| 1. |
- Bar, N., et al.
(författare)
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A reference map of potential determinants for the human serum metabolome
- 2020
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Ingår i: Nature. - : Nature Research. - 0028-0836 .- 1476-4687. ; 588:7836, s. 135-140
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Tidskriftsartikel (refereegranskat)abstract
- The serum metabolome contains a plethora of biomarkers and causative agents of various diseases, some of which are endogenously produced and some that have been taken up from the environment1. The origins of specific compounds are known, including metabolites that are highly heritable2,3, or those that are influenced by the gut microbiome4, by lifestyle choices such as smoking5, or by diet6. However, the key determinants of most metabolites are still poorly understood. Here we measured the levels of 1,251 metabolites in serum samples from a unique and deeply phenotyped healthy human cohort of 491 individuals. We applied machine-learning algorithms to predict metabolite levels in held-out individuals on the basis of host genetics, gut microbiome, clinical parameters, diet, lifestyle and anthropometric measurements, and obtained statistically significant predictions for more than 76% of the profiled metabolites. Diet and microbiome had the strongest predictive power, and each explained hundreds of metabolites—in some cases, explaining more than 50% of the observed variance. We further validated microbiome-related predictions by showing a high replication rate in two geographically independent cohorts7,8 that were not available to us when we trained the algorithms. We used feature attribution analysis9 to reveal specific dietary and bacterial interactions. We further demonstrate that some of these interactions might be causal, as some metabolites that we predicted to be positively associated with bread were found to increase after a randomized clinical trial of bread intervention. Overall, our results reveal potential determinants of more than 800 metabolites, paving the way towards a mechanistic understanding of alterations in metabolites under different conditions and to designing interventions for manipulating the levels of circulating metabolites.
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| 2. |
- Ingason, A. B., et al.
(författare)
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Comparison of the effectiveness and safety of direct oral anticoagulants: a nationwide propensity score-weighted study
- 2023
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 7:11, s. 2564-2572
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Tidskriftsartikel (refereegranskat)abstract
- In the pivotal randomized controlled trials (RCTs) for patients with atrial fibrillation, direct oral anticoagulants (DOACs) had similar or even superior efficacy and safety compared with warfarin. However, RCTs comparing different DOACs are nonexistent and previous observational studies have yielded conflicting results. In this nationwide cohort study, rates of any stroke or systemic embolism (stroke/SE) and major bleeding were compared among new users of apixaban, dabigatran, and rivaroxaban with atrial fibrillation from 2014 to 2019. Inverse probability weighting was used to yield balanced study groups, and outcomes were compared using Cox regression. Stroke/SE rates were similar in patients receiving apixaban, dabigatran, and rivaroxaban. Dabigatran was associated with twofold higher rates of myocardial infarction (MI) than rivaroxaban (1.4 events/100 person-years (py) vs 0.7 events/100-py, hazard ratio [HR] 2.21, 95% confidence interval [CI], 1.00-4.90) and apixaban (1.4 events/100-py vs 0.7 events/100-py, HR 2.26, 95% CI, 0.90-5.67), although the second comparison included the possibility of a null effect. Rivaroxaban was associated with higher major bleeding rates compared with apixaban (2.9 events/100-py vs 1.8 events/ 100-py, HR 1.64, 95% CI, 1.13-2.37) and dabigatran (2.9 events/100-py vs 1.4 events/100-py, HR 2.18, 95% CI, 1.21-3.93). Specifically, rivaroxaban had higher rates of major gastrointestinal bleeding and other major bleeding than apixaban. In conclusion, although stroke/SE rates were similar for DOACs, rivaroxaban was associated with higher rates of major bleeding than other DOACs and lower rates of MI than dabigatran. These results may help guide oral anticoagulant selection, especially in patients at high risk of bleeding or MI.
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| 3. |
- Aevarsson, Arnthór, et al.
