Landspítali University Hospital Research Archive
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Bronchodilator response and lung function decline: Associations with exhaled nitric oxide with regard to sex and smoking status.
Get PDFTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadBackground: Fractional exhaled nitric oxide (FeNO) is a marker of type-2 inflammation used both to support diagnosis of asthma and follow up asthma patients. The associations of FeNO with lung function decline and bronchodilator (BD) response have been studied only scarcely in large populations.
Objectives: To study the association between FeNO and a) retrospective lung function decline over 20 years, and b) lung function response to BD among asthmatic subjects compared with non-asthmatic subjects and with regards to current smoking and sex.
Methods: Longitudinal analyses of previous lung function decline and FeNO level at follow-up and cross-sectional analyses of BD response and FeNO levels in 4257 participants (651 asthmatics) from the European Community Respiratory Health Survey.
Results: Among asthmatic subjects, higher percentage declines of FEV1 and FEV1/FVC were associated with higher FeNO levels (p = 0.001 for both) at follow-up. These correlations were found mainly among non-smoking individuals (p = 0.001) and females (p = 0.001) in stratified analyses.Percentage increase in FEV1 after BD was positively associated with FeNO levels in non-asthmatic subjects. Further, after stratified for sex and smoking separately, a positive association was seen between FEV1 and FeNO levels in non-smokers and women, regardless of asthma status.
Conclusions: We found a relationship between elevated FeNO and larger FEV1 decline over 20 years among subjects with asthma who were non-smokers or women. The association between elevated FeNO levels and larger BD response was found in both non-asthmatic and asthmatic subjects, mainly in women and non-smoking subjects.
Keywords: Bronchodilatation; Epidemiology; FeNO; Lung function.UK Research & Innovation (UKRI)
Medical Research Council UK (MRC)
European Commission
Spanish Government
Generalitat de Catalunya
General Electri
Lifelong Reduction in LDL (Low-Density Lipoprotein) Cholesterol due to a Gain-of-Function Mutation in LDLR
No full textTo access publisher's full text version of this article click on the hyperlink belowBackground: Loss-of-function mutations in the LDL (low-density lipoprotein) receptor gene (LDLR) cause elevated levels of LDL cholesterol and premature cardiovascular disease. To date, a gain-of-function mutation in LDLR with a large effect on LDL cholesterol levels has not been described. Here, we searched for sequence variants in LDLR that have a large effect on LDL cholesterol levels.
Methods: We analyzed whole-genome sequencing data from 43 202 Icelanders. Single-nucleotide polymorphisms and structural variants including deletions, insertions, and duplications were genotyped using whole-genome sequencing-based data. LDL cholesterol associations were carried out in a sample of >100 000 Icelanders with genetic information (imputed or whole-genome sequencing). Molecular analyses were performed using RNA sequencing and protein expression assays in Epstein-Barr virus-transformed lymphocytes.
Results: We discovered a 2.5-kb deletion (del2.5) overlapping the 3' untranslated region of LDLR in 7 heterozygous carriers from a single family. Mean level of LDL cholesterol was 74% lower in del2.5 carriers than in 101 851 noncarriers, a difference of 2.48 mmol/L (96 mg/dL; P=8.4×10-8). Del2.5 results in production of an alternative mRNA isoform with a truncated 3' untranslated region. The truncation leads to a loss of target sites for microRNAs known to repress translation of LDLR. In Epstein-Barr virus-transformed lymphocytes derived from del2.5 carriers, expression of alternative mRNA isoform was 1.84-fold higher than the wild-type isoform (P=0.0013), and there was 1.79-fold higher surface expression of the LDL receptor than in noncarriers (P=0.0086). We did not find a highly penetrant detrimental impact of lifelong very low levels of LDL cholesterol due to del2.5 on health of the carriers.
Conclusions: Del2.5 is the first reported gain-of-function mutation in LDLR causing a large reduction in LDL cholesterol. These data point to a role for alternative polyadenylation of LDLR mRNA as a potent regulator of LDL receptor expression in humans.
