Recent Submissions

  • Association of Social Determinants of Health with Time to Diagnosis and Treatment Outcomes in Idiopathic Subglottic Stenosis.

    Lee, Jaclyn; Huang, Li-Ching; Berry, Lynn D; Anderson, Catherine; Amin, Milan R; Benninger, Michael S; Blumin, Joel H; Bock, Jonathan M; Bryson, Paul C; Castellanos, Paul F; et al. (SAGE Publications, 2021-02-25)
    Objectives: To examine whether social determinants of health (SDH) factors are associated with time to diagnosis, treatment selection, and time to recurrent surgical intervention in idiopathic subglottic stenosis (iSGS) patients. Methods: Adult patients with diagnosed iSGS were recruited prospectively (2015-2017) via clinical providers as part of the North American Airway Collaborative (NoAAC) and via an online iSGS support community on Facebook. Patient-specific SDH factors included highest educational attainment (self-reported), median household income (matched from home zip code via U.S. Census data), and number of close friends (self-reported) as a measure of social support. Main outcomes of interest were time to disease diagnosis (years from symptom onset), treatment selection (endoscopic dilation [ED] vs cricotracheal resection [CTR] vs endoscopic resection with adjuvant medical therapy [ERMT]), and time to recurrent surgical intervention (number of days from initial surgical procedure) as a surrogate for disease recurrence. Results: The total 810 participants were 98.5% female, 97.2% Caucasian, and had a median age of 50 years (IQR, 43-58). The cohort had a median household income of $62 307 (IQR, $50 345-$79 773), a median of 7 close friends (IQR, 4-10), and 64.7% of patients completed college or graduate school. Education, income, and number of friends were not associated with time to diagnosis via multivariable linear regression modeling. Univariable multinominal logistic regression demonstrated an association between education and income for selecting ED versus ERMT, but no associations were noted for CTR. No associations were noted for time to recurrent surgical procedure via Kaplan Meier modeling and Cox proportional hazards regression. Conclusions: Patient education, income, and social support were not associated with time to diagnosis or time to disease recurrence. This suggests additional patient, procedure, or disease-specific factors contribute to the observed variations in iSGS surgical outcomes.
  • 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: (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.
  • Comparison of EEG Signal Characteristics between Polysomnography and Self Applied Somnography Setup in a Pediatric Cohort

    Kainulainen, Samu; Korkalainen, Henri; Sigurdardottir, Sigriur; Myllymaa, Sami; Serwatko, Marta; Sigurdardottir, Sigurveig Pora; Clausen, Michael; Leppanen, Timo; Arnardottir, Erna Sif; 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 Technology, Reykjavik University Sleep Institute, Reykjavik University, Reykjavik, 102, Iceland d Department of Immunology, Landspitali University Hospital, Reykjavik, 101, Iceland e Faculty of Medicine, University of Iceland, Reykjavik, 108, Iceland f Children's Hospital Reykjavik, Reykjavik, 101, Iceland g Department of Allergy, Landspitali University Hospital, Reykjavik, 101, Iceland h Internal Medicine Services, Landspitali-The National University Hospital of Iceland, Reykjavik, 101, Iceland i Internal Medicine Services, Landspitali-The National University Hospital of Iceland, Reykjavik, 101, Iceland (Institute of Electrical and Electronics Engineers Inc., 2021-01-01)
    We aimed to investigate differences in the electroencephalography (EEG) signal characteristics recorded with a type II polysomnography (PSG) setup including the American Academy of Sleep Medicine recommended EEG montage and Self Applied Somnography (SAS) setup. The PSG and SAS monitoring were simultaneously performed in a pediatric cohort ( n=111 ) with Nox A1 equipment (Nox Medical, Reykjavik, Iceland). The PSG channels F4-M1 and F3-M2 were compared to the SAS channels AF4-E3E4 and AF3-E3E4. The analyses were conducted separately in each sleep stage. The amplitude levels were compared by investigating envelope curves of each epoch and the frequency content by investigating the power spectrums obtained with Welch's method. The EEG spectral morphology was similar between SAS and PSG. However, the SAS had consistently lower median amplitudes in all sleep stages compared to the PSG. In Stage N3 (slow-wave sleep), the lower and upper envelope curves had 42.4-47.4% lower median absolute amplitudes. Similarly, the SAS channels had consistently less power in the whole analysed frequency range of 0.3-35 Hz. In conclusion, the results illustrate that the SAS signals have similar EEG spectral morphology but consistently lower amplitudes and less power across the whole EEG frequency range compared to PSG signals. To achieve scoring corresponding to PSG, either the raw SAS signals should be digitally preprocessed or the amplitude threshold for identifying N3 should be lowered from 75μ V to e.g. 45μ V when using SAS instead of PSG. Further clinical validation studies are required to demonstrate scoring reliability using modified scoring rules.
  • The predictive ability of the 313 variant-based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant.

