• Kidney Transplant Outcomes in Patients With Adenine Phosphoribosyltransferase Deficiency.

      Runolfsdottir, Hrafnhildur Linnet; Palsson, Runolfur; Agustsdottir, Inger M Sch; Indridason, Olafur S; Li, Jennifer; Dao, Myriam; Knebelmann, Bertrand; Milliner, Dawn S; Edvardsson, Vidar O; 1Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland. 2Internal Medicine and Rehabilitation Services, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. 3Children's Medical Center, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. 4Centre for Transplant and Renal Research, Westmead Institute for Medical Research, Sydney University, Sydney, Australia. 5Department of Nephrology-Transplantation, Necker Hospital, APHP, Paris, France. 6Paris Descartes University, Sorbonne Paris Cité, Paris, France. 7Département Biologie cellulaire, INSERM U1151, Institut Necker Enfants Malades, Paris, France. 8Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN. (Lippincott Williams & Wilkins, 2020-11)
      Background: Adenine phosphoribosyltransferase (APRT) deficiency is a rare, hereditary cause of kidney stones and chronic kidney disease (CKD) which is characterized by 2,8-dihydroxyadenine renal parenchymal crystal deposition. The aim of this study was to examine outcomes of kidney transplantation in APRT deficiency patients. Methods: Included were 13 patients in the APRT Deficiency Registry of the Rare Kidney Stone Consortium, 2 from Westmead Hospital in Sydney, Australia, and 2 from Necker Hospital in Paris, France. The CKD-EPI and CKiD equations were used to calculate glomerular filtration rate estimates. Allograft survival was analyzed employing the Kaplan-Meier method. The Wilcoxon-Mann-Whitney test was used to compare alllograft outcomes according to xanthine oxidoreductase (XOR) inhibitor treatment status at transplantation. Results: Seventeen patients (9 females) received 22 kidney transplants. Age at first transplantation was 47.2 (14.9-67.0) years. Ten patients received XOR inhibitor therapy pretransplant (11 allografts), while 8 patients did not receive such treatment before transplantation (11 allografts). Two-year allograft survival was 91% and 55% in the 2 groups, respectively (P = 0.16). The median (range) estimated glomerular filtration rate at 2 years posttransplant was 61.3 (24.0-90.0) mL/min/1.73 m when XOR inhibitor therapy was initiated before transplantation, and 16.2 (10.0-39.0) mL/min/1.73 m (P = 0.009) when such treatment was not administered pretransplant. Conclusions: Kidney allograft outcomes are good in APRT deficiency patients beginning XOR inhibitor therapy pretransplant. Delay in such treatment is a major cause of premature graft loss in these patients. Increased awareness among clinicians is imperative, promoting early diagnosis of APRT deficiency and pharmacotherapy initiation before kidney transplantation.
    • Nationwide Incidence and Outcomes of Patients With Coronavirus Disease 2019 Requiring Intensive Care in Iceland.

      Kristinsson, Bjarki; Kristinsdottir, Linda B; Blondal, Asbjorn T; Thormar, Katrin M; Kristjansson, Mar; Karason, Sigurbergur; Sigvaldason, Kristinn; Sigurdsson, Martin I; 1Division of Anesthesia and Intensive Care Medicine, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. 2Division of Anesthesia and Intensive Care Medicine, Akureyri Hospital, Akureyri, Iceland. 3Division of Infectious Diseases, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. 4Faculty of Medicine, University of Iceland, Reykjavik, Iceland. (Lippincott Williams & Wilkins, 2020-11)
      Objectives: To determine the nationwide demographics and hospital mortality of patients with severe acute respiratory syndrome coronavirus 2 infection requiring admission to the ICU for coronavirus disease 2019 in Iceland. Design: Prospective observational study. Setting: All ICUs in Iceland (Landspitali University Hospital and Akureyri Regional Hospital). Patients: All patients admitted to the ICU for management of coronavirus disease 2019 between March 14, 2020, and April 13, 2020, with follow-up through May 5, 2020. Interventions: None. Measurements and main results: A total of 27 patients were admitted to the ICU for coronavirus disease 2019 out of 1,788 severe acute respiratory syndrome coronavirus 2 positive cases, rendering an overall admission ratio of 1.5% (95% CI, 1.0-2.2%). The population rate of ICU admission for coronavirus disease 2019 was 7.4 (95% CI, 4.9-10.8) admissions per 100,000 individuals. The hospital mortality of patients admitted to the ICU was 15% (95% CI, 4-34%), and the mortality of patients receiving mechanical ventilation was 19% (95% CI, 4-46%). Conclusions: We report a lower overall ratio of ICU admissions for coronavirus disease 2019 among severe acute respiratory syndrome coronavirus 2 positive patients and a lower hospital mortality for patients treated in the ICU for coronavirus disease 2019 compared with initial reports from Italy and China. Our results could be explained by the early adoption of widespread testing and a successful national response to the pandemic.
    • Interventions to prevent or reduce rationing or missed nursing care: A scoping review.

