0.001).Conclusion. CC17 is a major cause of GBS infection in infants in Iceland. This clone is associated with LOD, which has been increasing in incidence. Because intrapartum antibiotic prophylaxis only prevents EOD, it is important to continue the development of a GBS vaccine in order to prevent LOD infections.
  • Hepatitis B virus elimination status and strategies in circumpolar countries, 2020.

    Haering, Celia; McMahon, Brian; Harris, Aaron; Weis, Nina; Lundberg Ederth, Josefine; Axelsson, Maria; Olafsson, Sigurdur; Osiowy, Carla; Tomas, Kristina; Bollerup, Signe; et al. (Taylor & Francis, 2021-10)
    Hepatitis B virus (HBV) infection remains a global health threat. The World Health Organization (WHO) established a goal to eliminate HBV infection as a public health threat by 2030, and defined targets for key interventions to achieve that goal. We evaluated HBV burden and relevant national recommendations for progress towards WHO targets in circumpolar countries. Viral hepatitis experts of circumpolar countries were surveyed regarding their country's burden of HBV, achievement of WHO targets and national public health authority recommendations for HBV prevention and control. Eight of nine circumpolar countries responded. All countries continue to see new HBV infections. Data about HBV prevalence and progress in reaching WHO 2030 elimination targets are lacking. No country was able to report data for all seven WHO target measures. All countries have recommendations targeting the prevention of mother-to-child transmission. Only the USA and Greenland recommend universal birth dose vaccination. Four countries have recommendations to screen persons at high risk for HBV. Existing recommendations largely address prevention; however, recommendations for universal birth dose vaccination have not been widely introduced. Opportunities remain for the development of trackable targets and national elimination planning to screen and treat for HBV to reduce incidence and mortality. Keywords: Circumpolar Viral Hepatitis Working Group; Hepatitis B infection; elimination; policy survey; public health policy; vaccination recommendation.
  • Interstitial lung abnormalities - current knowledge and future directions.

    Axelsson, Gisli Thor; Gudmundsson, Gunnar; 1Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 2Icelandic Heart Association, Kopavogur, Iceland. 3Department of Respiratory Medicine and Sleep, Landspitali University Hospital, Reykjavik, Iceland. (Taylor & Francis, 2021-10-31)
    Efforts to grasp the significance of radiologic changes similar to interstitial lung disease (ILD) in undiagnosed individuals have intensified in the recent decade. The term interstitial lung abnormalities (ILA) is an emerging definition of such changes, defined by visual examination of computed tomography scans. Substantial insights have been made in the origins and clinical consequences of these changes, as well as automated measures of early lung fibrosis, which will likely lead to increased recognition of early fibrotic lung changes among clinicians and researchers alike. Interstitial lung abnormalities have an estimated prevalence of 7-10% in elderly populations. They correlate with many ILD risk factors, both epidemiologic and genetic. Additionally, histopathological similarities with IPF exist in those with ILA. While no established blood biomarker of ILA exists, several have been suggested. Distinct imaging patterns indicating advanced fibrosis correlate with worse clinical outcomes. ILA are also linked with adverse clinical outcomes such as increased mortality and risk of lung cancer. Progression of ILA has been noted in a significant portion of those with ILA and is associated with many of the same features as ILD, including advanced fibrosis. Those with ILA progression are at risk of accelerated FVC decline and increased mortality. Radiologic changes resembling ILD have also been attained by automated measures. Such measures associate with some, but not all the same factors as ILA. ILA and similar radiologic changes are in many ways analogous to ILD and likely represent a precursor of ILD in some cases. While warranting an evaluation for ILD, they are associated with poor clinical outcomes beyond possible ILD development and thus are by themselves a significant finding. Among the present objectives of this field are the stratification of patients with regards to progression and the discovery of biomarkers with predictive value for clinical outcomes.
  • Rural patients' experience of education, surveillance, and self-care support after heart disease related hospitalisation: a qualitative study.

