| 1. |
- Kaufmann, Tobias, et al.
(author)
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Common brain disorders are associated with heritable patterns of apparent aging of the brain
- 2019
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In: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 22:10, s. 1617-
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Journal article (peer-reviewed)abstract
- Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3-96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.
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| 2. |
- Ahadi, Aylin, et al.
(author)
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Simulation of Nanoindentation Response of Empty and Filled Viral Capsids
- 2009
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In: DCE Technical Memorandum. - 1901-7278. ; 11
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Conference paper (peer-reviewed)abstract
- The nanoindentation response of empty and filled viral capsids is modelled using three dimensional finite element analysis. Simulation with two different geometries, spherical and icosahedral, are performed using the finite element code Abaqus. The capsids are modeled as non-linear Hookean elastic and both small and large deformation analysis is performed. Force-indentation curves for three different viral capsids are directly compared to experimental data and the Young’s modulus is determined by calibrating the force-indentation curve to data from atomic force microscopy (AFM) experiments. Predictions are made for two additional viral capsids. The results from the simulation showed a good agreement with AFM data, see [1].
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| 3. |
- Aktaa, Suleman, et al.
(author)
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Data standards for heart failure : the European Unified Registries for Heart Care Evaluation and Randomized Trials (EuroHeart)
- 2022
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In: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 43:23, s. 2185-
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Journal article (peer-reviewed)abstract
- Standardized data definitions are essential for assessing the quality of care and patient outcomes in observational studies and randomized controlled trials. The European Unified Registries for Heart Care Evaluation and Randomized Trials (EuroHeart) project of the European Society of Cardiology (ESC) aims to create contemporary pan-European data standards for cardiovascular diseases, including heart failure (HF). We followed the EuroHeart methodology for cardiovascular data standard development. A Working Group including experts in HF registries, representatives from the Heart Failure Association of the ESC, and the EuroHeart was formed. Using Embase and Medline (2016-21), we conducted a systematic review of the literature on data standards, registries, and trials to identify variables pertinent to HF. A modified Delphi method was used to reach a consensus on the final set of variables. For each variable, the Working Group developed data definitions and agreed on whether it was mandatory (Level 1) or additional (Level 2). In total, 84 Level 1 and 79 Level 2 variables were selected for nine domains of HF care. These variables were reviewed by an international Reference Group with the Level 1 variables providing the dataset for registration of patients with HF on the EuroHeart IT platform. By means of a structured process and interaction with international stakeholders, harmonized data standards for HF have been developed. In the context of the EuroHeart, this will facilitate quality improvement, international observational research, registry-based randomized trials, and post-marketing surveillance of devices and pharmacotherapies across Europe.
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| 4. |
- Alnaes, Dag, et al.
(author)
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Brain Heterogeneity in Schizophrenia and Its Association With Polygenic Risk
- 2019
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In: JAMA psychiatry. - : AMER MEDICAL ASSOC. - 2168-6238 .- 2168-622X. ; 76:7, s. 739-748
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Journal article (peer-reviewed)abstract
