Recent Submissions

  • 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.
  • 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: emmas@hi.is. 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: herdis@hi.is. 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, https://clinicaltrials.gov/ct2/show/NCT01491815 .
  • Supplemented ERA-EDTA Registry data evaluated the frequency of dialysis, kidney transplantation, and comprehensive conservative management for patients with kidney failure in Europe.

    Stel, Vianda S; de Jong, Rianne W; Kramer, Anneke; Andrusev, Anton M; Baltar, José M; Barbullushi, Myftar; Bell, Samira; Castro de la Nuez, Pablo; Cernevskis, Harijs; Couchoud, Cécile; et al. (Elsevier, 2021-01-07)
    The aims of this study were to determine the frequency of dialysis and kidney transplantation and to estimate the regularity of comprehensive conservative management (CCM) for patients with kidney failure in Europe. This study uses data from the ERA-EDTA Registry. Additionally, our study included supplemental data from Armenia, Germany, Hungary, Ireland, Kosovo, Luxembourg, Malta, Moldova, Montenegro, Slovenia and additional data from Israel, Italy, Slovakia using other information sources. Through an online survey, responding nephrologists estimated the frequency of CCM (i.e. planned holistic care instead of kidney replacement therapy) in 33 countries. In 2016, the overall incidence of replacement therapy for kidney failure was 132 per million population (pmp), varying from 29 (Ukraine) to 251 pmp (Greece). On 31 December 2016, the overall prevalence of kidney replacement therapy was 985 pmp, ranging from 188 (Ukraine) to 1906 pmp (Portugal). The prevalence of peritoneal dialysis (114 pmp) and home hemodialysis (28 pmp) was highest in Cyprus and Denmark respectively. The kidney transplantation rate was nearly zero in some countries and highest in Spain (64 pmp). In 28 countries with five or more responding nephrologists, the median percentage of candidates for kidney replacement therapy who were offered CCM in 2018 varied between none (Slovakia and Slovenia) and 20% (Finland) whereas the median prevalence of CCM varied between none (Slovenia) and 15% (Hungary). Thus, the substantial differences across Europe in the frequency of kidney replacement therapy and CCM indicate the need for improvement in access to various treatment options for patients with kidney failure. Keywords: hemodialysis; peritoneal dialysis; transplantation.
  • Nordic Specialist Course in Palliative Medicine: Evaluation and Impact on the Development of Palliative Medicine in the Nordic Countries: A Survey among Participants from Seven Courses 2003-2017.

    Sigurdardottir, Valgerdur; Edenbrandt, Carl-Magnus; Hirvonen, Outi; Jespersen, Bodil Abild; Haugen, Dagny Faksvåg; 1Department of Medicine, University of Iceland, Reykjavik, Iceland. 2Palliative Care Unit, Landspitali-National University Hospital, Kopavogur, Iceland. 3Department of Clinical Sciences, Lund University, Lund, Sweden. 4Palliative Care Center, Turku University Hospital, Turku, Finland. 5Department of Clinical Oncology, University of Turku, Turku, Finland. 6Palliative Care Team, Department of Oncology, Aarhus University Hospital, Aarhus, Denmark. 7Regional Centre of Excellence for Palliative Care, Western Norway, Haukeland University Hospital, Bergen, Norway. 8Department of Clinical Medicine K1, University of Bergen, Bergen, Norway. (Mary Ann Liebert, 2021-08-20)
    Background: The five Nordic Associations for palliative medicine (PM) have since 2003 organized a common specialist course for six weeks in two years. Aim: To describe the course: participants, evaluations, impact on participants' careers, and on the development of PM in the Nordic countries. Methods: Information on participants taken from the course archive and national registries. A web survey sent to graduates from the courses 2003-2013 (n = 150) and 2013-2017 (n = 72). Results: Mean age at course start was 46.9 years; 66% were women. Mean overall evaluation score 5.7 (range 5.4-6.0, max 7.0). Survey response rate 84% (n = 186); 80% of respondents were working in PM, the majority as leaders, >90% engaged in teaching PM. About 40% were active in PM associations, lobbying, and guideline development. Conclusion: The Nordic Specialist Course in PM has had a profound impact on the participants' postcourse careers, influencing the development of PM in the Nordic countries.
  • Analyzing Metabolic States of Adipogenic and Osteogenic Differentiation in Human Mesenchymal Stem Cells via Genome Scale Metabolic Model Reconstruction.

