Landspítali University Hospital Research Archive
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Dili is rare amongst patients without liver metastases receiving cancer treatment in Iceland: a population-based cohort study.
No full textTo access publisher's full text version of this article click on the hyperlink belowBackground: There is limited information on the frequency of idiosyncratic drug-liver injury (DILI) among cancer patients. The aim of the study was to evaluate the frequency of DILI due to cancer treatment in a population-based setting.
Material and methods: All patients diagnosed with genitourinary cancer, breast cancer or metastatic malignant melanoma in 2007-2018 were matched with a database containing laboratory results for all major hospitals in Iceland. Medical chart review was performed for cases with ALT/AST ≥5× upper limit of normal (ULN), ALP ≥2× ULN or bilirubin ≥2× ULN. Patients with liver-, and/or bone metastases and isolated elevations of ALP and patients with other etiologies of liver enzyme elevations were excluded. Cases with a RUCAM score of probable or highly probable were included.
Results: Among 4956 patients, 840 patients had liver enzyme elevations. Overall, nine (0.2%) cases of DILI were identified, seven women (78%), median age 59 years (IQR 52-66). Four patients had kidney cancer, four breast cancer and one metastatic prostate cancer. In eight cases, a single agent was implicated: Pazopanib (n = 3), axitinib, docetaxel, gemcitabine, letrozole and paclitaxel. In all cases, the treatment was interrupted or discontinued due to the liver injury. No patient developed jaundice or liver failure and no death was linked to DILI. Time to normalization of liver enzymes was 17 days (IQR 25-120).
Conclusion: DILI was found to be rare and no cases of severe liver injury occurred. However, approximately 90% of patients switched to another treatment which might have affected prognosis.
Keywords: DILI; RUCAM; hepatotoxicity; liver enzymes; malignancy.Landspitali University Hospita
The first wave of COVID-19 and concurrent social restrictions were not associated with a negative impact on mental health and psychiatric well-being.
No full textBlack Swan/International Myeloma Foundation
European Union Horizon 2020 research framework
Icelandic Centre for Research
University of Iceland Research Fund
Landspitali University Hospital Research FundBackground: The coronavirus disease 2019 (COVID-19) pandemic and efforts to contain it have substantially affected the daily lives of most of the world's population.
Objective: We describe the impact of the first COVID-19 wave and associated social restrictions on the mental health of a large adult population.
Methods: We performed a cohort study nested in a prospective randomized clinical trial, comparing responses during the first COVID-19 wave to previous responses. We calculated the odds ratio (OR) of the population moving up one severity category on validated instruments used to measure stress (PSS-10), anxiety (GAD-7), depression (PHQ-9), and Satisfaction With Life Scale (SWLS). Responses were linked to inpatient and outpatient ICD-10 codes from registries. Models were adjusted for age, sex, comorbidities, and pre-existing diagnoses of mental illness.
Results: Of 63,848 invited participants, 42,253 (66%) responded. The median age was 60 (inter-quartile range 53-68) and 19,032 (45%) were male. Responses during the first wave of COVID-19 did not suggest increased stress (OR 0.97; 95% confidence interval [CI], 0.93-1.01; p = 0.28) or anxiety (OR 1.01; 95% CI, 0.96 to 1.05; p = 0.61), but were associated with decreased depression (OR 0.89; 95% CI, 0.85-0.93, p < 0.0001) and increased satisfaction with life (OR 1.12; 95% CI, 1.08-1.16, p < 0.0001). A secondary analysis of repeated measures data showed similar results.
Conclusions: Social restrictions were sufficient to contain the pandemic but did not negatively impact validated measures of mental illness or psychiatric well-being. However, responses to individual questions showed signs of fear and stress. This may represent a normal, rather than pathological, population response to a stressful situation.
Keywords: COVID-19; mental health; pandemics
Intussusception of appendix - a case report
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 DownloadGarnasmokkun á botnlanga er sjaldgæft ástand og erfitt að greina. Við
segjum frá garnasmokkun á botnlanga hjá 7 ára gömlum strák með sögu
um kviðverki.Intussusception of appendix is a rare condition and difficult to
diagnose. We report a case of intussusception of appendix in a seven
year old boy with history of abdominal pain
Managing the anxiety: The experience of Icelandic women with mental distress of the effects of using cognitive behavioural therapy offered by a primary health care clinic
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 DownloadTilgangur: Hugræn atferlismeðferð (HAM) er árangursrík meðferð sem er notuð við andlegri vanlíðan, streitu og kvíða. Tilgangur rannsóknarinnar var að kanna reynslu kvenna með andlega vanlíðan af áhrifum HAM-námskeiða sem haldin eru á heilsugæslunni og kanna hvaða áhrif námskeiðin hafði á líðan þeirra.