    Jóhannsdóttir, Thórunn Björg; Ingadottir, Brynja; Svavarsdóttir, Margrét Hrönn; 1The Health Directorate of East-Iceland, Egilsstadir, Iceland. 2Faculty of Nursing, School of Health Sciences, University of Iceland, Reykjavik, Iceland and Landspitali University Hospital, Reykjavik, Iceland. 3School of Health Sciences, Faculty of Nursing, University of Akureyri, Akureyri, Iceland. (Taylor & Francis, 2021-11)
    People living in rural Iceland have a higher rate of cardiovascular risk factors and healthcare utilisation compared to people in urban areas.The aim of this qualitative study was to explore the experiences of people with coronary heart disease, living in rural Iceland regarding patient education, surveillance, and self-care support. The participants (N = 14, age 52‒79 years, 8 male), were interviewed 6 to 12 months after hospital discharge following a cardiac event (in 2018‒2019). Systematic text-condensation was used for analysis. The findings were categorised into three main themes: Education and support describes inadequate patient education and support from health-care professionals after discharge from hospitaland how the internet was the main information source supplemented with spouse's and family support. Local healthcare services describe thelack of and importance of access to health-care professionals, stable services, and underutilisation of telemedicine and primary healthcare in the local area, and Self-care behaviour describes the lack of professional support with lifestyle changes and how the participants manage self-care as well as their attitudes towards the disease.The results indicate that access to continuous healthcare services and person-centred support focusing on prevention strategies are widely impaired in rural areas in Iceland.
  • Technical Performance of Textile-Based Dry Forehead Electrodes Compared with Medical-Grade Overnight Home Sleep Recordings

    Rusanen, Matias; Kainulainen, Samu; Korkalainen, Henri; Kalevo, Laura; Myllymaa, Katja; Leppanen, Timo; Toyras, Juha; Arnardottir, Erna Sif; Myllymaa, Sami; a Department of Applied Physics, University of Eastern Finland, Kuopio, 70210, Finland b Diagnostic Imaging Center, Kuopio University Hospital, Kuopio, 70210, Finland c School of Information Technology and Electrical Engineering, The University of Queensland, Brisbane, 4067, QLD, Australia d Science Service Center, Kuopio University Hospital, Kuopio, 70210, Finland e Reykjavik University Sleep Institute, School of Technology, Reykjavik University 102, Reykjavik, Iceland f Internal Medicine Services, Landspitali-The National University Hospital of Iceland 101, Reykjavik, Iceland (IEEE, 2021-01-01)
    The current clinically used electroencephalography (EEG) sensors are not self-applicable. This complicates the recording of the brain's electrical activity in unattended home polysomnography (PSG). When EEG is not recorded, the sleep architecture cannot be accurately determined, which decreases the accuracy of home-based diagnosis of sleep disorders. The aim of this study was to compare the technical performance of FocusBand, an easily applicable textile electrode headband, to that of clinical EEG and electrooculography (EOG) electrodes. Overnight unattended recordings were conducted at participants' (n = 10) homes. Signals were recorded using a portable Nox A1 PSG device. The FocusBand's forehead EEG (Fp1-Fp2) signals contained features that are visible at both, the standard EEG (F4-M1) and EOG (E1-M2) signals. The FocusBand's EEG signal amplitudes were significantly lower compared to standard EEG (F4-M1; average difference 98%) and EOG (E1-M2; average difference 29%) signals during all sleep stages. Despite the amplitude difference, forehead EEG signals displayed typical EEG characteristics related to certain sleep stages. However, the frequency content of the FocusBand-based signals was more similar to that of the standard EOG signals than that of standard EEG signals. The majority of the artifacts seen in the FocusBand signals were related to a loosened headband. High differences in the frequency content of the compared signals were also found during wakefulness, suggesting susceptibility of the textile electrodes to electrode movement artifacts. This study demonstrates that the forehead biopotential signals recorded using an easily attachable textile electrode headband could be useful in home-based sleep recordings.
  • X-linked serotonin 2C receptor is associated with a non-canonical pathway for sudden unexpected death in epilepsy.

