Recent Submissions

  • Short- and long-term mortality after deep sternal wound infection following cardiac surgery: experiences from SWEDEHEART.

    Kaspersen, Alexander Emil; Nielsen, Susanne J; Orrason, Andri Wilberg; Petursdottir, Astridur; Sigurdsson, Martin Ingi; Jeppsson, Anders; Gudbjartsson, Tomas; 1Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark. 2Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Aarhus, Denmark. 3Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden. 4Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden. 5Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden. 6Department of Cardiothoracic Surgery, Landspitali University Hospital, Reykjavik, Iceland. 7Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 8Department of Anaesthesia and Intensive Care, Landspitali University Hospital, Reykjavik, Iceland. (Oxford University Press, 2021-07)
    Objectives: Deep sternal wound infection (DSWI) is a serious complication after open-heart surgery. We investigated the association between DSWI and short- and long-term all-cause mortality in a large well-defined nationwide population. Methods: A retrospective, nationwide cohort study, which included 114676 consecutive patients who underwent coronary artery bypass grafting (CABG) and/or valve surgery from 1997 to 2015 in Sweden. Short- and long-term mortality was compared between DSWI patients and non-DSWI patients using propensity score inverse probability weighting adjustment based on patient characteristics and comorbidities. Median follow-up was 8.0 years (range 0-18.9). Results: Altogether, 1516 patients (1.3%) developed DSWI, most commonly in patients undergoing combined CABG and valve surgery (2.1%). DSWI patients were older and had more disease burden than non-DSWI patients. The unadjusted cumulative mortality was higher in the DSWI group compared with the non-DSWI group at 90 days (7.9% vs 3.0%, P < 0.001) and at 1 year (12.8% vs 4.5%, P < 0.001). The adjusted absolute difference in risk of death was 2.3% [95% confidence interval (CI): 0.8-3.9] at 90 days and 4.7% (95% CI: 2.6-6.7) at 1 year. DSWI was independently associated with 90-day [adjusted relative risk (aRR) 1.89 (95% CI: 1.38-2.59)], 1-year [aRR 2.13 (95% CI: 1.68-2.71)] and long-term all-cause mortality [adjusted hazard ratio 1.56 (95% CI: 1.30-1.88)]. Conclusions: Both short- and long-term mortality risks are higher in DSWI patients compared to non-DSWI patients. These results stress the importance of preventing these infections and careful postoperative monitoring of DSWI patients. Keywords: Cardiac surgery; Deep sternal wound infection; Incidence; Mediastinitis; Mortality.
  • Breathlessness across generations: results from the RHINESSA generation study.

    Ekström, Magnus; Johannessen, Ane; Abramson, Michael J; Benediktsdottir, Bryndis; Franklin, Karl; Gislason, Thorarinn; Gómez Real, Francisco; Holm, Mathias; Janson, Christer; Jogi, Rain; et al. (BMJ Publishing Group, 2021-06-14)
    Background: Breathlessness is a major cause of suffering and disability globally. The symptom relates to multiple factors including asthma and lung function, which are influenced by hereditary factors. No study has evaluated potential inheritance of breathlessness itself across generations. Methods: We analysed the association between breathlessness in parents and their offspring in the Respiratory Health in Northern Europe, Spain and Australia generation study. Data on parents and offspring aged ≥18 years across 10 study centres in seven countries included demographics, self-reported breathlessness, asthma, depression, smoking, physical activity level, measured Body Mass Index and spirometry. Data were analysed using multivariable logistic regression accounting for clustering within centres and between siblings. Results: A total of 1720 parents (mean age at assessment 36 years, 55% mothers) and 2476 offspring (mean 30 years, 55% daughters) were included. Breathlessness was reported by 809 (32.7%) parents and 363 (14.7%) offspring. Factors independently associated with breathlessness in parents and offspring included obesity, current smoking, asthma, depression, lower lung function and female sex. After adjusting for potential confounders, parents with breathlessness were more likely to have offspring with breathlessness, adjusted OR 1.8 (95% CI 1.1 to 2.9). The association was not modified by sex of the parent or offspring. Conclusion: Parents with breathlessness were more likely to have children who developed breathlessness, after adjusting for asthma, lung function, obesity, smoking, depression and female sex in both generations. The hereditary components of breathlessness need to be further explored. Keywords: asthma; clinical epidemiology; perception of asthma/breathlessness.
  • Evaluation of mechanism of change in transdiagnostic cognitive behaviour therapy using single case experimental design.

