Landspítali University Hospital Research Archive
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Baseline neutrophil-to-lymphocyte ratio as a predictive and prognostic biomarker in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel versus abiraterone or enzalutamide in the CARD study.
Full text linkSanofi-Aventis
Genzyme CorporationBackground: There is growing evidence that a high neutrophil-to-lymphocyte ratio (NLR) is associated with poor overall survival (OS) for patients with metastatic castration-resistant prostate cancer (mCRPC). In the CARD study (NCT02485691), cabazitaxel significantly improved radiographic progression-free survival (rPFS) and OS versus abiraterone or enzalutamide in patients with mCRPC previously treated with docetaxel and the alternative androgen-receptor-targeted agent (ARTA). Here, we investigated NLR as a biomarker.
Patients and methods: CARD was a multicenter, open-label study that randomized patients with mCRPC to receive cabazitaxel (25 mg/m2 every 3 weeks) versus abiraterone (1000 mg/day) or enzalutamide (160 mg/day). The relationships between baseline NLR [< versus ≥ median (3.38)] and rPFS, OS, time to prostate-specific antigen progression, and prostate-specific antigen response to cabazitaxel versus ARTA were evaluated using Kaplan-Meier estimates. Multivariable Cox regression with stepwise selection of covariates was used to investigate the prognostic association between baseline NLR and OS.
Results: The rPFS benefit with cabazitaxel versus ARTA was particularly marked in patients with high NLR {8.5 versus 2.8 months, respectively; hazard ratio (HR) 0.43 [95% confidence interval (CI) 0.27-0.67]; P < 0.0001}, compared with low NLR [7.5 versus 5.1 months, respectively; HR 0.69 (95% CI 0.45-1.06); P = 0.0860]. Higher NLR (continuous covariate, per 1 unit increase) independently associated with poor OS [HR 1.05 (95% CI 1.02-1.08); P = 0.0003]. For cabazitaxel, there was no OS difference between patients with high versus low NLR (15.3 versus 12.9 months, respectively; P = 0.7465). Patients receiving an ARTA with high NLR, however, had a worse OS versus those with low NLR (9.5 versus 13.3 months, respectively; P = 0.0608).
Conclusions: High baseline NLR predicts poor outcomes with an ARTA in patients with mCRPC previously treated with docetaxel and the alternative ARTA. Conversely, the activity of cabazitaxel is retained irrespective of NLR.
Keywords: abiraterone; cabazitaxel; enzalutamide; metastatic castration-resistant prostate cancer; neutrophil-to-lymphocyte ratio; prognostic factor
Cross-sectional study on exhaled nitric oxide in relation to upper airway inflammatory disorders with regard to asthma and perennial sensitization.
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 DownloadBackground: Fractional exhaled nitric oxide (FeNO) is a well-known marker of type-2 inflammation. FeNO is elevated in asthma and allergic rhinitis, with IgE sensitization as a major determinant.
Objective: We aimed to see whether there was an independent association between upper airway inflammatory disorders (UAID) and FeNO, after adjustment for asthma and sensitization, in a multi-centre population-based study.
Methods: A total of 741 subjects with current asthma and 4155 non-asthmatic subjects participating in the second follow-up of the European Community Respiratory Health Survey (ECRHS III) underwent FeNO measurements. Sensitization status was based on measurement of IgE against airborne allergens; information on asthma, UAID and medication was collected through interview-led questionnaires. Independent associations between UAID and FeNO were assessed in adjusted multivariate regression models and test for interaction with perennial sensitization and asthma on the relation between UAID and FeNO were made.
Results: UAID were associated with higher FeNO after adjusting for perennial sensitization, asthma and other confounders: with 4.4 (0.9-7.9) % higher FeNO in relation to current rhinitis and 4.8 (0.7-9.2) % higher FeNO in relation to rhinoconjunctivitis. A significant interaction with perennial sensitization was found in the relationship between current rhinitis and FeNO (p = .03) and between rhinoconjunctivitis and FeNO (p = .03). After stratification by asthma and perennial sensitization, the association between current rhinitis and FeNO remained in non-asthmatic subjects with perennial sensitization, with 12.1 (0.2-25.5) % higher FeNO in subjects with current rhinitis than in those without.
Conclusions & clinical relevance: Current rhinitis and rhinoconjunctivitis was associated with higher FeNO, with an interaction with perennial sensitization. This further highlights the concept of united airway disease, with correlations between symptoms and inflammation in the upper and lower airways and that sensitization needs to be accounted for in the relation between FeNO and rhinitis.