    Massey, Cory A; Thompson, Samantha J; Ostrom, Ryan W; Drabek, Janice; Sveinsson, Olafur A; Tomson, Torbjörn; Haas, Elisabeth A; Mena, Othon J; Goldman, Alica M; Noebels, Jeffrey L; et al. (Oxford University Press, 2021-07-09)
    Sudden Unexpected Death in Epilepsy is a leading cause of epilepsy-related mortality, and the analysis of mouse Sudden Unexpected Death in Epilepsy models is steadily revealing a spectrum of inherited risk phenotypes based on distinct genetic mechanisms. Serotonin (5-HT) signalling enhances post-ictal cardiorespiratory drive and, when elevated in the brain, reduces death following evoked audiogenic brainstem seizures in inbred mouse models. However, no gene in this pathway has yet been linked to a spontaneous epilepsy phenotype, the defining criterion of Sudden Unexpected Death in Epilepsy. Most monogenic models of Sudden Unexpected Death in Epilepsy invoke a failure of inhibitory synaptic drive as a critical pathogenic step. Accordingly, the G protein-coupled, membrane serotonin receptor 5-HT2C inhibits forebrain and brainstem networks by exciting GABAergic interneurons, and deletion of this gene lowers the threshold for lethal evoked audiogenic seizures. Here, we characterize epileptogenesis throughout the lifespan of mice lacking X-linked, 5-HT2C receptors (loxTB Htr2c). We find that loss of Htr2c generates a complex, adult-onset spontaneous epileptic phenotype with a novel progressive hyperexcitability pattern of absences, non-convulsive, and convulsive behavioural seizures culminating in late onset sudden mortality predominantly in male mice. RNAscope localized Htr2c mRNA in subsets of Gad2+ GABAergic neurons in forebrain and brainstem regions. To evaluate the contribution of 5-HT2C receptor-mediated inhibitory drive, we selectively spared their deletion in GAD2+ GABAergic neurons of pan-deleted loxTB Htr2c mice, yet unexpectedly found no amelioration of survival or epileptic phenotype, indicating that expression of 5-HT2C receptors in GAD2+ inhibitory neurons was not sufficient to prevent hyperexcitability and lethal seizures. Analysis of human Sudden Unexpected Death in Epilepsy and epilepsy genetic databases identified an enrichment of HTR2C non-synonymous variants in Sudden Unexpected Death in Epilepsy cases. Interestingly, while early lethality is not reflected in the mouse model, we also identified variants mainly among male Sudden Infant Death Syndrome patients. Our findings validate HTR2C as a novel, sex-linked candidate gene modifying Sudden Unexpected Death in Epilepsy risk, and demonstrate that the complex epilepsy phenotype does not arise solely from 5-HT2C-mediated synaptic disinhibition. These results strengthen the evidence for the serotonin hypothesis of Sudden Unexpected Death in Epilepsy risk in humans, and advance current efforts to develop gene-guided interventions to mitigate premature mortality in epilepsy.
  • Molecular Structure and Interactions of Lipids in the Outer Membrane of Living Cells Based on Surface-Enhanced Raman Scattering and Liposome Models.

    Živanović, Vesna; Milewska, Adrianna; Leosson, Kristjan; Kneipp, Janina; 1Department of Chemistry, Humboldt-Universität zu Berlin, Brook-Taylor-Strasse 2, Berlin 12489, Germany. 2Innovation Center Iceland, Árleynir 2-8, Reykjavík 112, Iceland. 3The Blood Bank, Landspitali University Hospital, Snorrabraut 60, Reykjavík 105, Iceland. 4School of Engineering and Natural Sciences, University of Iceland, Sæmundargötu 2, Reykjavík 101, Iceland. 5Science Institute, University of Iceland, Dunhaga 3, Reykjavík 107, Iceland. (American Chemical Society, 2021-07-15)
    The distribution and interaction of lipids determine the structure and function of the cellular membrane. Surface-enhanced Raman scattering (SERS) is used for selective molecular probing of the cell membrane of living fibroblast cells grown adherently on gold nanoisland substrates across their whole contact areas with the substrate, enabling mapping of the membrane's composition and interaction. From the SERS data, the localization and distribution of different lipids and their interactions, together with proteins in the outer cell membrane, are inferred. Interpretation of the spectra is mainly supported by comparison with the spectra of model liposomes composed of phosphatidylcholine, sphingomyelin, and cholesterol obtained on the same gold substrate. The interaction of the liposomes with the substrate differs from that with gold nanoparticles. The SERS maps indicate colocalization of ordered lipid domains with cholesterol in the living cells. They support the observation of ordered membrane regions of micrometer dimensions in the outer leaflet of the cell membrane that are rich in sphingomyelin. Moreover, the spectra of the living cells contain bands from the groups of the lipid heads, phosphate, choline, and ethanolamine, combined with those from membrane proteins, as indicated by signals assigned to prenyl attachment. Elucidating the composition and structure of lipid membranes in living cells can find application in many fields of research.
  • Clinical practice guideline on spinal stabilisation of adult trauma patients: Endorsement by the Scandinavian Society of Anaesthesiology and Intensive Care Medicine.