Aðferð: Notast var við aðferð Vancouver-skólans í fyrirbærafræði. Þátttakendur voru átta konur valdar með tilgangsúrtaki á tveim heilsugæslustöðvum á höfuðborgarsvæðinu og notast við hálfstaðlaðan viðtalsramma. Konurnar voru á aldrinum 26-47 ára og glímdu við andlega vanlíðan og höfðu lokið sex vikna hópnámskeiði í HAM á heilsugæslustöð. Samtals voru tekin átta einstaklingsviðtöl.
Niðurstöður: Yfirþema rannsóknarinnar var: að ná tökum á kvíðanum og láta hann ekki stjórna. Það lýsir reynslu kvenna með andlega vanlíðan af hugrænni atferlishópmeðferð. Alls voru greind fimm meginþemu; að reyna að gera það besta úr sínum aðstæðum; að ná tökum á kvíðanum og láta hann ekki stjórna; að hafa meiri stjórn á huganum og líkamanum; stuðningurinn og eftirfylgnin skiptir öllu máli; bjargráðin að nýta sér alls konar hluti. Niðurstöður rannsóknarinnar gefa vísbendingu um að upplifun kvenna af gagnsemi námskeiðsins í hugrænni atferlismeðferð sé góð og flestar lýsa jákvæðri upplifun við að ná tökum á kvíðanum og láta hann ekki stjórna sér. Konurnar reyndu að nýta sér það sem þær höfðu lært á HAM-námskeiðunum og áframhaldandi stuðning heilbrigðisstarfsfólks til að bæta líðan sína og aðstæður. Eftir námskeiðin náðu þær margar meiri stjórn á líðan sinni og í kjölfar meðferðar voru þær einnig meðvitaðri um að grípa til eigin bjargráða til að bæta líðan sína og félagsleg virkni þeirra
jókst.
Ályktun: Mikilvægt er að heilsugæslan haldi áfram að bæta og styrkja geðheilsuverndina sem veitt er á heilsugæslustöðvum fyrir konur sem glíma við andlega vanlíðan eða kvíða en hugræn atferlismeðferð virðist vera árangursrík meðferð.
Lykilorð: Hugræn atferlismeðferð (HAM), reynsla, konur, andleg vanlíðan, heilsugæsla.Aim: Cognitive behavioural therapy (CBT) is an effective
conversational therapy used for mental distress.
The aim of this study was to explore women’s
experiences of the effect of CBT and the impact on
women’s mental well-being.
Method: This was a qualitative study, using the Vancouver
school. Participants were eight women recruited
by a purposeful sample from two primary health
care clinics in the capital area of Iceland. The
women were between 26 and 47 years old and
had been dealing with mental distress. They had
all completed a six-week course of CBT offered at
the primary health care clinics. Each woman was
interviewed once for the study. Results: The main theme was: Managing the anxiety but
not let it control. Describing the experience of
CBT therapy among women with mental distress.
Five themes emerged: To make the best out of the
situation; to cope with the anxiety and not give it
permission to control; the support and follow-up
makes all the difference; Coping and different ways
to cope with the situation. The results indicate
that the women had a positive experience from
the CBT and most described a positive experience
in coping with anxiety and not letting the anxiety
control them. The women tried to improve their
well-being and situation after they went through
the CBT as well as support and follow-up offered
from healthcare professionals at the primary health
care clinic. Many were more conscious on how to
improve their well-being and became more socially
active.
Conclusion: It is important that primary health care clinics
continue to improve and strengthen the mental
health services offered to women who are
struggling with mental distress. The CBT therapy
seems to give good results and be an effective
treatment.Vísindasjóður Félags íslenskra hjúkrunarfræðinga og Fagdeild
heilsugæsluhjúkrunarfræðing
The CRTAC1 Protein in Plasma Is Associated With Osteoarthritis and Predicts Progression to Joint Replacement: A Large-Scale Proteomics Scan in Iceland.
Full text linkTo 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 DownloadObjective: Biomarkers for diagnosis and progression of osteoarthritis (OA) are lacking. This study was undertaken to identify circulating biomarkers for OA that could predict disease occurrence and/or progression to joint replacement.
Methods: Using the SomaScan platform, we measured 4,792 proteins in plasma from 37,278 individuals, of whom 12,178 individuals had OA and 2,524 had undergone joint replacement. We performed a case-control study for identification of potential protein biomarkers for hip, knee, and/or hand OA, and a prospective study for identification of biomarkers for joint replacement.
