Landspítali University Hospital Research Archive
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Þjónusta við umsækjendur um alþjóðlega vernd (UAV) hjá Reykjavíkurborg.
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Prevention and management of idiosyncratic drug-induced liver injury: Systematic review and meta-analysis of randomised clinical trials.
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 DownloadConducting 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.Instituto de Salud Carlos III
European Commission
Agencia Espanola del Medicamento. Plataforma de Investigaon Clinica
Instituto de Salud Carlos III
JR16/00015
Consejeria de Salud de Andalucia
European Cooperation in Science and Technology (COST
Comorbidities in multiple myeloma and implications on survival: A population-based study.
No full textTo access publisher's full text version of this article click on the hyperlink belowHigh proportion of patients with multiple myeloma suffer from comorbidities which may alter clinical management. Therefore, our aims were to evaluate the prevalence of comorbidities and their impact on survival. We included patients diagnosed with multiple myeloma 1990-2013 in Sweden and all diagnoses from each patient from 1985. A total of 13 656 patients with multiple myeloma were included in the study, thereof 7404 (54%) had comorbidity at diagnosis. The risk of death was increased for those with one comorbidity at diagnosis compared to those without any comorbidity (hazard ratio = 1.19; 95% confidence interval:1.14-1.25); this risk was higher for those with two (1.38; 1.30-1.47) and three or more comorbidities (1.72; 1.62-1.83). Furthermore, the risk of death was increased in patients with prior history of cancer, arrhythmia, heart failure, diabetes mellitus, cerebrovascular disease, chronic lung disease, psychological disease, peptic ulcer, neurological disease, peripheral vascular disease, chronic kidney disease, dementia, and inflammatory bowel disease. This large study shows that over 50% of multiple myeloma patients have a comorbidity at diagnosis and survival decreased with increasing numbers of comorbidities. This emphasizes the importance of comorbidities when evaluating patients and deciding on treatment strategies for individuals with multiple myeloma.
Keywords: comorbidities; multiple myeloma; survival.Research Fund of Landspitali, University Hospital of Iceland, The Nordic Cancer Union
Icelandic Centre for Researc
Identification of genetic loci associated with nocturnal enuresis: a genome-wide association study.
No full textTo access publisher's full text version of this article click on the hyperlink belowBackground: Nocturnal enuresis (bedwetting) is a common disorder affecting 10-16% of 7-year-old children globally. Nocturnal enuresis is highly heritable, but its genetic determinants remain unknown. We aimed to identify genetic variants associated with nocturnal enuresis and explore its genetic architecture and underlying biology.
Methods: We did a genome-wide association study (GWAS) of nocturnal enuresis. Nocturnal enuresis cases were identified in iPSYCH2012, a large Danish population-based case cohort established to investigate mental disorders, on the basis of 10th revision of the International Statistical Classification of Diseases (ICD-10) diagnoses and redeemed desmopressin prescriptions in Danish registers. The GWAS was done in a genetically homogeneous sample of unrelated individuals using logistic regression with relevant covariates. All genome-wide significant variants were analysed for their association with nocturnal enuresis in an independent Icelandic sample from deCODE genetics. Standardised polygenic risk scores for attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder were constructed from summary statistics of large GWASs and analysed for association with nocturnal enuresis.
