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Comparison of treatment retention and response to secukinumab versus tumour necrosis factor inhibitors in psoriatic arthritis.
No full textTo access publisher's full text version of this article click on the hyperlink belowObjectives: To compare treatment retention and response to secukinumab vs adalimumab, including the other four TNF inhibitors (TNFi) as comparators, in PsA.
Methods: All patients with PsA starting secukinumab or a TNFi in 2015-2018 were identified in the biologic registers of the Nordic countries. Data on comorbidities were linked from national registers. One-year treatment retention and hazard ratios (HRs) for treatment discontinuation were calculated. The proportion achieving a 6 month 28-joint Disease Activity Index for Psoriatic Arthritis (DAPSA28) remission was determined together with odds ratios (ORs) for remission (logistic regression). Both HRs and ORs were calculated with adalimumab as the reference and adjusted for baseline characteristics and concurrent comorbidities. All analyses were stratified by the line of biologic treatment (first, second, third+).
Results: We identified 6143 patients contributing 8307 treatment courses (secukinumab, 1227; adalimumab, 1367). Secukinumab was rarely used as the first biologic, otherwise baseline characteristics were similar. No clinically significant differences in treatment retention or response rates were observed for secukinumab vs adalimumab. The adjusted HRs for discontinuation per the first, second and third line of treatment were 0.98 (95% CI 0.68, 1.41), 0.94 (0.70, 1.26) and 1.07 (0.84, 1.36), respectively. The ORs for DAPSA28 remission in the first, second and third line of treatment were 0.62 (95% CI 0.30, 1.28), 0.85 (0.41, 1.78) and 0.74 (0.36, 1.51), respectively. In the subset of patients previously failing a TNFi due to ineffectiveness, the results were similar.
Conclusion: No significant differences in treatment retention or response were observed between secukinumab and adalimumab, regardless of the line of treatment. This suggests that even in patients who have failed a TNFi, choosing either another TNFi or secukinumab may be equally effective.
Keywords: adalimumab; psoriatic arthritis; response; retention; secukinumab; treatment.NordForsk
Foundation for Research in Rheumatology (FOREUM)
Finska Lakaresallskapet
Helsinki University Hospital Institutional gran
Obesity as a predictor of treatment-related toxicity in children with acute lymphoblastic leukaemia.
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 DownloadObesity is associated with poor outcomes in childhood acute lymphoblastic leukaemia (ALL). We explored whether severe treatment-related toxicity and treatment delays could explain this observation. This study included 1 443 children aged 2·0-17·9 years with ALL treated with the Nordic Society of Pediatric Haematology and Oncology (NOPHO) ALL2008 non-high-risk protocol. Prospective treatment-related toxicities registered every three-month interval were used. Patients were classified according to sex- and age-adjusted international childhood cut-off values, corresponding to adult body mass index: underweight, <17 kg/m2 ; healthy weight, 17 to <25 kg/m2 ; overweight, 25 to <30 kg/m2 ; and obese, ≥30 kg/m2 . Obese children had a higher incidence rate ratio (IRR) for severe toxic events {IRR: 1·55 [95% confidence interval (CI) 1·07-2·50]}, liver and kidney failures, bleeding, abdominal complication, suspected unexpected severe adverse reactions and hyperlipidaemia compared with healthy-weight children. Obese children aged ≥10 years had increased IRRs for asparaginase-related toxicities compared with healthy-weight older children: thromboses [IRR 2·87 (95% CI 1·00-8·21)] and anaphylactic reactions [IRR 7·95 (95% CI 2·15-29·37)] as well as higher risk for truncation of asparaginase [IRR 3·54 (95% CI 1·67-7·50)]. The high prevalence of toxicity and a higher risk of truncation of asparaginase may play a role in the poor prognosis of obese children aged ≥10 years with ALL.Barncancerfonden (Swedish Childhood Cancer Fund
Serum Biomarkers of Disease Activity in Longitudinal Assessment of Patients with ANCA-Associated Vasculitis.
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: Improved biomarkers of current disease activity and prediction of relapse are needed in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). For clinical relevance, biomarkers must perform well longitudinally in patients on treatment and in patients with nonsevere flares.
