Recent Submissions

  • The sarcopenia and physical frailty in older people: multi-component treatment strategies (SPRINTT) project: description and feasibility of a nutrition intervention in community-dwelling older Europeans.

    Jyväkorpi, S K; Ramel, A; Strandberg, T E; Piotrowicz, K; Błaszczyk-Bębenek, E; Urtamo, A; Rempe, H M; Geirsdóttir, Ó; Vágnerová, T; Billot, M; et al. (Springer, 2021-02-13)
    Background: The "Sarcopenia and Physical Frailty in Older People: Multicomponent Treatment Strategies" (SPRINTT) project sponsored a multi-center randomized controlled trial (RCT) with the objective to determine the effect of physical activity and nutrition intervention for prevention of mobility disability in community-dwelling frail older Europeans. We describe here the design and feasibility of the SPRINTT nutrition intervention, including techniques used by nutrition interventionists to identify those at risk of malnutrition and to carry out the nutrition intervention. Methods: SPRINTT RCT recruited older adults (≥ 70 years) from 11 European countries. Eligible participants (n = 1517) had functional limitations measured with Short Physical Performance Battery (SPPB score 3-9) and low muscle mass as determined by DXA scans, but were able to walk 400 m without assistance within 15 min. Participants were followed up for up to 3 years. The nutrition intervention was carried out mainly by individual nutrition counseling. Nutrition goals included achieving a daily protein intake of 1.0-1.2 g/kg body weight, energy intake of 25-30 kcal/kg of body weight/day, and serum vitamin D concentration ≥ 75 mmol/L. Survey on the method strategies and feasibility of the nutrition intervention was sent to all nutrition interventionists of the 16 SPRINTT study sites. Results: Nutrition interventionists from all study sites responded to the survey. All responders found that the SPRINTT nutrition intervention was feasible for the target population, and it was well received by the majority. The identification of participants at nutritional risk was accomplished by combining information from interviews, questionnaires, clinical and laboratory data. Although the nutrition intervention was mainly carried out using individual nutritional counselling, other assisting methods were used as appropriate. Conclusion: The SPRINTT nutrition intervention was feasible and able to adapt flexibly to varying needs of this heterogeneous population. The procedures adopted to identify older adults at risk of malnutrition and to design the appropriate intervention may serve as a model to deliver nutrition intervention for community-dwelling older people with mobility limitations. Keywords: Energy intake; Nutrition counselling; Nutrition intervention; Protein intake; SPRINTT.
  • Comorbidities in a Cohort of 66 Patients With Psoriatic Arthritis Mutilans-Results From the Nordic PAM Study.

    Mistegård, Josephine; Gudbjornsson, Bjorn; Lindqvist, Ulla; Laasonen, Leena; Ejstrup, Leif; Ståhle, Mona; Iversen, Lars; 1Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark. 2Faculty of Medicine, Centre for Rheumatology Research, Landspitali University Hospital, University of Iceland, Reykjavik, Iceland. 3Department of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden. 4Helsinki Medical Imaging Center, Helsinki University Central Hospital, Helsinki, Finland. 5Department of Rheumatology, Odense University Hospital, Odense, Denmark. 6Dermatology Division, Department of Medicine, Karolinska Institutet, Stockholm, Sweden. (Frontiers Media S.A., 2021-02-04)
    Objective: Psoriatic arthritis mutilans (PAM) is the most severe phenotype of psoriatic arthritis due to excessive bone erosion causing joint destruction and decreased functional capacity. The aim of this study was to investigate the prevalence of comorbidities among patients with PAM and the association between comorbidities and joint involvement. Methods: A total of 66 patients aged ≥18 years from the Nordic countries with past or present psoriasis along with at least one mutilated joint were included in the present study. Results: The median number of comorbid conditions per patient was 1 [interquartile range (IQR) 0-2] and 16.7% reported three or more comorbidities. The most frequent comorbidity was hypertension (36.4%). The median number of mutilated joints per patient was 3 (IQR 1-8.3; range 1-38). Conclusion: Two thirds of the patients with PAM reported comorbid conditions and the most frequent was hypertension which affected more than a third of the patients. However, this study was unable to detect any association between comorbidities and the severity of PAM.
  • Spermatogonia Loss Correlates with LAMA 1 Expression in Human Prepubertal Testes Stored for Fertility Preservation.

    Kurek, Magdalena; Åkesson, Elisabet; Yoshihara, Masahito; Oliver, Elizabeth; Cui, Yanhua; Becker, Martin; Alves-Lopes, João Pedro; Bjarnason, Ragnar; Romerius, Patrik; Sundin, Mikael; et al. (MDPI, 2021-01-27)
    Fertility preservation for male childhood cancer survivors not yet capable of producing mature spermatozoa, relies on experimental approaches such as testicular explant culture. Although the first steps in somatic maturation can be observed in human testicular explant cultures, germ cell depletion is a common obstacle. Hence, understanding the spermatogonial stem cell (SSC) niche environment and in particular, specific components such as the seminiferous basement membrane (BM) will allow progression of testicular explant cultures. Here, we revealed that the seminiferous BM is established from 6 weeks post conception with the expression of laminin alpha 1 (LAMA 1) and type IV collagen, which persist as key components throughout development. With prepubertal testicular explant culture we found that seminiferous LAMA 1 expression is disrupted and depleted with culture time correlating with germ cell loss. These findings highlight the importance of LAMA 1 for the human SSC niche and its sensitivity to culture conditions. Keywords: Sertoli cells; basal membrane; germ cells; infertility; late effects; seminiferous tubules; spermatogonia; stem cell niche.
  • Prevention and management of idiosyncratic drug-induced liver injury: Systematic review and meta-analysis of randomised clinical trials.

