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A descriptive study of the surge response and outcomes of ICU patients with COVID-19 during first wave in Nordic countries.
No full textTo access publisher's full text version of this article click on the hyperlink belowBackground: We sought to provide a description of surge response strategies and characteristics, clinical management and outcomes of patients with severe COVID-19 in the intensive care unit (ICU) during the first wave of the pandemic in Denmark, Finland, Iceland, Norway and Sweden.
Methods: Representatives from the national ICU registries for each of the five countries provided clinical data and a description of the strategies to allocate ICU resources and increase the ICU capacity during the pandemic. All adult patients admitted to the ICU for COVID-19 disease during the first wave of COVID-19 were included. The clinical characteristics, ICU management and outcomes of individual countries were described with descriptive statistics.
Results: Most countries more than doubled their ICU capacity during the pandemic. For patients positive for SARS-CoV-2, the ratio of requiring ICU admission for COVID-19 varied substantially (1.6%-6.7%). Apart from age (proportion of patients aged 65 years or over between 29% and 62%), baseline characteristics, chronic comorbidity burden and acute presentations of COVID-19 disease were similar among the five countries. While utilization of invasive mechanical ventilation was high (59%-85%) in all countries, the proportion of patients receiving renal replacement therapy (7%-26%) and various experimental therapies for COVID-19 disease varied substantially (e.g. use of hydroxychloroquine 0%-85%). Crude ICU mortality ranged from 11% to 33%.
Conclusion: There was substantial variability in the critical care response in Nordic ICUs to the first wave of COVID-19 pandemic, including usage of experimental medications. While ICU mortality was low in all countries, the observed variability warrants further attention.
Keywords: COVID-19; Nordic; SARS-CoV2; mortality.NordForsk (Nordic COVID-19 Activities)
Finnish Society of Intensive Car
Role of Ursodeoxycholic Acid in Treating and Preventing Idiosyncratic Drug-Induced Liver Injury. A Systematic Review.
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 DownloadIntroduction: Treatment is generally not available for drug-induced liver injury (DILI) patients except in some specific circumstances. The management of DILI is based on the withdrawal of the responsible drug and monitoring the patients and only a few patients need to be referred to a transplant center. Some studies on the role of ursodeoxycholic acid (UDCA) in DILI have been published. The aim of this study was to perform a systematic review of the role of UDCA in the treatment and prevention of DILI. Methods: A search was undertaken in PubMed, with the key words ursodeoxycholic acid, drug-induced liver injury and hepatotoxicity following the PRISMA guidelines. Results: A total of 33 publications were identified: 25 case reports and 8 case series. In 18 of the 25 cases reports (22 patients), authors reported improvement of liver injury associated with UDCA therapy whereas 7 case reports did not show clinical or biochemical improvement after UDCA treatment. There were 4 studies evaluating the role of UDCA in the treatment of DILI, three prospective (one being a clinical trial) and one retrospective studies. Three studies observed liver profile improvements associated with UDCA. In addition, four studies evaluated UDCA in the prevention of DILI: one pilot study, two randomized clinical trials (RCT) and one retrospective study. Three of these studies observed a lower percentage of patients with an increase in transaminases in the groups that used UDCA for DILI prevention. Conclusion: According to available data UDCA seems to have some benefits in the treatment and prevention of DILI. However, the design of the published studies does not allow a firm conclusion to be drawn on the efficacy of UDCA in DILI. A well designed RCT to evaluate the role of UDCA in DILI is needed
Effectiveness and treatment retention of TNF inhibitors when used as monotherapy versus comedication with csDMARDs in 15 332 patients with psoriatic arthritis. Data from the EuroSpA collaboration.
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: Comedication with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) during treatment with tumour necrosis factor inhibitors (TNFi) is extensively used in psoriatic arthritis (PsA), although the additive benefit remains unclear. We aimed to compare treatment outcomes in patients with PsA treated with TNFi and csDMARD comedication versus TNFi monotherapy.
Methods: Patients with PsA from 13 European countries who initiated a first TNFi in 2006-2017 were included. Country-specific comparisons of 1 year TNFi retention were performed by csDMARD comedication status, together with HRs for TNFi discontinuation (comedication vs monotherapy), adjusted for age, sex, calendar year, disease duration and Disease Activity Score with 28 joints (DAS28). Adjusted ORs of clinical remission (based on DAS28) at 12 months were calculated. Between-country heterogeneity was assessed using random-effect meta-analyses, combined results were presented when heterogeneity was not significant. Secondary analyses stratified according to TNFi subtype (adalimumab/infliximab/etanercept) and restricted to methotrexate as comedication were performed.
