Recent Submissions

  • The Impact of Histological Subtype on the Incidence, Timing, and Patterns of Recurrence in Patients with Renal Cell Carcinoma After Surgery-Results from RECUR Consortium.

    Abu-Ghanem, Yasmin; Powles, Thomas; Capitanio, Umberto; Beisland, Christian; Järvinen, Petrus; Stewart, Grant D; Gudmundsson, Eiríkur Orri; Lam, Thomas B; Marconi, Lorenzo; Fernandéz-Pello, Sergio; et al. (Elsevier, 2020-10-24)
    Background: Current follow-up strategies for patients with renal cell carcinoma (RCC) after curative surgery rely mainly on risk models and the treatment delivered, regardless of the histological subtype. Objective: To determine the impact of RCC histological subtype on recurrence and to examine the incidence, pattern, and timing of recurrences to improve follow-up recommendations. Design, setting, and participants: This study included consecutive patients treated surgically with curative intention (ie, radical and partial nephrectomy) for nonmetastatic RCC (cT1-4, M0) between January 2006 and December 2011 across 15 centres from 10 countries, as part of the euRopEan association of urology renal cell carcinoma guidelines panel Collaborative multicenter consortium for the studies of follow-Up and recurrence patterns in Radically treated renal cell carcinoma patients (RECUR) database project. Outcome measurements and statistical analysis: The impact of histological subtype (ie, clear cell RCC [ccRCC], papillary RCC [pRCC], and chromophobe RCC [chRCC]) on recurrence-free survival (RFS) was assessed via univariate and multivariate analyses, adjusting for potential interactions with important variables (stage, grade, risk score, etc.) Patterns of recurrence for all histological subtypes were compared according to recurrence site and risk criteria. Results and limitations: Of the 3331 patients, 62.2% underwent radical nephrectomy and 37.8% partial nephrectomy. A total of 2565 patients (77.0%) had ccRCC, 535 (16.1%) had pRCC, and 231 (6.9%) had chRCC. The median postoperative follow-up period was 61.7 (interquartile range: 47-83) mo. Patients with ccRCC had significantly poorer 5-yr RFS than patients with pRCC and chRCC (78% vs 86% vs 91%, p = 0.001). The most common sites of recurrence for ccRCC were the lung and bone. Intermediate-/high-risk pRCC patients had an increased rate of lymphatic recurrence, both mediastinal and retroperitoneal, while recurrence in chRCC was rare (8.2%), associated with higher stage and positive margins, and predominantly in the liver and bone. Limitations include the retrospective nature of the study. Conclusions: The main histological subtypes of RCC exhibit a distinct pattern and dynamics of recurrence. Results suggest that intermediate- to high-risk pRCC may benefit from cross-sectional abdominal imaging every 6 mo until 2 yr after surgery, while routine imaging might be abandoned for chRCC except for abdominal computed tomography in patients with advanced tumour stage or positive margins. Patient summary: In this analysis of a large database from 15 countries around Europe, we found that the main histological subtypes of renal cell carcinoma have a distinct pattern and dynamics of recurrence. Patients should be followed differently according to subtype and risk score. Keywords: Chromophobe; Clear cell; Follow-up; Papillary; RECUR database; Recurrence-free survival; Renal cell carcinoma.
  • A nationwide population-based prospective study of cirrhosis in Iceland.

    Olafsson, Sigurdur; Rögnvaldsson, Sigurjon; Bergmann, Ottar M; Jonasson, Jon G; Benitez Hernandez, Ubaldo; Björnsson, Einar S; 1Department of Internal Medicine, Division of Gastroenterology and Hepatology, Landspitali-National University Hospital of Iceland, Reykjavik, Iceland. 2Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 3Department of Surgery, Landspitali-National University Hospital of Iceland, Reykjavik, Iceland. 4Department of Pathology, Landspitali-National University Hospital of Iceland, Reykjavik, Iceland. 5Department of Science/Biostatistics, Landspitali-National University Hospital of Iceland, Reykjavik, Iceland. (Elsevier, 2021-03-31)
    Background & aims: The incidence of cirrhosis in Iceland has been the lowest in the world with only 3 cases per 100,000 inhabitants. Alcohol consumption has almost doubled in Iceland from 1980 to 2016. Obesity has also risen and hepatitis C virus has spread among people who inject drugs in Iceland. The aim of this study was to evaluate the effects of these risk factors on the incidence and aetiology of cirrhosis in Iceland. Methods: The study included all patients diagnosed with cirrhosis for the first time during 2010-2015. Diagnosis was based on liver histology or 2 of 4 criteria: cirrhosis on imaging, ascites, varices, and/or elevated INR. Results: Overall, 157 patients were diagnosed, 105 (67%) males, mean age 61 years. The overall incidence was 9.7 cases per 100,000 inhabitants annually. Alcohol was the only underlying cause in 48/157 (31%), non-alcoholic fatty liver disease (NAFLD) in 34/157(22%), and alcohol and hepatitis C together in 23/157(15%) were the most common causes. Only 6% of patients had an unknown cause of cirrhosis. Upon diagnosis, the median model for end-stage liver disease score was 11 (IQR 8-15), 53% were of Child-Pugh class A whereas 61 (39%) had ascites, 11% encephalopathy, and 8% variceal bleeding. In all, 25% of deaths were from HCC and 25% from liver failure. Conclusion: A major increase in incidence of cirrhosis has occurred in Iceland associated with increases in alcohol consumption, obesity, and hepatitis C. In a high proportion NAFLD was the aetiology and very few had unknown cause of cirrhosis. The highest death rate was from HCC. Lay summary: In a nationwide population-based study from Iceland, including all patients diagnosed with cirrhosis of the liver over a period of 5 years, we found the incidence of new cases had increased 3-fold compared with a previous study 20 years ago. The increase is attributable to increased alcohol consumption, an epidemic of diabetes and obesity, and infection with the hepatitis C virus. Furthermore, we found that with thorough investigations, a specific cause for cirrhosis could be found in 94% of patients. Patients with cirrhosis frequently die of liver cancer and other complications related to their liver disease. Keywords: AIH, autoimmune hepatitis; ALD, alcoholic liver disease; Aetiology of cirrhosis; Alcohol; CIF, cumulative incidence function; CRR, competing-risks regression; Cirrhosis; HCC, hepatocellular carcinoma; Hepatitis C; Incidence of cirrhosis; MELD, model for end-stage liver disease; NAFLD; NAFLD, non-alcoholic fatty liver disease; NALD, non-alcoholic liver disease; NASH, non-alcoholic steatohepatitis; PBC, primary biliary cirrhosis; PSC, primary sclerosing cholangitis; SHRs, subhazard ratios.
  • Changes in the incidence of invasive disease due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis during the COVID-19 pandemic in 26 countries and territories in the Invasive Respiratory Infection Surveillance Initiative: a prospective analysis of surveillance data.