    Niu, Hao; Sanabria-Cabrera, Judith; Alvarez-Alvarez, Ismael; Robles-Diaz, Mercedes; Stankevičiūtė, Simona; Aithal, Guruprasad P; Björnsson, Einar S; Andrade, Raul J; Lucena, M Isabel; 1Servicio de Farmacología Clínica, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga-IBIMA, Universidad de Málaga, Málaga, Spain. 2Servicio de Farmacología Clínica, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga-IBIMA, Universidad de Málaga, Málaga, Spain; Platform for Clinical Research and Clinical Trials IBIMA, Plataforma ISCiii de Investigación Clínica, Madrid, Spain. 3Servicio de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga-IBIMA, Universidad de Málaga, Málaga, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain. 4Lithuanian University of Health Sciences, Institute of Physiology and Pharmacology, Kaunas, Lithuania. 5NIHR Nottingham Biomedical Research Centre, Nottingham University Hospital NHS Trust and University of Nottingham, Nottingham, United Kingdom. 6Department of Internal Medicine, Section of Gastroenterology and Hepatology, Landspitali University Hospital, Reykjavik, Iceland. 7Servicio de Farmacología Clínica, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga-IBIMA, Universidad de Málaga, Málaga, Spain; Platform for Clinical Research and Clinical Trials IBIMA, Plataforma ISCiii de Investigación Clínica, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain. Electronic address: (Elsevier, 2020-12-24)
    Conducting randomised clinical trials (RCTs) in idiosyncratic drug-induced liver injury (DILI) is challenging. This systematic review aims to summarise the design and findings of RCTs in the prevention and management of idiosyncratic DILI. A systematic literature search up to January 31st, 2020 was performed. Recognised scales were used to assess methodological bias and quality of the studies. Quantitative and qualitative analyses were performed. Heterogeneity was assessed with I2 statistic. Overall, 22 RCTs were included: 12 on prevention (n = 2,471 patients) and 10 in management (n = 797) of DILI/non-acetaminophen DILI-related acute liver failure (ALF). Silymarin (eight studies), bicyclol (four), magnesium isoglycyrrhizinate (three), N-acetylcysteine (three), tiopronin (one), L-carnitine (one), and traditional Chinese medicines (two) were tested in the intervention arm, while control arm mostly received standard supportive care or placebo. Main efficacy criteria in the prevention RCTs was DILI incidence or peak of liver enzymes value. In management RCTs, the efficacy parameter was usually 50 % decrease or normalisation of liver enzymes, or survival rate in DILI-related ALF patients. Overall, 15 trials described the randomisation method, eight were double-blind (n = 672) and nine had sample size estimation (n = 880). Four RCTs involving 377 patients used an intention-to-treat analysis. Based on the scarce number of trials available, tested agents showed limited efficacy in DILI prevention and management and a favourable safety profile. In conclusion, heterogeneity among studies in DILI case qualification and methodologic quality was evident, and the RCTs performed demonstrated limited efficacy of specific interventions. International research networks are needed to establish a framework on RCTs design and therapeutic endpoints.
  • Patients in need of comprehensive geriatric assessment: The utility of the InterRAI emergency department screener.

    Gretarsdottir, Elfa; Jonsdottir, Anna Björg; Sigurthorsdottir, Ingibjörg; Gudmundsdottir, Ester Eir; Hjaltadottir, Ingibjörg; Jakobsdottir, Iris Bjork; Tomasson, Gunnar; Jonsson, Palmi V; Thorsteinsdottir, Thordis; 1Internal Medicine Services, Landspítali The National University Hospital of Iceland, Iceland; Faculty of Nursing, University of Iceland, Iceland. Electronic address: 2Geriatric Department, Landspítali The National University Hospital of Iceland, Iceland. 3Emergency, Geriatrics, Rehabilitation Service, Landspitali The National University Hospital of Iceland, Iceland. 4Faculty of Nursing, University of Iceland, Iceland. 5Faculty of Nursing, University of Iceland, Iceland; Emergency, Geriatrics, Rehabilitation Service, Landspitali The National University Hospital of Iceland, Iceland. 6Internal Medicine Services, Landspítali The National University Hospital of Iceland, Iceland; Faculty of Nursing, University of Iceland, Iceland. 7Department of Rheumatology, Landspítali The National University Hospital of Iceland, Iceland; Centre for Rheumatology Research, Landspítali The National University Hospital, Iceland; Faculty of Medicine, University of Iceland, Iceland. 8Geriatric Department, Landspítali The National University Hospital of Iceland, Iceland; Faculty of Medicine, University of Iceland, Iceland. 9Faculty of Nursing, University of Iceland, Iceland; Research Institute in Emergency Care, Landspítali The National University Hospital of Iceland, Iceland. (Elsevier, 2020-12-25)
    Introduction: The interRAI Emergency Department-Screener (ED-screener) is a risk stratification instrument incorporating functional and social aspects to identify older adults in EDs. The aim was to assess the construct validity and utility of the ED-screener in comparison with more established instruments. Methods: The ED-screener, Triage Risk Screening Tool (TRST) and Identification of Seniors at Risk (ISAR) were administered to older ED-patients. Construct validity was assessed by correlation with TRST and ISAR. The ED-screener scores that corresponded to the established cut-offs for ISAR and TRST were assessed with linear regression. The sensitivity and specificity of the ED-screener for mortality at 4-months were calculated. Results: Two hundred patients were included (mean age 78.5 years, 44% male). Majority (85%) lived at home, 43% lived alone and 53% received home care. The scores of 3.02 and 3.01 on ED-screener corresponded to the cut-off score of 2 on the other instruments. The correlation of the ED-screener with ISAR and TRST was 0.56 and 0.41 respectively. A score of 3 on the ED-screener was 100% sensitive and 28% specific for 4-month mortality. Conclusion: These findings provide support for the construct validity of the ED-screener and its ability to predict outcomes in its intended setting. Keywords: Comprehensive geriatric assessment; Emergency department; InterRAI ED-screener; Screening.
  • Is the Thoughts and Health programme feasible in the context of Swedish schools? A quasi-experimental controlled trial study protocol.