Results: In total, 15 332 patients were included (62% comedication, 38% monotherapy). TNFi retention varied across countries, with significant heterogeneity precluding a combined estimate. Comedication was associated with better remission rates, pooled OR 1.25 (1.12-1.41). Methotrexate comedication was associated with improved remission for adalimumab (OR 1.45 (1.23-1.72)) and infliximab (OR 1.55 (1.21-1.98)) and improved retention for infliximab. No effect of comedication was demonstrated for etanercept.
Conclusion: This large observational study suggests that, as used in clinical practice, csDMARD and TNFi comedication are associated with improved remission rates, and specifically, comedication with methotrexate increases remission rates for both adalimumab and infliximab.
Keywords: arthritis; methotrexate; psoriatic; tumour necrosis factor inhibitors.Novartis
NordFors
Caffeine exposure from beverages and its association with self-reported sleep duration and quality in a large sample of Icelandic adolescents.
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 DownloadPrevious risk assessments have concluded that adolescent's caffeine exposure from energy drinks (ED) are of limited concern. Recent surveys have, however, shown substantial increase in consumption. This cross-sectional survey conducted in 2020 estimated caffeine exposure from beverages among ∼80% of all 13-15-year-old adolescents (n = 10358) relative to the European Food Safety Authority's level of no safety concern of (3.0 mg/kg bw) and level for effects on sleep (1.4 mg/kg bw). Associations with self-reported sleep duration and quality were also explored. ED consumers were more likely to exceed the limit of no safety concern (prevelance: 12-14%) compared to non-ED-consumers (1-2%). Exceeding the limit for effects on sleep was also higher among ED consumers (31-38%) than non-ED-consumers (5-8%). Across categories of low (3.0 mg/kg bw) caffeine intake, the prevalence of participants sleeping <6 h increased from 3% to 24%, respectively. The corresponding adjusted Prevalence Ratio was 4.5 (95% CI: 3.6, 5.7) and mean decrease in duration of sleep was 0.74 h (95% CI: 0.65, 0.84). In conclusion, caffeine intake from beverages above the limit of no safety concern was largely confined to ED consumers. Consistent with effects from intervention studies in adults, caffeine intake was strongly associated with self-reported sleep duration in this representative population.
Keywords: Adolescents; Beverages; Caffeine; Energy drinks; Risk assessment; Sleep duration.Icelandic Ministry of Industries and Innovatio
COVID-19 and risk of subsequent life-threatening secondary infections: a matched cohort study in UK Biobank.
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: With the increasing number of people infected with and recovered from coronavirus disease 2019 (COVID-19), the extent of major health consequences of COVID-19 is unclear, including risks of severe secondary infections.
Methods: Based on 445,845 UK Biobank participants registered in England, we conducted a matched cohort study where 5151 individuals with a positive test result or hospitalized with a diagnosis of COVID-19 were included in the exposed group. We then randomly selected up to 10 matched individuals without COVID-19 diagnosis for each exposed individual (n = 51,402). The life-threatening secondary infections were defined as diagnoses of severe secondary infections with high mortality rates (i.e., sepsis, endocarditis, and central nervous system infections) from the UK Biobank inpatient hospital data, or deaths from these infections from mortality data. The follow-up period was limited to 3 months after the initial COVID-19 diagnosis. Using a similar study design, we additionally constructed a matched cohort where exposed individuals were diagnosed with seasonal influenza from either inpatient hospital or primary care data between 2010 and 2019 (6169 exposed and 61,555 unexposed individuals). After controlling for multiple confounders, Cox models were used to estimate hazard ratios (HRs) of life-threatening secondary infections after COVID-19 or seasonal influenza.
Results: In the matched cohort for COVID-19, 50.22% of participants were male, and the median age at the index date was 66 years. During a median follow-up of 12.71 weeks, the incidence rate of life-threatening secondary infections was 2.23 (123/55.15) and 0.25 (151/600.55) per 1000 person-weeks for all patients with COVID-19 and their matched individuals, respectively, which corresponded to a fully adjusted HR of 8.19 (95% confidence interval [CI] 6.33-10.59). The corresponding HR of life-threatening secondary infections among all patients with seasonal influenza diagnosis was 4.50, 95% CI 3.34-6.08 (p for difference < 0.01). Also, elevated HRs were observed among hospitalized individuals for life-threatening secondary infections following hospital discharge, both in the COVID-19 (HR = 6.28 [95% CI 4.05-9.75]) and seasonal influenza (6.01 [95% CI 3.53-10.26], p for difference = 0.902) cohorts.
Conclusion: COVID-19 patients have increased subsequent risks of life-threatening secondary infections, to an equal extent or beyond risk elevations observed for patients with seasonal influenza.
