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- Vieira-Silva, S., et al.
(author)
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Statin therapy is associated with lower prevalence of gut microbiota dysbiosis
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 581:7808, s. 310-315
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Journal article (peer-reviewed)abstract
- Microbiome community typing analyses have recently identified the Bacteroides2 (Bact2) enterotype, an intestinal microbiota configuration that is associated with systemic inflammation and has a high prevalence in loose stools in humans1,2. Bact2 is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium and low microbial cell densities1,2, and its prevalence varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease2. Reported changes in stool consistency3 and inflammation status4 during the progression towards obesity and metabolic comorbidities led us to propose that these developments might similarly correlate with an increased prevalence of the potentially dysbiotic Bact2 enterotype. Here, by exploring obesity-associated microbiota alterations in the quantitative faecal metagenomes of the cross-sectional MetaCardis Body Mass Index Spectrum cohort (n=888), we identify statin therapy as a key covariate of microbiome diversification. By focusing on a subcohort of participants that are not medicated with statins, we find that the prevalence of Bact2 correlates with body mass index, increasing from 3.90% in lean or overweight participants to 17.73% in obese participants. Systemic inflammation levels in Bact2-enterotyped individuals are higher than predicted on the basis of their obesity status, indicative of Bact2 as a dysbiotic microbiome constellation. We also observe that obesity-associated microbiota dysbiosis is negatively associated with statin treatment, resulting in a lower Bact2 prevalence of 5.88% in statin-medicated obese participants. This finding is validated in both the accompanying MetaCardis cardiovascular disease dataset (n = 282) and the independent Flemish Gut Flora Project population cohort (n=2,345). The potential benefits of statins in this context will require further evaluation in a prospective clinical trial to ascertain whether the effect is reproducible in a randomized population and before considering their application as microbiota-modulating therapeutics. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.
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- Andrikopoulos, Petros, et al.
(author)
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Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide
- 2023
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In: Nature Communications. - 2041-1723 .- 2041-1723. ; 14:1
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Journal article (peer-reviewed)abstract
- The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk.
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- Aslam, Tayyba N., et al.
(author)
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A survey of preferences for respiratory support in the intensive care unit for patients with acute hypoxaemic respiratory failure
- 2023
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In: Acta Anaesthesiologica Scandinavica. - : WILEY. - 0001-5172 .- 1399-6576. ; 67:10, s. 1383-1394
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Journal article (peer-reviewed)abstract
- BackgroundWhen caring for mechanically ventilated adults with acute hypoxaemic respiratory failure (AHRF), clinicians are faced with an uncertain choice between ventilator modes allowing for spontaneous breaths or ventilation fully controlled by the ventilator. The preferences of clinicians managing such patients, and what motivates their choice of ventilator mode, are largely unknown. To better understand how clinicians preferences may impact the choice of ventilatory support for patients with AHRF, we issued a survey to an international network of intensive care unit (ICU) researchers.MethodsWe distributed an online survey with 32 broadly similar and interlinked questions on how clinicians prioritise spontaneous or controlled ventilation in invasively ventilated patients with AHRF of different severity, and which factors determine their choice.ResultsThe survey was distributed to 1337 recipients in 12 countries. Of these, 415 (31%) completed the survey either fully (52%) or partially (48%). Most respondents were identified as medical specialists (87%) or physicians in training (11%). Modes allowing for spontaneous ventilation were considered preferable in mild AHRF, with controlled ventilation considered as progressively more important in moderate and severe AHRF. Among respondents there was strong support (90%) for a randomised clinical trial comparing spontaneous with controlled ventilation in patients with moderate AHRF.ConclusionsThe responses from this international survey suggest that there is clinical equipoise for the preferred ventilator mode in patients with AHRF of moderate severity. We found strong support for a randomised trial comparing modes of ventilation in patients with moderate AHRF.
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- Amarsi, A. M., et al.
(author)
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Inelastic O plus H collisions and the O I 777 nm solar centre-to-limb variation
- 2018
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In: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 616
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Journal article (peer-reviewed)abstract
- The O I 777 nm triplet is a key diagnostic of oxygen abundances in the atmospheres of FGK-type stars; however, it is sensitive to departures from local thermodynamic equilibrium (LTE). The accuracy of non-LTE line formation calculations has hitherto been limited by errors in the inelastic O+H collisional rate coefficients; several recent studies have used the Drawin recipe, albeit with a correction factor S-H that is calibrated to the solar centre-to-limb variation of the triplet. We present a new model oxygen atom that incorporates inelastic O+H collisional rate coefficients using an asymptotic two-electron model based on linear combinations of atomic orbitals, combined with a free electron model based on the impulse approximation. Using a 3D hydrodynamic STAGGER model solar atmosphere and 3D non-LTE line formation calculations, we demonstrate that this physically motivated approach is able to reproduce the solar centre-to-limb variation of the triplet to 0.02 dex, without any calibration of the inelastic collisional rate coefficients or other free parameters. We infer log epsilon(O) = 8.69 +/- 0.03 from the triplet alone, strengthening the case for a low solar oxygen abundance.
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- Collet, M. O., et al.