    Wikberg, Carl; Augustsson, Pia; Sveinsdottir, Gudny; Craighead, W Edward; Arnarson, Erikur Örn; Marteinsdottir, Ina; Lilja, Josefine L; 1Primary Health Care, School of Public Health and Community Medicine, University of Gothenburg Institute of Medicine, Sahlgrenska Academy, Gothenburg, Sweden 2Research and Development Primary Health Care, Region Västra Götaland, Gothenburg, Sweden. 3Primary Health Care, School of Public Health and Community Medicine, University of Gothenburg Institute of Medicine, Sahlgrenska Academy, Gothenburg, Sweden. 4Department of Psychology, Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia, USA. 5Faculty of Medicine, School of Health Sciences, Reykjavík, Iceland. 6Department of Psychiatry, Landspítali-University Hospital, Reykjavík, Iceland. 7Department of Medicine and Optometry, University of Kalmar, Kalmar, Sweden. 8Department of Psychology, University of Gothenburg, Goteborg, Sweden. (BMJ Publishing Group, 2021-01-22)
    Introduction: Clinical depression is a substantial problem among adolescents, increasing significantly at about age 15 years. It causes impairment in social, academic and familial relationships, as well as ongoing cognitive and emotional difficulties for the individual. A study in Iceland demonstrated that a cognitive-behavioural, developmentally based intervention programme, 'Thoughts and Health', prevented initial episodes of depression and/or dysthymia (DYS) (major depressive disorder/DYS) in adolescents for up to 12 months following completion of the programme. We would like to test the feasibility of implementing the Icelandic method in a Swedish context and to evaluate the long-term effects of such a programme. Methods and analysis: A quasi-experimental controlled design, combined with qualitative and quantitative methods, will be used to address the research questions.In this study, 617 children aged ~14 years will be screened for depression, and those "at risk" for development of clinical depression will be offered a 12 week course, 'Thoughts and Health'. This course aims to prevent first depression in adolescents. A comparable group of children will function as controls.Depending on the type of variable, baseline comparisons between the two groups of relevant initial measures will be evaluated with t-tests or χ2 analyses. The effects of the programme on the development of clinical levels of depression will be evaluated using the follow-up data of 6, 12 and 18 months. Index parental depression at baseline will be tested as a moderator in the evaluation of the effects of the prevention programme. Ethics and dissemination: This study is approved by the Swedish Ethical Review Board (reference number 2019-03347) in Gothenburg.We plan to disseminate the knowledge gained from this study by publishing our results in peer-reviewed scientific journals and other scholarly outlets. Trial registration number: NCT04128644; Pre-results. Keywords: child & adolescent psychiatry; depression & mood disorders; public health.
  • A narrative review of central nervous system involvement in acute leukemias.

    Deak, Dalma; Gorcea-Andronic, Nicolae; Sas, Valentina; Teodorescu, Patric; Constantinescu, Catalin; Iluta, Sabina; Pasca, Sergiu; Hotea, Ionut; Turcas, Cristina; Moisoiu, Vlad; et al. (AME Publishing Company, 2021-01)
    Acute leukemias (both myeloid and lymphoblastic) are a group of diseases for which each year more successful therapies are implemented. However, in a subset of cases the overall survival (OS) is still exceptionally low due to the infiltration of leukemic cells in the central nervous system (CNS) and the subsequent formation of brain tumors. The CNS involvement is more common in acute lymphocytic leukemia (ALL), than in adult acute myeloid leukemia (AML), although the rates for the second case might be underestimated. The main reasons for CNS invasion are related to the expression of specific adhesion molecules (VLA-4, ICAM-1, VCAM, L-selectin, PECAM-1, CD18, LFA-1, CD58, CD44, CXCL12) by a subpopulation of leukemic cells, called "sticky cells" which have the ability to interact and adhere to endothelial cells. Moreover, the microenvironment becomes hypoxic and together with secretion of VEGF-A by ALL or AML cells the permeability of vasculature in the bone marrow increases, coupled with the disruption of blood brain barrier. There is a single subpopulation of leukemia cells, called leukemia stem cells (LSCs) that is able to resist in the new microenvironment due to its high adaptability. The LCSs enter into the arachnoid, migrate, and intensively proliferate in cerebrospinal fluid (CSF) and consequently infiltrate perivascular spaces and brain parenchyma. Moreover, the CNS is an immune privileged site that also protects leukemic cells from chemotherapy. CD56/NCAM is the most important surface molecule often overexpressed by leukemic stem cells that offers them the ability to infiltrate in the CNS. Although asymptomatic or with unspecific symptoms, CNS leukemia should be assessed in both AML/ALL patients, through a combination of flow cytometry and cytological analysis of CSF. Intrathecal therapy (ITT) is a preventive measure for CNS involvement in AML and ALL, still much research is needed in finding the appropriate target that would dramatically lower CNS involvement in acute leukemia. Keywords: Acute leukemias; central nervous system involvement (CNS involvement); clinical management; pathophysiology.
  • Ábendingar og árangur ósæðarlokuísetningar með þræðingartækni (TAVI) á Íslandi