      Schubert, Maria; Ausserhofer, Dietmar; Bragadóttir, Helga; Rochefort, Christian M; Bruyneel, Luk; Stemmer, Renate; Andreou, Panayiota; Leppée, Marcel; Palese, Alvisa; 1School of Health Professions, ZHAW - Zurich University of Applied Science, Institute of Nursing, Winterthur, Switzerland. 2Nursing Science, Faculty of Medicine, Department of Public Health, University of Basel, Basel, Switzerland. 3Claudiana College of Health-Care Professions, Bolzano, Italy. 4Faculty of Nursing, School of Health Sciences and Landspítali University Hospital, University of Iceland, Reykjavik, Iceland. 5School of Nursing, Faculty of Medicine and Health Sciences - Centre de recherche Charles-Le Moyne - Saguenay-Lac-Saint-Jean sur les innovations en santé (CR-CSIS), Centre de recherche du Centre Hospitalier Universitaire de Sherbrooke (CR-CHUS), University of Sherbrooke, Longueuil, Canada. 6Department for Public Health and Primary Care, KU Leuven - University of Leuven, Leuven Institute for Healthcare Policy, Leuven, Belgium. 7Faculty of Health and Nursing, Catholic University of Applied Sciences Mainz, Mainz, Germany. 8Medical School, University of Nicosia, Nicosia, Cyprus. 9Project Department, Institute for Healthy Ageing, Zagreb, Croatia. 10Department of Medical Science, University Udine, Udine, Italy. (Blackwell Scientific Publications, 2020-10-22)
      Aims: To collate and synthesize published research on interventions developed and tested to prevent or reduce the rates of rationed or missed nursing care in healthcare institutions. Background: Rationed and missed nursing care has been widely studied, including its predictors and associations with patient and nurse outcomes. Design: Scoping review. Data sources: We searched for eligible studies, published between 1980-2019, in six electronic databases. Review methods: Researchers independently screened the abstracts of the retrieved studies using the inclusion and exclusion criteria. The decision of whether or not to include any given study was consensus-based. Results: The search yielded 1,815 records, of which 13 were included. Three studies reported structural interventions, namely increased nurse staffing and improved nursing teamwork, both resulted in significant reductions in the rates of rationed or missed nursing care. The remaining 10 studies reported on process interventions: four concerned reminders (via technology or designated persons) and seven described interventions to change or optimize the relevant care processes. All 10 process interventions contributed to significant reductions in the rates of missed nursing care. Conclusions: The results of the scoping review indicate that specific interventions can positively influence the performance of a selected nursing care activity, for example fall prevention. There is no evidence of a global reduction of rationed and missed nursing care through these interventions. Impact: Clinicians, managers and researchers can use the results for adapting and implementing interventions to reduce rationed and missed nursing care. Keywords: decision-making; interventions; nurse staffing; nursing care; prevention; quality of care; rationed and missed nursing care; scoping review; teamwork.
    • Salivary gland tumours in Iceland 1986-2015: a nationwide epidemiological analysis over a 30-year time period.

      Aegisdottir, Anna Lilja; Tryggvason, Geir; Jonsdottir, Anna Margret; Jonasson, Jon Gunnlaugur; 1Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 2Department of Otorhinolaryngology, The National University Hospital of Iceland, Reykjavik, Iceland. 3Department of Pathology, The National University Hospital of Iceland, Reykjavik, Iceland. (Wiley, 2020-10-16)
      Salivary gland tumours (SGT) are a vast and heterogenous group of neoplasms. There is a relative lack of comprehensive nationwide epidemiological studies on the subject. The aim of this nationwide analysis was to gain insight into epidemiological traits, such as site, incidence and histological subtypes of SGT in general. Patients diagnosed with a primary SGT between 1986 and 2015 were identified from The Icelandic Cancer Registry and registries from all pathology departments in Iceland. Information on age, sex, tumour location and histology was retrieved from pathology reports. A total of 687 patients were diagnosed with a SGT, 609 (89%) were benign and 78 (11%) malignant. 9% of parotid gland tumours, 22% of submandibular gland tumours and 26% of minor SGT were malignant. The most common malignant tumours were mucoepidermoid carcinoma, acinic cell carcinoma and adenoid cystic carcinoma. The incidence of benign SGT was 4.9 per 100 000 among men and 7.0 per 100 000 among women. The incidence of malignant tumours was 0.59 per 100 000 for men and 0.79 per 100 000 for women. The proportion of malignant SGT is lower than most often reported. Only 10% of parotid gland tumours, 20% of submandibular gland tumours and 25% of minor salivary gland tumours are malignant. Keywords: Salivary gland; epidemiology; histology; oncology; tumour.
    • Docosahexaenoic Acid Modulates NK Cell Effects on Neutrophils and Their Crosstalk.