Methods: Twenty-two proteins were measured in 347 serum samples from 74 patients with AAV enrolled in a clinical trial. Samples were collected at Month 6 after remission induction, then every 3 months until Month 18, or at the time of flare. Associations of protein concentrations with concurrent disease activity and with future flare were analyzed using mixed-effects models, Cox proportional hazards models, and conditional logistic regression.
Results: Forty-two patients had flares during the 12-month follow-up period, and 32 remained in remission. Twenty-two patients had severe flares. Six experimental markers (CXCL13, IL-6, IL-8, IL-15, IL-18BP, and matrix metalloproteinase-3 [MMP-3]) and ESR were associated with disease activity using all three methods (P < 0.05, with P < 0.01 in at least one method). A rise in IL-8, IL-15, or IL-18BP was associated temporally with flare. Combining C-reactive protein (CRP), IL-18BP, neutrophil gelatinase-associated lipocalin (NGAL), and sIL-2Rα improved association with active AAV. CXCL13 and MMP-3 were increased during treatment with prednisone, independent of disease activity. Marker concentrations during remission were not predictive of future flare.
Conclusion: Serum biomarkers of inflammation and tissue damage and repair have been previously shown to be strongly associated with severe active AAV were less strongly associated with active AAV in a longitudinal study that included mild flares and varying treatment. Markers rising contemporaneously with flare or with an improved association in combination merit further study.Vasculitis Clinical Research Consortium (VCRC)
United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
NIH National Center for Advancing Translational Sciences (NCATS)
Appeared in source as:NCATS
United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS)
Appeared in source as:National Institute of Arthritis and Musculoskeletal and Skin Diseases
Appeared in source as:National Institute of Arthritis and Musculoskeletal and Skin Diseases
Appeared in source as:National Institute of Arthritis and Musculoskeletal and Skin Diseases
United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
NIH National Center for Research Resources (NCRR) U54 RR019497
Immune Tolerance Network (NIH) - National Institute of Allergy and Infectious Diseases N01 AI15416
Roche Holding
Genentech
Biogen
Clinical and Translational Science Award from the National Center for Research Resources (NCRR) RR024150-01
United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
NIH National Center for Research Resources (NCRR)
Appeared in source as:NCRR
Clinical and Translational Science Award
United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
Appeared in source as:National Institutes of Health
Arthritis Foundatio
Population birth data and pandemic readiness in Europe
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 SARS-CoV-2 pandemic exposed multiple shortcomings in national and international capacity to respond to an infectious disease outbreak. It is essential to learn from these deficiencies to prepare for future epidemics. One major gap is the limited availability of timely and comprehensive population-based routine data about COVID-19's impact on pregnant women and babies. As part of the Horizon 2020 PHIRI (Population Health Information Research Infrastructure) project on the use of population data for COVID-19 surveillance, the Euro-Peristat research network investigated the extent to which routine information systems could be used to assess the effects of the pandemic by constructing indicators of maternal and child health and of COVID-19 infection. The Euro-Peristat network brings together researchers and statisticians from 31 countries to monitor population indicators of perinatal health in Europe and periodically compiles data on a set of 10 core and 20 recommended indicators.Horizon 2020 Framework Programm
Chronic airflow obstruction and ambient particulate air pollution.
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 DownloadSmoking is the most well-established cause of chronic airflow obstruction (CAO) but particulate air pollution and poverty have also been implicated. We regressed sex-specific prevalence of CAO from 41 Burden of Obstructive Lung Disease study sites against smoking prevalence from the same study, the gross national income per capita and the local annual mean level of ambient particulate matter (PM2.5) using negative binomial regression. The prevalence of CAO was not independently associated with PM2.5 but was strongly associated with smoking and was also associated with poverty. Strengthening tobacco control and improved understanding of the link between CAO and poverty should be prioritised.Wellcome Trust
European Commission
Operations Center Centre in Portland
Oregon from Altana
Sanofi-Aventis
AstraZenec
Taste education - A food-based intervention in a school setting, focusing on children with and without neurodevelopmental disorders and their families. A randomized controlled trial.