- ImportanceBetween-individual variability in brain structure is determined by gene-environment interactions, possibly reflecting differential sensitivity to environmental and genetic perturbations. Magnetic resonance imaging (MRI) studies have revealed thinner cortices and smaller subcortical volumes in patients with schizophrenia. However, group-level comparisons may mask considerable within-group heterogeneity, which has largely remained unnoticed in the literature. ObjectivesTo compare brain structural variability between individuals with schizophrenia and healthy controls and to test whether respective variability reflects the polygenic risk score (PRS) for schizophrenia in an independent sample of healthy controls. Design, Setting, and ParticipantsThis case-control and polygenic risk analysis compared MRI-derived cortical thickness and subcortical volumes between healthy controls and patients with schizophrenia across 16 cohorts and tested for associations between PRS and MRI features in a control cohort from the UK Biobank. Data were collected from October 27, 2004, through April 12, 2018, and analyzed from December 3, 2017, through August 1, 2018. Main Outcomes and MeasuresMean and dispersion parameters were estimated using double generalized linear models. Vertex-wise analysis was used to assess cortical thickness, and regions-of-interest analyses were used to assess total cortical volume, total surface area, and white matter, subcortical, and hippocampal subfield volumes. Follow-up analyses included within-sample analysis, test of robustness of the PRS threshold, population covariates, outlier removal, and control for image quality. ResultsA comparison of 1151 patients with schizophrenia (mean [SD] age,33.8[10.6] years; 68.6% male [n=790] and 31.4% female [n=361]) with 2010 healthy controls (mean [SD] age,32.6[10.4] years; 56.0% male [n=1126] and 44.0% female [n=884]) revealed higher heterogeneity in schizophrenia for cortical thickness and area (t = 3.34), cortical (t=3.24) and ventricle (t range, 3.15-5.78) volumes, and hippocampal subfields (t range, 2.32-3.55). In the UK Biobank sample of 12 490 participants (mean [SD] age,55.9 [7.5] years; 48.2% male [n=6025] and 51.8% female [n=6465]), higher PRS was associated with thinner frontal and temporal cortices and smaller left CA2/3 (t=-3.00) but was not significantly associated with dispersion. Conclusions and RelevanceThis study suggests that schizophrenia is associated with substantial brain structural heterogeneity beyond the mean differences. These findings may reflect higher sensitivity to environmental and genetic perturbations in patients, supporting the heterogeneous nature of schizophrenia. A higher PRS was associated with thinner frontotemporal cortices and smaller hippocampal subfield volume, but not heterogeneity. This finding suggests that brain variability in schizophrenia results from interactions between environmental and genetic factors that are not captured by the PRS. Factors contributing to heterogeneity in frontotemporal cortices and hippocampus are key to furthering our understanding of how genetic and environmental factors shape brain biology in schizophrenia.
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| 5. |
- Baumann, Pia, et al.
(author)
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Stereotactic body radiotherapy for medically inoperable patients with stage I non-small cell lung cancer - a first report of toxicity related to COPD/CVD in a non-randomized prospective phase II study.
- 2008
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In: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 88:3, s. 359-67
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Journal article (peer-reviewed)abstract
- BACKGROUND AND AIMS: In a retrospective study using stereotactic body radiotherapy (SBRT) in medically inoperable patients with stage I NSCLC we previously reported a local control rate of 88% utilizing a median dose of 15Gyx3. This report records the toxicity encountered in a prospective phase II trial, and its relation to coexisting chronic obstructive pulmonary disease (COPD) and cardio vascular disease (CVD). MATERIAL AND METHODS: Sixty patients were entered in the study between August 2003 and September 2005. Fifty-seven patients (T1 65%, T2 35%) with a median age of 75 years (59-87 years) were evaluable. The baseline mean FEV1% was 64% and median Karnofsky index was 80. A total dose of 45Gy was delivered in three fractions at the 67% isodose of the PTV. Clinical, pulmonary and radiological evaluations were made at 6 weeks, 3, 6, 9, 12, 18, and 36 months post-SBRT. Toxicity was graded according to CTC v2.0 and performance status was graded according to the Karnofsky scale. RESULTS: At a median follow-up of 23 months, 2 patients had relapsed locally. No grade 4 or 5 toxicity was reported. Grade 3 toxicity was seen in 12 patients (21%). There was no significant decline of FEV1% during follow-up. Low grade pneumonitis developed to the same extent in the CVD 3/17 (18%) and COPD 7/40 (18%) groups. The incidence of fibrosis was 9/17 (53%) and pleural effusions was 8/17 (47%) in the CVD group compared with 13/40 (33%) and 5/40 (13%) in the COPD group. CONCLUSION: SBRT for stage I NSCLC patients who are medically inoperable because of COPD and CVD results in a favourable local control rate with a low incidence of grade 3 and no grade 4 or 5 toxicity.
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| 6. |
- Córdova-Palomera, Aldo, et al.