    Lakeman, Inge M M; van den Broek, Alexandra J; Vos, Juliën A M; Barnes, Daniel R; Adlard, Julian; Andrulis, Irene L; Arason, Adalgeir; Arnold, Norbert; Arun, Banu K; Balmaña, Judith; et al. (Nature Publishing Group, 2021-06-10)
    Purpose: To evaluate the association between a previously published 313 variant-based breast cancer (BC) polygenic risk score (PRS313) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes. Methods: We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS313 and CBC risk. Results: For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS313 showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06-1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS313, HR = 1.15, 95% CI (1.07-1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC < age 40 years, the cumulative PRS313 5th and 95th percentile 10-year CBC risks were 22% and 32% for BRCA1 and 13% and 23% for BRCA2 heterozygotes, respectively. Conclusion: The PRS313 can be used to refine individual CBC risks for BRCA1/2 heterozygotes of European ancestry, however the PRS313 needs to be considered in the context of a multifactorial risk model to evaluate whether it might influence clinical decision-making.
  • 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.
  • DNA Methylation Signatures Predict Cytogenetic Subtype and Outcome in Pediatric Acute Myeloid Leukemia (AML).

    Krali, Olga; Palle, Josefine; Bäcklin, Christofer L; Abrahamsson, Jonas; Norén-Nyström, Ulrika; Hasle, Henrik; Jahnukainen, Kirsi; Jónsson, Ólafur Gísli; Hovland, Randi; Lausen, Birgitte; et al. (MDPI, 2021-06-10)
    Pediatric acute myeloid leukemia (AML) is a heterogeneous disease composed of clinically relevant subtypes defined by recurrent cytogenetic aberrations. The majority of the aberrations used in risk grouping for treatment decisions are extensively studied, but still a large proportion of pediatric AML patients remain cytogenetically undefined and would therefore benefit from additional molecular investigation. As aberrant epigenetic regulation has been widely observed during leukemogenesis, we hypothesized that DNA methylation signatures could be used to predict molecular subtypes and identify signatures with prognostic impact in AML. To study genome-wide DNA methylation, we analyzed 123 diagnostic and 19 relapse AML samples on Illumina 450k DNA methylation arrays. We designed and validated DNA methylation-based classifiers for AML cytogenetic subtype, resulting in an overall test accuracy of 91%. Furthermore, we identified methylation signatures associated with outcome in t(8;21)/RUNX1-RUNX1T1, normal karyotype, and MLL/KMT2A-rearranged subgroups (p < 0.01). Overall, these results further underscore the clinical value of DNA methylation analysis in AML.
  • Exposure to pesticides and childhood leukemia risk: A systematic review and meta-analysis.