(författare)
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Going to extremes - a metagenomic journey into the dark matter of life
- 2021
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Ingår i: FEMS Microbiology Letters. - : Oxford University Press (OUP). - 1574-6968. ; 368:12
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Forskningsöversikt (refereegranskat)abstract
- The Virus-X-Viral Metagenomics for Innovation Value-project was a scientific expedition to explore and exploit uncharted territory of genetic diversity in extreme natural environments such as geothermal hot springs and deep-sea ocean ecosystems. Specifically, the project was set to analyse and exploit viral metagenomes with the ultimate goal of developing new gene products with high innovation value for applications in biotechnology, pharmaceutical, medical, and the life science sectors. Viral gene pool analysis is also essential to obtain fundamental insight into ecosystem dynamics and to investigate how viruses influence the evolution of microbes and multicellular organisms. The Virus-X Consortium, established in 2016, included experts from eight European countries. The unique approach based on high throughput bioinformatics technologies combined with structural and functional studies resulted in the development of a biodiscovery pipeline of significant capacity and scale. The activities within the Virus-X consortium cover the entire range from bioprospecting and methods development in bioinformatics to protein production and characterisation, with the final goal of translating our results into new products for the bioeconomy. The significant impact the consortium made in all of these areas was possible due to the successful cooperation between expert teams that worked together to solve a complex scientific problem using state-of-the-art technologies as well as developing novel tools to explore the virosphere, widely considered as the last great frontier of life.
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| 4. |
- Carlsen, O. C. L., et al.
(författare)
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Physical activity in pregnancy: a Norwegian-Swedish mother-child birth cohort study
- 2021
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Ingår i: AJOG Global Reports. - : Elsevier BV. - 2666-5778. ; 1:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Physical activity during pregnancy is important for maternal and offspring health. Optimal conditions during pregnancy may help reduce the burden of noncommunicable diseases. National and international guidelines recommend at least 150 minutes of physical activity of at least moderate intensity per week. To optimize physical activity in pregnant women, it is important to identify factors associated with higher levels of physical activity. OBJECTIVE: This study aimed to explore types and levels of physical activity in midpregnancy in Norway and Sweden and to identify factors associated with higher levels of physical activity. MATERIALS AND METHODS: From the population-based mother-child cohort Preventing Atopic Dermatitis and Allergies in Children study recruiting 2697 women in Norway and Sweden from 2014 to 2016, we included 2349 women who answered an electronic questionnaire at enrollment in midpregnancy. Women were asked about regular physical activity in the last 2 weeks of pregnancy and afterward for types and levels of physical activity in pregnancy and before pregnancy and socioeconomic status, lifestyle, and maternal health. Logistic regression analyses were used to identify factors associated with higher levels of physical activity in pregnancy, defined as >30 minutes per session of ≥2 times per week of moderate- or high-intensity brisk walking, strength training, jogging, and bicycling. RESULTS: No regular physical activity during the last 2 weeks before answering the questionnaire at midpregnancy was reported by 689 women (29%). In this study, 1787 women (76%) reported weekly strolling during pregnancy. Regular physical activity at least twice weekly in the first half of pregnancy was reported as brisk walking by 839 women (36%), bicycling by 361 women (15%), strength training by 322 women (14%), and other activities by <10% of women. Among the 1430 women with regular moderate- or high-intensity physical activity, the estimated median duration per week was 120 minutes. Higher physical activity levels were achieved in 553 women (23.5%) by brisk walking, 287 women (12.2%) by strength training, 263 women (11.2%) by bicycling, and 114 women (4.9%) by jogging. Higher physical activity levels were positively associated with regular physical activity before pregnancy, dog ownership, and atopic dermatitis and negatively associated with higher body mass index, study location in Østfold, previous pregnancy or pregnancies, non-Nordic origin, suburban living, and sick leave. CONCLUSION: At midpregnancy, 29% of women were inactive, and less than 50% of women had at least 2 hours of moderate-intensity physical activity weekly. Awareness of physical activity in pregnancy should be discussed at pregnancy follow-up visits, particularly among women with higher body mass index, sick leave, previous pregnancy or pregnancies, and non-Nordic origin.
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| 5. |
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| 6. |
- Hilde, K., et al.