No full textTo access publisher's full text version of this article click on the hyperlink belowChildren with neurodevelopmental disorders (ND) such as Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactive Disorder (ADHD) have high levels of fussy eating. However, no school-based food interventions exist for children with ASD and ADHD. To investigate the effect of Taste Education, 81 children with ND (n = 33), and without (n = 48), aged 8-12 years, and their parents, participated in a 7-week food intervention. Children were matched on age, ND, and sex, and randomized into Immediate-intervention and Delayed-intervention groups. Parents completed the Children's Eating Behaviour Questionnaire (CEBQ), and a food-variety questionnaire. After adjusting for baseline measures, repeated-measures analysis-of-variance with time-points, and condition as factors (Immediate intervention and Delayed intervention) were used to examine changes in CEBQ-scores, with a robust linear mixed-model fitted. Changes in percentage of accepted foods were tested using a logistic-regression model adjusting for baseline acceptance. Results showed superior results for Intervention compared to waiting, on Food fussiness, but not Enjoyment of food, with stable effects through six-months follow-up. There were non-significant differences between children with and without ND. Results also showed increased odds of accepting vegetables by a factor of 1.6 (95% Confidence Interval [CI]: 1.33-1.93, p < .001); nuts and seeds by a factor of 1.4 (95% CI: 1.27-1.6, p < .001), but no significant association for fruit (OR 1.12, 95% CI: 0.92-1.34, p = .244). Trends were similar for children regardless of ND-status. The Taste Education program, shows promise, as a simple, non-invasive way to decrease fussy eating and increase food variety in the long-term.
Keywords: ADHD; Autism spectrum disorders; Fussy eating; Parent-child dyads; School setting; Taste education.University of Iceland's Research fund
Public Health Fund of the Directorate of Healt
Infliximab-induced liver injury: Clinical phenotypes, autoimmunity and the role of corticosteroid treatment.
No full textTo access publisher's full text version of this article click on the hyperlink belowBackground & aims: Infliximab has been associated with drug-induced liver injury (DILI), particularly drug-induced autoimmune hepatitis (DIAIH). DIAIH is commonly treated with corticosteroids, but there is limited data on the efficacy of corticosteroids in infliximab-induced DILI.
Methods: Patients were included for assessment if they had been treated with infliximab between 2009-2020 in Iceland and had developed elevated liver tests. Other specific etiologies of liver enzyme elevations were excluded. Patients treated with corticosteroids were compared to patients not receiving corticosteroids.
Results: A total of 36 patients with infliximab-induced DILI were identified: median age was 46 years (IQR 32-54) and 28 (78%) were female. Type of liver injury was predominantly hepatocellular (64%). Median peak liver enzymes were: alanine aminotransferase (ALT) 393 (328-695) U/L, aspartate aminotransferase 283 (158-564) U/L, alkaline phosphatase 116 (83-205) U/L, and bilirubin (10-20) 13 μmol/L. A total of 25 (69%) were positive for anti-nuclear antibody and/or had elevated IgG. Corticosteroids were initiated in 17 (47%). Median time from onset of liver injury to peak ALT value was longer in patients treated with corticosteroids, 22 (12-59) vs. 0 (0-3) days (p = 0.001). Time from peak ALT to normalization of liver enzymes was 45 days in the corticosteroid group vs. 77 days in others (p = 0.062). Corticosteroids were tapered in all patients, with no cases of relapse during the follow-up period of 1,245 (820-2,698) days. Overall 75% received another biologic, mostly adalimumab, without evidence of liver injury.
Conclusion: Approximately half of patients with infliximab-induced liver injury had slow improvement in ALT despite cessation of therapy and were treated with corticosteroids. Treatment response was good with prompt resolution of liver test abnormalities. Relapse of liver injury was not observed after tapering of corticosteroids despite prolonged follow-up and no patients developed DILI due to a second biologic.