    Katrín Júníana Lárusdóttir; Hjalti Guðmundsson; Árni Johnsen; Martin Ingi Sigurðsson; Tómas Guðbjartsson; Ingibjörg Jóna Guðmundsdóttir; 1 Læknadeild Háskóla Íslands, 2 hjartalækningadeild, 3 hjarta- og lungnaskurðdeild, 4 svæfinga- og gjörgæsludeild Landspítala (Læknafélag Íslands, 2021-03)
    INNGANGUR Ósæðarlokuþrengsl eru algengasti lokusjúkdómurinn á Vesturlöndum. Hefðbundin meðferð við alvarlegum þrengslum hefur verið opin ósæðarlokuskipti en síðastliðin ár hefur ósæðarlokuísetning með þræðingartækni (TAVI) rutt sér til rúms hér á landi sem erlendis. Markmið rannsóknarinnar var að kanna árangur TAVI-aðgerða á Íslandi með áherslu á ábendingar, fylgikvilla og lifun. EFNIVIÐUR OG AÐFERÐIR Rannsóknin var afturskyggn og tók til allra TAVI-aðgerða sem framkvæmdar hafa verið á Íslandi frá janúar 2012 til loka júní 2020. Skráðir voru bakgrunnsþættir sjúklinga, afdrif og fylgikvillar en einnig heildarlifun sem borin var saman við íslenskt viðmiðunarþýði af sama kyni og aldri. Meðal eftirfylgd var 2,4 ár. NIÐURSTÖÐUR Alls voru framkvæmdar 189 aðgerðir (meðalaldur 83 ± 6 ár, 41,8% konur), allar með sjálfþenjandi lífrænni gerviloku. Flestir sjúklingar (81,5%) höfðu alvarleg hjartabilunareinkenni (NYHA-flokkar III-IV) og miðgildi EuroSCORE-II var 4,9 (bil 0,9-32). Á hjartaómskoðun fyrir aðgerð var hámarks þrýstingsfallandi að meðaltali 78 mmHg og lokuflatarmál 0,67 cm2 . Rúmlega fjórðungur (26,5%) sjúklinga þurfti ísetningu varanlegs gangráðs í kjölfar TAVI-aðgerðar. Aðrir fylgikvillar voru oftast æðatengdir (13,8%), en hjartaþröng greindist í 3,2% tilfella og heilablóðfall í 2,6%. . Mikill randstæður leki við gerviloku sást hjá 0,5% sjúklinga. Dánartíðni innan 30 daga frá aðgerð var 1,6% (n=3) og lifun einu ári frá aðgerðadegi 93,5% (95% ÖB: 89.8-97.3). Heildarlifun var sambærileg lifun viðmiðunarþýðis af sama kyni og sama aldri (p=0,23). ÁLYKTANIR Árangur TAVI-aðgerða hér á landi er mjög góður, ekki síst þegar litið er til lágrar 30 daga dánartíðni og heildarlifunar sem var sambærileg og hjá viðmiðunarþýði. Auk þess var tíðni alvarlegra fylgikvilla lág.
  • Automatic fundus image quality assessment on a continuous scale.

    Karlsson, Robert A; Jonsson, Benedikt A; Hardarson, Sveinn H; Olafsdottir, Olof B; Halldorsson, Gisli H; Stefansson, Einar; 1Faculty of Medicine at the University of Iceland, Sæmundargata 2, 102, Reykjavík, Iceland; Faculty of Electrical and Computer Engineering at the University of Iceland, Sæmundargata 2, 102, Reykjavík, Iceland. Electronic address: 2Faculty of Electrical and Computer Engineering at the University of Iceland, Sæmundargata 2, 102, Reykjavík, Iceland. 3Faculty of Medicine at the University of Iceland, Sæmundargata 2, 102, Reykjavík, Iceland. 4Faculty of Medicine at the University of Iceland, Sæmundargata 2, 102, Reykjavík, Iceland; Landspitali - the National University Hospital of Iceland, Hringbraut 10, 101, Reykjavík, Iceland. 5Oxymap ehf, Vatnsmýrarvegur 16, 101, Reykjavík, Iceland. (Elsevier, 2020-11-12)
    Fundus photography is commonly used for screening, diagnosis, and monitoring of various diseases affecting the eye. In addition, it has shown promise in the diagnosis of brain diseases and evaluation of cardiovascular risk factors. Good image quality is important if diagnosis is to be accurate and timely. Here, we propose a method that automatically grades image quality on a continuous scale which is more flexible than binary quality classification. The method utilizes random forest regression models trained on image features discovered automatically by combining basic image filters using simulated annealing as well as features extracted with the discrete Fourier transform. The method was developed and tested on images from two different fundus camera models. The quality of those images was rated on a continuous scale from 0.0 to 1.0 by five experts. In addition, the method was tested on DRIMDB, a publicly available dataset with binary quality ratings. On the DRIMDB dataset the method achieves an accuracy of 0.981, sensitivity of 0.993 and specificity of 0.958 which is consistent with the state of the art. When evaluating image quality on a continuous scale the method outperforms human raters. Keywords: Fundus image quality assessment; Fundus imaging; Machine learning; Simulated annealing.
  • PopDel identifies medium-size deletions simultaneously in tens of thousands of genomes.