(author)
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Genetic control of variability in subcortical and intracranial volumes
- 2021
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In: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 26:8, s. 3876-3883
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Journal article (peer-reviewed)abstract
- Sensitivity to external demands is essential for adaptation to dynamic environments, but comes at the cost of increased risk of adverse outcomes when facing poor environmental conditions. Here, we apply a novel methodology to perform genome-wide association analysis of mean and variance in ten key brain features (accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, intracranial volume, cortical surface area, and cortical thickness), integrating genetic and neuroanatomical data from a large lifespan sample (n = 25,575 individuals; 8-89 years, mean age 51.9 years). We identify genetic loci associated with phenotypic variability in thalamus volume and cortical thickness. The variance-controlling loci involved genes with a documented role in brain and mental health and were not associated with the mean anatomical volumes. This proof-of-principle of the hypothesis of a genetic regulation of brain volume variability contributes to establishing the genetic basis of phenotypic variance (i.e., heritability), allows identifying different degrees of brain robustness across individuals, and opens new research avenues in the search for mechanisms controlling brain and mental health.
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| 7. |
- Hallberg, Håkan, et al.
(author)
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Modeling of Continuous Dynamic Recrystallization in Aluminum
- 2009
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In: DCE Technical Memorandum No. 11. - 1901-7278. ; 11, s. 59-62
-
Conference paper (peer-reviewed)abstract
- A constitutive model is presented, considering grain size refinement through continuous dynamic recrystallization together with an evolving dislocation density. The grain refinement is allowed to influence both the evolution of the dislocation density and the rate dependence of the material. The model is calibrated against experimental data on aluminum and numerical simulations of equal channel angular pressing (ECAP) material processing illustrates the capabilities of the model.
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| 8. |
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| 9. |
- Jadoon, Asim, et al.
(author)
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Hydrodynamic interaction of a particle pair at Reynolds number 600
- 2009
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In: [Host publication title missing]. - 1901-7278. ; DCE technical memorandum No. 11, s. 261-264
-
Conference paper (peer-reviewed)abstract
- In the current study the focus is on the flow and particle interaction effects in the chaotic regime. The influence on the forces (i.e drag and lift), wake structures and flow patterns from different inflow boundary conditions and varying separation distances of a particle pair in tandem is discussed at a particle Reynolds number of 600.
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| 10. |
- Kapelios, Chris J, et al.
(author)
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Association between loop diuretic dose changes and outcomes in chronic heart failure : observations from the ESC-EORP Heart Failure Long-Term Registry.
- 2020
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In: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 22:8, s. 1424-1437
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Journal article (peer-reviewed)abstract
- AIMS: Guidelines recommend down-titration of loop diuretics (LD) once euvolaemia is achieved. In outpatients with heart failure (HF), we investigated LD dose changes in daily cardiology practice, agreement with guideline recommendations, predictors of successful LD down-titration and association between dose changes and outcomes.METHODS AND RESULTS: We included 8130 HF patients from the ESC-EORP Heart Failure Long-Term Registry. Among patients who had dose decreased, successful decrease was defined as the decrease not followed by death, HF hospitalization, New York Heart Association class deterioration, or subsequent increase in LD dose. Mean age was 66 ± 13 years, 71% men, 62% HF with reduced ejection fraction, 19% HF with mid-range ejection fraction, 19% HF with preserved ejection fraction. Median [interquartile range (IQR)] LD dose was 40 (25-80) mg. LD dose was increased in 16%, decreased in 8.3% and unchanged in 76%. Median (IQR) follow-up was 372 (363-419) days. Diuretic dose increase (vs. no change) was associated with HF death [hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.12-2.08; P = 0.008] and nominally with cardiovascular death (HR 1.25, 95% CI 0.96-1.63; P = 0.103). Decrease of diuretic dose (vs. no change) was associated with nominally lower HF (HR 0.59, 95% CI 0.33-1.07; P = 0.083) and cardiovascular mortality (HR 0.62, 95% CI 0.38-1.00; P = 0.052). Among patients who had LD dose decreased, systolic blood pressure [odds ratio (OR) 1.11 per 10 mmHg increase, 95% CI 1.01-1.22; P = 0.032], and absence of (i) sleep apnoea (OR 0.24, 95% CI 0.09-0.69; P = 0.008), (ii) peripheral congestion (OR 0.48, 95% CI 0.29-0.80; P = 0.005), and (iii) moderate/severe mitral regurgitation (OR 0.57, 95% CI 0.37-0.87; P = 0.008) were independently associated with successful decrease.CONCLUSION: Diuretic dose was unchanged in 76% and decreased in 8.3% of outpatients with chronic HF. LD dose increase was associated with worse outcomes, while the LD dose decrease group showed a trend for better outcomes compared with the no-change group. Higher systolic blood pressure, and absence of (i) sleep apnoea, (ii) peripheral congestion, and (iii) moderate/severe mitral regurgitation were independently associated with successful dose decrease.