Keywords: cardiovascular disease; genetics; lipids; microRNA; polyadenylation.deCODE genetics/Amgen, In
“This changed my life”. Personal experiences from hypnosis treatment following psychological trauma
No full textTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadAð skoða reynslu fólks af dáleiðslumeðferð við
afleiðingum sálrænna áfalla með það að markmiði að
auka þekkingu og dýpka skilning fagfólks og almennings
á dáleiðslumeðferð sem meðferðarmöguleika.
Unnið var eftir Vancouver-skólanum í fyrirbærafræði
í tólf meginþrepum og sjö þrepa vitrænu ferli fylgt.
Þátttakendur voru níu, sex konur og þrír karlar, sem
höfðu fengið dáleiðslumeðferð hjá geðhjúkrunarfræðingi
með dáleiðslumenntun. Tvö viðtöl voru tekin við hvern
þátttakanda.
Yfirþemað „Þetta breytti lífi mínu“ lýsir vel reynslu
þátttakenda í þeim tilvikum þar sem árangur
dáleiðslumeðferðarinnar hafði jákvæð áhrif á líf þeirra.
Niðurstöður voru greindar í fimm undirþemu: reynsla
af áföllum, heilsufarslegar afleiðingar áfalla, reynsla af
öðrum meðferðarleiðum, reynsla af dáleiðslumeðferð
og reynsla af árangri dáleiðslumeðferðar. Þátttakendur
fundu að unnið var djúpt í tilfinningalífi þeirra og sú vinna
bætti líðan þeirra. Þeir lýstu því að dáleiðslumeðferðin
hefði hjálpað þeim að kryfja og vinna með tilfinningar
og komist að rót áhrifanna sem áfallareynslan hafði
haft á heilsu þeirra og líðan. Það leiddi til betri skilnings
og þekkingar á tengslum eigin tilfinninga og líðanar.
Auk þess skilaði dáleiðslumeðferðin betri sjálfsmynd,
bættum svefni, minni kvíða og þunglyndi, betri hvíld,
minni verkjum, bættri tilfinningastjórn og því að slæmar
endurminningar hurfu.
Dáleiðsla getur reynst vel við úrvinnslu sálrænna áfalla
og neikvæðum heilsufarslegum afleiðingum þeirra.
Mikilvægt er að í boði séu fjölbreytt meðferðarúrræði
fyrir fólk með heilsufarsvandamál sem gætu verið
afleiðingar af áföllum, því misjafnt er hvað hentar
hverjum og einum.To examine personal experiences of hypnosis
as treatment for consequences of psychological
trauma and to expand knowledge and deepen
professionals’ and public’s understanding of
hypnotic treatments.
The study follows the Vancouver’s School twelve
main steps of phenomenology as well as the
seven steps of cognitive process. The participants
were six women and three men who had received
hypnosis treatment by a mental nurse specialized in
hypnotherapy. Two interviews were conducted with
each participant.
Main theme of the study: “This changed my life”
is a good description of participants’ experience
as the hypnotic treatment had very positive
impact on their life. The results were divided
into five subthemes: Experience of trauma;
health consequences from trauma; experience of
other treatments; experience of hypnotherapy;
experience of the effectiveness of hypnotherapy.
Participants experienced a deep emotional healing
which resulted in increased mental wellbeing. The
treatment helped them dissect their emotions, self-analysis, and discover the roots of the traumatic
experience and how it had affected their health
and wellbeing. This led to an increased overall
understanding and knowledge about their own
feelings and emotions. Additionally, the hypnosis
treatment resulted in better self-esteem, improved
sleep, less anxiety and depression, better rest,
less pain, better emotional control, and the
disappearance of bad memories. Hypnosis can be useful for improving various
health related conditions as well as processing of
traumatic experiences. Therefore, it is important
to increase nurses’ awareness and knowledge
in this field and increase accessibility of diverse
treatments, as suitability can vary between
individuals
Invasive and in situ squamous cell carcinoma of the skin: a nationwide study in Iceland.