    Karalexi, Maria A; Tagkas, Christos F; Markozannes, Georgios; Tseretopoulou, Xanthippi; Hernández, Antonio F; Schüz, Joachim; Halldorsson, Thorhallur I; Psaltopoulou, Theodora; Petridou, Eleni Th; Tzoulaki, Ioanna; et al. (Elsevier, 2021-05-18)
    Despite the abundance of epidemiological evidence concerning the association between pesticide exposure and adverse health outcomes including acute childhood leukemia (AL), evidence remains inconclusive, and is inherently limited by heterogeneous exposure assessment and multiple statistical testing. We performed a literature search of peer-reviewed studies, published until January 2021, without language restrictions. Summary odds ratios (OR) and 95% confidence intervals (CI) were derived from stratified random-effects meta-analyses by type of exposure and outcome, exposed populations and window of exposure to address the large heterogeneity of existing literature. Heterogeneity and small-study effects were also assessed. We identified 55 eligible studies (n = 48 case-control and n = 7 cohorts) from over 30 countries assessing >200 different exposures of pesticides (n = 160,924 participants). The summary OR for maternal environmental exposure to pesticides (broad term) during pregnancy and AL was 1.88 (95%CI: 1.15-3.08), reaching 2.51 for acute lymphoblastic leukemia (ALL; 95%CI: 1.39-4.55). Analysis by pesticide subtype yielded an increased risk for maternal herbicide (OR: 1.41, 95%CI: 1.00-1.99) and insecticide (OR: 1.60, 95%CI: 1.11-2.29) exposure during pregnancy and AL without heterogeneity (p = 0.12-0.34). Meta-analyses of infant leukemia were only feasible for maternal exposure to pesticides during pregnancy. Higher magnitude risks were observed for maternal pesticide exposure and infant ALL (OR: 2.18, 95%CI: 1.44-3.29), and the highest for infant acute myeloid leukemia (OR: 3.42, 95%CI: 1.98-5.91). Overall, the associations were stronger for maternal exposure during pregnancy compared to childhood exposure. For occupational or mixed exposures, parental, and specifically paternal, pesticide exposure was significantly associated with increased risk of AL (ORparental: 1.75, 95%CI: 1.08-2.85; ORpaternal: 1.20, 95%CI: 1.07-1.35). The epidemiological evidence, supported by mechanistic studies, suggests that pesticide exposure, mainly during pregnancy, increases the risk of childhood leukemia, particularly among infants. Sufficiently powered studies using repeated biomarker analyses are needed to confirm whether there is public health merit in reducing prenatal pesticide exposure.
  • 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.
  • Molecular benchmarks of a SARS-CoV-2 epidemic.

    Jonsson, Hakon; Magnusson, Olafur T; Melsted, Pall; Berglund, Jonas; Agustsdottir, Arna B; Eiríksdottir, Berglind; Fridriksdottir, Run; Garðarsdottir, Elisabet Eir; Georgsson, Gudmundur; Gretarsdottir, Olafia S; et al. (Nature Publishing Group, 2021-06-15)
    A pressing concern in the SARS-CoV-2 epidemic and other viral outbreaks, is the extent to which the containment measures are halting the viral spread. A straightforward way to assess this is to tally the active cases and the recovered ones throughout the epidemic. Here, we show how epidemic control can be assessed with molecular information during a well characterized epidemic in Iceland. We demonstrate how the viral concentration decreased in those newly diagnosed as the epidemic transitioned from exponential growth phase to containment phase. The viral concentration in the cases identified in population screening decreased faster than in those symptomatic and considered at high risk and that were targeted by the healthcare system. The viral concentration persists in recovering individuals as we found that half of the cases are still positive after two weeks. We demonstrate that accumulation of mutations in SARS-CoV-2 genome can be exploited to track the rate of new viral generations throughout the different phases of the epidemic, where the accumulation of mutations decreases as the transmission rate decreases in the containment phase. Overall, the molecular signatures of SARS-CoV-2 infections contain valuable epidemiological information that can be used to assess the effectiveness of containment measures.
  • Understanding Nurses' Knowledge and Attitudes Toward Pain Assessment in Dementia: A Literature Review.