    Brueggemann, Angela B; Jansen van Rensburg, Melissa J; Shaw, David; McCarthy, Noel D; Jolley, Keith A; Maiden, Martin C J; van der Linden, Mark P G; Amin-Chowdhury, Zahin; Bennett, Désirée E; Borrow, Ray; et al. (Elsevier, 2021-06)
    Background Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, which are typically transmitted via respiratory droplets, are leading causes of invasive diseases, including bacteraemic pneumonia and meningitis, and of secondary infections subsequent to post-viral respiratory disease. The aim of this study was to investigate the incidence of invasive disease due to these pathogens during the early months of the COVID-19 pandemic. Methods In this prospective analysis of surveillance data, laboratories in 26 countries and territories across six continents submitted data on cases of invasive disease due to S pneumoniae, H influenzae, and N meningitidis from Jan 1, 2018, to May, 31, 2020, as part of the Invasive Respiratory Infection Surveillance (IRIS) Initiative. Numbers of weekly cases in 2020 were compared with corresponding data for 2018 and 2019. Data for invasive disease due to Streptococcus agalactiae, a non-respiratory pathogen, were collected from nine laboratories for comparison. The stringency of COVID-19 containment measures was quantified using the Oxford COVID-19 Government Response Tracker. Changes in population movements were assessed using Google COVID-19 Community Mobility Reports. Interrupted time-series modelling quantified changes in the incidence of invasive disease due to S pneumoniae, H influenzae, and N meningitidis in 2020 relative to when containment measures were imposed. Findings 27 laboratories from 26 countries and territories submitted data to the IRIS Initiative for S pneumoniae (62 837 total cases), 24 laboratories from 24 countries submitted data for H influenzae (7796 total cases), and 21 laboratories from 21 countries submitted data for N meningitidis (5877 total cases). All countries and territories had experienced a significant and sustained reduction in invasive diseases due to S pneumoniae, H influenzae, and N meningitidis in early 2020 (Jan 1 to May 31, 2020), coinciding with the introduction of COVID-19 containment measures in each country. By contrast, no significant changes in the incidence of invasive S agalactiae infections were observed. Similar trends were observed across most countries and territories despite differing stringency in COVID-19 control policies. The incidence of reported S pneumoniae infections decreased by 68% at 4 weeks (incidence rate ratio 0.32 [95% CI 0.27-0.37]) and 82% at 8 weeks (0.18 [0.14-0.23]) following the week in which significant changes in population movements were recorded. Interpretation The introduction of COVID-19 containment policies and public information campaigns likely reduced transmission of S pneumoniae, H influenzae, and N meningitidis, leading to a significant reduction in life-threatening invasive diseases in many countries worldwide.
  • Reliability and Validity of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): Portuguese Version.

    Marques, Cristiana Campos; Matos, Ana Paula; do Céu Salvador, Maria; Arnarson, Eiríkur Örn; Craighead, W Edward; 1Center for Research in Neuropsychology and Cognitive Behavioural Intervention (CINEICC), Faculty of Psychology and Educational Sciences, University of Coimbra, Rua do Colégio Novo, 3000-115, Coimbra, Portugal. 2Center for Research in Neuropsychology and Cognitive Behavioural Intervention (CINEICC), Faculty of Psychology and Educational Sciences, University of Coimbra, Rua do Colégio Novo, 3000-115, Coimbra, Portugal. 3School of Health Sciences, Faculty of Medicine, University of Iceland, Landspítali -University Hospital, 101, Reykjavik, Iceland. 4Department of Psychiatry and Behavioral Sciences, Department of Psychology, Emory University, Atlanta, GA, USA. (Springer, 2021-05-28)
    This study examined the test-retest reliability, consensual, convergent and divergent validities, sensitivity, specificity, positive and negative predictive values, and accuracy of the Portuguese version of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K-SADS-PL). Eighty-nine children/adolescents (65 psychiatric outpatients and 24 healthy controls) were interviewed with K-SADS-PL and completed measures of depressive and anxiety symptoms. The child's parent/caretaker completed the Child Behavior Checklist. Good to excellent values were obtained for test-retest reliability and consensual validity. For the convergent validity, moderate correlations between the K-SADS-PL and the corresponding self-report measures were observed. Divergent validity was acceptable for the K-SADS-PL diagnoses. The lowest values of sensitivity, specificity, and accuracy of the K-SADS-PL were 88, 88, and 91, respectively. The Portuguese version of K-SADS-PL proved to be a valid and reliable assessment instrument for children and adolescents, and was sensitive, specific and accurate when diagnosing mood, anxiety, adjustment, and attention-deficit/hyperactivity disorders. Keywords: Children/adolescents; K-SADS-PL; Portuguese version; Reliability; Validity.
  • Detection mode of childhood acute lymphoblastic leukaemia relapse and its effect on survival: a Nordic population-based cohort study.

