| 1. |
- Jung, Christian, et al.
(författare)
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A comparison of very old patients admitted to intensive care unit after acute versus elective surgery or intervention
- 2019
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Ingår i: Journal of critical care. - : W B SAUNDERS CO-ELSEVIER INC. - 0883-9441 .- 1557-8615. ; 52, s. 141-148
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Tidskriftsartikel (refereegranskat)abstract
- Background: We aimed to evaluate differences in outcome between patients admitted to intensive care unit (ICU) after elective versus acute surgery in a multinational cohort of very old patients (80 years; VIP). Predictors of mortality, with special emphasis on frailty, were assessed.Methods: In total, 5063 VIPs were induded in this analysis, 922 were admitted after elective surgery or intervention, 4141 acutely, with 402 after acute surgery. Differences were calculated using Mann-Whitney-U test and Wilcoxon test. Univariate and multivariable logistic regression were used to assess associations with mortality.Results: Compared patients admitted after acute surgery, patients admitted after elective surgery suffered less often from frailty as defined as CFS (28% vs 46%; p < 0.001), evidenced lower SOFA scores (4 +/- 5 vs 7 +/- 7; p < 0.001). Presence of frailty (CFS >4) was associated with significantly increased mortality both in elective surgery patients (7% vs 12%; p = 0.01), in acute surgery (7% vs 12%; p = 0.02).Conclusions: VIPs admitted to ICU after elective surgery evidenced favorable outcome over patients after acute surgery even after correction for relevant confounders. Frailty might be used to guide clinicians in risk stratification in both patients admitted after elective and acute surgery.
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| 2. |
- Boen, Rune, et al.
(författare)
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Beyond the global brain differences : intraindividual variability differences in 1q21.1 distal and 15q11.2 bp1-bp2 deletion carriers
- 2024
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Ingår i: Biological Psychiatry. - 0006-3223 .- 1873-2402. ; 95:2, s. 147-160
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Tidskriftsartikel (refereegranskat)abstract
- Background: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure.Methods: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., the standardized difference between an individual's regional difference and global difference, were used to test for regional differences that diverge from the global difference.Results: For the 1q21.1 distal deletion carriers, cortical surface area for regions in the medial visual cortex, posterior cingulate, and temporal pole differed less and regions in the prefrontal and superior temporal cortex differed more than the global difference in cortical surface area. For the 15q11.2 BP1-BP2 deletion carriers, cortical thickness in regions in the medial visual cortex, auditory cortex, and temporal pole differed less and the prefrontal and somatosensory cortex differed more than the global difference in cortical thickness.Conclusions: We find evidence for regional effects beyond differences in global brain measures in 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants. The results provide new insight into brain profiling of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants, with the potential to increase understanding of the mechanisms involved in altered neurodevelopment.
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| 3. |
- Coenen, Marieke J H, et al.
(författare)
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Genetic Variants in Toll-Like Receptors Are Not Associated with Rheumatoid Arthritis Susceptibility or Anti-Tumour Necrosis Factor Treatment Outcome
- 2010
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 5:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several studies point to a role of Toll-like receptors (TLRs) in the development of rheumatoid arthritis (RA). We investigated if genetic variants in TLR genes are associated with RA and response to tumour necrosis factor blocking (anti-TNF) medication. Methodology and Principal Findings: 22 single nucleotide polymorphisms (SNPs) in seven TLR genes were genotyped in a Dutch cohort consisting of 378 RA patients and 294 controls. Significantly associated variants were investigated in replication cohorts from The Netherlands, United Kingdom and Sweden (2877 RA patients and 2025 controls). 182 of the Dutch patients were treated with anti-TNF medication. Using these patients and a replication cohort (269 Swedish patients) we analysed if genetic variants in TLR genes were associated with anti-TNF outcome. In the discovery phase of the study we found a significant association of SNPs rs2072493 in TLR5 and rs3853839 in TLR7 with RA disease susceptibility. Meta-analysis of discovery and replication cohorts did not confirm these findings. SNP rs2072493 in TLR5 was associated with anti-TNF outcome in the Dutch but not in the Swedish population. Conclusion: We conclude that genetic variants in TLRs do not play a major role in susceptibility for developing RA nor in anti-TNF treatment outcome in a Caucasian population.
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| 4. |
- Cohen, Tim J., et al.
(författare)
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Hydrological transformation coincided with megafaunal extinction in central Australia
- 2015
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Ingår i: Geology. - 0091-7613 .- 1943-2682. ; 43:3, s. 195-198
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Tidskriftsartikel (refereegranskat)abstract
- Central to the debate over the extinction of many of Australia's last surviving megafauna is the question: Was climate changing significantly when humans arrived and megafauna went extinct? Here we present a new perspective on variations in climate and water resources over the last glacial cycle in arid Australia based on the study of the continent's largest lake basin and its tributaries. By dating paleoshorelines and river deposits in the Lake Eyre basin, we show that major hydrological change caused previously overflowing megalakes to enter a final and catastrophic drying phase at 48 +/- 2 ka just as the giant bird, Genyornis newtoni, went extinct (50-45 ka). The disappearance of Genyornis and other megafauna has been previously attributed to ecosystem collapse coincident with the spread of fire-wielding humans. Our findings suggest a climate-driven hydrological transformation in the critical window of human arrival and megafaunal extinction, and the results call for a re-evaluation of a human-mediated cause for such extinctions in arid Australia.