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| 11. |
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| 12. |
- Makubi, Abel, et al.
(author)
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Heart failure in Tanzania and Sweden: Comparative characterization and prognosis in the Tanzania Heart Failure (TaHeF) study and the Swedish Heart Failure Registry (SwedeHF)
- 2016
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In: International Journal of Cardiology. - : ELSEVIER IRELAND LTD. - 0167-5273 .- 1874-1754. ; 220, s. 750-758
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Journal article (peer-reviewed)abstract
- Background: Heart failure (HF) in developing countries is poorly described. We compare characteristics and prognosis of HF in Tanzania vs. Sweden. Methods: A prospective cohort study was conducted from the Tanzania HF study (TaHeF) and the Swedish HF Registry (SwedeHF). Patients were compared overall (n 427 vs. 51,060) and after matching 1: 3 by gender and age +/- 5 years (n 411 vs. 1232). The association between cohort and all-cause mortality was assessed with multivariable Cox regression. Results: In the unmatched cohorts, TaHeF (as compared to SwedeHF) patients were younger (median age [inter-quartile range] 55 [40-68] vs. 77 [64-84] years, p amp;lt; 0.001) and more commonly women (51% vs. 40%, p amp;lt; 0.001). The three-year survival was 61% in both cohorts. In the matched cohorts, TaHeF patients had more hypertension (47% vs. 37%, p amp;lt; 0.001), more anemia (57% vs. 9%), more preserved EF, more advanced HF, longer duration of HF, and less use of beta-blockers. Crude mortality was worse in TaHeF (HR 2.25 [95% CI 1.78-2.85], p amp;lt; 0.001), with three-year survival 61% vs. 83%. However, covariate-adjusted risk was similar (HR 1.07, 95% CI 0.69-1.66; p = 0.760). In both cohorts, preserved EF was associated with higher mortality in crude but not adjusted analysis. Conclusions: Compared to in Sweden, HF patients in Tanzania were younger and more commonly female, and after age and gender matching, had more frequent hypertension and anemia, more severe HF despite higher EF, and worse crude but similar adjusted prognosis. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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| 13. |
- Mortensen, Mike A., et al.
(author)
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Artificial intelligence-based versus manual assessment of prostate cancer in the prostate gland: a method comparison study
- 2019
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In: Clinical Physiology and Functional Imaging. - : Wiley. - 1475-0961 .- 1475-097X. ; 39:6, s. 399-406
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Journal article (peer-reviewed)abstract
- Aim : To test the feasibility of a fully automated artificial intelligence-based method providing PET measures of prostate cancer (PCa). Methods : A convolutional neural network (CNN) was trained for automated measurements in 18F-choline (FCH) PET/CT scans obtained prior to radical prostatectomy (RP) in 45 patients with newly diagnosed PCa. Automated values were obtained for prostate volume, maximal standardized uptake value (SUVmax), mean standardized uptake value of voxels considered abnormal (SUVmean) and volume of abnormal voxels (Volabn). The product SUVmean × Volabn was calculated to reflect total lesion uptake (TLU). Corresponding manual measurements were performed. CNN-estimated data were compared with the weighted surgically removed tissue specimens and manually derived data and related to clinical parameters assuming that 1 g ≈ 1 ml of tissue. Results : The mean (range) weight of the prostate specimens was 44 g (20–109), while CNN-estimated volume was 62 ml (31–108) with a mean difference of 13·5 g or ml (95% CI: 9·78–17·32). The two measures were significantly correlated (r = 0·77, P<0·001). Mean differences (95% CI) between CNN-based and manually derived PET measures of SUVmax, SUVmean, Volabn (ml) and TLU were 0·37 (−0·01 to 0·75), −0·08 (−0·30 to 0·14), 1·40 (−2·26 to 5·06) and 9·61 (−3·95 to 23·17), respectively. PET findings Volabn and TLU correlated with PSA (P<0·05), but not with Gleason score or stage. Conclusion : Automated CNN segmentation provided in seconds volume and simple PET measures similar to manually derived ones. Further studies on automated CNN segmentation with newer tracers such as radiolabelled prostate-specific membrane antigen are warranted.