    Sigmarsdottir, Thora Bjorg; McGarrity, Sarah; Yurkovich, James T; Rolfsson, Óttar; Sigurjónsson, Ólafur Eysteinn; 1School of Science and Engineering, Reykjavík University, Reykjavík, Iceland. 2Center for Systems Biology, University of Iceland, Reykjavík, Iceland. 3Department of Bioengineering, University of California, San Diego, La Jolla, CA, United States. 4The Blood Bank, Landspitali - The National University Hospital of Iceland, Reykjavík, Iceland. (Frontiers Media, 2021-06-04)
    Since their initial discovery in 1976, mesenchymal stem cells (MSCs) have been gathering interest as a possible tool to further the development and enhancement of various therapeutics within regenerative medicine. However, our current understanding of both metabolic function and existing differences within the varying cell lineages (e.g., cells in either osteogenesis or adipogenesis) is severely lacking making it more difficult to fully realize the therapeutic potential of MSCs. Here, we reconstruct the MSC metabolic network to understand the activity of various metabolic pathways and compare their usage under different conditions and use these models to perform experimental design. We present three new genome-scale metabolic models (GEMs) each representing a different MSC lineage (proliferation, osteogenesis, and adipogenesis) that are biologically feasible and have distinctive cell lineage characteristics that can be used to explore metabolic function and increase our understanding of these phenotypes. We present the most distinctive differences between these lineages when it comes to enriched metabolic subsystems and propose a possible osteogenic enhancer. Taken together, we hope these mechanistic models will aid in the understanding and therapeutic potential of MSCs. Keywords: GEM; MSCs; adipogenesis; metabolic differences; metabolic reconstruction; osteogenesis.
  • STOPPFall (Screening Tool of Older Persons Prescriptions in older adults with high fall risk): a Delphi study by the EuGMS Task and Finish Group on Fall-Risk-Increasing Drugs.

    Seppala, Lotta J; Petrovic, Mirko; Ryg, Jesper; Bahat, Gulistan; Topinkova, Eva; Szczerbińska, Katarzyna; van der Cammen, Tischa J M; Hartikainen, Sirpa; Ilhan, Birkan; Landi, Francesco; et al. (Oxford University Press, 2021-06)
    Background: Healthcare professionals are often reluctant to deprescribe fall-risk-increasing drugs (FRIDs). Lack of knowledge and skills form a significant barrier and furthermore, there is no consensus on which medications are considered as FRIDs despite several systematic reviews. To support clinicians in the management of FRIDs and to facilitate the deprescribing process, STOPPFall (Screening Tool of Older Persons Prescriptions in older adults with high fall risk) and a deprescribing tool were developed by a European expert group. Methods: STOPPFall was created by two facilitators based on evidence from recent meta-analyses and national fall prevention guidelines in Europe. Twenty-four panellists chose their level of agreement on a Likert scale with the items in the STOPPFall in three Delphi panel rounds. A threshold of 70% was selected for consensus a priori. The panellists were asked whether some agents are more fall-risk-increasing than others within the same pharmacological class. In an additional questionnaire, panellists were asked in which cases deprescribing of FRIDs should be considered and how it should be performed. Results: The panellists agreed on 14 medication classes to be included in the STOPPFall. They were mostly psychotropic medications. The panellists indicated 18 differences between pharmacological subclasses with regard to fall-risk-increasing properties. Practical deprescribing guidance was developed for STOPPFall medication classes. Conclusion: STOPPFall was created using an expert Delphi consensus process and combined with a practical deprescribing tool designed to optimise medication review. The effectiveness of these tools in falls prevention should be further evaluated in intervention studies. Keywords: accidental falls; adverse effects; aged; deprescribing; fall-risk-increasing drugs; older people.
  • Family caregivers' experiences of end-of-life care in the acute hospital setting. A qualitative study.

    Robertson, Svala Berglind; Hjörleifsdóttir, Elísabet; Sigurðardóttir, Þórhalla; 1Palliative Home-Care Unit, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland. 2Department of Nursing, University of Akureyri, Akureyri, Iceland. 3Department of Accident and Emergency, Akureyri Regional Hospital, Akureyri, Iceland. (Wiley, 2021-08-12)
    Background: Acute hospital settings are generally not considered adequate places for end-of-life care, but terminally ill patients will continue to die in acute medical wards in the unforeseeable future. Aim: The aim of this study was to investigate family caregivers' experiences of end-of-life care in an acute community hospital in Iceland. Methods: Fifteen in-depth qualitative semi-structured interviews were conducted with participants who had been primary caregivers. The transcribed interviews were analysed using thematic content analysis. Findings: Findings indicated that the acute hospital setting is not a suitable environment for end-of-life care. Effective communication and management of symptoms characterised by warmth and security give a sense of resilience. Three main themes emerged: (1) Environmental influences on quality of care; (2) Communication in end-of-life care; (3) The dying process. Each of the themes encompassed a variety of subthemes. Conclusions: Findings suggest that effective communication is the cornerstone of quality of care in the acute hospital environment and essential for establishing a sense of security. The severity of symptoms can deeply affect family caregivers' well-being. Acknowledging and appreciating the meaning of respect and dignity at the end-of-life from family caregivers' perspective is vital. Keywords: acute hospital settings; bereavement; communication; end-of-life care; environment; family caregivers; grief; palliative care.
  • Illness severity and risk of mental morbidities among patients recovering from COVID-19: a cross-sectional study in the Icelandic population.