    Jonsdottir, Thorbjorg; Gunnarsson, Esther Christina; 1Faculty of Nursing, School of Health Sciences, University of Akureyri, Akureyri, Iceland; School of Health Sciences, Faculty of Nursing, University of Akureyriv/Nordurslod, Akureyri, Iceland. Electronic address: 2Faculty of Nursing, School of Health Sciences, University of Akureyri, Akureyri, Iceland; The National University Hospital of Iceland, Eiriksgata, Reykjavik, Iceland. (Elsevier, 2020-12-14)
    Background: Pain is underrecognized and undertreated in patients with dementia. It has been suggested that nurses' attitudinal barriers may contribute to the challenges surrounding pain assessment and management in dementia. Aims: This integrative literature review aims to identify and explore nurses' knowledge and attitudes towards pain assessment in older people with dementia and how it may affect pain management in this patient group. Method: Electronic searches were conducted in Web of Science, MEDLINE, Scopus, ProQuest, PubMed, and EBSCOhost from January 2008 to December 2018 for articles specifically focusing on nurses' knowledge and attitudes towards pain assessment in older patients with dementia. Results: Ten studies were included in the review after meeting the inclusion criteria. Data extracted from each study included study design, aims and objectives, setting/sample, findings, and limitations. Patients with dementia are at greater risk of experiencing underassessment, undertreatment, and delayed treatment of pain due to nurses' knowledge deficits and uncertainty in the decision-making process. Nurses see providing comfort and reducing pain as ethical obligation. However, they find pain assessment a challenge due to the complexity of recognizing painful behaviors, and difficulty differentiating between pain and behavioral disturbances in dementia. Poor multidisciplinary communication, time constraints, and workload pressure, as well as uncertainty about opioid use, are important barriers to effective pain assessment and management among patients with dementia. Conclusion: It is essential that nurses gain confidence in distinguishing signs and symptoms of pain from behavioral changes in dementia. It is important to improve interdisciplinary communication and to get physicians to listen and prioritize pain assessment and management.
  • Effectiveness of a couple-based intervention on sexuality and intimacy among women in active cancer treatment: A quasi-experimental study.

    Jonsdottir, Jona Ingibjorg; Vilhjalmsson, Runar; Svavarsdottir, Erla Kolbrun; 1Landspitali-The National University Hospital of Iceland, Hringbraut, 101, Reykjavik, Iceland; School of Health Sciences, Faculty of Nursing, University of Iceland, Eirberg, Eiríksgata 34, 101, Reykjavík, Iceland. Electronic address: 2School of Health Sciences, Faculty of Nursing, University of Iceland, Eirberg, Eiríksgata 34, 101, Reykjavík, Iceland. Electronic address: 3Landspitali-The National University Hospital of Iceland, Hringbraut, 101, Reykjavik, Iceland; School of Health Sciences, Faculty of Nursing, University of Iceland, Eirberg, Eiríksgata 34, 101, Reykjavík, Iceland. Electronic address: (Elsevier, 2021-05-11)
    Purpose: To evaluate the effectiveness of a strenghts-oriented therapeutic conversation intervention on confidence about how illness beliefs affect sexuality and intimacy and on perceived relationship quality among women in active cancer treatment and their partners. Methods: A quasi-experimental single-group pre-post-follow-up design was used. Women in active cancer treatment and their intimate partners were randomly assigned to a nurse-managed couple-based intervention (experimental group, n = 30 couples) or wait-list (delayed intervention) control group (n = 27 couples) plus 4 additional couples who pilot tested feasibility of the intervention, prior to the RCT. However, baseline differences in demographic and clinical variables prevented comparisons between groups. Therefore, a repeated-one-group pre-post test setup was used, comparing women with cancer and their partners over three time points. The intervention consisted of three Couple-Strengths-Oriented Therapeutic Conversations (CO-SOTC) sessions. The participants also had access to web-based evidence-based educational information. Data were collected before intervention (T1, baseline), one to two weeks post-intervention (T2), and after a follow-up session at three months (T3). Data from 60 couples (N = 120) were analyzed. Results: Significant differences were observed, for both women and intimate partners, over time in more confidence about how illness beliefs affected sexuality and intimacy (T1 versus T2, and T1 versus T3), and increased overall quality of the relationship (T1 versus T2, and T1 versus T3). No differences were found between dyad members' scores on illness beliefs or relationship quality at any time point. Conclusions: The CO-SOTC intervention was effective in supporting sexual adjustment among women in cancer treatment and their intimate partners. Trial registration number: NCT03936400 at Keywords: Advanced practice nursing; Couples therapy; Neoplasms; Psychosocial support systems; Sexual health; Sexuality; Spouses; Women.
  • 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: 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.
  • Retinal oxygen saturation changes progressively over time in diabetic retinopathy.

