• 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.
    • 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)
    • 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.
    • 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.
    • Low Risk of Central Line-associated Bloodstream Infections in Pediatric Hematology/Oncology Patients.

      Kristinsdottir, Iris; Haraldsson, Asgeir; Gudlaugsson, Olafur; Thors, Valtyr; 1)From the Faculty of Medicine, University of Iceland. 2)Children's Hospital Iceland. 3)Division of Infection Control, Landspitali-University Hospital of Iceland. (Williams & Wilkins, 2021-10)
      Background: Central venous lines (CVLs) are essential for standard care of pediatric hematology/oncology patients providing safe administration of cytotoxic drugs and pain-free blood sampling. Central line-associated bloodstream infections (CLABSIs) cause significant morbidity. This study describes the epidemiology, microbiology, and risk factors for CLABSI in all children with malignancies in Iceland. Methods: All children that were diagnosed with malignancy in Iceland and received a CVL during 2008-2017 were included in the study. Characteristics of CVLs and patients were registered, information on risk factors, and microbiology was collected. International standards were used for CLABSI definition. Results: One hundred forty-three CVLs were placed in 94 children. Acute lymphoblastic leukemia was the most common underlying disease (31/94). Median age was 7 years. Implantable ports were the most commonly placed CVLs (82/143, 57%), tunneled lines were 39 (27%). Overall CLABSI rate was 0.24 infections/1000 line-days (14 episodes in 58,830 line-days), with little fluctuations. No CLABSI episodes occurred for 4 consecutive years (2012-2015). Staphylococci (of which 7 Staphylococcus aureus) were the cause of 10/14 episodes. Nine CLABSI episodes led to line removal, but no deaths were linked to CLABSIs. Conclusion: We report very low CLABSI rates over a 9-year period at our hospital, with 4 consecutive CLABSI-free years. Even with the addition of episodes of possible CLABSI, rates were still very low and lower than most published reports.
    • Comparison of Respiratory Support After Delivery in Infants Born Before 28 Weeks' Gestational Age: The CORSAD Randomized Clinical Trial.

      Donaldsson, Snorri; Drevhammar, Thomas; Li, Yinghua; Bartocci, Marco; Rettedal, Siren Irene; Lundberg, Fredrik; Odelberg-Johnson, Per; Szczapa, Tomasz; Thordarson, Thordur; Pilypiene, Ingrida; et al. (American Medical Association, 2021-09)
      Importance: Establishing stable breathing is a key event for preterm infants after birth. Delivery of pressure-stable continuous positive airway pressure and avoiding face mask use could be of importance in the delivery room. Objective: To determine whether using a new respiratory support system with low imposed work of breathing and short binasal prongs decreases delivery room intubations or death compared with a standard T-piece system with a face mask. Design, setting, and participants: In this unblinded randomized clinical trial, mothers threatening preterm delivery before week 28 of gestation were screened. A total of 365 mothers were enrolled, and 250 infants were randomized before birth and 246 liveborn infants were treated. The trial was conducted in 7 neonatal intensive care units in 5 European countries from March 2016 to May 2020. The follow-up period was 72 hours after intervention. Interventions: Infants were randomized to either the new respiratory support system with short binasal prongs (n = 124 infants) or the standard T-piece system with face mask (n = 122 infants). The intervention was providing continuous positive airway pressure for 10 to 30 minutes and positive pressure ventilation, if needed, with the randomized system. Main outcomes and measures: The primary outcome was delivery room intubation or death within 30 minutes of birth. Secondary outcomes included respiratory and safety variables. Results: Of 246 liveborn infants treated, the mean (SD) gestational age was 25.9 (1.3) weeks, and 127 (51.6%) were female. A total of 41 infants (33.1%) receiving the new respiratory support system were intubated or died in the delivery room compared with 55 infants (45.1%) receiving standard care. The adjusted odds ratio was statistically significant after adjusting for stratification variables (adjusted odds ratio, 0.53; 95% CI, 0.30-0.94; P = .03). No significant differences were seen in secondary outcomes or safety variables. Conclusions and relevance: In this study, using the new respiratory support system reduced delivery room intubation in extremely preterm infants. Stabilizing preterm infants with a system that has low imposed work of breathing and binasal prongs as interface is safe and feasible.
    • Sequence variants in malignant hyperthermia genes in Iceland: classification and actionable findings in a population database.