    Saevarsdóttir, Karen Sól; Hilmarsdóttir, Hildur Ýr; Magnúsdóttir, Ingibjörg; Hauksdóttir, Arna; Thordardottir, Edda Bjork; Gudjónsdóttir, Ásdís Braga; Tomasson, Gunnar; Rúnarsdóttir, Harpa; Jónsdóttir, Harpa Lind; Gudmundsdóttir, Berglind; et al. (BMJ Publishing Group, 2021-07-23)
    Objective: To test if patients recovering from COVID-19 are at increased risk of mental morbidities and to what extent such risk is exacerbated by illness severity. Design: Population-based cross-sectional study. Setting: Iceland. Participants: A total of 22 861 individuals were recruited through invitations to existing nationwide cohorts and a social media campaign from 24 April to 22 July 2020, of which 373 were patients recovering from COVID-19. Main outcome measures: Symptoms of depression (Patient Health Questionnaire), anxiety (General Anxiety Disorder Scale) and posttraumatic stress disorder (PTSD; modified Primary Care PTSD Screen for DSM-5) above screening thresholds. Adjusting for multiple covariates and comorbidities, multivariable Poisson regression was used to assess the association between COVID-19 severity and mental morbidities. Results: Compared with individuals without a diagnosis of COVID-19, patients recovering from COVID-19 had increased risk of depression (22.1% vs 16.2%; adjusted relative risk (aRR) 1.48, 95% CI 1.20 to 1.82) and PTSD (19.5% vs 15.6%; aRR 1.38, 95% CI 1.09 to 1.75) but not anxiety (13.1% vs 11.3%; aRR 1.24, 95% CI 0.93 to 1.64). Elevated relative risks were limited to patients recovering from COVID-19 that were 40 years or older and were particularly high among individuals with university education. Among patients recovering from COVID-19, symptoms of depression were particularly common among those in the highest, compared with the lowest tertile of influenza-like symptom burden (47.1% vs 5.8%; aRR 6.42, 95% CI 2.77 to 14.87), among patients confined to bed for 7 days or longer compared with those never confined to bed (33.3% vs 10.9%; aRR 3.67, 95% CI 1.97 to 6.86) and among patients hospitalised for COVID-19 compared with those never admitted to hospital (48.1% vs 19.9%; aRR 2.72, 95% CI 1.67 to 4.44). Conclusions: Severe disease course is associated with increased risk of depression and PTSD among patients recovering from COVID-19. Keywords: COVID-19; epidemiology; mental health; public health.
  • Risk of digestive cancers in a cohort of 69 460 five-year survivors of childhood cancer in Europe: the PanCareSurFup study.