    Niehus, Sebastian; Jónsson, Hákon; Schönberger, Janina; Björnsson, Eythór; Beyter, Doruk; Eggertsson, Hannes P; Sulem, Patrick; Stefánsson, Kári; Halldórsson, Bjarni V; Kehr, Birte; et al. (Nature Publishing Group, 2021-02-01)
    Thousands of genomic structural variants (SVs) segregate in the human population and can impact phenotypic traits and diseases. Their identification in whole-genome sequence data of large cohorts is a major computational challenge. Most current approaches identify SVs in single genomes and afterwards merge the identified variants into a joint call set across many genomes. We describe the approach PopDel, which directly identifies deletions of about 500 to at least 10,000 bp in length in data of many genomes jointly, eliminating the need for subsequent variant merging. PopDel scales to tens of thousands of genomes as we demonstrate in evaluations on up to 49,962 genomes. We show that PopDel reliably reports common, rare and de novo deletions. On genomes with available high-confidence reference call sets PopDel shows excellent recall and precision. Genotype inheritance patterns in up to 6794 trios indicate that genotypes predicted by PopDel are more reliable than those of previous SV callers. Furthermore, PopDel's running time is competitive with the fastest tested previous tools. The demonstrated scalability and accuracy of PopDel enables routine scans for deletions in large-scale sequencing studies.
  • Cumulative Occupational Exposures and Lung-Function Decline in Two Large General-Population Cohorts.

    Lytras, Theodore; Beckmeyer-Borowko, Anna; Kogevinas, Manolis; Kromhout, Hans; Carsin, Anne-Elie; Antó, Josep Maria; Bentouhami, Hayat; Weyler, Joost; Heinrich, Joachim; Nowak, Dennis; et al. (American Thoracic Society, 2021-02)
    Rationale: Few longitudinal studies have assessed the relationship between occupational exposures and lung-function decline in the general population with a sufficiently long follow-up.Objectives: To examine the potential association in two large cohorts: the ECRHS (European Community Respiratory Health Survey) and the SAPALDIA (Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults).Methods: General-population samples of individuals aged 18 to 62 were randomly selected in 1991-1993 and followed up approximately 10 and 20 years later. Spirometry (without bronchodilation) was performed at each visit. Coded complete job histories during follow-up visits were linked to a job-exposure matrix, generating cumulative exposure estimates for 12 occupational exposures. Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were jointly modeled in linear mixed-effects models, fitted in a Bayesian framework, taking into account age and smoking.Results: A total of 40,024 lung-function measurements from 17,833 study participants were analyzed. We found accelerated declines in FEV1 and the FEV1/FVC ratio for exposure to biological dust, mineral dust, and metals (FEV1 = -15.1 ml, -14.4 ml, and -18.7 ml, respectively; and FEV1/FVC ratio = -0.52%, -0.43%, and -0.36%, respectively; per 25 intensity-years of exposure). These declines were comparable in magnitude with those associated with long-term smoking. No effect modification by sex or smoking status was identified. Findings were similar between the ECRHS and the SAPALDIA cohorts.Conclusions: Our results greatly strengthen the evidence base implicating occupation, independent of smoking, as a risk factor for lung-function decline. This highlights the need to prevent or control these exposures in the workplace.
  • Hematopoietic Stem Cell Transplantation Resolves the Immune Deficit Associated with STAT3-Dominant-Negative Hyper-IgE Syndrome.

    Harrison, Stephanie C; Tsilifis, Christo; Slatter, Mary A; Nademi, Zohreh; Worth, Austen; Veys, Paul; Ponsford, Mark J; Jolles, Stephen; Al-Herz, Waleed; Flood, Terence; et al. (Springer, 2021-02-01)
    Autosomal dominant hyper-IgE syndrome caused by dominant-negative loss-of-function mutations in signal transducer and activator of transcription factor 3 (STAT3) (STAT3-HIES) is a rare primary immunodeficiency with multisystem pathology. The quality of life in patients with STAT3-HIES is determined by not only the progressive, life-limiting pulmonary disease, but also significant skin disease including recurrent infections and abscesses requiring surgery. Our early report indicated that hematopoietic stem cell transplantation might not be effective in patients with STAT3-HIES, although a few subsequent reports have reported successful outcomes. We update on progress of our patient now with over 18 years of follow-up and report on an additional seven cases, all of whom have survived despite demonstrating significant disease-related pathology prior to transplant. We conclude that effective cure of the immunological aspects of the disease and stabilization of even severe lung involvement may be achieved by allogeneic hematopoietic stem cell transplantation. Recurrent skin infections and abscesses may be abolished. Donor TH17 cells may produce comparable levels of IL17A to healthy controls. The future challenge will be to determine which patients should best be offered this treatment and at what point in their disease history.
  • Using Robson's Ten-Group Classification System for comparing caesarean section rates in Europe: an analysis of routine data from the Euro-Peristat study.