Results: Among the large panel of plasma proteins assessed, cartilage acidic protein 1 (CRTAC1) was the most strongly associated with both OA diagnosis (odds ratio 1.46 [95% confidence interval 1.41-1.52] for knee OA, odds ratio 1.36 [95% confidence interval 1.29-1.43] for hip OA, and odds ratio 1.33 [95% confidence interval 1.26-1.40] for hand OA) and progression to joint replacement (hazard ratio 1.40 [95% confidence interval 1.30-1.51] for knee replacement and hazard ratio 1.31 [95% confidence interval 1.19-1.45] for hip replacement). Patients with OA who were in the highest quintile of risk of joint replacement, based on known risk factors (i.e., age, sex, and body mass index) and plasma CRTAC1 level, were 16 times more likely to undergo knee replacement within 5 years of plasma sample collection than those in the lowest quintile, and 6.5 times more likely to undergo hip replacement. CRTAC1 was not associated with other types of inflammatory arthritis. A specific protein profile was identified in those patients who had undergone joint replacement prior to plasma sample collection.
Conclusion: Through a hypothesis-free approach, we identified CRTAC1 in plasma as a novel promising candidate biomarker for OA that is both associated with occurrence of OA and predictive of progression to joint replacement. This biomarker might also be useful in the selection of suitable patients for clinical trial enrollment.deCODE genetics, Inc./Amgen Inc
The Wittig bioconjugation of maleimide derived, water soluble phosphonium ylides to aldehyde-tagged proteins.
Full text linkTo 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 DownloadHerein we disclose the transformation of maleimides into water-soluble tris(2-carboxyethyl)phosphonium ylides and their subsequent application in the bioconjugation of protein- and peptide-linked aldehydes. The new entry into Wittig bioconjugate chemistry proceeds under mild conditions and relies on highly water soluble reagents, which are likely already part of most biochemists' inventory.Uppsala University
Swedish Research Counci
Flares after hydroxychloroquine reduction or discontinuation: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort.
Full text linkTo 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 DownloadObjectives: To evaluate systemic lupus erythematosus (SLE) flares following hydroxychloroquine (HCQ) reduction or discontinuation versus HCQ maintenance.
Methods: We analysed prospective data from the Systemic Lupus International Collaborating Clinics (SLICC) cohort, enrolled from 33 sites within 15 months of SLE diagnosis and followed annually (1999-2019). We evaluated person-time contributed while on the initial HCQ dose ('maintenance'), comparing this with person-time contributed after a first dose reduction, and after a first HCQ discontinuation. We estimated time to first flare, defined as either subsequent need for therapy augmentation, increase of ≥4 points in the SLE Disease Activity Index-2000, or hospitalisation for SLE. We estimated adjusted HRs (aHRs) with 95% CIs associated with reducing/discontinuing HCQ (vs maintenance). We also conducted separate multivariable hazard regressions in each HCQ subcohort to identify factors associated with flare.
Results: We studied 1460 (90% female) patients initiating HCQ. aHRs for first SLE flare were 1.20 (95% CI 1.04 to 1.38) and 1.56 (95% CI 1.31 to 1.86) for the HCQ reduction and discontinuation groups, respectively, versus HCQ maintenance. Patients with low educational level were at particular risk of flaring after HCQ discontinuation (aHR 1.43, 95% CI 1.09 to 1.87). Prednisone use at time-zero was associated with over 1.5-fold increase in flare risk in all HCQ subcohorts.
Conclusions: SLE flare risk was higher after HCQ taper/discontinuation versus HCQ maintenance. Decisions to maintain, reduce or stop HCQ may affect specific subgroups differently, including those on prednisone and/or with low education. Further study of special groups (eg, seniors) may be helpful.
Keywords: autoimmune diseases; epidemiology; hydroxychloroquine; systemic lupus erythematosus.Canadian Institutes of Health Research (CIHR)
Fonds de Recherche du Quebec Sante (FRQS)
Research Institute of the McGill University Health Centre (RI-MUHC)
Canadian Institutes of Health Research (CIHR)
Singer Family Fund for Lupus Research
Arthritis Society Chair in Rheumatic Diseases at the University of Calgary
Lupus UK
West Birmingham Hospitals NHS Trust
National Institute for Health Research (NIHR)/Wellcome Trust Birmingham Clinical Research Facility
tier 1 Canada Research Chair on Systemic Autoimmune Rheumatic Diseases
Bio & Medical Technology Development Programme of the National Research Foundation of the Republic of Korea
United States Department of Health & Human Services
National Institutes of Health (NIH) - US
Peroxidasin Enhances Basal Phenotype and Inhibits Branching Morphogenesis in Breast Epithelial Progenitor Cell Line D492.