(författare)
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Fetal Thoracic Circumference and Lung Volume and Their Relation to Fetal Size and Pulmonary Artery Blood Flow
- 2022
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Ingår i: Journal of Ultrasound in Medicine. - : Wiley. - 0278-4297 .- 1550-9613. ; 41:4, s. 985-993
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Tidskriftsartikel (refereegranskat)abstract
- Objective Research on early origins of lung disease suggests the need for studying the relationships of thoracic and lung size with fetal size and pulmonary circulation. The primary aim of this study is therefore to explore the associations between fetal thoracic circumference, lung volume, and fetal size. We also aim to assess if lung volume and thoracic circumference are associated with fetal pulmonary artery blood flow velocity measures. Methods Cross-sectional assessment of singleton pregnancies from the general population (n = 447) at 30 gestational weeks (GW) was performed using ultrasound measurement of fetal thoracic circumference, lung volume, head and abdominal circumference, and femur length. We obtained Doppler blood flow velocity measures from the proximal branches of the fetal pulmonary artery. Associations between variables were studied using Pearson's correlation and multiple linear regression analyses. Results Both thoracic circumference and lung volume correlated with fetal size measures, ranging from r = 0.64 between thoracic circumference and abdominal circumference, to r = 0.28 between lung volume and femur length. Adjustment for gestational age, maternal nicotine use, pre-pregnancy body mass index, and fetal sex marginally influenced the associations with abdominal circumference. The correlations of thoracic circumference and lung volume with pulmonary artery blood flow velocity measures were weak (r <= 0.17). Conclusion We found moderate to low correlation between thoracic circumference, lung volume, and fetal size at 30 GW. The closest relationship was with the abdominal circumference. We found low correlations of thoracic circumference and lung volume with pulmonary artery blood flow velocity measures.
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| 7. |
- Hygrell, T, et al.
(författare)
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An artificial intelligence-based model for prediction of atrial fibrillation from single-lead sinus rhythm electrocardiograms facilitating screening
- 2023
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Ingår i: Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology. - : Oxford University Press (OUP). - 1532-2092. ; 25:4, s. 1332-1338
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Tidskriftsartikel (refereegranskat)abstract
- AimsScreening for atrial fibrillation (AF) is recommended in the European Society of Cardiology guidelines. Yields of detection can be low due to the paroxysmal nature of the disease. Prolonged heart rhythm monitoring might be needed to increase yield but can be cumbersome and expensive. The aim of this study was to observe the accuracy of an artificial intelligence (AI)-based network to predict paroxysmal AF from a normal sinus rhythm single-lead ECG.Methods and resultsA convolutional neural network model was trained and evaluated using data from three AF screening studies. A total of 478 963 single-lead ECGs from 14 831 patients aged ≥65 years were included in the analysis. The training set included ECGs from 80% of participants in SAFER and STROKESTOP II. The remaining ECGs from 20% of participants in SAFER and STROKESTOP II together with all participants in STROKESTOP I were included in the test set. The accuracy was estimated using the area under the receiver operating characteristic curve (AUC). From a single timepoint ECG, the artificial intelligence–based algorithm predicted paroxysmal AF in the SAFER study with an AUC of 0.80 [confidence interval (CI) 0.78–0.83], which had a wide age range of 65–90+ years. Performance was lower in the age-homogenous groups in STROKESTOP I and STROKESTOP II (age range: 75–76 years), with AUCs of 0.62 (CI 0.61–0.64) and 0.62 (CI 0.58–0.65), respectively.ConclusionAn artificial intelligence–enabled network has the ability to predict AF from a sinus rhythm single-lead ECG. Performance improves with a wider age distribution.
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| 8. |
- Reulen, Raoul C, et al.