    Zeitlin, J; Durox, M; Macfarlane, A; Alexander, S; Heller, G; Loghi, M; Nijhuis, J; Sól Ólafsdóttir, H; Mierzejewska, E; Gissler, M; et al. (Wiley-Blackwell, 2020-12-18)
    Objective: Robson's Ten Group Classification System (TGCS) creates clinically relevant sub-groups for monitoring caesarean birth rates. This study assesses whether this classification can be derived from routine data in Europe and uses it to analyse national caesarean rates. Design: Observational study using routine data. Setting: Twenty-seven EU member states plus Iceland, Norway, Switzerland and the UK. Population: All births at ≥22 weeks of gestational age in 2015. Methods: National statistical offices and medical birth registers derived numbers of caesarean births in TGCS groups. Main outcome measures: Overall caesarean rate, prevalence and caesarean rates in each of the TGCS groups. Results: Of 31 countries, 18 were able to provide data on the TGCS groups, with UK data available only from Northern Ireland. Caesarean birth rates ranged from 16.1 to 56.9%. Countries providing TGCS data had lower caesarean rates than countries without data (25.8% versus 32.9%, P = 0.04). Countries with higher caesarean rates tended to have higher rates in all TGCS groups. Substantial heterogeneity was observed, however, especially for groups 5 (previous caesarean section), 6, 7 (nulliparous/multiparous breech) and 10 (singleton cephalic preterm). The differences in percentages of abnormal lies, group 9, illustrate potential misclassification arising from unstandardised definitions. Conclusions: Although further validation of data quality is needed, using TGCS in Europe provides valuable comparator and baseline data for benchmarking and surveillance. Higher caesarean rates in countries unable to construct the TGCS suggest that effective routine information systems may be an indicator of a country's investment in implementing evidence-based caesarean policies. Tweetable abstract: Many European countries can provide Robson's Ten-Group Classification to improve caesarean rate comparisons. Keywords: Caesarean birth; Europe; Robson classification; Ten-Group Classification System; health information systems; perinatal health indicators.
  • Arrest-related death on the basis of a drug-induced excited delirium syndrome.

    Kunz, S N; Þórðardóttir, S; Jónasson, J G; 1Institute of Forensic Medicine, Ulm University Hospital, Germany; Ulm University, Germany. Electronic address: 2Department of Pharmacology and Toxicology, University of Iceland, Reykjavik, Iceland. 3Department of Pathology, Landspítali University Hospital Reykjavik, Iceland. (Elsevier, 2020-11-26)
    Aims: In typical arrest-related death (ARD) scenarios, the victims often show signs of excited delirium syndrome (ExDS), intoxication, exhaustion and/or suffered from a preexisting physical or psychiatrical condition, all of which could have caused or at least triggered the person's death. Since autopsy findings are very rare in such cases, a clear clinicopathologic diagnosis and thus mechanism of death is rarely found. Methods: We present a case of a 25-year old woman, who died while being arrested by the police. Based on the patient's medical history, autopsy findings, contradicting witness testimonies, and reliable clinical and toxicological blood parameters, the most probable diagnosis is discussed. Results: The cause of death was determined as cardiac arrest subsequent to a combination of excited delirium syndrome, physical exhaustion and respiratory impairment. The manner of death was unnatural and juridically, the charges were dropped. Conclusions: In cases, where the cause and mechanism of death can only be diagnosed by exclusion, police collaboration, detailed clinical history (past and present) as well as clinical blood parameter analyses are necessary to help evaluating possible contributing factors and the most probable cause of death in ARD. Keywords: Amphetamine; Arrest-related death; Asphyxia; Excited delirium syndrome; Forensic medicine; Restraint.
  • Seaweed extract improves carbohydrate metabolism in overweight and obese adults

    Elidottir, Anita S.; Sveinsdottir, Kolbrun; Ingadottir, Bergros; Geirsdottir, Olof G.; Jonsson, Palmi V.; Rothenberg, Elisabeth; Hardardottir, Ingibjorg; Freysdottir, Jona; Ramel, Alfons; aFaculty of Food Science and Nutrition, University of Iceland, Reykjavik, Iceland bThe Icelandic Food and Biotech R&D Institute, Reykjavik, Iceland cThe Icelandic Gerontological Research Institute, Reykjavik, Iceland dDepartment of Food and Meal Science, Kristianstad University, kristianstad, Sweden eFaculty of Medicine, University of Iceland, Reykjavik, Iceland fDepartment of Immunology, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland (Bentham Science Publishers, 2021-01-01)
    Background: Obesity is characterized by chronic low-grade inflammation and associated with type 2 diabetes. Seaweed is one of the largest producers of biomass in the marine environment and is a rich arsenal of functional ingredients that may possess the potential to prevent type 2 diabetes. Objective: The aim was to investigate the effects of seaweed extract on glucose metabolism and markers of inflammation in overweight and obese individuals. Methods: Participants (N=76, >40 years, body mass index >25 kg/m 2 ) who volunteered for this 10week randomized, controlled, doubly blinded intervention study, were randomized into an intervention group (seaweed extract, 3 capsules=1200 mg/day) or a control group (placebo, 3 capsules/day). The extract derived from the brown seaweed bladder wrack (Fucus vesiculosus). At baseline and endpoint of the study, fasting samples were analysed for blood glucose, insulin, inflammation markers, liver enzymes and creatinine (renal function). Results: Drop out was 11.8% and not significantly different between groups. Fasting blood glucose and insulin were improved at the endpoint in the intervention group, but no changes were observed in the control group (corrected endpoint differences between groups: glucose=0.61 mmol/L, P=0.038; insulin=0.72 mu U/L, P=0.038). Measures of inflammation, liver enzymes and renal function did not change significantly during the study. Conclusion: Ingestion of seaweed extract over 10 weeks improves glucose metabolism without affecting measures of inflammation, liver function or renal function.
  • Parental occupational exposure pre- and post-conception and development of asthma in offspring.