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| 14. |
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| 15. |
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| 16. |
- Pennells, Lisa, et al.
(author)
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Equalization of four cardiovascular risk algorithms after systematic recalibration : individual-participant meta-analysis of 86 prospective studies
- 2019
-
In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:7, s. 621-
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Journal article (peer-reviewed)abstract
- Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
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| 17. |
- Rohrmann, Sabine, et al.
(author)
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Ethanol intake and risk of lung cancer in the European prospective investigation into cancer and nutrition (EPIC)
- 2006
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In: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 164:11, s. 1103-1114
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Journal article (peer-reviewed)abstract
- Within the European Prospective Investigation into Cancer and Nutrition (EPIC), the authors examined the association of ethanol intake at recruitment (1,119 cases) and mean lifelong ethanol intake (887 cases) with lung cancer. Information on baseline and past alcohol consumption, lifetime tobacco smoking, diet, and the anthropometric characteristics of 478,590 participants was collected between 1992 and 2000. Cox proportional hazards regression was used to calculate multivariate-adjusted hazard ratios and 95% confidence intervals. Overall, neither ethanol intake at recruitment nor mean lifelong ethanol intake was significantly associated with lung cancer. However, moderate intake (5-14.9 g/day) at recruitment (hazard ratio (HR) = 0.76, 95% confidence interval (CI): 0.63, 0.90) and moderate mean lifelong intake (HR = 0.80, 95% CI: 0.66, 0.97) were associated with a lower lung cancer risk in comparison with low consumption (0.1-4.9 g/day). Compared with low intake, a high (>= 60 g/day) mean lifelong ethanol intake tended to be related to a higher risk of lung cancer (HR = 1.29, 95% CI: 0.93, 1.74), but high intake at recruitment was not. Although there was no overall association between ethanol intake and risk of lung cancer, the authors cannot rule out a lower risk for moderate consumption and a possibly increased risk for high lifelong consumption.
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| 18. |
- Sahlen, Anders, et al.
(author)
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Arterial vasodilatory and ventricular diastolic reserves determine the stroke volume response to exercise in elderly female hypertensive patients
- 2011
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In: American Journal of Physiology. Heart and Circulatory Physiology. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 301:6, s. H2433-H2441
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Journal article (peer-reviewed)abstract
- Sahlen A, Abdula G, Norman M, Manouras A, Brodin LA, Lund LH, Shahgaldi K, Winter R. Arterial vasodilatory and ventricular diastolic reserves determine the stroke volume response to exercise in elderly female hypertensive patients. Am J Physiol Heart Circ Physiol 301: H2433-H2441, 2011. First published September 16, 2011; doi:10.1152/ajpheart.00555.2011.-Elderly female hypertensives with arterial stiffening constitute a majority of patients with heart failure with preserved ejection fraction (HFpEF), a condition characterized by inability to increase cardiac stroke volume (SV) with physical exercise. As SV is determined by the interaction between the left ventricle (LV) and its load, we wished to study the role of arterial hemodynamics for exertional SV reserve in patients at high risk of HFpEF. Twenty-one elderly (67 +/- 9 yr) female hypertensive patients were studied at rest and during supine bicycle stress using echocardiography including pulsed-wave Doppler to record flow in the LV outflow tract and arterial tonometry for central arterial pressure waveforms. Arterial compliance was estimated based on an exponential relationship between pressure and volume. The ratio of aortic pressure-to-flow in early systole was used to derive characteristic impedance, which was subsequently subtracted from total resistance (mean arterial pressure/cardiac output) to yield systemic vascular resistance (SVR). It was found that patients with depressed SV reserve (NoRes; reserve <15%; n = 10) showed decreased arterial compliance during exercise, while patients with SV reserve >= 15% (Res; n = 11) showed increased compliance. Exercise produced parallel increases in LV end-diastolic volume and arterial volume in Res patients while NoRes patients exhibited a lesser decrease in SVR and a drop in effective arterial volume. Poor SV reserve in elderly female hypertensives is due to simultaneous failure of LV preload and arterial vasodilatory reserves. Abnormal arterial function contributes to a high risk of HFpEF in these patients.