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| 5. |
- Evangelou, Evangelos, et al.
(författare)
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Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
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Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
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| 6. |
- Forouzanfar, Mohammad H, et al.
(författare)
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Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013 : a systematic analysis for the Global Burden of Disease Study 2013.
- 2015
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 386:10010, s. 2287-2323
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.FUNDING: Bill & Melinda Gates Foundation.
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| 7. |
- Gallo, Selene, et al.
(författare)
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Functional connectivity signatures of major depressive disorder: machine learning analysis of two multicenter neuroimaging studies
- 2023
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Ingår i: Molecular Psychiatry. - : SPRINGERNATURE. - 1359-4184 .- 1476-5578. ; 28:7, s. 3013-3022
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Tidskriftsartikel (refereegranskat)abstract
- The promise of machine learning has fueled the hope for developing diagnostic tools for psychiatry. Initial studies showed high accuracy for the identification of major depressive disorder (MDD) with resting-state connectivity, but progress has been hampered by the absence of large datasets. Here we used regular machine learning and advanced deep learning algorithms to differentiate patients with MDD from healthy controls and identify neurophysiological signatures of depression in two of the largest resting-state datasets for MDD. We obtained resting-state functional magnetic resonance imaging data from the REST-meta-MDD (N = 2338) and PsyMRI (N = 1039) consortia. Classification of functional connectivity matrices was done using support vector machines (SVM) and graph convolutional neural networks (GCN), and performance was evaluated using 5-fold cross-validation. Features were visualized using GCN-Explainer, an ablation study and univariate t-testing. The results showed a mean classification accuracy of 61% for MDD versus controls. Mean accuracy for classifying (non-)medicated subgroups was 62%. Sex classification accuracy was substantially better across datasets (73-81%). Visualization of the results showed that classifications were driven by stronger thalamic connections in both datasets, while nearly all other connections were weaker with small univariate effect sizes. These results suggest that whole brain resting-state connectivity is a reliable though poor biomarker for MDD, presumably due to disease heterogeneity as further supported by the higher accuracy for sex classification using the same methods. Deep learning revealed thalamic hyperconnectivity as a prominent neurophysiological signature of depression in both multicenter studies, which may guide the development of biomarkers in future studies.
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| 8. |
- Harder, Thomas, et al.
(författare)
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Evidence-based decision-making in infectious diseases epidemiology, prevention and control: matching research questions to study designs and quality appraisal tools
- 2014
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Ingår i: BMC Medical Research Methodology. - : BioMed Central. - 1471-2288. ; 14:69
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:The Project on a Framework for Rating Evidence in Public Health (PRECEPT) was initiated and is being funded by the European Centre for Disease Prevention and Control (ECDC) to define a methodology for evaluating and grading evidence and strength of recommendations in the field of public health, with emphasis on infectious disease epidemiology, prevention and control. One of the first steps was to review existing quality appraisal tools (QATs) for individual research studies of various designs relevant to this area, using a question-based approach.METHODS:Through team discussions and expert consultations, we identified 20 relevant types of public health questions, which were grouped into six domains, i.e. characteristics of the pathogen, burden of disease, diagnosis, risk factors, intervention, and implementation of intervention. Previously published systematic reviews were used and supplemented by expert consultation to identify suitable QATs. Finally, a matrix was constructed for matching questions to study designs suitable to address them and respective QATs. Key features of each of the included QATs were then analyzed, in particular in respect to its intended use, types of questions and answers, presence/absence of a quality score, and if a validation was performed.RESULTS:In total we identified 21 QATs and 26 study designs, and matched them. Four QATs were suitable for experimental quantitative study designs, eleven for observational quantitative studies, two for qualitative studies, three for economic studies, one for diagnostic test accuracy studies, and one for animal studies. Included QATs consisted of six to 28 items. Six of the QATs had a summary quality score. Fourteen QATs had undergone at least one validation procedure.CONCLUSIONS:The results of this methodological study can be used as an inventory of potentially relevant questions, appropriate study designs and QATs for researchers and authorities engaged with evidence-based decision-making in infectious disease epidemiology, prevention and control.
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| 9. |
- Harder, Thomas, et al.
(författare)
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Towards a framework for evaluating and grading evidence in public health
- 2015
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Ingår i: Health Policy. - : Elsevier. - 0168-8510 .- 1872-6054. ; 119:6, s. 732-736
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Tidskriftsartikel (refereegranskat)abstract
- The Project on a Framework for Rating Evidence in Public Health (PRECEPT) is an international collaboration of public health institutes and universities which has been funded by the European Centre for Disease Prevention and Control (ECDC) since 2012. Main objective is to define a framework for evaluating and grading evidence in the field of public health, with particular focus on infectious disease prevention and control. As part of the peer review process, an international expert meeting was held on 13-1 4 June 2013 in Berlin. Participants were members of the PRECEPT team and selected experts from national public health institutes, World Health Organization (WHO), and academic institutions. The aim of the meeting was to discuss the draft framework and its application to two examples from infectious disease prevention and control. This article introduces the draft PRECEPT framework and reports on the meeting, its structure, most relevant discussions and major conclusions.
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| 10. |
- Hegre, Håvard, 1964-, et al.
(författare)
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Forecasting fatalities
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)
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