    Hardarson, Sveinn Hakon; Stefánsson, Einar; Bek, Toke; 1Institute of Physiology, Department of Medicine, University of Iceland, Reykjavik, Iceland. 2Department of Ophthalmology, Landspitali University Hospital, Reykjavik, Iceland. 3Department of Ophthalmology, Aarhus University Hospital, Aarhus N, Denmark. (Public Library of Science, 2021-05-12)
    Purpose: According to cross-sectional studies, oxygen saturation is elevated in retinal vessels in diabetic patients. We evaluated how retinal oxygenation (metabolic marker), vessel diameters and retinopathy grade (structural markers) change over time in diabetic patients. Design: Prospective cohort study following screening in a hospital setting. Methods: Retinal oximetry images were acquired in 214 patients with the Oxymap T1 oximeter. Imaging was repeated after a median of 3.0 years (range 0.76-6.8 years). Oxygen saturation and vessel diameters were measured in the right eye. Semiquantitative grading of retinopathy according to international guidelines and red lesion count were performed on fundus photographs. Results: Retinopathy grade according to the international semiquantitative grading system was unchanged. Arteriolar saturation increased by 0.75±0.15 percentage points per year of follow-up (p<0.0001). Venular saturation increased by 1.74±0.26 percentage points per year (p<0.0001) and arteriovenous difference decreased by 0.99±0.20 percentage points per year (p<0.0001). Arteriolar diameters decreased by 2.7±8.5μm (p<0.0001) between visits and venular diameters decreased by 2.4±9.1μm (p = 0.0002). Median increase in red lesion count between visits was 2 lesions (range -128 to 212 lesions, p<0.0001). The change in red lesion count and change in diameters did not correlate with the length of follow-up (p>0.44). Conclusions: Oxygen saturation in larger retinal vessels can increase and arteriovenous difference can decrease over time in diabetic patients without any observable changes in retinopathy grade. The results suggest that changes in retinal oxygen saturation may precede progression of diabetic retinopathy or that oxygen saturation is more sensitive to disease progression than retinopathy grade.
  • The genetic architecture of age-related hearing impairment revealed by genome-wide association analysis.

    Ivarsdottir, Erna V; Holm, Hilma; Benonisdottir, Stefania; Olafsdottir, Thorhildur; Sveinbjornsson, Gardar; Thorleifsson, Gudmar; Eggertsson, Hannes P; Halldorsson, Gisli H; Hjorleifsson, Kristjan E; Melsted, Pall; et al. (Nature Publishing Group, 2021-06-09)
    Age-related hearing impairment (ARHI) is the most common sensory disorder in older adults. We conducted a genome-wide association meta-analysis of 121,934 ARHI cases and 591,699 controls from Iceland and the UK. We identified 21 novel sequence variants, of which 13 are rare, under either additive or recessive models. Of special interest are a missense variant in LOXHD1 (MAF = 1.96%) and a tandem duplication in FBF1 covering 4 exons (MAF = 0.22%) associating with ARHI (OR = 3.7 for homozygotes, P = 1.7 × 10-22 and OR = 4.2 for heterozygotes, P = 5.7 × 10-27, respectively). We constructed an ARHI genetic risk score (GRS) using common variants and showed that a common variant GRS can identify individuals at risk comparable to carriers of rare high penetrance variants. Furthermore, we found that ARHI and tinnitus share genetic causes. This study sheds a new light on the genetic architecture of ARHI, through several rare variants in both Mendelian deafness genes and genes not previously linked to hearing.
  • Optimal communication associated with lower risk of acute traumatic stress after lung cancer diagnosis.