      Jensen, Kirstine Nolling; Omarsdottir, Sunnefa Yeatman; Reinhardsdottir, Margret Sol; Hardardottir, Ingibjorg; Freysdottir, Jona; 1Faculty of Medicine, Biomedical Center, University of Iceland, Reykjavik, Iceland. 2Department of Immunology, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. 3Center for Rheumatology Research, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. 4Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavik, Iceland. (FRONTIERS MEDIA SA, 2020-10-05)
      Natural killer (NK) cells and neutrophils engage in crosstalk that is important in inflammation and likely also for resolution of inflammation. NK cells activate neutrophils and induce their infiltration to the inflamed sites but may also influence their apoptosis and their subsequent efferocytosis by macrophages. Several studies indicate that docosahexaenoic acid (DHA) can inhibit NK cell cytotoxicity but the effects of DHA on the ability of NK cells to engage in crosstalk with neutrophils and affect their functions have not been described. This study explored the kinetics of the effects of NK cells and NK cells pre-treated with DHA on neutrophil surface molecule expression and apoptosis, as well as the ability of NK cells to affect other neutrophil functions. In addition, the study explored the effects of neutrophils on NK cell phenotype and function. Primary NK cells were pre-incubated with or without DHA, then stimulated and co-cultured with freshly isolated neutrophils. When co-cultured with NK cells, neutrophils had higher expression levels of CD11b and CD47; secreted more IL-8, IL-1ra, and CXCL10; had increased phagocytic ability; and their apoptosis was increased early after initiation of the co-culture while dampened at a later time-point. Pre-incubation of NK cells with DHA attenuated NK cell-induced upregulation of CD11b and CD47 on neutrophils, had minor effects on NK cell induction of cytokine/chemokine secretion or their phagocytic ability. Neutrophils also affected the function of NK cells, lowering the frequency of NKp46+ and CXCR3+ NK cells and increasing the concentrations of IFN-γ, TNF-α, and GM-CSF in the co-cultures. Pre-incubation of NK cells with DHA further decreased the frequency of NKp46+ NK cells in the co-culture with neutrophils and decreased the concentrations of IFN-γ, CCL3 and GM-CSF. These findings indicate that NK cells have mostly pro-inflammatory effects on neutrophils and that DHA can attenuate some of these pro-inflammatory effects. Neutrophils had both anti- and pro-inflammatory effects on NK cells. When NK cells had been pre-treated with DHA, the anti-inflammatory effects were increased and some of the pro-inflammatory effects attenuated. Overall, the results suggest that DHA may lead to a more anti-inflammatory microenvironment for NK cell and neutrophil crosstalk.
    • Indexing haemodynamic variables in young children.

      Sigurdsson, Theodor S; Lindberg, Lars; 1Department of Paediatric Anaesthesiology and Intensive Care Medicine, Lund Children´s Hospital, Skåne University Hospital, Lund, Sweden. 2Department of Anaesthesiology and Intensive Care Medicine, Landspitalinn University Hospital, Reykjavik, Iceland. (https://onlinelibrary.wiley.com/doi/10.1111/aas.13720, 2020-10-05)
      Background: Haemodynamic studies in children are rare and most studies have included few subjects in the youngest age group. Haemodynamic variables need to be indexed to establish a reference of normality that is valid in all populations. The traditional way to index haemodynamic variables with body surface area (BSA) is complicated in young children due to its non-linear relationship with body weight (BW). We examined several haemodynamic variables in children by indexing them with BSA and BW. Methods: A single-centre, observational cohort study comparing non-indexed and indexed haemodynamic variables in children undergoing heart surgery (divided into three weight groups: 1-5 kg, >5-10 kg and >10-15 kg). Results: A total of 68 children were included in this study, mean age 11.1 months ± 11.1 month (range 0 to 43 months). All haemodynamic variables, cardiac output (CO), stroke volume (SV), total end-diastolic volume (TEDV), central blood volume (CBV) and active circulation volume (ACV), increased with weight without indexing (P < .05). Indexing variables with BW produced a more linear relationship for all haemodynamic variables between weight groups than BSA. The mean BSA-indexed haemodynamic values were CIBSA 3.5 ± 1.1 L/min/m2 and SVIBSA 27.3 ± 8.9 ml/min/m2 . The mean BW-indexed haemodynamic values were CIBW 180 ± 50 ml/min/kg and SVIBW 1.34 ± 0.38 ml/kg. Blood volume variables indexed with BW were TEDVBW 12.0 ± 2.8 ml/kg, CBVBW 21.3 ± 6.6 ml/kg and ACVBW 70.3 ± 15.2 ml/kg. Conclusions: Indexing haemodynamic variables with BW produces a more appropriate body size-independent scale in young children than BSA. Summary statement: In this study, we studied indexing of haemodynamic variables and estimation of blood volumes in young children undergoing corrective heart surgery using an indicator dilution technology. Keywords: blood volume; body surface area; body weight; cardiac output; children; indexing.
    • The Impact of Receiving a Family-Oriented Therapeutic Conversation Intervention Before and During Bereavement Among Family Cancer Caregivers: A Nonrandomized Trial.