    Jensen, Karen S; Oskarsson, Trausti; Lähteenmäki, Päivi M; Flaegstad, Trond; Schmiegelow, Kjeld; Vedsted, Peter; Albertsen, Birgitte K; Schrøder, Henrik; 1Department of Paediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark. 2Department of Paediatric Oncology, Karolinska University Hospital, Stockholm, Sweden. 3Childhood Cancer Research Unit, Department of Women´s and Children´s Health, Karolinska Institutet, Stockholm, Sweden. 4Children's Hospital, Landspitali University Hospital, Reykjavik, Iceland. 5Department of Paediatric and Adolescent Haematology/Oncology, Turku University Hospital, FICAN-West, Turku University, Turku, Finland. 6Department of Paediatrics, University of Tromsø and University Hospital of North Norway, Tromsø, Norway. 7Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital, Copenhagen, Denmark. 8Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 9Research Unit for General Practice, Department of Public Health, Aarhus University, Aarhus, Denmark. (Wiley, 2021-05-27)
    Relapse constitutes the greatest threat to event-free survival after completion of treatment for childhood acute lymphoblastic leukaemia (ALL). However, evidence on optimal follow-up schedules is limited. The aims of the present population-based cohort study were to assess the value of current follow-up schedules after completion of Nordic Society of Paediatric Haematology and Oncology ALL protocol treatment and to estimate the impact of relapse detection mode on overall survival (OS). Among 3262 patients diagnosed between 1992 and 2014 and who completed treatment, 338 developed a relapse. Relapse detection was equally distributed between extra visits (50·8%) and scheduled follow-up visits (49·2%). All cases detected at an extra visit and 64·3% of cases detected at a scheduled visit presented with symptoms or objective findings. Neither the mode of detection {adjusted hazard ratio 0·95, [95% confidence interval (CI) 0·61-1·48] for scheduled visits} nor the duration of symptoms was an independent risk factor for OS after relapse. The estimated number of scheduled blood samples needed to diagnose one subclinical relapse during the first 5 years after treatment cessation was 1269 (95% CI 902-1637). In conclusion, based on OS data, scheduled visits after cessation of therapy seem to yield no extra benefit. These results should frame future follow-up strategies. Keywords: acute lymphoblastic leukaemia; cancer survivors; childhood leukaemia; recurrence; surveillance.
  • Genetic insight into sick sinus syndrome.

    Thorolfsdottir, Rosa B; Sveinbjornsson, Gardar; Aegisdottir, Hildur M; Benonisdottir, Stefania; Stefansdottir, Lilja; Ivarsdottir, Erna V; Halldorsson, Gisli H; Sigurdsson, Jon K; Torp-Pedersen, Christian; Weeke, Peter E; et al. (Oxford University Press, 2021-05)
    Aims: The aim of this study was to use human genetics to investigate the pathogenesis of sick sinus syndrome (SSS) and the role of risk factors in its development. Methods and results: We performed a genome-wide association study of 6469 SSS cases and 1 000 187 controls from deCODE genetics, the Copenhagen Hospital Biobank, UK Biobank, and the HUNT study. Variants at six loci associated with SSS, a reported missense variant in MYH6, known atrial fibrillation (AF)/electrocardiogram variants at PITX2, ZFHX3, TTN/CCDC141, and SCN10A and a low-frequency (MAF = 1.1-1.8%) missense variant, p.Gly62Cys in KRT8 encoding the intermediate filament protein keratin 8. A full genotypic model best described the p.Gly62Cys association (P = 1.6 × 10-20), with an odds ratio (OR) of 1.44 for heterozygotes and a disproportionally large OR of 13.99 for homozygotes. All the SSS variants increased the risk of pacemaker implantation. Their association with AF varied and p.Gly62Cys was the only variant not associating with any other arrhythmia or cardiovascular disease. We tested 17 exposure phenotypes in polygenic score (PGS) and Mendelian randomization analyses. Only two associated with the risk of SSS in Mendelian randomization, AF, and lower heart rate, suggesting causality. Powerful PGS analyses provided convincing evidence against causal associations for body mass index, cholesterol, triglycerides, and type 2 diabetes (P > 0.05). Conclusion: We report the associations of variants at six loci with SSS, including a missense variant in KRT8 that confers high risk in homozygotes and points to a mechanism specific to SSS development. Mendelian randomization supports a causal role for AF in the development of SSS. Keywords: KRT8; Atrial fibrillation; GWAS; Mendelian randomization; Sick sinus syndrome.
  • Iceland screens, treats, or prevents multiple myeloma (iStopMM): a population-based screening study for monoclonal gammopathy of undetermined significance and randomized controlled trial of follow-up strategies.

    Rögnvaldsson, Sæmundur; Love, Thorvardur Jon; Thorsteinsdottir, Sigrun; Reed, Elín Ruth; Óskarsson, Jón Þórir; Pétursdóttir, Íris; Sigurðardóttir, Guðrún Ásta; Viðarsson, Brynjar; Önundarson, Páll Torfi; Agnarsson, Bjarni A; et al. (Nature Publishing Group, 2021-05-17)
    Monoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma (MM). Population-based screening for MGUS could identify candidates for early treatment in MM. Here we describe the Iceland Screens, Treats, or Prevents Multiple Myeloma study (iStopMM), the first population-based screening study for MGUS including a randomized trial of follow-up strategies. Icelandic residents born before 1976 were offered participation. Blood samples are collected alongside blood sampling in the Icelandic healthcare system. Participants with MGUS are randomized to three study arms. Arm 1 is not contacted, arm 2 follows current guidelines, and arm 3 follows a more intensive strategy. Participants who progress are offered early treatment. Samples are collected longitudinally from arms 2 and 3 for the study biobank. All participants repeatedly answer questionnaires on various exposures and outcomes including quality of life and psychiatric health. National registries on health are cross-linked to all participants. Of the 148,704 individuals in the target population, 80 759 (54.3%) provided informed consent for participation. With a very high participation rate, the data from the iStopMM study will answer important questions on MGUS, including potentials harms and benefits of screening. The study can lead to a paradigm shift in MM therapy towards screening and early therapy.
  • Molecular genetics of inherited retinal degenerations in Icelandic patients.