    Yli-Hankala, Arvi; Chew, Michelle S; Olkkola, Klaus T; Rehn, Marius; Sverrisson, Kristinn Ö; Møller, Morten H; 1Department of Anaesthesia, Tampere University Hospital, Tampere, Finland. 2Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland. 3Department of Anaesthesia and Intensive Care, Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden. 4Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. 5Division of Prehospital Services, Air Ambulance Department, Oslo University Hospital, Oslo, Norway. 6The Norwegian Air Ambulance Foundation, Oslo, Norway. 7Faculty of Health Sciences, University of Stavanger, Stavanger, Norway. 8Department of Anaesthesia and Intensive Care Medicine, Landspítali University Hospital, Reykjavík, Iceland. 9Department of Intensive Care, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark. 10Collaboration for Research in Intensive Care (CRIC), Copenhagen, Denmark. (Wiley, 2021-06-24)
    The Clinical Practice Committee of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine endorses the clinical practice guideline New clinical guidelines on the spinal stabilisation of adult trauma patients-consensus and evidence based. The guideline can serve as a useful decision aid for clinicians caring for patients with traumatic spinal cord injury. However, it is important to acknowledge that the overall certainty of evidence supporting the guideline recommendations was low, implying that further research is likely to have an important impact on the confidence in the estimate of effect. Keywords: SSAI; clinical practice guideline; endorsement; spinal stabilisation; trauma.
  • Cell-phone traces reveal infection-associated behavioral change.

    Vigfusson, Ymir; Karlsson, Thorgeir A; Onken, Derek; Song, Congzheng; Einarsson, Atli F; Kishore, Nishant; Mitchell, Rebecca M; Brooks-Pollock, Ellen; Sigmundsdottir, Gudrun; Danon; et al. (National Academy of Sciences, 2021-11)
    Epidemic preparedness depends on our ability to predict the trajectory of an epidemic and the human behavior that drives spread in the event of an outbreak. Changes to behavior during an outbreak limit the reliability of syndromic surveillance using large-scale data sources, such as online social media or search behavior, which could otherwise supplement healthcare-based outbreak-prediction methods. Here, we measure behavior change reflected in mobile-phone call-detail records (CDRs), a source of passively collected real-time behavioral information, using an anonymously linked dataset of cell-phone users and their date of influenza-like illness diagnosis during the 2009 H1N1v pandemic. We demonstrate that mobile-phone use during illness differs measurably from routine behavior: Diagnosed individuals exhibit less movement than normal (1.1 to 1.4 fewer unique tower locations; [Formula: see text]), on average, in the 2 to 4 d around diagnosis and place fewer calls (2.3 to 3.3 fewer calls; [Formula: see text]) while spending longer on the phone (41- to 66-s average increase; [Formula: see text]) than usual on the day following diagnosis. The results suggest that anonymously linked CDRs and health data may be sufficiently granular to augment epidemic surveillance efforts and that infectious disease-modeling efforts lacking explicit behavior-change mechanisms need to be revisited. Keywords: call detail records; disease; influenza; outbreak; surveillance.
  • Low levels of respiratory syncytial virus activity in Europe during the 2020/21 season: what can we expect in the coming summer and autumn/winter?