      Petursdottir, Asta B; Sigurdardottir, Valgerdur; Rayens, Mary Kay; Svavarsdottir, Erla Kolbrun; 1 ]‎ Univ Iceland, Sch Hlth Sci, Reykjavik, Iceland Show more [ 2 ]‎ Landspitali Natl Univ Hosp, Palliat Care Unit, Reykjavik, Iceland Show more [ 3 ]‎ Univ Iceland, Fac Nursing, Sch Hlth Sci, Reykjavik, Iceland Show more [ 4 ]‎ Univ Kentucky, Lexington, KY USA Show more [ 5 ]‎ Landspitali Natl Univ Hosp, Res & Dev Family Nursing, Reykjavik, Iceland (LIPPINCOTT WILLIAMS & WILKINS, 2020-10)
      Effective communication is the foundation of quality care in palliative nursing. As frontline palliative home care providers, nurses could foster more effective bereavement coping skills through therapeutic conversations. The purpose of this study was to evaluate the impact of a nursing intervention offered to bereaved family cancer caregivers. This was a quasi-experimental design, with a posttest-only comparison of the intervention and control groups receiving usual care. Bereaved caregivers (n = 51) receiving services from a specialized palliative home care unit participated and completed measures of depression, anxiety, stress, and grief reactions 3, 5, and 6 months after their close relative had died.There was a significant decrease in anxiety symptoms in the intervention group compared with the control group across all 3 time points. Anxiety and stress symptoms also decreased over time in the 2 groups combined, but this decrease was not observed for depression. When evaluating grief reactions, the intervention group had a lower mean of controlled grief responses, across the posttest period, than the control group.Results demonstrate that providing bereaved family caregivers the opportunity to participate in a therapeutic conversation intervention might reduce distressing symptoms in early bereavement.
    • Self-reported concussion history among Icelandic female athletes with and without a definition of concussion.

      Kristjánsdóttir, Hafrún; Brynjarsdóttir, Ragna Margrét; Kristensen, Ingunn S U; Sigurjónsdóttir, Helga Á; Claessen, Lára Ósk Eggertsdóttir; Jónsdóttir, María K; 1Physical Activity, Physical Education, Sport and Health (PAPESH) Research Centre, Sports Science Department, School of Social Sciences, Reykjavik University, Reykjavík, Iceland. 2Psychology Department, School of Social Sciences, Reykjavik University, Reykjavík, Iceland. 3Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavík, Iceland. 4Landspitali - The National Hospital of Iceland, Reykjavík, Iceland. (Taylor & Francis, 2020-09-29)
      Objective: This study examined whether Icelandic female athletes in contact sports, based their self-reported concussion history on adequate medical definitions, by assessing self-reported concussion history with and without a definition of concussion. Another aim was to examine whether currently active athletes were more knowledgeable of concussions than retired athletes. Methods: Participants (age = 26.9, SD = 7.1) were 508 former (34.5%) and current (65.5%) elite female athletes in soccer (41%), handball (30.6%), basketball (19.1%), ice hockey (4.5%) and combat sports (4.7%). An online questionnaire (QuestionPro) was distributed to females in contact sports (snowball sampling). Participants later came for an in-person interview where the authenticity of previous responses was confirmed. In the questionnaire, participants answered background questions and questions about concussion history. First, they reported the total number of sustained concussions without a prompt. They reported the number of sustained concussions again after reading a definition of concussion. Participants could not correct their previous answers. Pearson's Chi-square was used for group comparisons. Results: The prevalence of reported concussions increased from 40.2% to 64.8% following a definition. There was no significant difference in how many participants changed their answer when asked about sustaining SRCs before and after reading the definition based on whether the participants were still competitive or retired X 2(1) = 0.69, p = 0.41. Conclusions: Our data suggest that understanding of concussions is inadequate among female athletes. Self-report will continue to be an essential source of clinical information and prompting with a definition can increase the reliability of self-reported concussions. Keywords: Concussion knowledge; contact sports; high-concussion risk sports; self-report; sport-related concussions.
    • A shorter breastfeeding duration in late preterm infants than term infants during the first year.

      Jonsdottir, Rakel B; Jonsdottir, Helga; Orlygsdottir, Brynja; Flacking, Renée; 1Neonatal Intensive Care Unit, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland. 2Faculty of Nursing, School of Health Sciences, University of Iceland, Reykjavik, Iceland. 3School of Education, Health and Social Studies, Dalarna University, Falun, Sweden. (Wiley, 2020-09-26)
      Aim: Little attention has been paid to breastfeeding late preterm (LPT) infants. This study compared breastfeeding, worries, depression and stress in mothers of LPT and term-born infants throughout the first year. We also described factors associated with shorter breastfeeding duration of LPT infants. Methods: This longitudinal cohort study of the mothers of singleton infants-129 born LPT and 277 born at term-was conducted at Landspitali-The National University Hospital of Iceland, which has the country's only neonatal intensive care unit. The mothers answered questionnaires when their infants were 1, 4, 8 and 12 months of age. Results: Mothers breastfed LPT infants for a significantly shorter time than term infants: a median of 7 months (95% confidence interval 5.53-8.48) vs 9 months (95% confidence interval 8.39-9.61) (P < .05). Starting solids at up to 4 months was the strongest risk factor for LPT breastfeeding cessation during the first year, after adjusting for confounders (P < .001). Their mothers reported more worries about their infants' health and behaviour during the first year and were more likely to experience depression at 4 months. Conclusion: Mothers with LPT infants are vulnerable and need greater practical breastfeeding and emotional support in hospital and at home. Keywords: depression; exclusive breastfeeding; gestational age; late preterm; well-being.
    • Impact of body mass index on relapse in children with acute lymphoblastic leukemia treated according to Nordic treatment protocols.