    Thorsteinsson, Daniel A; Stefansdottir, Vigdis; Eysteinsson, Thor; Thorisdottir, Sigridur; Jonsson, Jon J; 1Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 2Department of Genetics and Molecular Medicine, Landspitali - National University Hospital of Iceland, Reykjavik, Iceland. 3Department of Physiology, BioMedical Center, Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 4Department of Ophthalmology, Landspitali - National University Hospital of Iceland, Reykjavik, Iceland. 5Department of Biochemistry and Molecular Biology, BioMedical Center, Faculty of Medicine, University of Iceland, Reykjavik, Iceland. (Wiley, 2021-05-07)
    The study objective was to delineate the genetics of inherited retinal degenerations (IRDs) in Iceland, a small nation of 364.000 and a genetic isolate. Benefits include delineating novel pathogenic genetic variants and defining genetically homogenous patients as potential investigative molecular therapy candidates. The study sample comprised patients with IRD in Iceland ascertained through national centralized genetic and ophthalmological services at Landspitali, a national social support institute, and the Icelandic patient association. Information on patients' disease, syndrome, and genetic testing was collected in a clinical registry. Variants were reevaluated according to ACMG/AMP guidelines. Overall, 140 IRD patients were identified (point prevalence of 1/2.600), of which 70 patients had a genetic evaluation where two-thirds had an identified genetic cause. Thirteen disease genes were found in patients with retinitis pigmentosa, with the RLBP1 gene most common (n = 4). The c.1073 + 5G > A variant in the PRPF31 gene was homozygous in two RP patients. All tested patients with X-linked retinoschisis (XLRS) had the same possibly unique RS1 pathogenic variant, c.441G > A (p.Trp147X). Pathologic variants and genes for IRDs in Iceland did not resemble those described in ancestral North-Western European nations. Four variants were reclassified as likely pathogenic. One novel pathogenic variant defined a genetically homogenous XLRS patient group. Keywords: Iceland; eye diseases; genetics; hereditary; human genetics; population; retinitis pigmentosa.
  • COVID-19 in pregnancy-characteristics and outcomes of pregnant women admitted to hospital because of SARS-CoV-2 infection in the Nordic countries.

    Engjom, Hilde; Aabakke, Anna J M; Klungsøyr, Kari; Svanvik, Teresia; Äyräs, Outi; Jonasdottir, Eva; Thurn, Lars; Jones, Elin; Pettersson, Karin; Nyfløt, Lill T; et al. (Wiley, 2021-05-07)
    Introduction: Population-based studies about the consequences of SARS-CoV-2 infection (COVID-19) in pregnancy are few and have limited generalizability to the Nordic population and healthcare systems. Material and methods: This study examines pregnant women with COVID-19 in the five Nordic countries. Pregnant women were included if they were admitted to hospital between 1 March and 30 June 2020 and had a positive SARS-CoV-2 PCR test ≤14 days prior to admission. Cause of admission was classified as obstetric or COVID-19-related. Results: In the study areas, 214 pregnant women with a positive test were admitted to hospital, of which 56 women required hospital care due to COVID-19. The risk of admission due to COVID-19 was 0.4/1000 deliveries in Denmark, Finland and Norway, and 3.8/1000 deliveries in the Swedish regions. Women hospitalized because of COVID-19 were more frequently obese (p < 0.001) and had a migrant background (p < 0.001) compared with the total population of women who delivered in 2018. Twelve women (21.4%) needed intensive care. Among the 56 women admitted due to COVID-19, 48 women delivered 51 infants. Preterm delivery (n = 12, 25%, p < 0.001) and cesarean delivery (n = 21, 43.8%, p < 0.001) were more frequent in women with COVID-19 compared with women who delivered in 2018. No maternal deaths, stillbirths or neonatal deaths were reported. Conclusions: The risk of admission due to COVID-19 disease in pregnancy was low in the Nordic countries. A fifth of the women required intensive care and we observed higher rates of preterm and cesarean deliveries. National public health policies appear to have had an impact on the risk of admission due to severe COVID-19 disease in pregnancy. Nordic collaboration is important in collecting robust data and assessing rare outcomes. Keywords: COVID-19; cohort studies; obstetric delivery; pregnancy; pregnancy complications; pregnancy outcome; prospective studies; severe acute respiratory syndrome coronavirus 2.
  • Heart rate variability during wakefulness as a marker of obstructive sleep apnea severity.

    Qin, Hua; Keenan, Brendan T; Mazzotti, Diego R; Vaquerizo-Villar, Fernando; Kraemer, Jan F; Wessel, Niels; Tufik, Sergio; Bittencourt, Lia; Cistulli, Peter A; de Chazal, Philip; et al. (Oxford University Press, 2021-05)
    Study objectives: Patients with obstructive sleep apnea (OSA) exhibit heterogeneous heart rate variability (HRV) during wakefulness and sleep. We investigated the influence of OSA severity on HRV parameters during wakefulness in a large international clinical sample. Methods: 1247 subjects (426 without OSA and 821 patients with OSA) were enrolled from the Sleep Apnea Global Interdisciplinary Consortium. HRV parameters were calculated during a 5-minute wakefulness period with spontaneous breathing prior to the sleep study, using time-domain, frequency-domain and nonlinear methods. Differences in HRV were evaluated among groups using analysis of covariance, controlling for relevant covariates. Results: Patients with OSA showed significantly lower time-domain variations and less complexity of heartbeats compared to individuals without OSA. Those with severe OSA had remarkably reduced HRV compared to all other groups. Compared to non-OSA patients, those with severe OSA had lower HRV based on SDNN (adjusted mean: 37.4 vs. 46.2 ms; p < 0.0001), RMSSD (21.5 vs. 27.9 ms; p < 0.0001), ShanEn (1.83 vs. 2.01; p < 0.0001), and Forbword (36.7 vs. 33.0; p = 0.0001). While no differences were found in frequency-domain measures overall, among obese patients there was a shift to sympathetic dominance in severe OSA, with a higher LF/HF ratio compared to obese non-OSA patients (4.2 vs. 2.7; p = 0.009). Conclusions: Time-domain and nonlinear HRV measures during wakefulness are associated with OSA severity, with severe patients having remarkably reduced and less complex HRV. Frequency-domain measures show a shift to sympathetic dominance only in obese OSA patients. Thus, HRV during wakefulness could provide additional information about cardiovascular physiology in OSA patients. Clinical trial information: A Prospective Observational Cohort to Study the Genetics of Obstructive Sleep Apnea and Associated Co-Morbidities (German Clinical Trials Register - DKRS, DRKS00003966) Keywords: autonomic nervous activity; frequency domain analysis; heart rate variability; nonlinear dynamic analysis; obstructive sleep apnea; time domain analysis; wakefulness.
  • When does fetal head rotation occur in spontaneous labor at term: results of an ultrasound-based longitudinal study in nulliparous women.