Findings: The GWAS included 3882 nocturnal enuresis cases and 31 073 controls. We found two loci at chromosome 6 and chromosome 13 significantly associated with nocturnal enuresis. Six genetic variants at the two loci (five variants at chromosome 6q16.2 and one variant at chromosome 13q22.3) surpassed the threshold for genome-wide significance (p<5 × 10-8). There were two lead variants: rs9376454 (chromosome 6q16.2), with an odds ratio (OR) of 1·199 (95% CI 1·135-1·267; p=9·91 × 10-11), and rs60721117 (chromosome 13q22.3), with an OR of 1·149 (1·095-1·205; p=1·21 × 10-8). All associated variants in the chromosome 6 locus were replicated (p<8 × 10-3) in the independent Icelandic cohort of 5475 nocturnal enuresis cases and 303 996 controls, whereas the associated variant in the chromosome 13 locus showed nominal significant association (p=0·031). The percentage of nocturnal enuresis phenotypic variance explained by the common genetic variants was 23·9-30·4%. Polygenic risk for ADHD was associated with nocturnal enuresis (OR 1·06, 95% CI, 1·01-1·10; p=0·011). Among the potential nocturnal enuresis risk genes mapped, PRDM13 and EDNRB have biological functions associated with known pathophysiological mechanisms in nocturnal enuresis, and SIM1 regulates the formation of the hypothalamic neuroendocrine lineage that produces arginine vasopressin, a well known nocturnal enuresis drug target.
Interpretation: This study shows that common genetic variants contribute considerably to nocturnal enuresis, and it identifies potential nocturnal enuresis risk genes with roles in sleep, urine production, and bladder function. Given that available treatments target these mechanisms, any of the identified genes and their functional gene networks are potential drug targets.Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH)
Stanley Foundatio
Positive Behavior Support (PBS) in Icelandic Elementary Schools: A Review of the Literature
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 DownloadErfið hegðun nemenda í skólum er algengur vandi sem erfitt getur verið að takast á við. Heildstæður
stuðningur við jákvæða hegðun (e. positive behavior support; PBS) er alhliða stuðningskerfi sem
samanstendur af mismunandi úrræðum á þremur þrepum þar sem tekið er tillit til ólíkrar hegðunar
nemenda og þeim veitt íhlutun í samræmi við þarfir hvers og eins. Rannsóknir hafa sýnt að PBS
dregur meðal annars úr hegðunarvanda og bætir námsástundun. Á Íslandi hafa verið gerðar nokkrar
rannsóknir á árangri af innleiðingu PBS í grunnskólum. Markmið þessarar yfirlitsrannsóknar var
að kanna hvað niðurstöður þeirra rannsókna sýndu og varpa þannig skýrara ljósi á næstu skref
í rannsóknum á PBS á Íslandi. Í heild virðist PBS yfirleitt áhrifaríkt, en þó eru ákveðnir vankantar
á innleiðingunni í sumum tilfellum. Sömuleiðis þarf að gera fleiri og fjölbreyttari rannsóknir á
Íslandi, sérstaklega á miðþrepi kerfisins.
Efnisorð: Heildstæður stuðningur við jákvæða hegðun, PBS, grunnskólar, hegðun, hegðunarvandiAddressing student behavior problems represents a variety
of challenges for educators. Positive behavior support
(PBS) is a comprehensive, evidence–based, service–delivery
model aimed at promoting student academic and
behavioral achievement that has been implemented across
several schools in Iceland. PBS consists of a number of
prevention and intervention strategies delivered across
three tiers of varying intensity, based on student need.
Overall, research has demonstrated that implementation
of PBS can reduce problem behavior (e.g., as measured by
number of office discipline referrals), increase academic
engagement and promote prosocial behavior. A few studies
have been conducted regarding the effectiveness of
PBS in elementary schools in Iceland. In the present study,
we reviewed the available research literature concerning
the effects of PBS implementation on student behavior in
Icelandic elementary schools, with the aim of identifying
major and minor findings, limitations, and future research
directions. Taken together, results were mostly positive;
however, several limitations also were noted, including a
lack of supervision for school staff and follow–up support,
as well as intervention fidelity and maintenance. Collectively,
our findings indicate PBS holds much promise as
a model for school–based service–delivery within the
Icelandic education system.