Keywords: FeNO; asthma; exhaled nitric oxide; nasal polyposis; population-based; rhinitis.UK Research & Innovation (UKRI)
Medical Research Council UK (MRC)
European Commission
National Health and Medical Research Council of Australia
Belgium: Antwerp South, Antwerp City-Research Foundation Flanders (FWO)
Estonia: Estonian Ministry of Education Tartu-SF0180060s09
Estonian Research Council
France: Ministere de la Sante, Programme Hospitalier de Recherche Clinique (PHRC)
Bordeaux-INSERM U897 Universite Bordeaux Segalen
Grenoble-Comite Scientifique AGIRadom
Paris-Agence Nationale de la Sante, Region Ile de France, domaine d'interet majeur (DIM)
Germany: Erfurt-German Research Foundation
Hamburg-German Research Foundation
Iceland: Reykjavik-The Landspitali University Hospital Research Fund
Iceland: Iceland Research Fund
Iceland: ResMed Foundation, California, USA
Iceland: Orkuveita Reykjavikur (Geothermal plant), Vegageroin (The Icelandic Road Administration (ICERA)
Italy: Italian Ministry of Health
Chiesi Pharmaceuticals Inc
Fondazione Cariverona
Education Ministry (MIUR)
Norway: Norwegian Research Council
Norway: Western Norway Regional Health Authorities grant
Norway: Bergen Medical Research Foundation
Spain: Fondo de Investigacion Sanitaria
Spain: Servicio Andaluz de Salud
Spain: Sociedad Espanola de Neumologia y Cirurgia Toracica
Galdakao-Fondo de Investigacion Sanitaria
Huelva-Fondo de Investigacion Sanitaria
Huelva-Servicio Andaluz de Salud
Oviedo-Fondo de Investigacion Sanitaria
Spanish Ministry of Science and Innovation through the "Centro de Excelencia Severo Ochoa 2019-2023" Program
Generalitat de Catalunya through the CERCA Program
Sweden: Swedish Heart and Lung Foundation
Sweden: Swedish Asthma and Allergy Association
Sweden: Swedish Association against Lung and Heart Disease
Sweden: Swedish Research Council for Health, Working Life and Welfare (FORTE)
Swedish Research Council
Swedish Research Council for Health Working Life & Welfare (Forte)
Vasterbotten County Council ALF grant
Swiss National Science Foundation (SNSF)
Switzerland: Federal Office for Forest, Environment and Landscape
Switzerland: Federal Office of Public Health
Switzerland: Federal Office of Roads and Transpor
Niraparib for Advanced Breast Cancer with Germline and Mutations: the EORTC 1307-BCG/BIG5-13/TESARO PR-30-50-10-C BRAVO Study.
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 DownloadPurpose: To investigate the activity of niraparib in patients with germline-mutated BRCA1/2 (gBRCAm) advanced breast cancer.
Patients and methods: BRAVO was a randomized, open-label phase III trial. Eligible patients had gBRCAm and HER2-negative advanced breast cancer previously treated with ≤2 prior lines of chemotherapy for advanced breast cancer or had relapsed within 12 months of adjuvant chemotherapy, and were randomized 2:1 between niraparib and physician's choice chemotherapy (PC; monotherapy with eribulin, capecitabine, vinorelbine, or gemcitabine). Patients with hormone receptor-positive tumors had to have received ≥1 line of endocrine therapy and progressed during this treatment in the metastatic setting or relapsed within 1 year of (neo)adjuvant treatment. The primary endpoint was centrally assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), PFS by local assessment (local-PFS), objective response rate (ORR), and safety.
Results: After the pre-planned interim analysis, recruitment was halted on the basis of futility, noting a high degree of discordance between local and central PFS assessment in the PC arm that resulted in informative censoring. At the final analysis (median follow-up, 19.9 months), median centrally assessed PFS was 4.1 months in the niraparib arm (n = 141) versus 3.1 months in the PC arm [n = 74; hazard ratio (HR), 0.96; 95% confidence interval (CI), 0.65-1.44; P = 0.86]. HRs for OS and local-PFS were 0.95 (95% CI, 0.63-1.42) and 0.65 (95% CI, 0.46-0.93), respectively. ORR was 35% (95% CI, 26-45) with niraparib and 31% (95% CI, 19-46) in the PC arm.
Conclusions: Informative censoring in the control arm prevented accurate assessment of the trial hypothesis, although there was clear evidence of niraparib's activity in this patient population.TESARO
United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
NIH National Cancer Institute (NCI
Ventilator-induced lung-injury in mouse models: Is there a trap?