Keywords: COVID-19; Life-threatening infections; Sepsis; Severe secondary infections.1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University
National Natural Science Foundation of China (NSFC)
Appeared in source as:National Natural Science Foundation of China
NordForsk gran
Dietary patterns in adolescence and risk of colorectal cancer: a population-based study.
No full textTo access publisher's full text version of this article click on the hyperlink belowPurpose: To study whether dietary patterns in adolescence are associated with risk of colorectal cancer (CRC).
Methods: Food frequency data were obtained from the AGES-Reykjavik study, conducted between 2002 and 2006, which included 5,078 (58% women) participants with mean age of 77 (± 5.8) years. Principal component analysis was used to identify dietary patterns. Participants were followed through linkage to the Icelandic Cancer Registry. Multivariable Cox models were used to calculate hazard ratios (HR) of CRC and 95% confidence interval (CI) by dietary patterns.
Results: During the follow-up period (mean 8.2 years), 136 participants (75 women and 61 men) were diagnosed with CRC. The main dietary pattern in adolescence was characterized by high intake of traditional food items consumed in the earlier half of the twentieth century, namely, salted or smoked meat and fish, milk, offal, rye bread, and oatmeal. Compared to the lowest tertile, the middle tertile of this pattern was associated with increased risk of CRC (HR 1.63, 95% CI 1.04-2.57), while the highest tertile was not statistically associated with CRC (HR 1.48, 95% CI 0.93-2.37), except among women (HR 2.06, 95% CI 1.11-3.84).
Conclusion: These data suggest that strong adherence to a traditional Icelandic diet in adolescence might increase the risk of CRC, particularly among women. More research is need on the association between food items and dietary patterns of relevance to CRC at different points in the life cycle.
Keywords: Adolescent; Colorectal cancer; Dietary pattern; Epidemiology; Factor analysis.United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
Appeared in source as:NIH
United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
NIH National Institute on Aging (NIA)
Appeared in source as:Intramural Research Program of the National Institute on Aging
United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
NIH National Eye Institute (NEI)
Icelandic Heart Association
Icelandic Parliament
University of Iceland Research Fund
United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
NIH National Institute on Aging (NIA
Effects of immunosuppressive drugs on COVID-19 severity in patients with autoimmune hepatitis.
No full textTo access publisher's full text version of this article click on the hyperlink belowBackground: We investigated associations between baseline use of immunosuppressive drugs and severity of Coronavirus Disease 2019 (COVID-19) in autoimmune hepatitis (AIH).
Patients and methods: Data of AIH patients with laboratory confirmed COVID-19 were retrospectively collected from 15 countries. The outcomes of AIH patients who were on immunosuppression at the time of COVID-19 were compared to patients who were not on AIH medication. The clinical courses of COVID-19 were classified as (i)-no hospitalization, (ii)-hospitalization without oxygen supplementation, (iii)-hospitalization with oxygen supplementation by nasal cannula or mask, (iv)-intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v)-ICU admission with invasive mechanical ventilation or (vi)-death and analysed using ordinal logistic regression.
Results: We included 254 AIH patients (79.5%, female) with a median age of 50 (range, 17-85) years. At the onset of COVID-19, 234 patients (92.1%) were on treatment with glucocorticoids (n = 156), thiopurines (n = 151), mycophenolate mofetil (n = 22) or tacrolimus (n = 16), alone or in combinations. Overall, 94 (37%) patients were hospitalized and 18 (7.1%) patients died. Use of systemic glucocorticoids (adjusted odds ratio [aOR] 4.73, 95% CI 1.12-25.89) and thiopurines (aOR 4.78, 95% CI 1.33-23.50) for AIH was associated with worse COVID-19 severity, after adjusting for age-sex, comorbidities and presence of cirrhosis. Baseline treatment with mycophenolate mofetil (aOR 3.56, 95% CI 0.76-20.56) and tacrolimus (aOR 4.09, 95% CI 0.69-27.00) were also associated with more severe COVID-19 courses in a smaller subset of treated patients.
Conclusion: Baseline treatment with systemic glucocorticoids or thiopurines prior to the onset of COVID-19 was significantly associated with COVID-19 severity in patients with AIH.
Keywords: SARS-CoV-2; autoimmunity; azathioprine; budesonide; liver transplantation; mercaptopurine.Ministry of Education, Universities and Research (MIUR
Functional Connectivity and Speech Entrainment Speech Entrainment Improves Connectivity Between Anterior and Posterior Cortical Speech Areas in Non-fluent Aphasia.
No full textTo access publisher's full text version of this article click on the hyperlink belowBackground: Speech entrainment (SE), the online mimicking of an audio-visual speech model, has been shown to increase speech fluency in individuals with non-fluent aphasia. One theory that may explain why SE improves speech output is that it synchronizes functional connectivity between anterior and posterior language regions to be more similar to that of neurotypical speakers.