Keywords: Positive behavior support, elementary schools,
Iceland, behavior problems, conduct problem
Hjúkrunarfræðingar á tímum covid-19 - Könnun á starfsumhverfi hjúkrunarfræðinga, aðbúnaði og líðan í starfi
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Recurrent depression: Defining features and effectiveness of treatment and prevention strategies
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 DownloadOft er skrifað að þunglyndi sé algeng og alvarleg geðröskun sem kosti samfélagið mikið. Þunglyndi
er þó ekki einsleitt fyrirbæri. Þótt meiri athygli hafi beinst að stökum lotum þunglyndis og
meðferð í bráðafasa hefur áhugi beinst í auknum mæli að því að hluti fólks upplifir endurteknar
þunglyndislotur yfir ævina. Í þessari grein er lýst einkennum alvarlegs þunglyndis (e. major
depressive disorder) hjá fullorðnum, sem hrjáir 15–18% fólks einhvern tíma ævinnar. Um helmingur
upplifir þunglyndi aftur, oftast innan fimm ára. Hætta á nýrri lotu eykst með auknum lotufjölda
en meðalfjöldi lota í úrtökum fólks með endurtekið þunglyndi er á bilinu fimm til níu. Í greininni
er fjallað er um lýðfræðilega og sálfélagslega þætti sem tengjast þunglyndi og endurtekningu
þess. Einnig er fjallað um árangur tveggja helstu meðferðarinngripa, lyfjameðferðar og hugrænnar
atferlismeðferðar (HAM), ásamt árangri forvarnarmiðaðrar (ForHAM) og núvitundarmiðaðrar
(NúHAM) hugrænnar atferlismeðferðar. Í lok greinarinnar er leitast við að draga saman atriði
úr rannsóknum sem gætu verið gagnleg fyrir sálfræðinga að hafa í huga sem koma að mati og
meðferð þunglyndis. Nokkur atriði eru einnig rædd sem geta verið mikilvæg í áframhaldandi
rannsóknum á þunglyndi og þróun meðferðar við því.
Efnisorð: þunglyndi, endurtekið þunglyndi, fullorðnir, meðferð, forvörn.Major depressive disorder (MDD) is a prevalent mental
disorder, with 15–18% of adults suffering from it at some
point in their life. The resulting social costs are therefore
high. However, MDD is not a unitary phenomenon, and
different forms have been identified. In recent years,
increased attention has been given to the recurrent nature
of MDD. Research shows that around half of those who
experience depression for the first time experience recurrent
episodes, with risk for onset increasing with every
new episode. In this paper, symptoms of MDD in adults
are described along with major demographic and psychosocial
factors that are associated with onset and recurrence
of depression. Efficacy of empirically supported treatment
and prevention protocols are reviewed, focusing on pharmacotherapy,
cognitive behavioural therapy, mindfulness
based cognitive therapy and preventive cognitive therapy.
Main research findings, that may be useful for practicing
psychologists involved in assessing and treating depression,
are summarised. Finally, several issues are discussed,
that may be important for future research and treatment
development in the field of depression.
Keywords: depression, recurrence, adults, treatment,
prevention
Multidisciplinary Pain Treatment at Landspitali through the years
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Parenchymal lung changes on CT in patients with coronavirus disease 2019 (COVID-19)
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Sýking af völdum kórónuveiru sem veldur kórónuveirusjúkdómi
2019 (COVID-19) getur leitt til lungnabólgu sem í sumum tilvikum er
lífshættuleg eða jafnvel banvæn. Þekkt er að þeir sem fá alvarlegri
sjúkdóm hafa meiri breytingar í lungnavef á tölvusneiðmyndum (TS)
af brjóstholi. Tilgangur rannsóknarinnar var að lýsa myndbreytingum
í lungum í bráðafasa COVID-19 og í eftirliti og um leið að meta hvort
umfang lungnabreytinga á TS hefði tengsl við alvarleika sjúkdómsins,
bakgrunnsþætti og fyrra heilsufar.
EFNIVIÐUR OG AÐFERÐIR
Rannsóknin náði til allra einstaklinga með staðfest COVID-19 sem
komu í eftirlit á göngudeild og fóru í TS eftirlitsrannsókn af brjóstholi
á Landspítala frá 6. maí 2020 til 24. september 2020. Upplýsingar
um sjúkrasögu sjúklinga voru fengnar úr gagnagrunni Landspítala á
afturskyggnan máta. Allar tölvusneiðmyndir voru endurskoðaðar og notað
var við alþjóðlegt stigunarkerfi til að meta umfang lungnabreytinga.