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 DownloadVentilator-induced lung injury (VILI) is a serious acute injury to the lung tissue that can develop during mechanical ventilation of patients. Due to the mechanical strain of ventilation, damage can occur in the bronchiolar and alveolar epithelium resulting in a cascade of events that may be fatal to the patients. Patients requiring mechanical ventilation are often critically ill, which limits the possibility of obtaining patient samples, making VILI research challenging. In vitro models are very important for VILI research, but the complexity of the cellular interactions in multi-organ animals, necessitates in vivo studies where the mouse model is a common choice. However, the settings and duration of ventilation used to create VILI in mice vary greatly, causing uncertainty in interpretation and comparison of results. This review examines approaches to induce VILI in mouse models for the last 10 years, to our best knowledge, summarizing methods and key parameters presented across the studies. The results imply that a more standardized approach is warranted.
Keywords: Acute lung injury; Animal models; Mouse studies; Ventilator-induced lung injury.Landspitali research fun
Parent-youth agreement on psychiatric diagnoses and symptoms: results from an adolescent outpatient clinical sample.
No full textTo access publisher's full text version of this article click on the hyperlink belowObjective: Previous research suggests that agreement, between youths and their parents, regarding assessment of youth psychiatric problems is limited. Due to this discrepancy, a multi-informant, multimethod approach is recommended when gathering psychopathological information. This study examines parent-youth agreement regarding youth psychiatric problems. It does so at a diagnostic level and at a symptom level, as well as studying the influence of age, gender, depressive disorder, anxiety disorder and attention-deficit/hyperactivity disorder (ADHD) as potential moderators of agreement.
Methods: The participants in this study were 61 adolescents aged 12-18 years and their parents. The K-SADS-PL DSM-5 was administered in two outpatient units, with adolescents and their parents interviewed separately. Participants also rated symptoms using a broad rating scale (Child Behavior Checklist and the Youth Self-Report) prior to being interviewed.
Results: Parent-youth agreement at a diagnostic level ranged from fair to excellent. Agreement at a symptom level was lower than that at a diagnostic level, ranging from poor to fair. These results indicate that parent-youth agreement regarding diagnosis and symptoms is higher than in most previous studies. The results also suggest that some variables, such as age, gender, depressive disorders, and ADHD, potentially influence agreement on symptoms.
Conclusion: These findings support the importance of gathering information from both children and parents, and that clinicians should consider moderating factors when integrating data from multiple informants.
Keywords: Agreement; assessment; children; parent–youth agreement; schedule for affective disorders and schizophrenia for school-age children Kiddie-SADS-PL (K-SADS).University of Iceland Research Fun
Validity of chronic disease diagnoses in Icelandic healthcare registries.
No full textTo access publisher's full text version of this article click on the hyperlink belowAims: To evaluate the validity of recorded chronic disease diagnoses in Icelandic healthcare registries.
Methods: Eight different chronic diseases from multiple sub-specialties of medicine were validated with respect to accuracy, but not to timeliness. For each disease, 30 patients with a recorded diagnosis and 30 patients without the same diagnosis were randomly selected from >80,000 participants in the iStopMM trial, which includes 54% of the Icelandic population born before 1976. Each case was validated by chart review by physicians using predefined criteria.
Results: The overall accuracy of the chronic disease diagnoses was 96% (95% CI 94-97%), ranging from 92 to 98% for individual diseases. After weighting for disease prevalence, the accuracy was estimated to be 98.5%. The overall positive predictive value (PPV) of chronic disease diagnosis was 93% (95% CI 89-96%) and the overall negative predictive value (NPV) was 99% (95% CI 96-100%). There were disease-specific differences in validity, most notably multiple sclerosis, where the PPV was 83%. Other disorders had PPVs between 93 and 97%. The NPV of most disorders was 100%, except for hypertension and heart failure, where it was 97 and 93%, respectively. Those who had the registered chronic disease had objective findings of disease in 96% of cases.
Conclusions: When determining the presence of chronic disease, diagnosis data from the Icelandic healthcare registries has a high PPV, NPV and accuracy. Furthermore, most diagnoses can be confirmed by objective findings such as imaging or blood testing. These findings can inform the interpretation of studies using diagnostic data from the Icelandic healthcare registries.
Keywords: Chronic diseases; Iceland; comorbidity; data accuracy; registries; validation study.Black Swan Research Initiative by the International Myeloma Foundation
Icelandic Centre for Research
European Research Council (ERC)
University of Iceland
Landspitali University Hospital
Icelandic Cancer Societ
Alice in Wonderland and anti-vaccine misinformation
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
Rivaroxaban Is Associated With Higher Rates of Gastrointestinal Bleeding Than Other Direct Oral Anticoagulants : A Nationwide Propensity Score-Weighted Study.
No full textTo access publisher's full text version of this article click on the hyperlink belowBackground: Gastrointestinal bleeding (GIB) rates for direct oral anticoagulants (DOACs) and warfarin have been extensively compared. However, population-based studies comparing GIB rates among different DOACs are limited.
Objective: To compare rates of GIB among apixaban, dabigatran, and rivaroxaban.
Design: Nationwide population-based cohort study.