(författare)
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Risk Factors for Primary Bone Cancer After Childhood Cancer : A PanCare Childhood and Adolescent Cancer Survivor Care and Follow-Up Studies Nested Case-Control Study
- 2023
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Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 41:21, s. 3735-3746
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Radiation to the bone and exposure to alkylating agents increases the risk of bone cancer among survivors of childhood cancer, but there is uncertainty regarding the risks of bone tissue radiation doses below 10 Gy and the dose-response relationship for specific types of chemotherapy.METHODS: Twelve European countries contributed 228 cases and 228 matched controls to a nested case-control study within a cohort of 69,460 5-year survivors of childhood cancer. Odds ratios (ORs) of developing bone cancer for different levels of cumulative radiation exposure and cumulative doses of specific types of chemotherapy were calculated. Excess ORs were calculated to investigate the shape and extent of any dose-response relationship.RESULTS: The OR associated with bone tissue exposed to 1-4 Gy was 4.8-fold (95% CI, 1.2 to 19.6) and to 5-9 Gy was 9.6-fold (95% CI, 2.4 to 37.4) compared with unexposed bone tissue. The OR increased linearly with increasing dose of radiation ( P trend < .001) up to 78-fold (95% CI, 9.2 to 669.9) for doses of ≥40 Gy. For cumulative alkylating agent doses of 10,000-19,999 and ≥20,000 mg/m 2, the radiation-adjusted ORs were 7.1 (95% CI, 2.2 to 22.8) and 8.3 (95% CI, 2.8 to 24.4), respectively, with independent contributions from each of procarbazine, ifosfamide, and cyclophosphamide. Other cytotoxics were not associated with bone cancer. CONCLUSION: To our knowledge, we demonstrate-for the first time-that the risk of bone cancer is increased 5- to 10-fold after exposure of bone tissue to cumulative radiation doses of 1-9 Gy. Alkylating agents exceeding 10,000 mg/m 2 increase the risk 7- to 8-fold, particularly following procarbazine, ifosfamide, and cyclophosphamide. These substantially elevated risks should be used to develop/update clinical follow-up guidelines and survivorship care plans.
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| 9. |
- Saevarsdottir, KS, et al.
(författare)
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Illness severity and risk of mental morbidities among patients recovering from COVID-19: a cross-sectional study in the Icelandic population
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:7, s. e049967-
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Tidskriftsartikel (refereegranskat)abstract
- To test if patients recovering from COVID-19 are at increased risk of mental morbidities and to what extent such risk is exacerbated by illness severity.DesignPopulation-based cross-sectional study.SettingIceland.ParticipantsA total of 22 861 individuals were recruited through invitations to existing nationwide cohorts and a social media campaign from 24 April to 22 July 2020, of which 373 were patients recovering from COVID-19.Main outcome measuresSymptoms of depression (Patient Health Questionnaire), anxiety (General Anxiety Disorder Scale) and posttraumatic stress disorder (PTSD; modified Primary Care PTSD Screen for DSM-5) above screening thresholds. Adjusting for multiple covariates and comorbidities, multivariable Poisson regression was used to assess the association between COVID-19 severity and mental morbidities.ResultsCompared with individuals without a diagnosis of COVID-19, patients recovering from COVID-19 had increased risk of depression (22.1% vs 16.2%; adjusted relative risk (aRR) 1.48, 95% CI 1.20 to 1.82) and PTSD (19.5% vs 15.6%; aRR 1.38, 95% CI 1.09 to 1.75) but not anxiety (13.1% vs 11.3%; aRR 1.24, 95% CI 0.93 to 1.64). Elevated relative risks were limited to patients recovering from COVID-19 that were 40 years or older and were particularly high among individuals with university education. Among patients recovering from COVID-19, symptoms of depression were particularly common among those in the highest, compared with the lowest tertile of influenza-like symptom burden (47.1% vs 5.8%; aRR 6.42, 95% CI 2.77 to 14.87), among patients confined to bed for 7 days or longer compared with those never confined to bed (33.3% vs 10.9%; aRR 3.67, 95% CI 1.97 to 6.86) and among patients hospitalised for COVID-19 compared with those never admitted to hospital (48.1% vs 19.9%; aRR 2.72, 95% CI 1.67 to 4.44).ConclusionsSevere disease course is associated with increased risk of depression and PTSD among patients recovering from COVID-19.