    van Summeren, Jojanneke; Meijer, Adam; Aspelund, Guðrún; Casalegno, Jean Sebastien; Erna, Guðrún; Hoang, Uy; Lina, Bruno; de Lusignan, Simon; Teirlinck, Anne C; Thors, Valtýr; et al. (European Centre for Disease Prevention and Control (ECDC), 2021-11)
    Since the introduction of non-pharmacological interventions to control COVID-19, respiratory syncytial virus (RSV) activity in Europe has been limited. Surveillance data for 17 countries showed delayed RSV epidemics in France (≥ 12 w) and Iceland (≥ 4 w) during the 2020/21 season. RSV cases (predominantly small children) in France and Iceland were older compared with previous seasons. We hypothesise that future RSV epidemic(s) could start outside the usual autumn/winter season and be larger than expected. Year-round surveillance of RSV is of critical importance. Keywords: COVID-19 pandemic; RSV; Respiratory syncytial virus; epidemiology; surveillance data.
  • Benchmarking European Home Care Models for Older Persons on Societal Costs: The IBenC Study.

    van Lier, Lisanne I; van der Roest, Henriëtte G; Garms-Homolová, Vjenka; Onder, Graziano; Jónsson, Pálmi V; Declercq, Anja; Hertogh, Cees Mpm; van Hout, Hein Pj; Bosmans, Judith E; 1Departments of General Practice & Medicine of Older Persons, Amsterdam Public Health research institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands. 2Department on Aging, Netherlands Institute of Mental Health and Addiction (Trimbos Institute), Utrecht, the Netherlands. 3Department III, Economy and Law, Hochschule für Technik und Wirtschaft Berlin, University of Applied Sciences, Berlin, Germany. 4Department of Cardiovascular, Endocrine-metabolic Diseases and Aging Istituto Superiore di Sanità, Rome, Italy. 5Department of Geriatrics, Landspitali University Hospital, and Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 6LUCAS, Centre for Care Research and Consultancy, and CESO, Center for Sociological Research, KU Leuven (University of Leuven), Leuven, Belgium. 7Department of Health Sciences, Faculty of Science, Amsterdam Public Health research institute, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands. (SAGE Publications, 2021-06-21)
    This study aims to benchmark mean societal costs per client in different home care models and to describe characteristics of home care models with the lowest societal costs. In this prospective longitudinal study in 6 European countries, 6-month societal costs of resource utilization of 2060 older home care clients were estimated. Three care models were identified and compared based on level of patient-centered care (PCC), availability of specialized professionals (ASP) and level of monitoring of care performance (MCP). Differences in costs between care models were analyzed using linear regression while adjusting for case mix differences. Societal costs incurred in care model 2 (low ASP; high PCC & MCP) were significantly higher than in care model 1 (high ASP, PCC & MCP, mean difference €2230 (10%)) and in care model 3 (low ASP & PCC; high MCP, mean difference €2552 (12%)). Organizations within both models with the lowest societal costs, systematically monitor their care performance. However, organizations within one model arranged their care with a low focus on patient-centered care, and employed mainly generalist care professionals, while organizations in the other model arranged their care delivery with a strong focus on patient-centered care combined with a high availability of specialized care professionals. Keywords: Home care models; international benchmarking; older adults; societal costs.
  • Early pregnancy plasma fatty acid profiles of women later diagnosed with gestational diabetes.