Setting: Landspítali-The National University Hospital of Iceland and the 4 regional hospitals in Iceland.
Patients: New users of apixaban, dabigatran, and rivaroxaban from 2014 to 2019.
Measurements: Rates of GIB were compared using inverse probability weighting, Kaplan-Meier survival estimates, and Cox regression.
Results: In total, 2157 patients receiving apixaban, 494 patients receiving dabigatran, and 3217 patients receiving rivaroxaban were compared. For all patients, rivaroxaban had higher overall rates of GIB (3.2 vs. 2.5 events per 100 person-years; hazard ratio [HR], 1.42 [95% CI, 1.04 to 1.93]) and major GIB (1.9 vs. 1.4 events per 100 person-years; HR, 1.50 [CI, 1.00 to 2.24]) compared with apixaban. Rivaroxaban also had higher GIB rates than dabigatran, with similar point estimates, although the CIs were wider and included the possibility of a null effect. When only patients with atrial fibrillation were included, rivaroxaban was associated with higher rates of overall GIB than apixaban (HR, 1.40 [CI, 1.01 to 1.94]) or dabigatran (HR, 2.04 [CI, 1.17 to 3.55]). Dabigatran was associated with lower rates of upper GIB than rivaroxaban in both analyses.
Limitations: Unmeasured confounding and small subgroup analyses.
Conclusion: Rivaroxaban was associated with higher GIB rates than apixaban and dabigatran regardless of treatment indication.Icelandic Centre for Research
Landspitali University Hospital Research Fun
Temporal trends in the epidemiology, management, and outcome of sepsis-A nationwide observational study.
No full textTo access publisher's full text version of this article click on the hyperlink belowBackground: Registry-based studies have shown increasing incidence of sepsis and declining mortality rates in recent years, but are inherently at risk of bias. The objectives of this study were to describe 11-year trends in the incidence, treatment and outcome of sepsis using clinical criteria with chart review.
Methods: This was a retrospective, observational study. All adult admissions to Icelandic ICUs during years 2006, 2008, 2010, 2012, 2014, and 2016 were screened for severe sepsis or septic shock by ACCP/SCCM criteria (sepsis-2). Incidence, patient characteristics, treatment and outcome were compared across the study years.
Results: During the six study years, 9166 patients were admitted to Icelandic ICUs, 971 (10.6%) because of severe sepsis or septic shock. The crude incidence of sepsis requiring admission to ICU remained stable between 0.55 and 0.75 per 1000 inhabitants. No statistically significant trends were observed over time in median patient age (67 years), APACHE II score (21), SOFA score (8) or Charlson Comorbidity Index (4). The time to antibiotic administration (median 1.8 h) in the emergency departments was stable over the study period but the time to lactate measurements decreased from 4.1 h in 2006 to 1.2 h in 2016, p < .001. The 28-day mortality was 25% and 1-year mortality 41%, both with no observed change with time.
Conclusions: In a nationwide cohort, diagnosed with clinical criteria, the incidence of sepsis requiring intensive care did not change over an 11-year period. Mortality remained stable and only minimal changes were observed in initial resuscitation in the emergency departments.
Keywords: critical care; epidemiology; mortality; sepsis; septic shock; surviving sepsis campaign.Landspitali Research Fun
Lower Intake of Saturated Fatty Acids Is Associated with Improved Lipid Profile in a 6-Year-Old Nationally Representative Population.
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 DownloadTo strengthen the organization of new national dietary surveys and interventions in childhood, our aim was to study macronutrient intake and blood lipid profile at 6 years of age by comparing results from two earlier population-based cohorts. Subjects were n = 131 and n = 162 in the years 2001-2002 and 2011-2012, respectively. Three-day weighed food records were used to estimate diet and calculate nutrient intake. Total cholesterol, HDL-cholesterol and triacylglycerol were measured in serum and LDL-cholesterol was calculated. The average intake of saturated fatty acids (SFA) and trans FA was lower in 2011-2012 than 2001-2002 (13.3E% vs. 14.7E%, p < 0.001, and 0.8E% vs. 1.4E%, p < 0.001, respectively), replaced by a higher intake of unsaturated fatty acids. Total cholesterol and LDL-cholesterol were significantly lower in 2011-2012 than 2001-2002 (4.6 vs. 4.4 mmol/L, p = 0.003 and 2.8 vs. 2.5 mmol/L, p < 0.001, respectively). In a multiple linear regression model, one E% increase in SFA intake was related to a 0.03 mmol/L increase in LDL cholesterol (p = 0.04). A lower intake of saturated and trans fatty acids, replaced by unsaturated fatty acids, may have contributed to an improved lipid profile in a healthy 6-year-old population. Biological data for analysis of blood lipids are important in national dietary surveys in healthy children to monitor important health outcomes of interventions