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| 19. |
- Solomon, Scott D, et al.
(author)
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Sacubitril/Valsartan Across the Spectrum of Ejection Fraction in Heart Failure.
- 2020
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In: Circulation. - 0009-7322 .- 1524-4539. ; 141:5, s. 352-361
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Journal article (peer-reviewed)abstract
- Background: While disease modifying therapies exist for heart failure (HF) with reduced left ventricular ejection fraction (LVEF), few options are available for patients in the higher range of LVEF (>40%). Sacubitril/valsartan has been compared with a renin-angiotensin- system (RAS) inhibitor alone in two similarly designed clinical trials of patients with reduced and preserved LVEF, permitting examination of its effects across the full spectrum of LVEF. Methods: We combined data from PARADIGM-HF (LVEF eligibility≤40%; n=8,399) and PARAGON-HF (LVEF eligibility≥45%; n=4,796) in a prespecified pooled analysis. We divided randomized patients into LVEF categories:≤22.5% (n=1269), >22.5% to 32.5% (n=3987), >32.5% to 42.5% (n=3143), > 42.5% to 52.5% (n=1427), > 52.5% to 62.5% (n=2166), >62.5% (n=1202). We assessed time to first cardiovascular death and HF hospitalization, its components, and total heart failure hospitlizations, all-cause mortality and non-cardiovascular mortality. Incidence rates and treatment effects were examined across categories of LVEF. Results: Among 13,195 randomized patients, we observed lower rates of cardiovascular death and HF hospitalization, but similar rates of non-cardiovascular death, among patients in the highest vs. lowest groups. Overall sacubitril/valsartan was superior to RAS inhibition for first cardiovascular death or heart failure hospitalization (HR 0.84, 95% CI 0.78, 0.90), cardiovascular death (HR 0.84, 95% CI 0.76, 0.92), heart failure hospitalization (HR 0.84, 95% CI 0.77, 0.91), and all-cause mortality (HR 0.88, 95% CI 0.81, 0.96). The effect of sacubitril/valsartan was modified by LVEF (treatment-by-continuous LVEF interaction p=0.02), and benefit appeared to be present for individuals with EF primarily below the normal range, although the treatment benefit for cardiovascular death diminished at a lower ejection fraction. We observed effect modification by LVEF on the efficacy of sacubitril/valsartan in both men and women with respect to composite total HF hospitalizations and cardiovascular death, although women derived benefit to higher ejection fractions. Conclusions:The therapeutic effects of sacubitril/valsartan, compared with a RAS inhibitor alone, vary by LVEF, with treatment benefits, particularly for heart failure hospitalization, that appear to extend to patients with heart failure and mildly reduced ejection fraction. These therapeutic benefits appeared to extend to a higher LVEF range in women compared with men. Clinical Trial Registration: URL: https://clinicaltrials.gov PARAGON-HF Unique Identifier: NCT01920711. PARADIGM-HF Unique Identifier: NCT01035255.
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| 20. |
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| 21. |
- Aad, G., et al.
(author)
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The ATLAS Experiment at the CERN Large Hadron Collider
- 2008
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In: Journal of Instrumentation. - 1748-0221. ; 3:S08003
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Research review (peer-reviewed)abstract
- The ATLAS detector as installed in its experimental cavern at point 1 at CERN is described in this paper. A brief overview of the expected performance of the detector when the Large Hadron Collider begins operation is also presented.
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| 22. |
- Adamo, Marianna, et al.
(author)
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Epidemiology, pathophysiology, diagnosis and management of chronic right-sided heart failure and tricuspid regurgitation. A clinical consensus statement of the Heart Failure Association (HFA) and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC
- 2024
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In: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844.