    Tryggvadottir, Ellen Alma; Gunnarsdottir, Ingibjorg; Birgisdottir, Bryndis Eva; Hrolfsdottir, Laufey; Landberg, Rikard; Hreidarsdottir, Ingibjorg Th; Hardardottir, Hildur; Halldorsson, Thorhallur Ingi; 1Faculty of Food Science and Nutrition, University of Iceland, Reykjavik, Iceland 2Unit for Nutrition Research, Landspitali University Hospital, Reykjavík, Iceland. 3Faculty of Food Science and Nutrition, University of Iceland, Reykjavik, Iceland. 4Department of Education and Science, Akureyri Hospital, Akureyri, Iceland. 5Biology and Biological Engineering, Chalmers University of Technology, Goteborg, Sweden. 6Department of Obstetrics and Gynecology, Landspítali University Hospital, Reykjavík, Iceland. 7Faculty of Medicine, University of Iceland, Reykjavik, Iceland. (BMJ Publishing Group, 2021-08)
    Introduction: Fatty acid (FA) concentrations have previously been associated with gestational diabetes mellitus (GDM). However, few studies on GDM have examined FA profiles in early pregnancy or before diagnosis. This study aimed to compare early pregnancy plasma FA profiles of women with and without GDM diagnoses as well as their reported dietary consumption. Research design and methods: The subjects comprised 853 women from the prospective study: Pregnant Women in Iceland II (PREWICE II), attending their 11-14 weeks ultrasound appointment in 2017-2018. During the visit, blood samples were collected for plasma FA analysis, and dietary habits were assessed using a short food frequency questionnaire. Information on GDM diagnoses was then later extracted from medical records. Differences in FA profile between GDM cases and non-cases were evaluated using the Mann-Whitney U test. Results: GDM was diagnosed in 127 women (14.9%). Concentrations of saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids (PUFA) n-6, PUFA n-3 and total FA were higher in the women who later developed GDM compared with those who did not (p≤0.05). The medians for total FA were 2898 μg/mL for the women with GDM and 2681 μg/mL for those without GDM. Mean adjusted difference for total FA between the groups was 133 μg/mL (95% CI 33 to 233). Similar results were observed in prepregnancy normal-weight women and overweight women/women with obesity. Overall diet quality in early pregnancy appeared to be lower among the women later diagnosed with GDM. Conclusion: We found that plasma FA profiles in early pregnancy were different for women later diagnosed with GDM compared with those who were not, independent of the women's body mass index. Keywords: diabetes; diet; fatty acids; gestational; pregnancy.
  • DNA-thioguanine concentration and relapse risk in children and young adults with acute lymphoblastic leukemia: an IPD meta-analysis.

    Toksvang, Linea N; Grell, Kathrine; Nersting, Jacob; Degn, Matilda; Nielsen, Stine N; Abrahamsson, Jonas; Lund, Bendik; Kanerva, Jukka; Jónsson, Ólafur G; Lepik, Kristi; et al. (Nature Publishing Group, 2021-06-26)
    Methotrexate/6-mercaptopurine maintenance therapy improves acute lymphoblastic leukemia (ALL) outcome. Cytotoxicity is mediated by DNA incorporation of thioguanine nucleotides (DNA-TG). We investigated the association of DNA-TG to relapse risk in 1 910 children and young adults with non-high risk ALL. In a cohort-stratified Cox regression analysis adjusted for sex, age, and white cell count at diagnosis, the relapse-specific hazard ratio (HRa) per 100 fmol/μg increase in weighted mean DNA-TG (wmDNA-TG) was 0.87 (95% CI 0.78-0.97; p = 0.013) in the 839 patients who were minimal residual disease (MRD) positive at end of induction therapy (EOI), whereas this was not the case in EOI MRD-negative patients (p = 0.76). Validation analysis excluding the previously published Nordic NOPHO ALL2008 pediatric cohort yielded a HRa of 0.92 (95% CI 0.82-1.03; p = 0.15) per 100 fmol/μg increase in wmDNA-TG in EOI MRD-positive patients. If also excluding the United Kingdom cohort, in which samples were taken non-randomly in selected patients, the HRa for the EOI MRD-positive patients was 0.82 (95% CI 0.68-0.99; p = 0.044) per 100 fmol/μg increase in wmDNA-TG. The importance of DNA-TG as a biomarker for maintenance therapy intensity calls for novel strategies to increase DNA-TG, although its clinical value may vary by protocol backbone.
  • Hsa-miR-21-3p associates with breast cancer patient survival and targets genes in tumor suppressive pathways.