(author)
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Functional and cognitive rehabilitation interventions during intensive care admission: A protocol for a systematic integrative review
- 2023
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In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 67:5, s. 670-4
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Journal article (peer-reviewed)abstract
- BackgroundLong-term cognitive impairment occurs in up to 60% of intensive care unit (ICU) survivors. Early use of functional and cognitive rehabilitation interventions, while patients are still in ICU, may reduce cognitive decline. We aim to describe the functional and cognitive interventions used during the ICU stay, the healthcare professionals providing interventions, and the potential impact on functional and cognitive rehabilitation. MethodIn this integrative systematic review, we will include empirical qualitative, quantitative, mixed- and multiple-methods studies assessing the use of functional and cognitive rehabilitation provided in ICU. We will identify studies in relevant electronic databases from 2012 to 2022, which will be screened for eligibility by at least two reviewers. Literature reported as narrative reviews and editorials will be excluded. We will assess the impact of interventions evaluating a cognitive and functional function, quality of life, and all-cause mortality at 6-12 months after ICU discharge. The Revised Cochrane risk-of-bias Tool will be used for assessing risk of bias in clinical trials. For observational studies, we will use the National Institutes of Health Quality Assessment tool for Observational Cohort and Cross-Sectional Studies. Furthermore, we will use the critical appraisal skills programme for qualitative studies and the mixed methods appraisal tool for mixed methods studies. We will construct four matrices, including results describing which ICU patients and healthcare professionals were engaged in rehabilitation, which interventions were included in early rehabilitation in ICU, the potential impact on patient outcomes of rehabilitation interventions provided in ICU and a narrative synthesis of themes. A summary of the main results will be reported using modified GRADE methodology. ImpactThis integrative review will inform the feasibility randomised clinical trial testing the development of a complex intervention targeting functional and cognitive rehabilitation for patients in ICU.
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| 19. |
- Forslund, Sofia K., et al.
(author)
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Combinatorial, additive and dose-dependent drug–microbiome associations
- 2021
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 600:7889, s. 500-505
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Journal article (peer-reviewed)abstract
- During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery1–5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug–host–microbiome interactions in cardiometabolic disease.
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- Egerod, I., et al.
(author)
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Trends and recommendations for critical care nursing research in the Nordic countries: Triangulation of review and survey data
- 2020
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In: Intensive and Critical Care Nursing. - : Elsevier BV. - 0964-3397. ; 56
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Journal article (peer-reviewed)abstract
- Background: Priorities for critical care nursing research have evolved with societal trends and values. In the 1980s priorities were the nursing workforce, in 1990s technical nursing, in 2000s evidence-based nursing and in 2010s symptom management and family-centred care. Objectives: To identify current trends and future recommendations for critical care nursing research in the Nordic countries. Methods: We triangulated the results of a literature review and a survey. A review of two selected critical care nursing journals (2016-2017) was conducted using content analysis to identify contemporary published research. A self-administered computerised cross-sectional survey of Nordic critical care nursing researchers (2017) reported current and future areas of research. Results: A review of 156 papers identified research related to the patient (13%), family (12%), nurse (31%), and therapies (44%). Current trends in the survey (n = 76, response rate 65%) included patient and family involvement, nurse performance and education, and evidence-based protocols. The datasets showed similar trends, but aftercare was only present in the survey. Future trends included symptom management, transitions, rehabilitation, and new nursing roles. Conclusion: Critical care nursing research is trending toward increased collaboration with patient and family, delineating a shift toward user values. Recommendations include long-term outcomes and impact of nursing. (C) 2019 Elsevier Ltd. All rights reserved.
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| 22. |
- Halvorsen, K., et al.
(author)
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Patients' experiences of well-being when being cared for in the intensive care unit—An integrative review
- 2022
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In: Journal of Clinical Nursing. - : Wiley. - 0962-1067 .- 1365-2702. ; 31:1-2, s. 3-19
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Journal article (peer-reviewed)abstract
- Objective: The aim of this integrative review was to identify facilitators and barriers to patients’ well-being when being cared for in an ICU setting, from the perspective of the patients. Background: To become critically ill and hospitalised in an ICU is a stressful, chaotic event due to the life-threatening condition itself, as well as therapeutic treatments and the environment. A growing body of evidence has revealed that patients often suffer from physical, psychological and cognitive problems after an ICU stay. Several strategies, such as sedation and pain management, are used to reduce stress and increase well-being during ICU hospitalisation, but the ICU experience nevertheless affects the body and mind. Design; Methods: Since research exploring patients’ sense of well-being in an ICU setting is limited, an integrative review approach was selected. Searches were performed in CINAHL, Medline, Psych Info, Eric and EMBASE. After reviewing 66 studies, 12 studies were included in the integrative review. Thematic analysis was used to analyse the studies. The PRISMA checklist for systematic reviews was used. Results: The results are presented under one main theme, ‘Well-being as a multidimensional experience—interwoven in barriers and facilitators’ and six sub-themes representing barriers to and facilitators of well-being in an ICU. Barriers identified were physical stressors, emotional stressors, environmental disturbances and insecurity relating to time and space. Facilitators were meeting physical needs and activities that included dimensions of a caring and relational environment. Conclusion: Our main findings were that experiences of well-being were multidimensional and included physical, emotional, relational and environmental aspects, and they were more often described through barriers than facilitators of well-being. Relevance for clinical practice: This integrative review has shown that it is necessary to adopt an individual focus on patient well-being in an ICU setting since physical, emotional, relational and environmental stressors might impact each patient differently. © 2021 The Authors. Journal of Clinical Nursing published by John Wiley & Sons Ltd.
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| 23. |
- Molinaro, Antonio, et al.
(author)
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Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology
- 2020
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism.
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