Full text linkTo 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 DownloadThe human breast is composed of terminal duct lobular units (TDLUs) that are surrounded by stroma. In the TDLUs, basement membrane separates the stroma from the epithelial compartment, which is divided into an inner layer of luminal epithelial cells and an outer layer of myoepithelial cells. Stem cells and progenitor cells also reside within the epithelium and drive a continuous cycle of gland remodelling that occurs throughout the reproductive period. D492 is an epithelial cell line originally isolated from the stem cell population of the breast and generates both luminal and myoepithelial cells in culture. When D492 cells are embedded into 3D reconstituted basement membrane matrix (3D-rBM) they form branching colonies mimicking the TDLUs of the breast, thereby providing a well-suited in vitro model for studies on branching morphogenesis and breast development. Peroxidasin (PXDN) is a heme-containing peroxidase that crosslinks collagen IV with the formation of sulfilimine bonds. Previous studies indicate that PXDN plays an integral role in basement membrane stabilisation by crosslinking collagen IV and as such contributes to epithelial integrity. Although PXDN has been linked to fibrosis and cancer in some organs there is limited information on its role in development, including in the breast. In this study, we demonstrate expression of PXDN in breast epithelium and stroma and apply the D492 cell line to investigate the role of PXDN in cell differentiation and branching morphogenesis in the human breast. Overexpression of PXDN induced basal phenotype in D492 cells, loss of plasticity and inhibition of epithelial-to-mesenchymal transition as is displayed by complete inhibition of branching morphogenesis in 3D culture. This is supported by results from RNA-sequencing which show significant enrichment in genes involved in epithelial differentiation along with significant negative enrichment of EMT factors. Taken together, we provide evidence for a novel role of PXDN in breast epithelial differentiation and mammary gland development.
Keywords: Branching morphogenesis; D492; Mammary gland; Mammary stem cells; Peroxidasin; p63.Icelandic Science and Technology Policy Grant of Excellence 152144051
Icelandic Cancer Society
group for basic research of breast cancer in Icelan
Low dose rabbit antithymocyte globulin is non-inferior to higher dose in low-risk pediatric kidney transplant recipients.
No full textTo access publisher's full text version of this article click on the hyperlink belowBackground: Currently, there is no consensus among pediatric kidney transplant centers regarding the use and regimen for immunosuppressive induction therapy.
Methods: In this single center, retrospective cohort study, pediatric kidney transplant recipients transplanted between 1 May 2013 and 1 May 2018 with rabbit antithymocyte globulin (rATG) induction were included. We stratified patients based on immunological risk, with high risk defined as those with repeat transplant, preformed donor specific antibody, current panel-reactive antibodies > 20%, 0 antigen match and/or African-American heritage. Outcome of interest was the incidence of biopsy proven acute rejection by 1 year.
Results: A total of 166 patients met inclusion criteria. Age of patients was 12 years (11 mo-21 y), (median, range), 21.5% received a living donor transplant and 50.6% were female. Low-immunologic-risk patients were divided into 2 groups, those who received the lower cumulative rATG dose of ≤ 3.5 mg/kg (n = 52) versus the higher cumulative dose of > 3.5 mg/kg (n = 47). The median total dose in the lower dose group was 3.1 (IQR 0.3) and 4.4 (IQR 0.8) in the higher dose group, P < 0.001. Rejection rate did not differ significantly between the 2 treatment groups (7/52 vs. 6/47). None in the lower dose group developed BK nephropathy versus 3 in the higher dose group. Graft loss due to BK nephropathy occurred in 1 patient in the higher dose group. Graft loss in the whole cohort at 12 months was a rare event (n = 1) with 99.5% graft survival and 100% patient survival.
Conclusions: Reduced rATG dosing (≤ 3.5 mg/kg) when compared to higher dosing (> 3.5 mg/kg) is safe and effective in low-risk pediatric kidney transplant recipients without increasing risk of rejection. A higher resolution version of the Graphical abstract is available as Supplementary information.
Keywords: Acute allograft rejection; Immunosuppression; Induction therapy; Thymoglobulin; Transplantation.Tashia and John Morgridge Endowed Postdoctoral Fellow of the Stanford Maternal and Child Health Research Institut
Science and the future of the Icelandic health care system - high expectations for the new Minister of Health
Full text linkTo 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 Downloa