      Egnell, Christina; Ranta, Susanna; Banerjee, Joanna; Merker, Andrea; Niinimäki, Riitta; Lund, Bendik; Mogensen, Pernille Rudebeck; Jonsson, Ólafur G; Vaitkeviciene, Goda; Lepik, Kristi; et al. (Wiley, 2020-09-20)
      Objectives: High body mass index (BMI) is associated with poorer survival in childhood acute lymphoblastic leukemia (ALL), but the actual impact on the risk of relapse still needs to be clarified. We evaluated the impact of BMI at diagnosis on the risk of relapse in children with ALL treated according to Nordic Society of Paediatric Haematology and Oncology (NOPHO) protocols. Method: In a multicenter study, we collected data on BMI at diagnosis and outcome of 2558 children aged 2.0-17.9 years diagnosed between 1992 and 2016. Patients were divided into four groups according to International Obesity Task Force (IOTF) childhood BMI cut-offs: underweight, <17; healthy weight, 17-25; overweight, 25-30; and obese, ≥30 kg/m2 . Results: In Cox multivariate regression analyses, an increased risk of relapse was observed in children aged 10-17.9 years with unhealthy BMI at diagnosis (underweight hazard ratio HR: 2.90 [95% confidence interval: 1.24-6.78], P = .01; overweight, HR: 1.95 [1.11-3.43], P = .02, and obese HR: 4.32 [95% 2.08-8.97], P < .001), compared to children with healthy weight. BMI had no impact on relapse in children under 10 years of age. Conclusion: High BMI, and especially obesity at diagnosis, is an independent adverse prognostic factor for relapse in older children with ALL. Keywords: acute lymphoblastic leukemia; body mass index; children; obesity; survival.
    • Breast cancer survival in Nordic BRCA2 mutation carriers-unconventional association with oestrogen receptor status.

      Olafsdottir, Elinborg J; Borg, Ake; Jensen, Maj-Britt; Gerdes, Anne-Marie; Johansson, Anna L V; Barkardottir, Rosa B; Johannsson, Oskar T; Ejlertsen, Bent; Sønderstrup, Ida Marie Heeholm; Hovig, Eivind; et al. (Nature Publishing Group on behalf of Cancer Research UK, 2020-09-17)
      Background: The natural history of breast cancer among BRCA2 carriers has not been clearly established. In a previous study from Iceland, positive ER status was a negative prognostic factor. We sought to identify factors that predicted survival after invasive breast cancer in an expanded cohort of BRCA2 carriers. Methods: We studied 608 women with invasive breast cancer and a pathogenic BRCA2 mutation (variant) from four Nordic countries. Information on prognostic factors and treatment was retrieved from health records and by analysis of archived tissue specimens. Hazard ratios (HR) were estimated for breast cancer-specific survival using Cox regression. Results: About 77% of cancers were ER-positive, with the highest proportion (83%) in patients under 40 years. ER-positive breast cancers were more likely to be node-positive (59%) than ER-negative cancers (34%) (P < 0.001). The survival analysis included 584 patients. Positive ER status was protective in the first 5 years from diagnosis (multivariate HR = 0.49; 95% CI 0.26-0.93, P = 0.03); thereafter, the effect was adverse (HR = 1.91; 95% CI 1.07-3.39, P = 0.03). The adverse effect of positive ER status was limited to women who did not undergo endocrine treatment (HR = 2.36; 95% CI 1.26-4.44, P = 0.01) and patients with intact ovaries (HR = 1.99; 95% CI 1.11-3.59, P = 0.02). Conclusions: The adverse effect of a positive ER status in BRCA2 carriers with breast cancer may be contingent on exposure to ovarian hormones.
    • Global Public Perceptions of Genomic Data Sharing: What Shapes the Willingness to Donate DNA and Health Data?