    Hjartardóttir, Hulda; Lund, Sigrún H; Benediktsdóttir, Sigurlaug; Geirsson, Reynir T; Eggebø, Torbjørn M; 1Department of Obstetrics and Gynecology, Landspitali - The National University Hospital of Iceland, Reykjavík, Iceland; Faculty of Medicine, University of Iceland, Reykjavík, Iceland. Electronic address: 2deCODE genetics, Reykjavík, Iceland. 3Department of Obstetrics and Gynecology, Landspitali - The National University Hospital of Iceland, Reykjavík, Iceland; Faculty of Medicine, University of Iceland, Reykjavík, Iceland. 4National Center for Fetal Medicine, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway; Department of Obstetrics and Gynecology, Stavanger University Hospital, Stavanger, Norway; Institute of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway. (Elsevier, 2020-11-15)
    Background: Improved information about the evolution of fetal head rotation during labor is required. Ultrasound methods have the potential to provide reliable new knowledge about fetal head position. Objective: The aim of the study was to describe fetal head rotation in women in spontaneous labor at term using ultrasound longitudinally throughout the active phase. Study design: This was a single center, prospective cohort study at Landspitali - The National University Hospital of Iceland, Reykjavík, Iceland, from January 2016 to April 2018. Nulliparous women with a single fetus in cephalic presentation and spontaneous labor onset at ≥37 weeks' gestation were eligible. Inclusion occurred when the active phase could be clinically established by labor ward staff. Cervical dilatation was clinically examined. Fetal head position and subsequent rotation were determined using both transabdominal and transperineal ultrasound. Occiput positions were marked on a clockface graph with 24 half-hour divisions and categorized into occiput anterior (≥10- and ≤2-o'clock positions), left occiput transverse (>2- and <4-o'clock positions), occiput posterior (≥4- and ≤8 o'clock positions), and right occiput transverse positions (>8- and <10-o'clock positions). Head descent was measured with ultrasound as head-perineum distance and angle of progression. Clinical vaginal and ultrasound examinations were performed by separate examiners not revealing the results to each other. Results: We followed the fetal head rotation relative to the initial position in the pelvis in 99 women, of whom 75 delivered spontaneously, 16 with instrumental assistance, and 8 needed cesarean delivery. At inclusion, the cervix was dilated 4 cm in 26 women, 5 cm in 30 women, and ≥6 cm in 43 women. Furthermore, 4 women were examined once, 93 women twice, 60 women 3 times, 47 women 4 times, 20 women 5 times, 15 women 6 times, and 3 women 8 times. Occiput posterior was the most frequent position at the first examination (52 of 99), but of those classified as posterior, most were at 4- or 8-o'clock position. Occiput posterior positions persisted in >50% of cases throughout the first stage of labor but were anterior in 53 of 80 women (66%) examined by and after full dilatation. The occiput position was anterior in 75% of cases at a head-perineum distance of ≤30 mm and in 73% of cases at an angle of progression of ≥125° (corresponding to a clinical station of +1). All initial occiput anterior (19), 77% of occiput posterior (40 of 52), and 93% of occiput transverse positions (26 of 28) were thereafter delivered in an occiput anterior position. In 6 cases, the fetal head had rotated over the 6-o'clock position from an occiput posterior or transverse position, resulting in a rotation of >180°. In addition, 6 of the 8 women ending with cesarean delivery had the fetus in occiput posterior position throughout the active phase of labor. Conclusion: We investigated the rotation of the fetal head in the active phase of labor in nulliparous women in spontaneous labor at term, using ultrasound to provide accurate and objective results. The occiput posterior position was the most common fetal position throughout the active phase of the first stage of labor. Occiput anterior only became the most frequent position at full dilatation and after the head had descended below the midpelvic plane. Keywords: active phase; angle of progression; cesarean delivery; fetal head position; head-perineum distance; progress of labor; transabdominal ultrasound; transperineal ultrasound.
  • Inter-Visit Reliability of Smooth Pursuit Neck Torsion Test in Patients with Chronic Neck Pain and Healthy Individuals.

    Majcen Rosker, Ziva; Vodicar, Miha; Kristjansson, Eythor; 1Faculty of Sport, University of Ljubljana, 1000 Ljubljana, Slovenia. 2Department of Orthopaedic Surgery, University Medical Centre, 1000 Ljubljana, Slovenia. 3Landspitali University Hospital, 101 Reykjavik, Iceland. (MDPI, 2021-04-22)
    Visual disturbances are commonly reported in patients with neck pain. Smooth pursuit neck torsion (SPNT) test performed in neutral position and with trunk rotated under the stationary head has been used to discriminate between those with cervical component and those without. However, no studies investigated the reliability of the SPNT-test in patients with chronic neck pain and healthy controls. The aim of this study was to assess inter-visit reliability of the SPNT-test while applying different amplitudes and velocities of target movement. Thirty-two controls and thirty-one patients were enrolled in the study. The SPNT-test was performed in neutral position and through 45° torsion positions. The test was performed at 20°/s, 30°/s and 40°/s velocities and at 30°, 40° and 50° amplitudes of cyclic sinusoidal target movements. Interclass correlation coefficient and smallest detectable change were calculated for parameters of gain and SPNT-differences. In patients, moderate to good reliability was observed for gain at 40° and 50° amplitudes and for 20°/s and 30°/s velocities, while moderate to excellent reliability for gain was observed in controls. Both groups presented with moderate to good reliability for SPNT-difference. Our findings imply that amplitudes of 40° and 50° and velocities of 20°/s and 30°/s are the most reliable and should be applied in future studies assessing oculomotor functions during the SPNT test. Keywords: neck pain; oculomotor functions; reliability; smooth pursuit neck torsion test.
  • Relapse risk following truncation of pegylated asparaginase in childhood acute lymphoblastic leukemia.