      Fridriksdottir, Run; Jonsson, Arnar J; Jensson, Brynjar O; Sverrisson, Kristinn O; Arnadottir, Gudny A; Skarphedinsdottir, Sigurbjorg J; Katrinardottir, Hildigunnur; Snaebjornsdottir, Steinunn; Jonsson, Hakon; Eiriksson, Ogmundur; et al. (Nature Publishing Group, 2021-08-31)
      Malignant hyperthermia (MH) susceptibility is a rare life-threatening disorder that occurs upon exposure to a triggering agent. MH is commonly due to protein-altering variants in RYR1 and CACNA1S. The American College of Medical Genetics and Genomics recommends that when pathogenic and likely pathogenic variants in RYR1 and CACNA1S are incidentally found, they should be reported to the carriers. The detection of actionable variants allows the avoidance of exposure to triggering agents during anesthesia. First, we report a 10-year-old Icelandic proband with a suspected MH event, harboring a heterozygous missense variant NM_000540.2:c.6710G>A r.(6710g>a) p.(Cys2237Tyr) in the RYR1 gene that is likely pathogenic. The variant is private to four individuals within a three-generation family and absent from 62,240 whole-genome sequenced (WGS) Icelanders. Haplotype sharing and WGS revealed that the variant occurred as a somatic mosaicism also present in germline of the proband's paternal grandmother. Second, using a set of 62,240 Icelanders with WGS, we assessed the carrier frequency of actionable pathogenic and likely pathogenic variants in RYR1 and CACNA1S. We observed 13 actionable variants in RYR1, based on ClinVar classifications, carried by 43 Icelanders, and no actionable variant in CACNA1S. One in 1450 Icelanders carries an actionable variant for MH. Extensive sequencing allows for better classification and precise dating of variants, and WGS of a large fraction of the population has led to incidental findings of actionable MH genotypes.
    • Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations.

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

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

      Kristinsdottir, Iris; Haraldsson, Asgeir; Löve, Arthur; Asgeirsdottir, Tinna Laufey; Thors, Valtyr; 1Faculty of Medicine, University of Iceland, Reykjavik, Iceland; Children's Hospital Iceland, Landspitali University Hospital, Reykjavik, Iceland. 2Faculty of Medicine, University of Iceland, Reykjavik, Iceland; Department of Clinical Microbiology, Division of Virology, Landspitali University Hospital, Reykjavik, Iceland. 3Faculty of Economics, University of Iceland, Reykjavik, Iceland. 4Faculty of Medicine, University of Iceland, Reykjavik, Iceland; Children's Hospital Iceland, Landspitali University Hospital, Reykjavik, Iceland. Electronic address: valtyr@landspitali.is. (Elsevier, 2021-08-09)
      Background: Acute gastroenteritis poses a significant burden on young children, families, health care facilities and societies. Rotavirus is the most common pathogen, but rotavirus infections are vaccine preventable. Information on the epidemiology of gastroenteritis in Icelandic children has until now not been available and rotavirus vaccination is currently not offered to Icelandic infants. The objective of this study was to assess the burden of rotavirus acute gastroenteritis in young children in Iceland and determine the potential benefit of adding rotavirus vaccine to the Icelandic childhood immunization schedule. Methods: For a two-year period, children < 6 years old attending a children's emergency department for acute gastroenteritis were recruited at the Children's Hospital in Reykjavík, Iceland. Demographic information and Vesikari scores were registered. Stool samples were analyzed for pathogens. Duration of symptoms, treatment given, and secondary household infections were among the collected information. Annual cost of the infections in young children was estimated based on health care expenditures and lost days of parental work. Results: 325 children were included in the study, 75% of which were ≤ 24 months old. A pathogen was identified in 80% of cases, of which rotavirus was identified in 54%. Rotavirus caused a more severe disease than other pathogens, more often leading to fluid treatment in the emergency department and admissions. Median duration of rotavirus-illness was six days and caused a median of four days lost from work by parents. The estimated annual cost of rotavirus acute gastroenteritis was €2.9 million. Conclusions: Rotavirus causes significant disease burden in young children. Although rarely life-threatening in high income countries, the costs for society are substantial. The inclusion of rotavirus vaccine in the national immunization schedule will reduce the disease burden and would be cost-saving in Iceland.
    • Evaluation of a Novel Teleradiology Technology for Image-Based Distant Consultations: Applications in Neurosurgery.