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Journal article (peer-reviewed)abstract
- Right-sided heart failure and tricuspid regurgitation are common and strongly associated with poor quality of life and an increased risk of heart failure hospitalizations and death. While medical therapy for right-sided heart failure is limited, treatment options for tricuspid regurgitation include surgery and, based on recent developments, several transcatheter interventions. However, the patients who might benefit from tricuspid valve interventions are yet unknown, as is the ideal time for these treatments given the paucity of clinical evidence. In this context, it is crucial to elucidate aetiology and pathophysiological mechanisms leading to right-sided heart failure and tricuspid regurgitation in order to recognize when tricuspid regurgitation is a mere bystander and when it can cause or contribute to heart failure progression. Notably, early identification of right heart failure and tricuspid regurgitation may be crucial and optimal management requires knowledge about the different mechanisms and causes, clinical course and presentation, as well as possible treatment options. The aim of this clinical consensus statement is to summarize current knowledge about epidemiology, pathophysiology and treatment of tricuspid regurgitation in right-sided heart failure providing practical suggestions for patient identification and management.
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| 23. |
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| 24. |
- Agarwal, Anubha, et al.
(author)
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Toward a Universal Definition of Etiologies in Heart Failure : Categorizing Causes and Advancing Registry Science
- 2024
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In: Circulation Heart Failure. - : American Heart Association. - 1941-3289 .- 1941-3297. ; 17:4
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Research review (peer-reviewed)abstract
- Heart failure (HF) is a well-described final common pathway for a broad range of diseases however substantial confusion exists regarding how to describe, study, and track these underlying etiologic conditions. We describe (1) the overlap in HF etiologies, comorbidities, and case definitions as currently used in HF registries led or managed by members of the global HF roundtable; (2) strategies to improve the quality of evidence on etiologies and modifiable risk factors of HF in registries; and (3) opportunities to use clinical HF registries as a platform for public health surveillance, implementation research, and randomized registry trials to reduce the global burden of noncommunicable diseases. Investment and collaboration among countries to improve the quality of evidence in global HF registries could contribute to achieving global health targets to reduce noncommunicable diseases and overall improvements in population health.
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| 25. |
- Ahmad, Tariq, et al.
(author)
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Machine Learning Methods Improve Prognostication, Identify Clinically Distinct Phenotypes, and Detect Heterogeneity in Response to Therapy in a Large Cohort of Heart Failure Patients
- 2018
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In: Journal of the American Heart Association. - : WILEY. - 2047-9980. ; 7:8
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Journal article (peer-reviewed)abstract
- Background-Whereas heart failure (HF) is a complex clinical syndrome, conventional approaches to its management have treated it as a singular disease, leading to inadequate patient care and inefficient clinical trials. We hypothesized that applying advanced analytics to a large cohort of HF patients would improve prognostication of outcomes, identify distinct patient phenotypes, and detect heterogeneity in treatment response. Methods and Results-The Swedish Heart Failure Registry is a nationwide registry collecting detailed demographic, clinical, laboratory, and medication data and linked to databases with outcome information. We applied random forest modeling to identify predictors of 1-year survival. Cluster analysis was performed and validated using serial bootstrapping. Association between clusters and survival was assessed with Cox proportional hazards modeling and interaction testing was performed to assess for heterogeneity in response to HF pharmacotherapy across propensity-matched clusters. Our study included 44 886 HF patients enrolled in the Swedish Heart Failure Registry between 2000 and 2012. Random forest modeling demonstrated excellent calibration and discrimination for survival (C-statistic=0.83) whereas left ventricular ejection fraction did not (C-statistic=0.52): there were no meaningful differences per strata of left ventricular ejection fraction (1-year survival: 80%, 81%, 83%, and 84%). Cluster analysis using the 8 highest predictive variables identified 4 clinically relevant subgroups of HF with marked differences in 1-year survival. There were significant interactions between propensity-matched clusters (across age, sex, and left ventricular ejection fraction and the following medications: diuretics, angiotensin-converting enzyme inhibitors, )i-blockers, and nitrates, Pamp;lt;0.001, all). Conclusions-Machine learning algorithms accurately predicted outcomes in a large data set of HF patients. Cluster analysis identified 4 distinct phenotypes that differed significantly in outcomes and in response to therapeutics. Use of these novel analytic approaches has the potential to enhance effectiveness of current therapies and transform future HF clinical trials.
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