    Amirfallah, Arsalan; Knutsdottir, Hildur; Arason, Adalgeir; Hilmarsdottir, Bylgja; Johannsson, Oskar T; Agnarsson, Bjarni A; Barkardottir, Rosa B; Reynisdottir, Inga; 1Cell Biology Unit, Department of Pathology, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. 2Biomedical Center, Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 3Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America. 4Molecular Pathology Unit, Department of Pathology, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. 5Department of Pathology, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. 6Department of Oncology, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. 7Faculty of Medicine, University of Iceland, Reykjavik, Iceland. (Public Library of Science, 2021-11-19)
    Breast cancer is the cancer most often diagnosed in women. MicroRNAs (MIRs) are short RNA molecules that bind mRNA resulting in their downregulation. MIR21 has been shown to be an oncomiR in most cancer types, including breast cancer. Most of the effects of miR-21 have been attributed to hsa-miR-21-5p that is transcribed from the leading strand of MIR21, but hsa-miR-21-3p (miR-21-3p), transcribed from the lagging strand, is much less studied. The aim of the study is to analyze whether expression of miR-21-3p is prognostic for breast cancer. MiR-21-3p association with survival, clinical and pathological characteristics was analyzed in a large breast cancer cohort and validated in three separate cohorts, including TCGA and METABRIC. Analytical tools were also used to infer miR-21-3p function and to identify potential target genes and functional pathways. The results showed that in the exploration cohort, high miR-21-3p levels associated with shorter survival and lymph node positivity. In the three validation cohorts, high miR-21-3p levels associated with pathological characteristics that predict worse prognosis. Specifically, in the largest validation cohort, METABRIC (n = 1174), high miR-21-3p levels associated with large tumors, a high grade, lymph node and HER2 positivity, and shorter breast-cancer-specific survival (HR = 1.38, CI 1.13-1.68). This association remained significant after adjusting for confounding factors. The genes with expression levels that correlated with miR-21-3p were enriched in particular pathways, including the epithelial-to-mesenchymal transition and proliferation. Among the most significantly downregulated targets were MAT2A and the tumor suppressive genes STARD13 and ZNF132. The results from this study emphasize that both 3p- and 5p-arms from a MIR warrant independent study. The data show that miR-21-3p overexpression in breast tumors is a marker of worse breast cancer progression and it affects genes in pathways that drive breast cancer by down-regulating tumor suppressor genes. The results suggest miR-21-3p as a potential biomarker.
  • Enhanced Antenatal Care: Combining one-to-one and group Antenatal Care models to increase childbirth education and address childbirth fear.

    Swift, Emma Marie; Zoega, Helga; Stoll, Kathrin; Avery, Melissa; Gottfreðsdóttir, Helga; 1Faculty of Nursing/Department of Midwifery, University of Iceland, Eirberg við Eiríksgötu, 101 Reykjavík, Iceland. Electronic address: 2Centre of Public Health Sciences, Faculty of Medicine, University of Iceland, Sturlugata 8, 101 Reykjavík, Iceland; Centre for Big Data Research in Health, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia. 3Division of Midwifery, University of British Columbia, Vancouver, Canada. 4University of Minnesota, School of Nursing, Minneapolis, MN, USA. 5Faculty of Nursing/Department of Midwifery, University of Iceland, Eirberg við Eiríksgötu, 101 Reykjavík, Iceland; Women's Clinic, Landspitali University Hospital, 101 Reykjavik, Iceland. (Elsevier, 2020-07-24)
    Background: We designed and implemented a new model of care, Enhanced Antenatal Care (EAC), which offers a combined approach to midwifery-led care with six one-to-one visits and four group sessions. Aim: To assess EAC in terms of women's satisfaction with care, autonomy in decision-making, and its effectiveness in lowering childbirth fear. Methods: This was a quasi-experimental controlled trial comparing 32 nulliparous women who received EAC (n=32) and usual antenatal care (n=60). We compared women's satisfaction with care and autonomy in decision-making post-intervention using chi-square test. We administered a Fear of Birth Scale pre- and post-intervention and assessed change in fear of birth in each group using the Cohen's d for effect size. To isolate the effect of EAC, we then restricted this analysis to women who did not attend classes alongside maternal care (n=13 in EAC and n=13 in usual care). Findings: Women's satisfaction with care in terms of monitoring their and their baby's health was similar in both groups. Women receiving EAC were more likely than those in usual care to report having received enough information about the postpartum period (75% vs 30%) and parenting (91% vs 55%). Overall, EAC was more effective than usual care in reducing fear of birth (Cohen's d=-0.21), especially among women not attending classes alongside antenatal care (Cohen's d=-0.83). Conclusion: This study is the first to report findings on EAC and suggests that this novel model may be beneficial in terms of providing education and support, as well as lowering childbirth fear. Keywords: Education; Enhanced Antenatal Care; Fear of birth; Group antenatal care; Pregnancy.
  • Health related quality of life in patients having total knee replacement and associations with symptoms, recovery, and patient education: A six month follow up study.