    Hardardottir, Hronn; Aspelund, Thor; Zhu, Jianwei; Fall, Katja; Hauksdottir, Arna; Fang, Fang; Lu, Donghao; Janson, Christer; Jonsson, Steinn; Valdimarsdottir, Heiddis; et al. (Springer, 2021-07-17)
    Purpose: The aim of this study was to assess the role of the patient's background and perceived healthcare-related factors in symptoms of acute stress after lung cancer diagnosis. Methods: The study population consisted of 89 individuals referred for diagnostic work-up at Landspitali National University Hospital in Iceland and subsequently diagnosed with lung cancer. Before diagnosis, the patients completed questionnaires on sociodemographic characteristics, pre-diagnostic distress (Hospital Anxiety and Depression Scale), social support, and resilience. At a median of 16 days after diagnosis, the patients reported symptoms of acute stress on the Impact of Event Scale-Revised (IES-R) and experience of communication and support from healthcare professionals and family during the diagnostic period. Results: Patients were on average 68 years and 52% reported high levels of post-diagnostic acute stress (IES-R > 23) while 24% reported symptoms suggestive of clinical significance (IES-R > 32). Prior history of cancer (β = 6.7, 95% CI: 0.1 to 13.3) and pre-diagnostic distress were associated with higher levels of post-diagnostic acute stress (β = 8.8, 95% CI: 2.7 to 14.9), while high educational level (β = - 7.9, 95% CI: - 14.8 to - 1.1) was associated with lower levels. Controlling for the abovementioned factors, the patients' perception of optimal doctor-patient (β = - 9.1, 95% CI: - 14.9 to - 3.3) and family communication (β = - 8.6, 95% CI: - 14.3 to - 2.9) was inversely associated with levels of post-diagnostic acute stress after lung cancer diagnosis. Conclusions: A high proportion of patients with newly diagnosed lung cancer experience high levels of acute traumatic stress of potential clinical significance. Efforts to improve doctor-patient and family communication may mitigate the risk of these adverse symptoms. Keywords: Doctor-patient communication; Lung cancer diagnosis; Post-diagnostic acute stress; Posttraumatic stress disorder (PTSD); Prospective cohort study.
  • Cardiac arrest due to accidental overdose with norepinephrine dissolved in crystalloid.

    Hansel, Jan; Ármannsson, Gunnar Skúli; 1Department of Anaesthetics, Blackpool Teaching Hospitals NHS Foundation Trust, Blackpool, UK 2Department of Anaesthesia and Intensive Care, Landspítali University Hospital, Reykjavík, Iceland. (BMJ Pub. Group, 2020-12-09)
    Vasoactive agents should be administered through a controlled well-marked infusor pump, ideally via a central venous catheter if given over longer periods of time. During transfer of haemodynamically unstable patients with limited staffing and resources on site, a peripheral vasopressor infusion is sometimes resorted to as a temporary measure of optimising haemodynamic parameters. We report a case of accidental norepinephrine overdose after such practice, resulting in cardiac arrest. It illustrates the importance of careful use and labelling of vasoactive agents during the transport and handover of critically ill patients. Finally, we explore human factor issues associated with transfer from the pre-hospital to the in-hospital environment when such preparations are used. Keywords: adult intensive care; anaesthesia; resuscitation; safety; toxicology.
  • Are the target exposure index and deviation index used efficiently?