    Gottschalk Højfeldt, Sofie; Grell, Kathrine; Abrahamsson, Jonas; Lund, Bendik; Vettenranta, Kim; Jónsson, Ólafur G; Frandsen, Thomas L; Wolthers, Benjamin O; Marquart, Hanne Vibeke; Vaitkeviciene, Goda; et al. (Elsevier, 2021-04)
    Truncation of asparaginase treatment due to asparaginase-related toxicities or silent inactivation (SI) is common and may increase relapse risk in acute lymphoblastic leukemia (ALL). We investigated relapse risk following suboptimal asparaginase exposure among 1401 children aged 1 to 17 years, diagnosed with ALL between July 2008 and February 2016, treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol (including extended asparaginase exposure [1000 IU/m2 intramuscularly weeks 5-33]). Patients were included with delayed entry at their last administered asparaginase treatment, or detection of SI, and followed until relapse, death, secondary malignancy, or end of follow-up (median, 5.71 years; interquartile range, 4.02-7.64). In a multiple Cox model comparing patients with (n = 358) and without (n = 1043) truncated asparaginase treatment due to clinical toxicity, the adjusted relapse-specific hazard ratio (HR; aHR) was 1.33 (95% confidence interval [CI], 0.86-2.06; P = .20). In a substudy including only patients with information on enzyme activity (n = 1115), the 7-year cumulative incidence of relapse for the 301 patients with truncation of asparaginase treatment or SI (157 hypersensitivity, 53 pancreatitis, 14 thrombosis, 31 other, 46 SI) was 11.1% (95% CI, 6.9-15.4) vs 6.7% (95% CI, 4.7-8.6) for the 814 remaining patients. The relapse-specific aHR was 1.69 (95% CI, 1.05-2.74, P=.03). The unadjusted bone marrow relapse-specific HR was 1.83 (95% CI, 1.07-3.14, P=.03) and 1.86 (95% CI, 0.90- 3.87, P=.095) for any central nervous system relapse. These results emphasize the importance of therapeutic drug monitoring and appropriate adjustment of asparaginase therapy when feasible. This trial was registered at as #NCT03987542.
  • The impact and cost-effectiveness of introducing the 10-valent pneumococcal conjugate vaccine into the paediatric immunisation programme in Iceland-A population-based time series analysis.

    Eythorsson, Elias; Ásgeirsdóttir, Tinna L; Erlendsdóttir, Helga; Hrafnkelsson, Birgir; Kristinsson, Karl G; Haraldsson, Ásgeir; 1Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 2Faculty of Economics, University of Iceland, Reykjavik, Iceland. 3Department of Clinical Microbiology, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. 4Department of Mathematics, University of Iceland, Reykjavik, Iceland. 5Children's Hospital Iceland, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. (Public Library of Science, 2021-04-08)
    Introduction: Streptococcus pneumoniae is a cause of infections that range in severity from acute otitis media (AOM) to pneumonia and invasive pneumococcal disease (IPD). The 10-valent pneumococcal conjugate vaccine (PHiD-CV10) was introduced into the Icelandic paediatric immunisation programme in 2011. The aim was to estimate the population impact and cost-effectiveness of PHiD-CV10 introduction. Methods: Data on primary care visits from 2005-2015 and hospitalisations from 2005-2017 were obtained from population-based registries. A Bayesian time series analysis with synthetic controls was employed to estimate the number of cases of AOM, pneumonia and IPD that would have occurred between 2013-2017, had PHiD-CV10 not been introduced. Prevented cases were calculated by subtracting the observed number of cases from this estimate. The cost of the programme was calculated accounting for cost-savings due to prevented cases. Results: The introduction of PHiD-CV10 prevented 13,767 (95% credible interval [CI] 2,511-29,410) visits for AOM from 2013-2015, and prevented 1,814 (95%CI -523-4,512) hospitalisations for pneumonia and 53 (95%CI -17-177) admissions for IPD from 2013-2017. Visits for AOM decreased both among young children and among children 4-19 years of age, with rate ratios between 0.72-0.89. Decreases were observed in both pneumonia hospitalisations (rate ratios between 0.67-0.92) and IPD (rate ratios between 0.27-0.94). The total cost of implementing PHiD-CV10 in Iceland was -7,463,176 United States Dollars (USD) (95%CI -16,159,551-582,135) with 2.1 USD (95%CI 0.2-4.7) saved for every 1 USD spent. Conclusions: The introduction of PHiD-CV10 was associated with large decreases in visits and hospitalisations for infections commonly caused by pneumococcus and was cost-saving during the first five years of the immunisation programme.
  • Alzheimer's disease neuropathology in the hippocampus and brainstem of people with obstructive sleep apnea.

    Owen, Jessica E; Benediktsdottir, Bryndis; Cook, Elizabeth; Olafsson, Isleifur; Gislason, Thorarinn; Robinson, Stephen R; 1School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria, Australia. 2Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 3Department of Sleep Medicine, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland. 4Department of Clinical Biochemistry, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland. 5Institute for Breathing and Sleep (IBAS), Austin Health, Heidelberg, Victoria, Australia. (Owen JE, Benediktsdottir B, Cook E, Olafsson I, Gislason T, Robinson SR. Alzheimer's disease neuropathology in the hippocampus and brainstem of people with obstructive sleep apnea. Sleep. 2021 Mar 12;44(3):zsaa195. doi: 10.1093/sleep/zsaa195., 2021-03)
    Obstructive sleep apnea (OSA) involves intermittent cessations of breathing during sleep. People with OSA can experience memory deficits and have reduced hippocampal volume; these features are also characteristic of Alzheimer's disease (AD), where they are accompanied by neurofibrillary tangles (NFTs) and amyloid beta (Aβ) plaques in the hippocampus and brainstem. We have recently shown reduced hippocampal volume to be related to OSA severity, and although OSA may be a risk factor for AD, the hippocampus and brainstems of clinically verified OSA cases have not yet been examined for NFTs and Aβ plaques. The present study used quantitative immunohistochemistry to investigate postmortem hippocampi of 34 people with OSA (18 females, 16 males; mean age 67 years) and brainstems of 24 people with OSA for the presence of NFTs and Aβ plaques. OSA severity was a significant predictor of Aβ plaque burden in the hippocampus after controlling for age, sex, body mass index (BMI), and continuous positive airway pressure (CPAP) use. OSA severity also predicted NFT burden in the hippocampus, but not after controlling for age. Although 71% of brainstems contained NFTs and 21% contained Aβ plaques, their burdens were not correlated with OSA severity. These results indicate that OSA accounts for some of the "cognitively normal" individuals who have been found to have substantial Aβ burdens, and are currently considered to be at a prodromal stage of AD. Keywords: Alzheimer’s disease; amyloid beta; continuous positive airway pressure; neurofibrillary tangles; tau.
  • Trail Making Test, Stroop, and Verbal Fluency: Regression-Based Norms for the Icelandic Population.