No full textTo access publisher's full text version of this article click on the hyperlink below1Faculty of Medicine, University of Iceland, Saemundargata 2, Reykjavik, 101, Iceland.
2Department of Dermatology, University of Connecticut, 21 South Road, Farmington, CT, USA.
3Icelandic Cancer Registry, Skogarhlid 8, Reykjavik, 105, Iceland.
4Department of Dermatology, NYU Langone Health, New York, NY, USA.
5Department of Dermatology, The Mount Sinai Hospital, 1 Gustave L. Levy Place, NY, USA.
6The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
7Department of Pathology, Landspitali National-University Hospital, Hringbraut, Reykjavik, 101, Iceland
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.
Get PDFTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadMonoclonal 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.Black Swan Research Initiative by the International Myeloma Foundation
Icelandic Centre for Research
European Research Council (ERC)
University of Iceland
Landspitali University Hospita
Detection mode of childhood acute lymphoblastic leukaemia relapse and its effect on survival: a Nordic population-based cohort study.
No full textTo access publisher's full text version of this article click on the hyperlink belowRelapse 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.Danish Cancer Society
A.P. MOller Foundation
TOmrermester JOrgen Holm & Hustru Elisa F. Hansens Foundatio
Prevalence and early-life risk factors of school-age allergic multimorbidity: The EuroPrevall-iFAAM birth cohort.
Get PDFTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadBackground: Coexistence of childhood asthma, eczema and allergic rhinitis is higher than can be expected by chance, suggesting a common mechanism. Data on allergic multimorbidity from a pan-European, population-based birth cohort study have been lacking. This study compares the prevalence and early-life risk factors of these diseases in European primary school children.
Methods: In the prospective multicentre observational EuroPrevall-iFAAM birth cohort study, we used standardized questionnaires on sociodemographics, medical history, parental allergies and lifestyle, and environmental exposures at birth, 12 and 24 months. At primary school age, parents answered ISAAC-based questions on current asthma, rhinitis and eczema. Allergic multimorbidity was defined as the coexistence of at least two of these.
Results: From 10,563 children recruited at birth in 8 study centres, we included data from 5,572 children (mean age 8.2 years; 51.8% boys). Prevalence estimates were as follows: asthma, 8.1%; allergic rhinitis, 13.3%; and eczema, 12.0%. Allergic multimorbidity was seen in 7.0% of the whole cohort, ranging from 1.2% (Athens, Greece) to 10.9% (Madrid, Spain). Risk factors for allergic multimorbidity, identified with AICc, included family-allergy-score, odds ratio (OR) 1.50 (95% CI 1.32-1.70) per standard deviation; early-life allergy symptoms, OR 2.72 (2.34-3.16) for each symptom; and caesarean birth, OR 1.35 (1.04-1.76). Female gender, OR 0.72 (0.58-0.90); older siblings, OR 0.79 (0.63-0.99); and day care, OR 0.81 (0.63-1.06) were protective factors.
Conclusion: Allergic multimorbidity should be regarded as an important chronic childhood disease in Europe. Some of the associated early-life factors are modifiable and may be considered for prevention strategies.
Keywords: allergic multimorbidity; allergic rhinitis; asthma; children; eczema.European Commission under the 6th Framework Programme within the collaborative research initiative 'EuroPrevall'
European Commission under 7th Framework Programme (FP7-KBBE-2012-6) within the collaborative project 'iFAAM'
Icelandic birth cohort centre from Landspitali University Hospital Iceland Science Fund
GlaxoSmithKline
UK birth cohort centre from the UK Food Standards Agenc
Medication calculation skills of graduating nursing students within European context.
Get PDFTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadAim: The aim of this study is to evaluate the medication calculation skills of graduating nursing students in six European countries and analyse the associated factors.
Background: Medication calculation skills are fundamental to medication safety, which is a substantial part of patient safety. Previous studies have raised concerns about the medication calculation skills of nurses and nursing students.
Design: As part of a broader research project, this study applies a multinational cross-sectional survey design with three populations: graduating nursing students, nurse managers and patients.