NIÐURSTÖÐUR
Alls voru 85 þátttakendur í rannsókninni, meðalaldur var 59 ár og karlar
í meirihluta (52%). Sextíu (71%) lögðust inn á sjúkrahús, þar af 18 (21%)
á gjörgæslu. Útbreiddari lungnabreytingar sáust oftar hjá karlmönnum
og sjúklingum sem voru inniliggjandi á gjörgæslu. Jafnframt voru þeir
líklegri til að þurfa öndunarvélameðferð. Í eftirliti sáust marktæk tengsl
færri TS-stiga við kvenkyn en marktæk tengsl fleiri TS-stiga voru við
hækkandi aldur, gjörgæslulegu og lengd gjörgæslulegu. Lungnabreytingar
voru horfnar hjá tæplega þriðjungi þátttakenda við eftirlit (að miðgildi 68,5
dögum eftir bráðarannsókn).
ÁLYKTUN
Einstaklingar með alvarlegan COVID-19 hafa umfangsmeiri
lungnabreytingar í bráðum veikindum og við eftirlit en þeir sem fá vægari
sjúkdóm. Eldri einstaklingar og karlmenn eru í aukinni áhættu.INTRODUCTION Infections due to COVID-19 can lead to life threatening pneumonia.
Accompanying severe disease are more prominent pulmonary changes on Computed
Tomography (CT) scan of the chest. The goal of this study was to describe pulmonary CT
changes during acute COVID-19 and at follow up and whether the extent of changes correlate
with severity of illness, demographics or other risk factors.
MATERIALS AND METHODS Included in this study are all individuals that had confirmed
COVID-19 and came for a follow up CT of the chest at Landspitali from May to September 2020.
Information regarding medical history was obtained retrospectively from medical charts. All
CT scans were reviewed using an international staging system to evaluate the extent of lung
changes.
RESULTS Eighty-five patients with a mean age of 59 years were included in the study. Sixty
patients (71%) were hospitalized during the acute phase and 18 (21%) were admitted to the ICU.
During the acute phase more pronounced lung involvement was seen in males and patients
admitted to the ICU. At follow-up females had less lung involvement but there was a significant
relationship between a higher CT score and age, ICU admissions and days in the ICU. Full
recovery was seen at follow-up CT in 31% of patients (median 68,5 days between acute and
follow-up imaging).
CONCLUSION Patients with severe COVID-19 have more pronounced lung involvement on CT
than patients with milder disease during the acute phase and follow-up. Older patients and
males are at greater risk of acute and persistent COVID-19 related lung changes
DNA Methylation Signatures Predict Cytogenetic Subtype and Outcome in Pediatric Acute Myeloid Leukemia (AML).
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 DownloadPediatric acute myeloid leukemia (AML) is a heterogeneous disease composed of clinically relevant subtypes defined by recurrent cytogenetic aberrations. The majority of the aberrations used in risk grouping for treatment decisions are extensively studied, but still a large proportion of pediatric AML patients remain cytogenetically undefined and would therefore benefit from additional molecular investigation. As aberrant epigenetic regulation has been widely observed during leukemogenesis, we hypothesized that DNA methylation signatures could be used to predict molecular subtypes and identify signatures with prognostic impact in AML. To study genome-wide DNA methylation, we analyzed 123 diagnostic and 19 relapse AML samples on Illumina 450k DNA methylation arrays. We designed and validated DNA methylation-based classifiers for AML cytogenetic subtype, resulting in an overall test accuracy of 91%. Furthermore, we identified methylation signatures associated with outcome in t(8;21)/RUNX1-RUNX1T1, normal karyotype, and MLL/KMT2A-rearranged subgroups (p < 0.01). Overall, these results further underscore the clinical value of DNA methylation analysis in AML.European Commission
Swedish Research Council
European Commission
Goran Gustafssons Foundatio