    Magnusdottir, B B; Haraldsson, H M; Sigurdsson, E; 1Department of Psychiatry, Landspitali University Hospital, 101 Reykjavik, Iceland. 2Department of Psychology, Reykjavik University, 101 Reykjavik, Iceland. 3School of Health Sciences, University of Iceland, 101 Reykjavik, Iceland. (Oxford University Press, 2021-02)
    Objective: The aim of this study was to construct regression-based norms for 3 executive-function tests: the Trail Making Test, Stroop, and Verbal Fluency. Method: A sample of 1,034 healthy Icelandic adults (18-64 years) was used to calculate predicted scores for test measures from all 3 tests, controlled for the effects of age, gender, and education, as well as the interaction between these variables. Results: The 3 demographic variables showed significant effects on most test measures and were included in the final equation for estimating predicted scores. An older age and less education predicted worse cognitive performances in most cases, and women tended to outperform men. Conclusion: These results highlight the importance of adjusting for age, gender, and educational level when constructing normative data. Controlling for age alone may be insufficient or misleading in clinical-practice settings. A simple, user-friendly program for predicting executive-function test scores is provided. Keywords: Assessment; Executive functions; Fluency (verbal/nonverbal); Norms/normative studies.
  • Cerebrospinal Fluid C18 Ceramide Associates with Markers of Alzheimer's Disease and Inflammation at the Pre- and Early Stages of Dementia.

    Teitsdottir, Unnur D; Halldorsson, Skarphedinn; Rolfsson, Ottar; Lund, Sigrun H; Jonsdottir, Maria K; Snaedal, Jon; Petersen, Petur H; 1Faculty of Medicine, Department of Anatomy, Biomedical Center, University of Iceland, Reykjavik, Iceland. 2Center for Systems Biology, University of Iceland, Reykjavik, Iceland. 3deCODE Genetics/Amgen, Inc., Reykjavik, Iceland. 4Department of Psychology, Reykjavik University, Reykjavik, Iceland. 5Department of Psychiatry, Landspitali -National University Hospital, Reykjavik, Iceland. 6Memory Clinic, Department of Geriatric Medicine, Landspitali - National University Hospital, Reykjavik, Iceland. (IOS Press, 2021-05)
    Background: Understanding how dysregulation in lipid metabolism relates to the severity of Alzheimer's disease (AD) pathology might be critical in developing effective treatments. Objective: To identify lipid species in cerebrospinal fluid (CSF) associated with signature AD pathology and to explore their relationships with measures reflecting AD-related processes (neurodegeneration, inflammation, deficits in verbal episodic memory) among subjects at the pre- and early symptomatic stages of dementia. Methods: A total of 60 subjects that had been referred to an Icelandic memory clinic cohort were classified as having CSF AD (n = 34) or non-AD (n = 26) pathology profiles. Untargeted CSF lipidomic analysis was performed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) for the detection of mass-to-charge ratio (m/z) features. CSF proteins reflecting neurodegeneration (neurofilament light [NFL]) and inflammation (chitinase-3-like protein 1 [YKL-40], S100 calcium-binding protein B [S100B], glial fibrillary acidic protein [GFAP]) were also measured. Rey Auditory Verbal Learning (RAVLT) and Story tests were used for the assessment of verbal episodic memory. Results: Eight out of 1008 features were identified as best distinguishing between the CSF profile groups. Of those, only the annotation of the m/z feature assigned to lipid species C18 ceramide was confirmed with a high confidence. Multiple regression analyses, adjusted for age, gender, and education, demonstrated significant associations of CSF core AD markers (Aβ42: st.β= -0.36, p = 0.007; T-tau: st.β= 0.41, p = 0.005) and inflammatory marker S100B (st.β= 0.51, p = 0.001) with C18 ceramide levels. Conclusion: Higher levels of C18 ceramide associated with increased AD pathology and inflammation, suggesting its potential value as a therapeutic target. Keywords: Alzheimer’s disease; biomarkers; cerebrospinal fluid; inflammation; lipidomics.
  • Effect of replacing ambulance physicians with paramedics on outcome of resuscitation for prehospital cardiac arrest.

    Bjornsson, Hjalti Mar; Bjornsdottir, Gudrun G; Olafsdottir, Hronn; Mogensen, Brynjolfur Arni; Mogensen, Brynjolfur; Thorgeirsson, Gestur; 1Department of Emergency Medicine, Faculty of Medicine, University of Iceland, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. 2Department of Aneaesthesia, Glasgow Royal Infirmary, Scotland, UK. 3Department of Orthopedic Surgery, Drammen Hospital, Norway. 4Department of Cardiology. 5Faculty of Medicine, University of Iceland, Research Institute in Emergency Medicine. 6Department of Cardiology, Landspitali-The National University Hospital of Iceland. Reykjavik, Iceland. (Lippincott Williams & Wilkins, 2021-06)
    Introduction: Limited evidence suggests that the presence of a prehospital physician improves survival from cardiac arrest. A retrospective study is undertaken to examine this question. In Reykjavik, Iceland, prehospital physicians on ambulances were replaced by emergency medical technicians (EMTs) in 2007. The aim of this study is to compare the outcome of prehospital resuscitation from cardiac arrest during periods of time with and without prehospital physician involvement. Methods: All cardiac arrests that underwent prehospital resuscitation by emergency medical systems between 2004 and 2014 were included. The primary outcome was survival to hospital discharge, and the secondary outcome was return of spontaneous circulation (ROSC). Subgroup analyses were performed according to the type of cardiac arrest. Results: A total of 471 cardiac arrests were included for analysis, 200 treated by prehospital physicians from 2004 to 2007 and 271 treated by EMTs from 2008 to 2014. The overall rate of survival to hospital discharge and ROSC was 23 and 50% during the study period. No significant difference was observed in the rate of survival to hospital discharge [25 vs 22%, difference 3% (95% confidence interval (CI): 11-5%)] or ROSC [53 vs 47%, difference -6% (95% CI: 15-3%)] between these two time periods. In the subgroup of patients with pulseless electrical activity, survival to hospital discharge did not differ between the two periods, but the rate of ROSC was higher in the 'physician period' [50 vs 30%, difference -20% (95% CI: -40 to -1%)]. Conclusions: The presence of a prehospital physician on the ambulance was not found to result in a significant improvement in survival or ROSC after cardiac arrest compared to care by EMTs. Patients with pulseless electrical activity experienced an increase in ROSC when a physician was present but without improvement in survival to hospital discharge.
  • Emu Oil and Saireito in combination reduce tumour development and clinical indicators of disease in a mouse model of colitis-associated colorectal cancer.