    Reulen, Raoul C; Wong, Kwok F; Bright, Chloe J; Winter, David L; Alessi, Daniela; Allodji, Rodrigue M; Bagnasco, Francesca; Bárdi, Edit; Bautz, Andrea; Byrne, Julianne; et al. (BMJ Publishing Group, 2020-11-02)
    Background: Survivors of childhood cancer are at risk of subsequent primary neoplasms (SPNs), but the risk of developing specific digestive SPNs beyond age 40 years remains uncertain. We investigated risks of specific digestive SPNs within the largest available cohort worldwide. Methods: The PanCareSurFup cohort includes 69 460 five-year survivors of childhood cancer from 12 countries in Europe. Risks of digestive SPNs were quantified using standardised incidence ratios (SIRs), absolute excess risks and cumulative incidence. Results: 427 digestive SPNs (214 colorectal, 62 liver, 48 stomach, 44 pancreas, 59 other) were diagnosed in 413 survivors. Wilms tumour (WT) and Hodgkin lymphoma (HL) survivors were at greatest risk (SIR 12.1; 95% CI 9.6 to 15.1; SIR 7.3; 95% CI 5.9 to 9.0, respectively). The cumulative incidence increased the most steeply with increasing age for WT survivors, reaching 7.4% by age 55% and 9.6% by age 60 years (1.0% expected based on general population rates). Regarding colorectal SPNs, WT and HL survivors were at greatest risk; both seven times that expected. By age 55 years, 2.3% of both WT (95% CI 1.4 to 3.9) and HL (95% CI 1.6 to 3.2) survivors had developed a colorectal SPN-comparable to the risk among members of the general population with at least two first-degree relatives affected. Conclusions: Colonoscopy surveillance before age 55 is recommended in many European countries for individuals with a family history of colorectal cancer, but not for WT and HL survivors despite a comparable risk profile. Clinically, serious consideration should be given to the implementation of colonoscopy surveillance while further evaluation of its benefits, harms and cost-effectiveness in WT and HL survivors is undertaken. Keywords: CANCER EPIDEMIOLOGY; COLORECTAL CANCER; COLORECTAL CANCER SCREENING; GASTROINTESTINAL CANCER.
  • Clinical practice guideline on the management of septic shock and sepsis-associated organ dysfunction in children: Endorsement by the Scandinavian Society of Anaesthesiology and Intensive Care Medicine.

    Rehn, Marius; Chew, Michelle S; Olkkola, Klaus T; Sigurðsson, Martin Ingi; Yli-Hankala, Arvi; Møller, Morten Hylander; 1Pre-hospital Division, Air Ambulance Department, Oslo University Hospital, Oslo, Norway. 2The Norwegian Air Ambulance Foundation, Drøbak, Norway. 3Faculty of Health Sciences, University of Stavanger, Stavanger, Norway. 4Department of Anaesthesia and Intensive Care, Medicine and Health, Linköping University, Linkoping, Sweden. 5Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. 6Department of Anaesthesia and Intensive Care Medicine, Landspitali University Hospital, Reykjavík, Iceland. 7Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 8Department of Anaesthesia, Tampere University Hospital, Tampere, Finland. 9Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland. 10Department of Intensive Care, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. 11Collaboration for Research in Intensive Care (CRIC), Copenhagen, Denmark. (Wiley, 2021-08-04)
    The Clinical Practice Committee of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine endorses the clinical practice guideline Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children. The guideline can serve as a useful decision aid for clinicians managing children with suspected and confirmed septic shock and sepsis-associated organ dysfunction. Keywords: AGREE II; children; clinical practice guideline; paediatrics; sepsis; septic shock.
  • Correction to: Current evidence on the impact of medication optimization or pharmacological interventions on frailty or aspects of frailty: a systematic review of randomized controlled trials.

    Pazan, Farhad; Petrovic, Mirko; Cherubini, Antonio; Onder, Graziano; Cruz-Jentoft, Alfonso J; Denkinger, Michael; van der Cammen, Tischa J M; Stevenson, Jennifer M; Ibrahim, Kinda; Rajkumar, Chakravarthi; et al. (Springer, 2021-11)
  • Current evidence on the impact of medication optimization or pharmacological interventions on frailty or aspects of frailty: a systematic review of randomized controlled trials.

    Pazan, Farhad; Petrovic, Mirko; Cherubini, Antonio; Onder, Graziano; Cruz-Jentoft, Alfonso J; Denkinger, Michael; van der Cammen, Tischa J M; Stevenson, Jennifer M; Ibrahim, Kinda; Rajkumar, Chakravarthi; et al. (Springer, 2020-08-07)
    Background: Frailty and adverse drug effects are linked in the fact that polypharmacy is correlated with the severity of frailty; however, a causal relation has not been proven in older people with clinically manifest frailty. Methods: A literature search was performed in Medline to detect prospective randomized controlled trials (RCTs) testing the effects of pharmacological interventions or medication optimization in older frail adults on comprehensive frailty scores or partial aspects of frailty that were published from January 1998 to October 2019. Results: Twenty-five studies were identified, 4 on comprehensive frailty scores and 21 on aspects of frailty. Two trials on comprehensive frailty scores showed positive results on frailty although the contribution of medication review in a multidimensional approach was unclear. In the studies on aspects related to frailty, ten individual drug interventions showed improvement in physical performance, muscle strength or body composition utilizing alfacalcidol, teriparatide, piroxicam, testosterone, recombinant human chorionic gonadotropin, or capromorelin. There were no studies examining negative effects of drugs on frailty. Conclusion: So far, data on a causal relationship between drugs and frailty are inconclusive or related to single-drug interventions on partial aspects of frailty. There is a clear need for RCTs on this topic that should be based on a comprehensive, internationally consistent and thus reproducible concept of frailty assessment. Keywords: Frailty; Inappropriate drug treatment; Medication optimization; Older people; Polypharmacy; Prefrailty.
  • Correction to: Longitudinal Assessment of Chlorpyrifos Exposure in Farmers and Residents of an Italian Alpine Region (Exposure and Health, (2021), 10.1007/s12403-021-00409-5)