Methods: The students performed two calculations (tablet and fluid) testing medication calculation skills requiring different levels of conceptual understanding and arithmetic. The managers and patients answered one question about the students' medication kills. In total, 1,796 students, 538 managers and 1,327 patients participated the study. The data were analysed statistically. The STROBE guideline for cross-sectional studies was applied.
Results: Almost all (99%) of the students performed the tablet calculation correctly, and the majority (71%) answered the fluid calculation correctly. Older age, a previous degree in health care and satisfaction with their current degree programme was positively associated with correct fluid calculations. The patients evaluated the students' medication skills higher than the nurse managers did and the evaluations were not systematically aligned with the calculation skills tested.
Conclusions: Nursing students have the skills to perform simple medication calculations, but a significant number of students have difficulties with calculations involving multiple operations and a higher level of conceptual understanding. Due to the variation in students' medication calculation skills and the unalignment between the managers' and patients' evaluations and the calculation tests, further research is needed.
Relevance to clinical practice: Graduating nursing students enter clinical field as qualified professionals, but there is still room for improvement in their medication calculation skills. This calls for attention in the fields of clinical nursing, education and research.
Keywords: drug dosage calculations; graduating nursing students; medication calculation skills; nurse managers; patients.Academy of Finland
European Commissio
Detailed Multiplex Analysis of SARS-CoV-2 Specific Antibodies in COVID-19 Disease.
Get PDFTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadA detailed understanding of the antibody response against SARS-CoV-2 is of high importance, especially with the emergence of novel vaccines. A multiplex-based assay, analyzing IgG, IgM, and IgA antibodies against the receptor binding domain (RBD), spike 1 (S1), and nucleocapsid proteins of the SARS-CoV-2 virus was set up. The multiplex-based analysis was calibrated against the Elecsys® Anti-SARS-CoV-2 assay on a Roche Cobas® instrument, using positive and negative samples. The calibration of the multiplex based assay yielded a sensitivity of 100% and a specificity of 97.7%. SARS-CoV-2 specific antibody levels were analyzed by multiplex in 251 samples from 221 patients. A significant increase in all antibody types (IgM, IgG, and IgA) against RBD was observed between the first and the third weeks of disease. Additionally, the S1 IgG antibody response increased significantly between weeks 1, 2, and 3 of disease. Class switching appeared to occur earlier for IgA than for IgG. Patients requiring hospital admission and intensive care had higher levels of SARS-CoV-2 specific IgA levels than outpatients. These findings describe the initial antibody response during the first weeks of disease and demonstrate the importance of analyzing different antibody isotypes against multiple antigens and include IgA when examining the immunological response to COVID-19.Student Innovation Fun
Opportunistic genomic screening. Recommendations of the European Society of Human Genetics.
Get PDFTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadIf genome sequencing is performed in health care, in theory the opportunity arises to take a further look at the data: opportunistic genomic screening (OGS). The European Society of Human Genetics (ESHG) in 2013 recommended that genome analysis should be restricted to the original health problem at least for the time being. Other organizations have argued that 'actionable' genetic variants should or could be reported (including American College of Medical Genetics and Genomics, French Society of Predictive and Personalized Medicine, Genomics England). They argue that the opportunity should be used to routinely and systematically look for secondary findings-so-called opportunistic screening. From a normative perspective, the distinguishing characteristic of screening is not so much its context (whether public health or health care), but the lack of an indication for having this specific test or investigation in those to whom screening is offered. Screening entails a more precarious benefits-to-risks balance. The ESHG continues to recommend a cautious approach to opportunistic screening. Proportionality and autonomy must be guaranteed, and in collectively funded health-care systems the potential benefits must be balanced against health care expenditures. With regard to genome sequencing in pediatrics, ESHG argues that it is premature to look for later-onset conditions in children. Counseling should be offered and informed consent is and should be a central ethical norm. Depending on developing evidence on penetrance, actionability, and available resources, OGS pilots may be justified to generate data for a future, informed, comparative analysis of OGS and its main alternatives, such as cascade testing.Netherlands Organization for Health Research and Developmen