    Pape, Kathrine; Svanes, Cecile; Sejbæk, Camilla S; Malinovschi, Andrei; Benediktsdottir, Byndis; Forsberg, Bertil; Janson, Christer; Benke, Geza; Tjalvin, Gro; Sánchez-Ramos, José Luis; et al. (Oxford University Press, 2021-01)
    Background: While direct effects of occupational exposures on an individual's respiratory health are evident, a new paradigm is emerging on the possible effects of pre-conception occupational exposure on respiratory health in offspring. We aimed to study the association between parental occupational exposure starting before conception and asthma in their offspring (at 0-15 years of age). Methods: We studied 3985 offspring participating in the Respiratory Health in Northern Europe, Spain and Australia (RHINESSA) generation study. Their mothers or fathers (n = 2931) previously participated in the European Community Respiratory Health Survey (ECRHS). Information was obtained from questionnaires on parental job history pre- and post-conception which was linked to an asthma-specific job-exposure matrix (JEM). We assessed the association between parental occupational exposure and offspring asthma, applying logistic regression models, clustered by family and adjusted for study centre, offspring sex, parental characteristics (age, asthma onset, place of upbringing, smoking) and grandparents' level of education. Results: Parental occupational exposure to microorganisms, pesticides, allergens or reactive chemicals pre-conception or both pre- and post-conception was not related to offspring asthma; in general, subgroup analyses confirmed this result. However, maternal exposure both pre- and post-conception to allergens and reactive chemicals was associated with increased odds for early-onset asthma in offspring (0-3 years of age); odds ratio 1.70 (95% CI: 1.02-2.84) and 1.65 (95% CI: 0.98-2.77), respectively. Conclusions: This study did not find evidence that parental occupational exposure, defined by an asthma JEM before conception only or during pre- and post-conception vs non-exposed, was associated with offspring asthma. Keywords: job-exposure matrices; Epidemiology; air pollutants; asthma; generation study; occupation; occupational exposure.
  • The applications of transcranial Doppler in ischemic stroke.

    Finnsdóttir, Herdis; Szegedi, István; Oláh, László; Csiba, László; 1University of Debrecen, Faculty of Medicine, Department of Surgery, Debrecen, Hungary. 2Landspítali - National University Hospital of Iceland, Department of Surgery, Reykjavík, Iceland. (Literatura Medica, 2020-11)
    Background: This overview provides a summary of the applications of transcranial Doppler (TCD) in ischemic stroke. Results: A fast-track neurovascular ultrasound protocol has been developed for detecting occlusion or stenosis. The technique is more reliable in the carotid area than in the posterior circulation. By monitoring the pulsatility index the in-crea-sed intracranial pressure can be diagnosed. TIBI score was developed for grading residual flow. TCD has been shown to accurately predict complete or any recanalization. Regarding recanalization, TCD has a sensitivity of 92%, a specificity of 88%, a positive predictive value of 96%, a negative predictive value of 78% and an overall accuracy of 91%, respectively. Sonothrombolysis seemed to be a promising application but randomized controlled trials have shown that it does not improve clinical outcome. TCD examination can detect microembolic signals (MES) which are associated with an increased risk of stroke. Micro-em-boli were detected in symptomatic and asymptomatic carotid artery stenosis and during carotid endarterectomy. The number of microemboli can be decreased by antithrombotic therapy. Contrast en-chan-ced examination and Valsalva maneuver with continuous TCD monitoring can accurately screen for right-to-left shunt. Keywords: ischemic stroke; stroke; transcranial Doppler; ultrasound.
  • Analysis of graduating nursing students' moral courage in six European countries.

    Koskinen, Sanna; Pajakoski, Elina; Fuster, Pilar; Ingadottir, Brynja; Löyttyniemi, Eliisa; Numminen, Olivia; Salminen, Leena; Scott, P Anne; Stubner, Juliane; Truš, Marija; et al. (SAGE Publications, 2020-10-29)
    Background: Moral courage is defined as courage to act according to one's own ethical values and principles even at the risk of negative consequences for the individual. In a complex nursing practice, ethical considerations are integral. Moral courage is needed throughout nurses' career. Aim: To analyse graduating nursing students' moral courage and the factors associated with it in six European countries. Research design: A cross-sectional design, using a structured questionnaire, as part of a larger international ProCompNurse study. In the questionnaire, moral courage was assessed with a single question (visual analogue scale 0-100), the questionnaire also covered several background variables. Participants and research context: The sample comprised graduating nursing students (n = 1796) from all participating countries. To get a comprehensive view about graduating nursing students' moral courage, the views of nurse managers (n = 538) and patients (n = 1327) from the same units in which the graduating nursing students practised were also explored, with parallel questionnaires. Ethical considerations: Ethical approvals and research permissions were obtained according to national standards in every country and all participants gave their informed consent. Results: The mean of graduating nursing students' self-assessed moral courage was 77.8 (standard deviation 17.0; on a 0-100 scale), with statistically significant differences between countries. Higher moral courage was associated with many factors, especially the level of professional competence. The managers assessed the graduating nursing students' moral courage lower (66.5; standard deviation 18.4) and the patients slightly higher (80.6; standard deviation 19.4) than the graduating nursing students themselves. Discussion and conclusions: In all countries, the graduating nursing students' moral courage was assessed as rather high, with differences between countries and populations. These differences and associations between moral courage and ethics education require further research. Keywords: Ethical competence; graduating nursing student; international survey; moral courage; nursing education.
  • Fish skin grafts compared to human amnion/chorion membrane allografts: A double-blind, prospective, randomized clinical trial of acute wound healing.