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| 10. |
- Skjerven, H. O., et al.
(författare)
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Skin emollient and early complementary feeding to prevent infant atopic dermatitis (PreventADALL): a factorial, multicentre, cluster-randomised trial
- 2020
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Ingår i: The Lancet. - 0140-6736. ; 395:10228, s. 951-961
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Tidskriftsartikel (refereegranskat)abstract
- Background: Skin emollients applied during early infancy could prevent atopic dermatitis, and early complementary food introduction might reduce food allergy in high-risk infants. The study aimed to determine if either regular skin emollients applied from 2 weeks of age, or early complementary feeding introduced between 12 and 16 weeks of age, reduced development of atopic dermatitis by age 12 months in the general infant population. Methods: This population-based 2×2 factorial, randomised clinical trial was done at Oslo University Hospital and Østfold Hospital Trust, Oslo, Norway; and Karolinska University Hospital, Stockholm, Sweden. Infants of women recruited antenatally at the routine ultrasound pregnancy screening at 18 weeks were cluster-randomised at birth from 2015 to 2017 to the following groups: (1) controls with no specific advice on skin care while advised to follow national guidelines on infant nutrition (no intervention group); (2) skin emollients (bath additives and facial cream; skin intervention group); (3) early complementary feeding of peanut, cow's milk, wheat, and egg (food intervention group); or (4) combined skin and food interventions (combined intervention group). Participants were randomly assigned (1:1:1:1) using computer- generated cluster randomisation based on 92 geographical living area blocks as well as eight 3-month time blocks. Carers were instructed to apply the interventions on at least 4 days per week. Atopic dermatitis by age 12 months was the primary outcome, based on clinical investigations at 3, 6 and 12 months by investigators masked to group allocation. Atopic dermatitis was assessed after completing the 12-month investigations and diagnosed if either of the UK Working Party and Hanifin and Rajka (12 months only) diagnostic criteria were fulfilled. The primary efficacy analyses was done by intention-to-treat analysis on all randomly assigned participants. Food allergy results will be reported once all investigations at age 3 years are completed in 2020. This was a study performed within ORAACLE (the Oslo Research Group of Asthma and Allergy in Childhood; the Lung and Environment). The study is registered at clinicaltrials.gov, NCT02449850. Findings: 2697 women were recruited between Dec 9, 2014, and Oct 31, 2016, from whom 2397 newborn infants were enrolled from April 14, 2015, to April 11, 2017. Atopic dermatitis was observed in 48 (8%) of 596 infants in the no intervention group, 64 (11%) of 575 in the skin intervention group, 58 (9%) of 642 in the food intervention group, and 31 (5%) of 583 in the combined intervention group. Neither skin emollients nor early complementary feeding reduced development of atopic dermatitis, with a risk difference of 3·1% (95% CI –0·3 to 6·5) for skin intervention and 1·0% (–2·1 to 4·1) for food intervention, in favour of control. No safety concerns with the interventions were identified. Reported skin symptoms and signs (including itching, oedema, exanthema, dry skin, and urticaria) were no more frequent in the skin, food, and combined intervention groups than in the no intervention group. Interpretation: Neither early skin emollients nor early complementary feeding reduced development of atopic dermatitis by age 12 months. Our study does not support the use of these interventions to prevent atopic dermatitis by 12 months of age in infants. Funding: The study was funded by several public and private funding bodies: The Regional Health Board South East, The Norwegian Research Council, Health and Rehabilitation Norway, The Foundation for Healthcare and Allergy Research in Sweden-Vårdalstiftelsen, Swedish Asthma and Allergy Association's Research Foundation, Swedish Research Council—the Initiative for Clinical Therapy Research, The Swedish Heart-Lung Foundation, SFO-V at the Karolinska Institute, Freemason Child House Foundation in Stockholm, Swedish Research Council for Health, Working Life and Welfare—FORTE, Oslo University Hospital, the University of Oslo, and Østfold Hospital Trust. © 2020 Elsevier Ltd
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