Lay summary: A rare side effect of infliximab, a biologic medicine used to treat multiple inflammatory diseases, is liver injury and liver inflammation. Steroid treatment has been used in some patients with liver injury caused by infliximab, but there have been few studies supporting this treatment. In this study of 36 patients with infliximab-induced liver injury, approximately half of patients were treated with steroids and the results suggest that patients receiving steroids recover more quickly.
Keywords: DILI; drug-induced liver injury; hepatotoxicity; liver enzymes; steroids.Research Fund of The National University Hospital of Icelan
Increased use of genetic health care in Iceland 2012-2017
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 DownloadINNGANGUR
Formleg erfðaráðgjafareining hefur verið starfrækt á Landspítala
við Hringbraut frá árinu 2006. Samhliða hefur áhugi og þörf á
erfðalæknisfræði í almennri heilbrigðisþjónustu aukist til muna. Í
þessari grein er starfsemi og útkoma erfðarannsókna hjá erfða- og
sameindalæknisfræðideild Landspítala á 5 ára tímabili (2012-2017) tekin
saman. Sérstaklega var horft til fjölda einstaklinga, ástæðu komu, ástæðu
erfðarannsókna án aðkomu erfðaráðgjafar Landspítala og eins var nýtni
(heildarhlutfall rannsókna sem skila jákvæðri niðurstöðu) erfðarannsókna
skoðuð.
AÐFERÐIR
Gögn um komur voru fengin upp úr sjúkraskrárkerfi erfðaráðgjafar, Shire
og Sögu/Heilsugátt.
NIÐURSTAÐA
Fjöldi þeirra sem sóttu þjónustu erfðaráðgjafareiningarinnar
jókst árlega allt tímabilið. Ástæður fyrir erfðaráðgjöf reyndust
vera krabbameinstengdar í tveimur þriðju hlutum tilfella. Aðrir
komu vegna fjölskyldulægra sjúkdóma sem eru algengir á Íslandi,
ýmist sjúkdóma sem erfast ríkjandi (dæmi: vöðvaspennuvisnun og
ofvaxtarhjartavöðvasjúkdómur) eða vegna víkjandi sjúkdóma (dæmi:
mænuvöðvarýrnun og GM1-ganglio-síðkvilli). Algengast var að fólk
færi í erfðarannsókn án aðkomu erfðaráðgjafar Landspítala vegna
meðhöndlanlegra sjúkdóma, svo sem arfgengrar járnofhleðslu og
bláæðasegatilhneigingar. Nýtni erfðarannsókna var metin fyrir a)
leit að þekktum meinvaldandi breytingum, b) leit að meinvaldandi
breytingum í stökum genum (eingenarannsóknir), c) fjölgenarannsóknir
og d) tákn- og heilerfðamengisrannsóknir. Leit að þekktri breytingu
skilaði jákvæðri niðurstöðu í 33% tilvika og leit í stöku geni í 46%
tilvika. Nýtni fjölgenarannsókna vegna krabbameina var lægri (20%)
samanborið við aðrar fjölgenarannsóknir (40%). Þá var nýtni tákn- og
heilerfðamengisrannsókna 46%.INTRODUCTION: A genetic counselling unit at Landspitali hospital (LSH) was established
in 2006. Meanwhile, genetic testing has become an integral part of general health care.
In this article we detail the outcome of genetic testing at the Department of Genetic and
Molecular Medicine (DGM) at Landspitali over a five year period (2012-2017). Factors that
were analyzed for the time period were: Number of patients, reason for referral, reason
for genetic testing without genetic counselling and yield (proportion of positive tests) of
genetic testing.
METHODS: Data was analysed from two medical record databases, Shire and Saga, used
by the DGM in the time period.
RESULTS: The number of individuals coming for genetic counselling increased every year
over the time period. Reasons for referral were cancer-related in two-thirds of cases.