Objectives: The present study tested this by measuring functional connectivity between 2 regions shown to be necessary for speech production, and their right hemisphere homologues, in 24 persons with aphasia compared to 20 controls during both free (spontaneous) speech and SE.
Methods: Regional functional connectivity in participants with aphasia were normalized to the control data. Two analyses were then carried out: (1) normalized functional connectivity was compared between persons with aphasia and controls during free speech and SE and (2) stepwise linear models with leave-one-out cross-validation including normed functional connectivity during both tasks and proportion damage to the left hemisphere as independent variables were created for each language score.
Results: Left anterior-posterior functional connectivity and left posterior to right anterior functional connectivity were significantly more similar to connectivity of the control group during SE compared to free speech. Additionally, connectivity during free speech was more associated with language measures than connectivity during SE.
Conclusions: Overall, these results suggest that SE promotes normalization of functional connectivity (i.e., return to patterns observed in neurotypical controls), which may explain why individuals with non-fluent aphasia produce more fluent speech during SE compared to spontaneous speech.
Keywords: aphasia; aphasia recovery; chronic stroke; functional connectivity; speech entrainment.United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
NIH National Institute on Deafness & Other Communication Disorders (NIDCD
Angiotensin converting enzyme inhibitors/cyclodextrin inclusion complexes: solution and solid-state characterizations and their thermal stability
No full textTo access publisher's full text version of this article click on the hyperlink belowAngiotensin converting enzyme (ACE) inhibitors have recently gained attention as a new class of drug in the therapeutic management of glaucoma. However, the application of eye drops is limited because of their chemical instability in aqueous solutions. To overcome such a problem, cyclodextrins (CDs) were introduced to form inclusion complexes. Three ACE inhibitors, namely, captopril, quinapril and fosinopril (FOS), were chosen and the effect of CDs on their thermal stability in aqueous solutions was investigated. All three drugs formed inclusion complexes of 1:1 stoichiometry with all three natural CDs and the FOS/γCD inclusion complex possessed the highest stability constant, resulting in thermal stability enhancement. Furthermore, the addition of antioxidants could greatly enhance the thermal stability of FOS in the presence of γCD in aqueous solutions. The inclusion complex formation of FOS/γCD was further examined by computational and experimental characterizations. All these characterization results confirmed that FOS and γCD formed a true inclusion complex that provided drug stabilization in the aqueous eye drop medium. © 2021, The Author(s), under exclusive licence to Springer Nature B.V.
Author keywords
ACE inhibitors; Complexation; Cyclodextrins; Glaucoma; StabilityEuropean Union's program Eurostar PREVIN E11008
90th Anniversary of Chulalongkorn University under Rachadapisek Somphot Fun
Universal prediction of cell-cycle position using transfer learning.
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: The cell cycle is a highly conserved, continuous process which controls faithful replication and division of cells. Single-cell technologies have enabled increasingly precise measurements of the cell cycle both as a biological process of interest and as a possible confounding factor. Despite its importance and conservation, there is no universally applicable approach to infer position in the cell cycle with high-resolution from single-cell RNA-seq data.
Results: Here, we present tricycle, an R/Bioconductor package, to address this challenge by leveraging key features of the biology of the cell cycle, the mathematical properties of principal component analysis of periodic functions, and the use of transfer learning. We estimate a cell-cycle embedding using a fixed reference dataset and project new data into this reference embedding, an approach that overcomes key limitations of learning a dataset-dependent embedding. Tricycle then predicts a cell-specific position in the cell cycle based on the data projection. The accuracy of tricycle compares favorably to gold-standard experimental assays, which generally require specialized measurements in specifically constructed in vitro systems. Using internal controls which are available for any dataset, we show that tricycle predictions generalize to datasets with multiple cell types, across tissues, species, and even sequencing assays.
Conclusions: Tricycle generalizes across datasets and is highly scalable and applicable to atlas-level single-cell RNA-seq data.
Keywords: Cell cycle; Single-cell RNA-sequencing; Transfer learning.Chan Zuckerberg Initiative DAF
Silicon Valley Community Foundation
United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
NIH National Institute of General Medical Sciences (NIGMS)
Appeared in source as:National Institute of General Medical Sciences of the National Institutes of Health
National Science Foundation (NSF)
National Institute of Agin
Maryland Stem Cell Research Foundation
Kavli Neurodiscovery Institute
Johns Hopkins Provost Award Program
BRAIN Initiative
United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
NIH National Institute of Neurological Disorders & Stroke (NINDS)
Appeared in source as:National Institute of Neurological Disorder