    Guðjónsdóttir, J; Paalsson, K E; Sveinsdóttir, G P; 1University of Iceland, Faculty of Medicine, Radiography, Stapa við Hringbraut 31, 101 Reykjavík, Iceland; Icelandic Radiation Safety Authority, Rauðarárstígur 10, 105 Reykjavík, Iceland. Electronic address: 2Landspítali - the National University Hospital of Iceland, 101 Reykjavík, Iceland. 3University of Iceland, Faculty of Medicine, Radiography, Stapa við Hringbraut 31, 101 Reykjavík, Iceland. Electronic address: (Elsevier, 2021-03-09)
    Exposure index (EI) is important to evaluate correct exposure in radiography and thus important for image quality. The purpose of this study was to evaluate whether the target exposure index (EIT) and deviation index (DI) were used efficiently.
  • Fertility preservation in boys: recent developments and new insights .

    Goossens, E; Jahnukainen, K; Mitchell, R T; van Pelt, Amm; Pennings, G; Rives, N; Poels, J; Wyns, C; Lane, S; Rodriguez-Wallberg, K A; et al. (Oxford University Press, 2020-06-06)
    Background: Infertility is an important side effect of treatments used for cancer and other non-malignant conditions in males. This may be due to the loss of spermatogonial stem cells (SSCs) and/or altered functionality of testicular somatic cells (e.g. Sertoli cells, Leydig cells). Whereas sperm cryopreservation is the first-line procedure to preserve fertility in post-pubertal males, this option does not exist for prepubertal boys. For patients unable to produce sperm and at high risk of losing their fertility, testicular tissue freezing is now proposed as an alternative experimental option to safeguard their fertility. Objective and rationale: With this review, we aim to provide an update on clinical practices and experimental methods, as well as to describe patient management inclusion strategies used to preserve and restore the fertility of prepubertal boys at high risk of fertility loss. Search methods: Based on the expertise of the participating centres and a literature search of the progress in clinical practices, patient management strategies and experimental methods used to preserve and restore the fertility of prepubertal boys at high risk of fertility loss were identified. In addition, a survey was conducted amongst European and North American centres/networks that have published papers on their testicular tissue banking activity. Outcomes: Since the first publication on murine SSC transplantation in 1994, remarkable progress has been made towards clinical application: cryopreservation protocols for testicular tissue have been developed in animal models and are now offered to patients in clinics as a still experimental procedure. Transplantation methods have been adapted for human testis, and the efficiency and safety of the technique are being evaluated in mouse and primate models. However, important practical, medical and ethical issues must be resolved before fertility restoration can be applied in the clinic.Since the previous survey conducted in 2012, the implementation of testicular tissue cryopreservation as a means to preserve the fertility of prepubertal boys has increased. Data have been collected from 24 co-ordinating centres worldwide, which are actively offering testis tissue cryobanking to safeguard the future fertility of boys. More than 1033 young patients (age range 3 months to 18 years) have already undergone testicular tissue retrieval and storage for fertility preservation. Limitations reasons for caution: The review does not include the data of all reproductive centres worldwide. Other centres might be offering testicular tissue cryopreservation. Therefore, the numbers might be not representative for the entire field in reproductive medicine and biology worldwide. The key ethical issue regarding fertility preservation in prepubertal boys remains the experimental nature of the intervention. Wider implications: The revised procedures can be implemented by the multi-disciplinary teams offering and/or developing treatment strategies to preserve the fertility of prepubertal boys who have a high risk of fertility loss. Study funding/competing interests: The work was funded by ESHRE. None of the authors has a conflict of interest. Keywords: cryopreservation; fertility preservation; fertility restoration; in vitro spermatogenesis; prepubertal boys; spermatogonial stem cell; testicular tissue freezing; testis; transplantation.
  • 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.
  • 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.

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