      Middleton, Anna; Milne, Richard; Almarri, Mohamed A; Anwer, Shamim; Atutornu, Jerome; Baranova, Elena E; Bevan, Paul; Cerezo, Maria; Cong, Yali; Critchley, Christine; et al. (Cell Press, 2020-09-17)
      Analyzing genomic data across populations is central to understanding the role of genetic factors in health and disease. Successful data sharing relies on public support, which requires attention to whether people around the world are willing to donate their data that are then subsequently shared with others for research. However, studies of such public perceptions are geographically limited and do not enable comparison. This paper presents results from a very large public survey on attitudes toward genomic data sharing. Data from 36,268 individuals across 22 countries (gathered in 15 languages) are presented. In general, publics across the world do not appear to be aware of, nor familiar with, the concepts of DNA, genetics, and genomics. Willingness to donate one's DNA and health data for research is relatively low, and trust in the process of data's being shared with multiple users (e.g., doctors, researchers, governments) is also low. Participants were most willing to donate DNA or health information for research when the recipient was specified as a medical doctor and least willing to donate when the recipient was a for-profit researcher. Those who were familiar with genetics and who were trusting of the users asking for data were more likely to be willing to donate. However, less than half of participants trusted more than one potential user of data, although this varied across countries. Genetic information was not uniformly seen as different from other forms of health information, but there was an association between seeing genetic information as special in some way compared to other health data and increased willingness to donate. The global perspective provided by our "Your DNA, Your Say" study is valuable for informing the development of international policy and practice for sharing genomic data. It highlights that the research community not only needs to be worthy of trust by the public, but also urgent steps need to be taken to authentically communicate why genomic research is necessary and how data donation, and subsequent sharing, is integral to this. Keywords: attitudes; data donation; data sharing; genomic data; genomic data sharing; global; health data; public; survey; trust.
    • Preserving Mobility in Older Adults with Physical Frailty and Sarcopenia: Opportunities, Challenges, and Recommendations for Physical Activity Interventions.

      Billot, Maxime; Calvani, Riccardo; Urtamo, Annele; Sánchez-Sánchez, Juan Luis; Ciccolari-Micaldi, Cecilia; Chang, Milan; Roller-Wirnsberger, Regina; Wirnsberger, Gerhard; Sinclair, Alan; Vaquero-Pinto, Nieves; et al. (Dove Medical Press, 2020-09-16)
      One of the most widely conserved hallmarks of aging is a decline in functional capabilities. Mobility loss is particularly burdensome due to its association with negative health outcomes, loss of independence and disability, and the heavy impact on quality of life. Recently, a new condition, physical frailty and sarcopenia, has been proposed to define a critical stage in the disabling cascade. Physical frailty and sarcopenia are characterized by weakness, slowness, and reduced muscle mass, yet with preserved ability to move independently. One of the strategies that have shown some benefits in combatting mobility loss and its consequences for older adults is physical activity. Here, we describe the opportunities and challenges for the development of physical activity interventions in people with physical frailty and sarcopenia. The aim of this article is to review age-related physio(patho)logical changes that impact mobility in old age and to provide recommendations and procedures in accordance with the available literature.
    • Azithromycin ameliorates sulfur dioxide-induced airway epithelial damage and inflammatory responses.

      Joelsson, Jon Petur; Kricker, Jennifer A; Arason, Ari J; Sigurdsson, Snaevar; Valdimarsdottir, Bryndis; Gardarsson, Fridrik Runar; Page, Clive P; Lehmann, Fredrik; Gudjonsson, Thorarinn; Ingthorsson, Saevar; et al. (BioMed Central, 2020-09-10)
      Background: The airway epithelium (AE) forms the first line of defence against harmful particles and pathogens. Barrier failure of the airway epithelium contributes to exacerbations of a range of lung diseases that are commonly treated with Azithromycin (AZM). In addition to its anti-bacterial function, AZM has immunomodulatory effects which are proposed to contribute to its clinical effectiveness. In vitro studies have shown the AE barrier-enhancing effects of AZM. The aim of this study was to analyze whether AE damage caused by inhalation of sulfur dioxide (SO2) in a murine model could be reduced by pre-treatment with AZM. Methods: The leakiness of the AE barrier was evaluated after SO2 exposure by measuring levels of human serum albumin (HSA) in bronchoalveolar lavage fluid (BALF). Protein composition in BALF was also assessed and lung tissues were evaluated across treatments using histology and gene expression analysis. Results: AZM pre-treatment (2 mg/kg p.o. 5 times/week for 2 weeks) resulted in reduced glutathione-S-transferases in BALF of SO2 injured mice compared to control (without AZM treatment). AZM treated mice had increased intracellular vacuolization including lamellar bodies and a reduction in epithelial shedding after injury in addition to a dampened SO2-induced inflammatory response. Conclusions: Using a mouse model of AE barrier dysfunction we provide evidence for the protective effects of AZM in vivo, possibly through stabilizing the intracellular microenvironment and reducing inflammatory responses. Our data provide insight into the mechanisms contributing to the efficacy of AZM in the treatment of airway diseases. Keywords: Azithromycin; Glutathione-S-transferase; Immunomodulation; Lamellar bodies; Lung barrier enhancement.
    • Incidence and recurrence rate of sigmoid diverticulitis in patients requiring admission to hospital in Iceland from 1985 to 2014: nationwide population-based register study.