    Sighvatsson, Magnus Blondahl; Salkovskis, Paul M; Sigurdsson, Engilbert; Valdimarsdottir, Heiddis B; Thorsdottir, Fanney; Sigurdsson, Jon Fridrik; 1Faculty of Medicine, University of Iceland, Saemundargotu 2, 101, RVK, Iceland; Faculty of Psychology, Reykjavik University, Menntavegi 1, 101, RVK, Iceland. Electronic address: magnus.blondahl@gmail.com. 2Faculty of Psychology, Reykjavik University, Menntavegi 1, 101, RVK, Iceland; Oxford Centre for Psychological Health, Oxford Institute of Clinical Psychology Training and Oxford Cognitive Therapy Center, Warneford Hospital, Oxford University, Oxford, OX3 7JX, UK. Electronic address: paul.salkovskis@hms.ox.ac.uk. 3Faculty of Medicine, University of Iceland, Saemundargotu 2, 101, RVK, Iceland; Landspitali-The National University Hospital of Iceland, Iceland. Electronic address: engilbs@landspitali.is. 4Faculty of Psychology, Reykjavik University, Menntavegi 1, 101, RVK, Iceland; Mount Sinai School of Medicine, USA. Electronic address: heiddisb@ru.is. 5Faculty of Psychology, University of Iceland, Saemundargotu 2, 101, RVK, Iceland. Electronic address: fanneyt@hi.is. 6Faculty of Medicine, University of Iceland, Saemundargotu 2, 101, RVK, Iceland; Faculty of Psychology, Reykjavik University, Menntavegi 1, 101, RVK, Iceland. Electronic address: jonfsig@ru.is. (Elsevier, 2020-12-13)
    Background and objectives: Transdiagnostic mechanisms of change (txMOC) specific to cognitive behaviour therapy are poorly understood. Salkovskis (1996) proposed one such mechanism in terms of the shift towards an alternative, less negative view of their problems or cognitive flexibility. This hypothesis has been described as involving a shift in beliefs, from "theory A″ to "theory B". The objective of this research was to evaluate this hypothesis. Methods: Effectiveness of a novel txCBT and temporal changes in process and symptom measures were evaluated using a non-concurrent multiple baseline design and Tau-U calculations with thirteen participants (five with obsessive-compulsive disorder, two with panic disorder with agoraphobia and six with major depressive disorder). As a secondary analysis authors calculated Kendall's - Tau correlation between process and symptom measures, performed the Wilcoxon signed-rank test to assess treatment modules effect on negative thought and calculated Reliable change index (RCI). Results: The txCBT was clearly effective for eight participants. The results varied dependent on the stimuli evaluated as negative or threatening. Level and trend of the ratings of belief in theory A followed the level and trend of symptom measures to a greater extent than the (inverse) level and trend of belief in theory B. Limitations: Only thirteen participants were recruited and evaluated. Conclusions: The results are consistent with the view that effective treatment may involve a txMOC characterized by the ability to shift from a relatively fixed negative view of their experience to a less negative psychologically focused alternative. Keywords: Anxiety; Depression; Mechanism of change; Single case experimental design; Transdiagnostic cognitive behavior therapy.
  • Recovery of kidney function in patients treated with maintenance dialysis-a report from the ERA-EDTA Registry.

    Jakulj, Lily; Kramer, Anneke; Åsberg, Anders; de Meester, Johan; Santiuste de Pablos, Carmen; Helve, Jaakko; Hemmelder, Marc H; Hertig, Alexandre; Arici, Mustafa; Bell, Samira; et al. (Oxford University Press, 2021-05)
    Background: Literature on recovery of kidney function (RKF) in patients with end-stage kidney disease treated with maintenance dialysis (i.e. >90 days) is limited. We assessed the incidence of RKF and its associated characteristics in a European cohort of dialysis patients. Methods: We included adult patients from the European Renal Association-European Dialysis and Transplant Association Registry who started maintenance dialysis in 1997-2016. Sustained RKF was defined as permanent discontinuation of dialysis. Temporary discontinuation of ≥30 days (non-sustained RKF) was also evaluated. Factors associated with RKF adjusted for potential confounders were studied using Cox regression analyses. Results: RKF occurred in 7657 (1.8%) of 440 996 patients, of whom 71% experienced sustained RKF. Approximately 90% of all recoveries occurred within the first 2 years after Day 91 of dialysis. Of patients with non-sustained RKF, 39% restarted kidney replacement therapy within 1 year. Sustained RKF was strongly associated with the following underlying kidney diseases (as registered by the treating physician): tubular necrosis (irreversible) or cortical necrosis {adjusted hazard ratio [aHR] 20.4 [95% confidence interval (CI) 17.9-23.1]}, systemic sclerosis [aHR 18.5 (95% CI 13.8-24.7)] and haemolytic uremic syndrome [aHR 17.3 (95% CI 13.9-21.6)]. Weaker associations were found for haemodialysis as a first dialysis modality [aHR 1.5 (95% CI 1.4-1.6)] and dialysis initiation at an older age [aHR 1.8 (95% CI 1.6-2.0)] or in a more recent time period [aHR 2.4 (95% CI 2.1-2.7)]. Conclusions: Definitive discontinuation of maintenance dialysis is a rare and not necessarily an early event. Certain clinical characteristics, but mostly the type of underlying kidney disease, are associated with a higher likelihood of RKF.
  • 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. marco18@ru.is. 2Institute for Biomedical and Neural Engineering, Reykjavík University, Reykjavík, Iceland; Department of Electrical Engineering and Information Technology, University of Naples 'Federico II', Naples. carloricciardi.93@gmail.com. 3Institute for Biomedical and Neural Engineering, Reykjavík University, Reykjavík. kyle14@ru.is. 4Institute for Biomedical and Neural Engineering, Reykjavík University, Reykjavík. deborah20@ru.is. 5Umberto I Hospital, ASL Salerno, Nocera Inferiore. m.gambacorta@aslsalerno.it. 6Institute for Biomedical and Neural Engineering, Reykjavík University, Reykjavík, Iceland; Department of Science, Landspítali, Reykjavík. paologar@landspitali.is. (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 eat2@hi.is. 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.

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