      Cewe, Paulina; Burström, Gustav; Drnasin, Ivan; Ohlsson, Marcus; Skulason, Halldor; Vucica, Stanislav; Elmi-Terander, Adrian; Edström, Erik; 1Department of Trauma and Musculoskeletal Radiology, Karolinska University Hospital, 171 64 Stockholm, Sweden. 2Department of Clinical Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden. 3Department of Neurosurgery, Karolinska University Hospital, 171 64 Stockholm, Sweden. 4Image Over Globe, 21000 Split, Croatia. 5Department of Neuroradiology, Karolinska University Hospital, 171 64 Stockholm, Sweden. 6Department of Neurosurgery, Landspitali University Hospital, 101 Reykjavik, Iceland. (MDPI, 2021-08-04)
      In emergency settings, fast access to medical imaging for diagnostic is pivotal for clinical decision making. Hence, a need has emerged for solutions that allow rapid access to images on small mobile devices (SMD) without local data storage. Our objective was to evaluate access times to full quality anonymized DICOM datasets, comparing standard access through an authorized hospital computer (AHC) to a zero-footprint teleradiology technology (ZTT) used on a personal computer (PC) or SMD using national and international networks at a regional neurosurgical center. Image datasets were sent to a senior neurosurgeon, outside the hospital network using either an AHC and a VPN connection or a ZTT (Image Over Globe (IOG)), on a PC or an SMD. Time to access DICOM images was measured using both solutions. The mean time using AHC and VPN was 250 ± 10 s (median 249 s (233-274)) while the same procedure using IOG took 50 ± 8 s (median 49 s (42-60)) on a PC and 47 ± 20 s (median 39 (33-88)) on a SMD. Similarly, an international consultation was performed requiring 23 ± 5 s (median 21 (16-33)) and 27 ± 1 s (median 27 (25-29)) for PC and SMD respectively. IOG is a secure, rapid and easy to use telemedicine technology facilitating efficient clinical decision making and remote consultations. Keywords: clinical decision-making; neurosurgery; remote consultation; telemedicine; teleradiology.
    • 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.
    • 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.
    • Changes in obstetric interventions and preterm birth during COVID-19: A nationwide study from Iceland.

      Einarsdóttir, Kristjana; Swift, Emma Marie; Zoega, Helga; 1Center of Public Health Sciences, Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 2Faculty of Nursing/Department of Midwifery, University of Iceland, Reykjavík, Iceland. 3Women's Clinic, Landspitali National University Hospital of Iceland, Reykjavik, Iceland. 4Centre for Big Data Research in Health, Faculty of Medicine, University of New South Wales Sydney, Sydney, Australia. (Wiley, 2021-07-28)
      Introduction: Previous evidence has been conflicting regarding the effect of coronavirus disease 2019 (COVID-19) pandemic lockdowns on obstetric intervention and preterm birth rates. The literature to date suggests potentially differential underlying mechanisms based on country economic setting. We aimed to study these outcomes in an Icelandic population where uniform lockdown measures were implemented across the country. Material and methods: The study included all singleton births (n = 20 680) during 2016-2020 identified from the population-based Icelandic Medical Birth Register. We defined two lockdown periods during March-May and October-December in 2020 according to government implemented nationwide lockdown. We compared monthly rates of cesarean section, induction of labor and preterm birth during lockdown with the same time periods in the 4 previous years (2016-2019) using logit binomial regression adjusted for confounders. Results: Our results indicated a reduction in the overall cesarean section rate, which was mainly evident for elective cesarean section, both during the first (adjusted odd ratio [aOR] 0.71, 95% CI 0.51-0.99) and second (aOR 0.72, 95% CI 0.52-0.99) lockdown periods, and not for emergency cesarean section. No change during lockdown was observed in induction of labor. Our results also suggested a reduction in the overall preterm birth rate during the first lockdown (aOR 0.69, 95% CI 0.49-0.97) and in the months immediately following the lockdown (June-September) (aOR 0.67, 95% CI 0.49-0.89). The reduction during the first lockdown was mainly evident for medically indicated preterm birth (although not statistically significant) and the reduction during June-September was mainly evident for spontaneous preterm birth. Conclusions: This study suggested a reduction in elective cesarean section during COVID-19 lockdown, possibly reflecting changes in prioritization of non-urgent health care during lockdown. We also found a reduction in overall preterm birth during the first lockdown and spontaneous preterm birth following the first lockdown, but further research is needed to shed light on the underlying mechanisms for these findings. Keywords: COVID-19; cesarean section; induction of labor; lockdown; preterm birth.
    • Cyclodextrin-based formulation of carbonic anhydrase inhibitors for ocular delivery - A review.