      Alexandersson, B T; Stefánsson, T; 1Department of Internal Medicine, Section of Gastroenterology and Hepatology, Reykjavik, Iceland. 2Department of Surgery, The National University Hospital of Iceland, Reykjavik, Iceland. (John Wiley & Sons, 2020-09-09)
      Background: Diverticulitis is the most common complication of diverticular disease, affecting 10-25 per cent of patients with diverticula. A retrospective, nationwide, population-based cohort study was performed to analyse the incidence and recurrence rate of sigmoid diverticulitis requiring hospital admission. Methods: All patients discharged from hospital in Iceland during 1985-2014 who were diagnosed with diverticular disease were included. The χ2 test was used to analyse the trend of the incidence in the period 2002-2014. The Kaplan-Meier method and the Cox model were used to analyse recurrence. Results: Of 8660 admissions for diverticular disease, 4746 were due to diverticulitis, of which 2939 were for diverticulitis diagnosed for the first time. After the first attack, surgery was used to treat 661 patients. Of 2278 patients not treated by resection, 537 had a second attack (23·6 per cent). There was a significant decrease in the incidence of diverticulitis in patients aged 40-89 years during the period from 2002 to 2014 (P = 0·033). The risk of recurrence was associated with younger age at first attack and female sex (P < 0·001). Conclusion: There was a decline in the incidence of patients hospitalized with diverticulitis between 1995 and 2014, most prominent in older age groups. Different recurrence rates were reported in men and women, and in younger compared with older age groups.
    • Overview of the Side-Effects of FDA- and/or EMA-Approved Targeted Therapies for the Treatment of Hematological Malignancies.

      Constantinescu, Catalin; Pasca, Sergiu; Zimta, Alina-Andreea; Tat, Tiberiu; Rus, Ioana; Teodorescu, Patric; Iluta, Sabina; Tanase, Alina; Colita, Anca; Sigurjonsson, Olafur; et al. (MDPI AG, 2020-09-08)
      In the last decade there has been tremendous effort in offering better therapeutic management strategies to patients with hematologic malignancies. These efforts have ranged from biological to clinical approaches and resulted in the rapid development of new approaches. The main "problem" that comes with the high influx of newly approved drugs, which not only influences hematologists that frequently work with these drugs but also affects other healthcare professionals that work with hematologists in patient management, including intensive care unit (ICU) physicians, is they have to keep up within their specialty and, in addition, with the side-effects that can occur when encountering hematology-specific therapies. Nonetheless, there are few people that have an in-depth understanding of a specialty outside theirs. Thus, this manuscript offers an overview of the most common side-effects caused by therapies used in hematology nowadays, or that are currently being investigated in clinical trials, with the purpose to serve as an aid to other specialties. Nevertheless, because of the high amount of information on this subject, each chapter will offer an overview of the side-effects of a drug class with each reference of the section being intended as further reading. Keywords: hematological malignancies; life-threatening side-effects; novel therapies.
    • Predicting food allergy: The value of patient history reinforced.

      Lyons, Sarah A; Knulst, André C; Burney, Peter G J; Fernandez-Rivas, Montserrat; Ballmer-Weber, Barbara K; Barreales, Laura; Bieli, Christian; Clausen, Michael; Dubakiene, Ruta; Fernandez-Perez, Cristina; et al. (Wiley, 2020-09-07)
      Background: EAACI guidelines emphasize the importance of patient history in diagnosing food allergy (FA) and the need for studies investigating its value using standardized allergy-focused questionnaires. Objective: To determine the contribution of reaction characteristics, allergic comorbidities and demographics to prediction of FA in individuals experiencing food-related adverse reactions. Methods: Adult and school-age participants in the standardized EuroPrevall population surveys, with self-reported FA, were included. Penalized multivariable regression was used to assess the association of patient history determinants with "probable" FA, defined as a food-specific case history supported by relevant IgE sensitization. Results: In adults (N = 844), reproducibility of reaction (OR 1.35 [95% CI 1.29-1.41]), oral allergy symptoms (OAS) (4.46 [4.19-4.75]), allergic rhinitis (AR) comorbidity (2.82 [2.68-2.95]), asthma comorbidity (1.38 [1.30-1.46]) and male sex (1.50 [1.41-1.59]) were positively associated with probable FA. Gastrointestinal symptoms (0.88 [0.85-0.91]) made probable FA less likely. The AUC of a model combining all selected predictors was 0.85 after cross-validation. In children (N = 670), OAS (2.26 [2.09-2.44]) and AR comorbidity (1.47 [CI 1.39-1.55]) contributed most to prediction of probable FA, with a combined cross-validation-based AUC of 0.73. When focusing on plant foods, the dominant source of FA in adults, the pediatric model also included gastrointestinal symptoms (inverse association), and the AUC increased to 0.81. Conclusions: In both adults and school-age children from the general population, reporting of OAS and of AR comorbidity appear to be the strongest predictors of probable FA. Patient history particularly allows for good discrimination between presence and absence of probable plant FA. Keywords: Europe; food allergy; food sensitization; patient history; prediction.
    • Transforming growth factor β-mediated micromechanics modulates disease progression in primary myelofibrosis.