    Paglia, Giuseppe; Del Greco, Fabiola M.; Carli, Cristoph; Sigurdsson, Baldur B.; Smarason, Sigurdur; Wegher, Mario; Pattaro, Cristian; Wegher, Lino; a School of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy b Institute for Biomedicine, Eurac Research, Bolzano, Italy c Südtiroler Sanitätsbetrieb, Azienda Sanitaria DellAlto Adige, Bolzano, Italy d Department of Clinical Biochemistry, Landspitali - University Hospital of Iceland, Reykjavik, Iceland e Center Agriculture Food Environment (C3A), University of Trento, Trento, Italy (Springer Science and Business Media B.V., 2021-01-01)
    The aim of this study was to obtain a longitudinal evaluation of the exposure to chlorpyrifos (CP) and chlorpyrifos-methyl (CPM) in agricultural workers in South Tyrol and in a residential group living in the same area. CP and CPM are widely used pesticides in agriculture. Biological monitoring of CP and CPM exposure in humans can be achieved by analyzing urinary levels of 3,5,6-trichloro-2-pyridinol (TCPy). TCPy a metabolite of CP and CPM which is produced by a two-step metabolic transformation. Between May 14th, 2014 and March 16th, 2015 we conducted a longitudinal study on 28 farmers actively working in spray pesticide treatment and 43 non-farmers living in the same agricultural area of South Tyrol (Italy). Urine samples were collected at two time points: during the pesticide treatment period and in a temporally distant season that should guarantee metabolite clearance. We developed and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of urinary TCPy levels. During the treatment season, both farmers and residents showed higher TCPy levels (median = 6.8 and 6.73 ug/g creatinine, respectively) than during the non-treatment season (median = 2.54 and 3.22 ug/g creatinine, respectively), suggesting a similar effect of the pesticide spraying on both groups. However, the observed TCPy levels resulted in a daily CP and CPM intake well below the limits recommended by FAO/WHO. During the non-treatment season, non-farmers showed higher TCPy levels values than farmers, suggesting the existence of TCPy of other unmeasured sources of exposure not considered in this study. This suggests that, for a comprehensive evaluation of the risks associated with TCPy exposure, additional sources should be identified in addition to CP and CPM pesticides.
  • Children may need higher vancomycin doses to achieve therapeutic levels.

    Oskarsdottir, Kristin; Haraldsson, Asgeir; Thorkelsson, Thordur; Oskarsdottir, Thorunn; Gunnarsson, Petur; Thors, Valtyr; 1Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 2Children's Hospital Iceland, Landspitali University Hospital, Reykjavik, Iceland. 3Pharmacy department, Landspitali University Hospital, Reykjavik, Iceland. 4Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik, Iceland. (Wiley, 2021-07-14)
    Aim: Vancomycin is frequently used in paediatric hospitals. Data suggest trough levels of 10-20 mg/L are needed to achieve bacterial killing. This study aimed to evaluate if commonly used dosing regimens are efficient in reaching these levels and if therapeutic drug monitoring (TDM) was appropriately used. Methods: All children receiving intravenous vancomycin at the Children´s Hospital Iceland between 2012 and 2016 were included. Vancomycin trough levels were registered. Student t test, Wilcoxon test and regression models were used for statistical analysis. Results: A total of 105 children received 163 vancomycin treatments (55/105 neonates). Average daily dose in neonates was 23.4 mg/kg/day and 38.4 mg/kg/day for older children. No TDM was done in 58 treatments (35.6%). First trough levels were <10mg/L in 52.4% and <15mg/L in 92% of cases. Therapeutic levels were less likely achieved in children with malignancy (11.8%) compared with others (36.8%, p = 0.09). Conclusions: In more than half of the cases, trough drug levels were <10 mg/L and malignancy was associated with the lowest probability of reaching therapeutic levels. This study suggests that starting doses of vancomycin in children should be higher, especially in relation to malignant diseases and supports the importance of antibiotic stewardship to ensure optimal antibiotic use. Keywords: children; empiric treatment; malignancy; therapeutic drug monitoring; vancomycin.

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