Other reasons for referral included various other familial disorders. Most common were
autosomal dominant disorders like myotonic dystrophy, hypertrophic cardiomyopathy
and autosomal recessive disorders like spinal muscular atrophy (SMA) and GM1-
gangliosidosis. Most common reasons for genetic testing outside of the LSH GC unit was
because of managable diseases like hemochromatosis and F5/Prothrombin-related
thrombophilia. Yield of genetic testing was assessed for a) known mutation testing /
carrier testing, b) single gene testing, c) gene panel testing and d) whole genome and
whole exome sequencing. Known mutation testing was positive in 33% of cases and single
gene testing in 46% of cases. The yield of gene panel testing for cancer was found to be
lower (20%) than gene panel testing for other disorders (40%). The yield of whole exome
and whole genome sequencing was 46%
Higher Alkylresorcinol Concentrations, a Consequence of Whole-Grain Intake, are Inversely Associated with Gestational Diabetes Mellitus in Iceland.
No full textTo access publisher's full text version of this article click on the hyperlink belowBackground: A diet rich in whole grains may provide benefits for pregnant women due to whole grains' high nutritional value and dietary fiber content.
Objectives: To study the associations of whole-grain consumption, as well as the plasma alkylresorcinol concentration, a whole-grain consumption biomarker, in early pregnancy with gestational diabetes mellitus (GDM) diagnoses.
Methods: Subjects were women from the prospective study Pregnant Women in Iceland II (PREWICE II; n = 853) who attended their ultrasound appointment in gestational weeks 11-14 during the period from October 2017 to March 2018. During that visit, whole-grain consumption was estimated using a diet screening questionnaire, and blood samples were collected for analysis of plasma alkylresorcinols (ARs). Information on GDM diagnoses was later extracted from medical records. Multivariate log-binomial regression was used to evaluate the association of dietary whole-grain and AR concentrations with GDM.
Results: In total, 14.9% of the women adhered to the national food-based dietary guidelines (n = 127), which recommend 2 portions of whole grains daily. GDM was diagnosed in 127 women (14.9%). The frequency of whole-grain consumption was lower in women who were later diagnosed with GDM compared to the women without GDM (median, 5 times/week vs. 6 times/week, respectively; P = 0.02). This difference was reflected in the lower median concentration of total AR in women diagnosed with GDM (163 nmol/L vs. 209 nmol/L, respectively; P < 0.01). The quartile with the highest concentrations of AR had a RR of 0.50 (95% CI: 0.27-0.90) of being diagnosed with GDM, in comparison to the lowest quartile. There was a significant dose response in the GDM risk with higher AR levels.
Conclusions: We found that a higher consumption of whole grains, reflected both by reported consumption according to the FFQ and AR biomarkers, was associated with a decreased risk of receiving a GDM diagnosis.University of Iceland Research Fund
Science Fund of The National University Hospital in Icelan
Evaluation of mechanism of change in transdiagnostic cognitive behaviour therapy using single case experimental design.
No full textTo access publisher's full text version of this article click on the hyperlink belowBackground and objectives: Transdiagnostic mechanisms of change (txMOC) specific to cognitive behaviour therapy are poorly understood. Salkovskis (1996) proposed one such mechanism in terms of the shift towards an alternative, less negative view of their problems or cognitive flexibility. This hypothesis has been described as involving a shift in beliefs, from "theory A″ to "theory B". The objective of this research was to evaluate this hypothesis.
Methods: Effectiveness of a novel txCBT and temporal changes in process and symptom measures were evaluated using a non-concurrent multiple baseline design and Tau-U calculations with thirteen participants (five with obsessive-compulsive disorder, two with panic disorder with agoraphobia and six with major depressive disorder). As a secondary analysis authors calculated Kendall's - Tau correlation between process and symptom measures, performed the Wilcoxon signed-rank test to assess treatment modules effect on negative thought and calculated Reliable change index (RCI).
Results: The txCBT was clearly effective for eight participants. The results varied dependent on the stimuli evaluated as negative or threatening. Level and trend of the ratings of belief in theory A followed the level and trend of symptom measures to a greater extent than the (inverse) level and trend of belief in theory B.
Limitations: Only thirteen participants were recruited and evaluated.
Conclusions: The results are consistent with the view that effective treatment may involve a txMOC characterized by the ability to shift from a relatively fixed negative view of their experience to a less negative psychologically focused alternative.
Keywords: Anxiety; Depression; Mechanism of change; Single case experimental design; Transdiagnostic cognitive behavior therapy