| 1. |
- Allesøe, Rosa Lundbye, et al.
(författare)
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Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models
- 2023
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Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 41:3, s. 399-408
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Tidskriftsartikel (refereegranskat)abstract
- The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug–omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug–drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities.
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| 2. |
- Ashar, Foram N., et al.
(författare)
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A comprehensive evaluation of the genetic architecture of sudden cardiac arrest
- 2018
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 39:44, s. 3961-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Sudden cardiac arrest (SCA) accounts for 10% of adult mortality in Western populations. We aim to identify potential loci associated with SCA and to identify risk factors causally associated with SCA.Methods and results: We carried out a large genome-wide association study (GWAS) for SCA (n = 3939 cases, 25 989 non-cases) to examine common variation genome-wide and in candidate arrhythmia genes. We also exploited Mendelian randomization (MR) methods using cross-trait multi-variant genetic risk score associations (GRSA) to assess causal relationships of 18 risk factors with SCA. No variants were associated with SCA at genome-wide significance, nor were common variants in candidate arrhythmia genes associated with SCA at nominal significance. Using cross-trait GRSA, we established genetic correlation between SCA and (i) coronary artery disease (CAD) and traditional CAD risk factors (blood pressure, lipids, and diabetes), (ii) height and BMI, and (iii) electrical instability traits (QT and atrial fibrillation), suggesting aetiologic roles for these traits in SCA risk.Conclusions: Our findings show that a comprehensive approach to the genetic architecture of SCA can shed light on the determinants of a complex life-threatening condition with multiple influencing factors in the general population. The results of this genetic analysis, both positive and negative findings, have implications for evaluating the genetic architecture of patients with a family history of SCA, and for efforts to prevent SCA in high-risk populations and the general community.
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| 3. |
- Terwee, Caroline B., et al.
(författare)
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Patient-reported outcomes for people with diabetes : what and how to measure? A narrative review
- 2023
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 66:8, s. 1357-1377
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Forskningsöversikt (refereegranskat)abstract
- Patient-reported outcomes (PROs) are valuable for shared decision making and research. Patient-reported outcome measures (PROMs) are questionnaires used to measure PROs, such as health-related quality of life (HRQL). Although core outcome sets for trials and clinical practice have been developed separately, they, as well as other initiatives, recommend different PROs and PROMs. In research and clinical practice, different PROMs are used (some generic, some disease-specific), which measure many different things. This is a threat to the validity of research and clinical findings in the field of diabetes. In this narrative review, we aim to provide recommendations for the selection of relevant PROs and psychometrically sound PROMs for people with diabetes for use in clinical practice and research. Based on a general conceptual framework of PROs, we suggest that relevant PROs to measure in people with diabetes are: disease-specific symptoms (e.g. worries about hypoglycaemia and diabetes distress), general symptoms (e.g. fatigue and depression), functional status, general health perceptions and overall quality of life. Generic PROMs such as the 36-Item Short Form Health Survey (SF-36), WHO Disability Assessment Schedule (WHODAS 2.0), or Patient-Reported Outcomes Measurement Information System (PROMIS) measures could be considered to measure commonly relevant PROs, supplemented with disease-specific PROMs where needed. However, none of the existing diabetes-specific PROM scales has been sufficiently validated, although the Diabetes Symptom Self-Care Inventory (DSSCI) for measuring diabetes-specific symptoms and the Diabetes Distress Scale (DDS) and Problem Areas in Diabetes (PAID) for measuring distress showed sufficient content validity. Standardisation and use of relevant PROs and psychometrically sound PROMs can help inform people with diabetes about the expected course of disease and treatment, for shared decision making, to monitor outcomes and to improve healthcare. We recommend further validation studies of diabetes-specific PROMs that have sufficient content validity for measuring disease-specific symptoms and consider generic item banks developed based on item response theory for measuring commonly relevant PROs.
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| 4. |
- Zijlstra, Jolande A, et al.
(författare)
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Different defibrillation strategies in survivors after out-of-hospital cardiac arrest.
- 2018
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 104:23, s. 1929-1936
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In the last decade, there has been a rapid increase in the dissemination of automated external defibrillators (AEDs) for prehospital defibrillation of out-of-hospital cardiac arrest patients. The aim of this study was to study the association between different defibrillation strategies on survival rates over time in Copenhagen, Stockholm, Western Sweden and Amsterdam, and the hypothesis was that non-EMS defibrillation increased over time and was associated with increased survival.METHODS: We performed a retrospective analysis of four prospectively collected cohorts of out-of-hospital cardiac arrest patients between 2008 and 2013. Emergency medical service (EMS)-witnessed arrests were excluded.RESULTS: A total of 22 453 out-of-hospital cardiac arrest patients with known survival status were identified, of whom 2957 (13%) survived at least 30 days postresuscitation. Of all survivors with a known defibrillation status, 2289 (81%) were defibrillated, 1349 (59%) were defibrillated by EMS, 454 (20%) were defibrillated by a first responder AED and 429 (19%) were defibrillated by an onsite AED and 57 (2%) were unknown. The percentage of survivors defibrillated by first responder AEDs (from 13% in 2008 to 26% in 2013, p<0.001 for trend) and onsite AEDs (from 14% in 2008 to 30% in 2013, p<0.001 for trend) increased. The increased use of these non-EMS AEDs was associated with the increase in survival rate of patients with a shockable initial rhythm.CONCLUSION: Survivors of out-of-hospital cardiac arrest are increasingly defibrillated by non-EMS AEDs. This increase is primarily due to a large increase in the use of onsite AEDs as well as an increase in first-responder defibrillation over time. Non-EMS defibrillation accounted for at least part of the increase in survival rate of patients with a shockable initial rhythm.
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