      Jansook, Phatsawee; Hnin, Hay Marn; Loftsson, Thorsteinn; Stefánsson, Einar; 1Faculty of Pharmaceutical Sciences, Chulalongkorn University, 254 Phyathai Road, Pathumwan, Bangkok 10330, Thailand. Electronic address: phatsawee.j@chula.ac.th. 2Faculty of Pharmaceutical Sciences, Chulalongkorn University, 254 Phyathai Road, Pathumwan, Bangkok 10330, Thailand. 3Faculty of Pharmaceutical Sciences, University of Iceland, Hofsvallagata 53, IS-107 Reykjavik, Iceland. 4Department of Ophthalmology, Faculty of Medicine, National University Hospital, University of Iceland, Landspitalinn, IS-101 Reykjavik, Iceland. (Elsevier, 2021-07-28)
      Carbonic anhydrase inhibitors (CAIs) are used as systemic and topical agents for lowering intraocular pressure (IOP) in patients with glaucoma. Owing to the wide distribution of CAs and their physiological functions in various tissues, systemic administration of CAIs may lead to unwanted side effects. Thus, exploration of drugs targeting the specific CA isoenzyme in ocular tissues and application of the same as topical eye drops would be desirable. However, the anatomical and physiological barriers of the eyes can limit drug availability at the site. The very low aqueous solubility of CAI agents can further hamper drug bioavailability, consequently resulting in insufficient therapeutic efficacy. Solubilization of drugs using cyclodextrin (CD) complexes can enhance both solubility and permeability of the drugs. The use of CD for such purposes and development and testing of topical CAI eye drops containing CD have been discussed in detail. Further, pharmaceutical nanotechnology platforms were discussed in terms of investigation of their IOP-lowering efficacies. Future prospects in drug discovery and the use of CD nanoparticles and CD-based nanocarriers to develop potential topical CAI formulations have also been described here. Keywords: Carbonic anhydrase inhibitor; Cyclodextrin; Glaucoma; Intraocular pressure; Nanocarrier; Solubilization.
    • 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.
    • Distinction between the effects of parental and fetal genomes on fetal growth.

      Juliusdottir, Thorhildur; Steinthorsdottir, Valgerdur; Stefansdottir, Lilja; Sveinbjornsson, Gardar; Ivarsdottir, Erna V; Thorolfsdottir, Rosa B; Sigurdsson, Jon K; Tragante, Vinicius; Hjorleifsson, Kristjan E; Helgadottir, Anna; et al. (Nature Publishing Group, 2021-07-19)
      Birth weight is a common measure of fetal growth that is associated with a range of health outcomes. It is directly affected by the fetal genome and indirectly by the maternal genome. We performed genome-wide association studies on birth weight in the genomes of the child and parents and further analyzed birth length and ponderal index, yielding a total of 243 fetal growth variants. We clustered those variants based on the effects of transmitted and nontransmitted alleles on birth weight. Out of 141 clustered variants, 22 were consistent with parent-of-origin-specific effects. We further used haplotype-specific polygenic risk scores to directly test the relationship between adult traits and birth weight. Our results indicate that the maternal genome contributes to increased birth weight through blood-glucose-raising alleles while blood-pressure-raising alleles reduce birth weight largely through the fetal genome.