      Teodorescu, Patric; Pasca, Sergiu; Jurj, Ancuta; Gafencu, Grigore; Joelsson, Jon-Petur; Selicean, Sonia; Moldovan, Cristian; Munteanu, Raluca; Onaciu, Anca; Tigu, Adrian-Bogdan; et al. (Wiley, 2020-09-05)
      Primary myelofibrosis (PMF) is a Ph-negative myeloproliferative neoplasm (MPN), characterized by advanced bone marrow fibrosis and extramedullary haematopoiesis. The bone marrow fibrosis results from excessive proliferation of fibroblasts that are influenced by several cytokines in the microenvironment, of which transforming growth factor-β (TGF-β) is the most important. Micromechanics related to the niche has not yet been elucidated. In this study, we hypothesized that mechanical stress modulates TGF-β signalling leading to further activation and subsequent proliferation and invasion of bone marrow fibroblasts, thus showing the important role of micromechanics in the development and progression of PMF, both in the bone marrow and in extramedullary sites. Using three PMF-derived fibroblast cell lines and transforming growth factor-β receptor (TGFBR) 1 and 2 knock-down PMF-derived fibroblasts, we showed that mechanical stress does stimulate the collagen synthesis by the fibroblasts in patients with myelofibrosis, through the TGFBR1, which however seems to be activated through alternative pathways, other than TGFBR2. Keywords: TGF-β; fibroblast activation; invasion; micromechanics; myelofibrosis; proliferation.
    • Effects of germline DHFR and FPGS variants on methotrexate metabolism and relapse of leukemia.

      Tulstrup, Morten; Moriyama, Takaya; Jiang, Chuang; Grosjean, Marie; Nersting, Jacob; Abrahamsson, Jonas; Grell, Kathrine; Hjalgrim, Lisa Lyngsie; Jónsson, Ólafur Gísli; Kanerva, Jukka; et al. (American Society of Hematology, 2020-09-03)
      Methotrexate (MTX) during maintenance therapy is essential for curing acute lymphoblastic leukemia (ALL), but dosing strategies aiming at adequate treatment intensity are challenged by interindividual differences in drug disposition. To evaluate genetic factors associated with MTX metabolism, we performed a genome-wide association study in 447 ALL cases from the Nordic Society for Pediatric Haematology and Oncology ALL2008 study, validating results in an independent set of 196 patients. The intergenic single-nucleotide polymorphism rs1382539, located in a regulatory element of DHFR, was associated with increased levels of short-chain MTX polyglutamates (P = 1.1 × 10-8) related to suppression of enhancer activity, whereas rs35789560 in FPGS (p.R466C, P = 5.6 × 10-9) was associated with decreased levels of long-chain MTX polyglutamates through reduced catalytic activity. Furthermore, the FPGS variant was linked with increased relapse risk (P = .044). These findings show a genetic basis for interpatient variability in MTX response and could be used to improve future dosing algorithms.
    • Towards an app to estimate patient-specific perioperative femur fracture risk

      Esposito, L.; Minutolo, V.; Gargiulo, P.; Jonsson, H.; Gislason, M. K.; Fraldi, M.; 1 ]‎ Univ Campania Luigi Vanvitelli, Dept Engn, I-81031 Aversa, Italy Show more [ 2 ]‎ Reykjav Univ, Inst Biomed & Neural Engn, IS-101 Reykjavik, Iceland Show more [ 3 ]‎ Landspitali Univ Hosp, Dept Sci, IS-101 Reykjavik, Iceland Show more [ 4 ]‎ Univ Iceland, Landspitali Univ Hosp, Dept Orthopaed Surg, IS-101 Reykjavik, Iceland Show more [ 5 ]‎ Univ Napoli Federico II, Dept Struct Engn & Architecture, I-80125 Naples, Italy (Multidisciplinary Digital Publishing Institute (MDPI), 2020-09-01)
      Total Hip Arthroplasty is one of the most successful surgery. However, due to the worldwide growing population life expectancy and the related incidence of age-dependent bone diseases, a growing number of cases of intra-operative fractures lead to revision surgery with high rates of morbidity and mortality. Surgeons choose the type of the implant, either cemented or cementless prosthesis, on the basis of the age, the quality of the bone and the general medical conditions of the patients. Generally, no quantitative measures are available to assess the intra-operative fracture risk. Consequently, the decision-making process is mainly based on medical operators’ expertise and qualitative information obtained by imaging. Motivated by this scenario, we here propose a mechanical-supported strategy to assist surgeons in their decisions, by giving intelligible maps of the risk fracture which take into account the interplay between actual strength distribution inside the bone tissue and its response to the forces exerted by the implant. To this end, we produce charts and patient-specific synthetic “traffic-light” indicators of fracture risk, by making use of ad hoc analytical solutions to predict the stress levels in the bone by means of CT-based mechanical and geometrical parameters of the patient. We felt that, if implemented in a friendly software or proposed as an app, the strategy could constitute a practical tool to help the medical decision-making process, in particular with respect to the choice of adopting cemented or cementless implant