    Sveinsdóttir, Herdís; Kristiansen, Kolbrún; Skúladóttir, Hafdís; 1University of Iceland, Faculty of Nursing, Eirberg, Eiríksgötu 34, 101, Reykjavík, Iceland; Landspitali University Hospital, Surgical Services, 101, Reykjavík, Iceland. Electronic address: 2Landspitali University Hospital, Surgical Services, 101, Reykjavík, Iceland. 3University of Iceland, Faculty of Nursing, Eirberg, Eiríksgötu 34, 101, Reykjavík, Iceland; University of Akureyri, School of Health Sciences, Iceland. (Elsevier, 2020-11-02)
    Aim: To describe the symptoms, recovery, patient education, and health related quality of life (HRQOL) of patients having total knee replacements at three time points and to detect experiences and situations that predict HRQOL six weeks and six months post-surgery. Method: A prospective exploratory two-site study assessing 123 patients, while in hospital (T1), at six weeks (T2), and at six months (T3) post-discharge. HRQOL was measured using the SF-36v2 and symptoms were measured with the Hospital and Anxiety Scale. Two questions considered pain and two considered movement and tiredness while two questions addressed recovery and patient education. Linear regression models were used to calculate predictors of mental and physical HRQOL at T2 and T3. Results: HRQOL improved from T1 to T3. The main predictors of higher physical scores at T2 were; being older, fewer symptoms of depression and little distress related to movement. At T3 the main predictors were; having resumed work, finding patient education very useful, experiencing no pain in the last 24 h and fewer symptoms of depression. The main predictors of higher mental scores at T2 were fewer symptoms of anxiety and depression and little distress related to movement while at T3 these were fewer symptoms of anxiety and depression and experiencing no pain last 24 h. Conclusion: Apart from pain, function and resumption of activities, the symptoms of anxiety and depression influence HRQOL. These symptoms should be assessed during the hospital stay. Keywords: HRQOL; Recovery; Total knee replacement.
  • Plasma interferon-alpha is associated with double-positivity for autoantibodies but is not a predictor of remission in early rheumatoid arthritis-a spin-off study of the NORD-STAR randomized clinical trial.

    Stockfelt, Marit; Lundell, Anna-Carin; Hetland, Merete Lund; Østergaard, Mikkel; Uhlig, Till; Heiberg, Marte Schrumpf; Haavardsholm, Espen A; Nurmohamed, Michael T; Lampa, Jon; Nordström, Dan; et al. (BioMed Central, 2021-07-13)
    Background: The type I interferon (IFN) gene signature is present in a subgroup of patients with early rheumatoid arthritis (RA). Protein levels of IFNα have not been measured in RA and it is unknown whether they associate with clinical characteristics or treatment effect. Methods: Patients with early untreated RA (n = 347) were randomized to methotrexate combined with prednisone, certolizumab-pegol, abatacept, or tocilizumab. Plasma IFNα protein levels were determined by single molecular array (Simoa) before and 24 weeks after treatment initiation and were related to demographic and clinical factors including clinical disease activity index, disease activity score in 28 joints, swollen and tender joint counts, and patient global assessment. Results: IFNα protein positivity was found in 26% of the patients, and of these, 92% were double-positive for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). IFNα protein levels were reduced 24 weeks after treatment initiation, and the absolute change was similar irrespective of treatment. IFNα protein positivity was associated neither with disease activity nor with achievement of CDAI remission 24 weeks after randomization. Conclusion: IFNα protein positivity is present in a subgroup of patients with early RA and associates with double-positivity for autoantibodies but not with disease activity. Pre-treatment IFNα positivity did not predict remission in any of the treatment arms, suggesting that the IFNα system is distinct from the pathways of TNF, IL-6, and T-cell activation in early RA. A spin-off study of the NORD-STAR randomized clinical trial, NCT01491815 (ClinicalTrials), registered 12/08/2011, .

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