    Chartier, Lauren C; Fujino, Junko; Howarth, Gordon S; Freysdottir, Jona; Hardardottir, Ingibjorg; Mashtoub, Suzanne; 1Discipline of Physiology, Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia; Gastroenterology Department, Women's and Children's Hospital, North Adelaide, South Australia, Australia. Electronic address: 2Department of Paediatric Surgery, Saitama Medical Centre, Dokkyo Medical University, Saitama, Japan. Electronic address: 3Discipline of Physiology, Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia; Gastroenterology Department, Women's and Children's Hospital, North Adelaide, South Australia, Australia; School of Animal & Veterinary Sciences, The University of Adelaide, Roseworthy, South Australia, Australia. Electronic address: 4Faculty of Medicine, Biomedical Centre, University of Iceland and Landspitali-the National University Hospital of Iceland, Reykjavik, Iceland. Electronic address: 5Faculty of Medicine, Biomedical Centre, University of Iceland and Landspitali-the National University Hospital of Iceland, Reykjavik, Iceland. Electronic address: 6Discipline of Physiology, Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia; Gastroenterology Department, Women's and Children's Hospital, North Adelaide, South Australia, Australia; School of Medicine, The University of Western Australia, Murdoch, Western Australia, Australia. Electronic address: (Elsevier, 2021-03-20)
    Background: Emu Oil (EO) previously demonstrated therapeutic potential in a mouse model of colitis-associated CRC (CA-CRC). Saireito, a traditional Japanese medicine, has not been investigated in CA-CRC. Aim: To determine whether EO and Saireito could be therapeutic in an azoxymethane (AOM)/dextran sulphate sodium (DSS) model of CA-CRC. Methods: Female C57BL/6 mice were assigned to groups (n = 10/group); 1) saline control, 2) saline+Saireito, 3) saline+EO, 4) saline+EO/Saireito, 5) AOM/DSS control, 6) AOM/DSS+Saireito, 7) AOM/DSS+EO and 8) AOM/DSS+EO/Saireito. Mice were intraperitoneally injected with saline or AOM (7.4 mg/kg) on day 0 and underwent three DSS/water cycles (2%w/v DSS for 7 days, 14 days water). Mice were orally-gavaged with either water (80 µL), Saireito (80 µL), EO (80 µL) or EO/Saireito (160 µL; 80 µL EO + 80 µL Saireito) thrice weekly. Daily bodyweight and disease activity index (DAI) were recorded and colonoscopies performed on days 20, 41 and 62. Mice were euthanized on day 63. p < 0.05 was considered statistically significant. Results: AOM/DSS induced significant bodyweight loss throughout the trial (max -36%), which was attenuated by Saireito (max +7%), EO (max +5%) and EO/Saireito (max +14%; p < 0.05). AOM/DSS increased DAI compared to saline controls (p < 0.05), which was reduced by Saireito, EO and EO/Saireito (p < 0.05). All treatments reduced colonoscopically-assessed colitis severity (days 20 and 41; p < 0.05). EO/Saireito further decreased colitis severity compared to Saireito and EO alone (day 20; p < 0.05). Finally, EO and EO/Saireito resulted in fewer colonic tumours compared to AOM/DSS controls (p < 0.05). Conclusion: Combined EO and Saireito reduced disease and tumour development in AOM/DSS mice, suggesting therapeutic potential in CA-CRC. Keywords: Colorectal cancer; Emu Oil; Kampo medicine; Mouse model; Nutraceuticals; Ulcerative colitis.
  • Validation of the Hospital Frailty Risk Score in older surgical patients: A population-based retrospective cohort study.

    Gunnarsdottir, Gudrun M; Helgadottir, Solveig; Einarsson, Sveinn G; Hreinsson, Kari; Whittle, John; Karason, Sigurbergur; Sigurdsson, Martin I; 1Division of Anaesthesia and Intensive Care Medicine, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. 2Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 3Department of Surgical Sciences, Anesthesiology and Intensive Care Medicine, Uppsala University, Uppsala, Sweden. 4Centre for Perioperative Medicine, Division of Surgery and Interventional Science, University College London, London, UK. (Wiley, 2021-05-18)
    Background: There is a need for standardized and cost-effective identification of frailty risk. The objective was to validate the Hospital Frailty Risk Score which utilizes International Classification Diagnoses in a cohort of older surgical patients, assess the score as an independent risk factor for adverse outcomes and compare discrimination properties of the frailty risk score with other risk stratification scores. Methods: Data were analysed from all patients ≥65 years undergoing primary surgical procedures from 2006-2018. Patients were categorized based on the frailty risk score. The primary outcomes were 30-day mortality and 180-day risk of readmission. Results: Of 16 793 patients evaluated, 7480 (45%), 7605 (45%) and 1708 (10%) had a low, intermediate and high risk of frailty. There was a higher incidence of 30-day mortality for individuals with intermediate (2.9%) and high (8.3%) compared with low (1.4%) risk of frailty (P < .001 for both comparisons). Similarly, the hazard of readmission within the first 180 days was higher for intermediate (HR 1.25; 95% CI: 1.16-1.34) and high (HR 1.84; 95% CI: 1.66-2.03) compared with low (HR 1.00, P < .001 for both comparisons) risk of frailty. The hazard of long-term mortality was higher for intermediate (HR 1.70; 95% CI: 1.61-1.80) and high (HR 4.16; 95% CI: 3.84-4.49) compared with low (HR 1.00, P < .001 for both comparisons) risk of frailty. Finally, long length of primary hospitalization occurred for 9.3%, 15.0% and 27.3% of individuals with low, intermediate and high frailty risk (P < .001 for all comparisons). A model including age and ASA classification had the best discrimination for 30-day mortality (AUC 0.862; 95% CI: 0.847-0.877). Conclusion: Our findings suggest that the Hospital Frailty Risk Score might be used to screen older surgical patients for risk of frailty. While only slightly improving prediction of 30-day mortality using the ASA classification, the Hospital Frailty Risk Score can be used to independently classify older patients for the risk of important outcomes using pre-existing readily available electronic data.

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