    Kirsner, Robert S; Margolis, David J; Baldursson, Baldur T; Petursdottir, Kristin; Davidsson, Olafur B; Weir, Dot; Lantis, John C; 1Dr Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida. 2Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. 3Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. 4Department of Dermatology, Landspitali University Hospital of Iceland, Reykjavik, Iceland. 5Mathematics Division of the Science Institute, University of Iceland, Reykjavik, Iceland. 6Catholic Health Advanced Wound Healing Centers, Buffalo, New York. 7Division of Vascular/Endovascular Surgery, Mount Sinai St. Luke's-West Hospitals, Icahn School of Medicine, New York, New York. (2019-10-25)
    Chronic, nonhealing wounds consume a great deal of healthcare resources and are a major public health problem, associated with high morbidity and significant economic costs. Skin grafts are commonly used to facilitate wound closure. The grafts can come from the patient's own skin (autograft), a human donor (allograft), or from a different species (xenograft). A fish skin xenograft from cold-water fish (Atlantic cod, Gadus morhua) is a relatively recent option that shows promising preclinical and clinical results in wound healing. Chronic wounds vary greatly in etiology and nature, requiring large cohorts for effective comparison between therapeutic alternatives. In this study, we attempted to imitate the status of a freshly debrided chronic wound by creating acute full-thickness wounds, 4 mm in diameter, on healthy volunteers to compare two materials frequently used to treat chronic wounds: fish skin and dHACM. The purpose is to give an indication of the efficacy of the two therapeutic alternatives in the treatment of chronic wounds in a simple, standardized, randomized, controlled, double-blind study. All volunteers were given two identical punch biopsy wounds, one of which was treated with a fish skin graft and the other with dehydrated human amnion/chorion membrane allograft (dHACM). In the study, 170 wounds were treated (85 wounds per group). The primary endpoint was defined as time to heal (full epithelialization) by blinded assessment at days 14, 18, 21, 25, and 28. The superiority hypothesis was that the fish skin grafts would heal the wounds faster than the dHACM. To evaluate the superiority hypothesis, a mixed Cox proportional hazard model was used. Wounds treated with fish skin healed significantly faster (hazard ratio 2.37; 95% confidence interval: (1.75-3.22; p = 0.0014) compared with wounds treated with dHACM. The results show that acute biopsy wounds treated with fish skin grafts heal faster than wounds treated with dHACM.
  • Integration of nursing services provided to patients with heart failure living at home: A longitudinal ethnographic study.

    Bjornsdottir, Kristin; Ketilsdottir, Audur; Gudnadottir, Margret; Kristinsdottir, Inga V; Ingadottir, Brynja; 1Faculty of Nursing, School of Health Sciences, University of Iceland, Reykjavik, Iceland. 2Division of Clinical Services II (Cardiovascular Center, Landspitali - the National University Hospital of Iceland, Reykjavik, Iceland. (Wiley, 2021-01-12)
    Aims and objectives: This study aimed to (1) describe the development of integrated services between hospital-based heart failure nursing services and municipally located home care nurses' services and (2) identify the benefits of this collaboration for the development of home care nursing services. Background: Governments have called for better integration of healthcare services to respond to demographic ageing. Clinical pathways have been used to enhance integration and assure continuity between primary and secondary care. Competencies in addressing advanced health issues among home care nurses must be improved. Design: A longitudinal ethnographic study of the development of home care nursing services for persons living with heart failure. Methods: Data were field notes from observations at meetings of the steering group designing the services, visits to patients' homes and from educational sessions. Interviews were conducted with the home care nurses, heart failure nurses and focus group meetings with nurses working in home care nursing. Reporting adhered to the Consolidated Criteria for Reporting Qualitative Studies checklist. Results: In a collaborative project, nurses from the two settings developed nursing services to address signs indicating exacerbation of heart failure and risk of hospital visits, involving advanced heart failure monitoring and treatment in patients' homes. A clinical pathway was developed to assure effective assessment of patients' condition. The home care nurses gained new knowledge and developed work practices that called for different competencies. Access to consultation from specialised heart failure nurses was instrumental in this transition. Conclusions: The development of nursing services by integrating primary and secondary services facilitates translation of knowledge, competencies and understandings between nurses at different settings. Such integration can foster expertise in nursing services. Relevance to clinical practice: The transfer of specialised healthcare services to primary care facilitates collaboration and sharing of knowledge, understanding and work practices. Keywords: advanced practice nurses; competencies; ethnography; expertise; heart failure; home care nurses; integrated services; knowledge; trans-situational.

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