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| 6. |
- Schwarz, E, et al.
(författare)
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Reproducible grey matter patterns index a multivariate, global alteration of brain structure in schizophrenia and bipolar disorder
- 2019
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9:1, s. 12-
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia is a severe mental disorder characterized by numerous subtle changes in brain structure and function. Machine learning allows exploring the utility of combining structural and functional brain magnetic resonance imaging (MRI) measures for diagnostic application, but this approach has been hampered by sample size limitations and lack of differential diagnostic data. Here, we performed a multi-site machine learning analysis to explore brain structural patterns of T1 MRI data in 2668 individuals with schizophrenia, bipolar disorder or attention-deficit/ hyperactivity disorder, and healthy controls. We found reproducible changes of structural parameters in schizophrenia that yielded a classification accuracy of up to 76% and provided discrimination from ADHD, through it lacked specificity against bipolar disorder. The observed changes largely indexed distributed grey matter alterations that could be represented through a combination of several global brain-structural parameters. This multi-site machine learning study identified a brain-structural signature that could reproducibly differentiate schizophrenia patients from controls, but lacked specificity against bipolar disorder. While this currently limits the clinical utility of the identified signature, the present study highlights that the underlying alterations index substantial global grey matter changes in psychotic disorders, reflecting the biological similarity of these conditions, and provide a roadmap for future exploration of brain structural alterations in psychiatric patients.
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| 9. |
- Cosmi, F., et al.
(författare)
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Treatment with insulin is associated with worse outcome in patients with chronic heart failure and diabetes
- 2018
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 20:5, s. 888-895
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Tidskriftsartikel (refereegranskat)abstract
- Aims Up to one-third of patients with diabetes mellitus and heart failure (HF) are treated with insulin. As insulin causes sodium retention and hypoglycaemia, its use might be associated with worse outcomes. Methods and results We examined two datasets: 24 012 patients with HF from four large randomized trials and an administrative database of 4 million individuals, 103 857 of whom with HF. In the former, survival was examined using Cox proportional hazards models adjusted for baseline variables and separately for propensity scores. Fine-Gray competing risk regression models were used to assess the risk of hospitalization for HF. For the latter, a case-control nested within a population-based cohort study was conducted with propensity score. Prevalence of diabetes mellitus at study entry ranged from 25.5% to 29.5% across trials. Insulin alone or in combination with oral hypoglycaemic drugs was prescribed at randomization to 24.4% to 34.5% of the patients with diabetes. The rates of death from any cause and hospitalization for HF were higher in patients with vs. without diabetes, and highest of all in patients prescribed insulin [propensity score pooled hazard ratio for all-cause mortality 1.27 (1.16-1.38), for HF hospitalization 1.23 (1.13-1.33)]. In the administrative registry, insulin prescription was associated with a higher risk of all-cause death [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.87-2.19] and rehospitalization for HF (OR 1.42, 95% CI 1.32-1.53). Conclusions Whether insulin use is associated with poor outcomes in HF should be investigated further with controlled trials, as should the possibility that there may be safer alternative glucose-lowering treatments for patients with HF and type 2 diabetes mellitus.
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- Shadman, R., et al.
(författare)
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A novel method to predict the proportional risk of sudden cardiac death in heart failure: Derivation of the Seattle Proportional Risk Model
- 2015
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Ingår i: Heart Rhythm. - : Elsevier BV. - 1547-5271. ; 12:10, s. 2069-2077
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Patients with heart failure are at increased risk of both sudden death and pump failure death. Strategies to better identify those who have greatest net benefit from implantable cardioverter-defibrillator (ICD) implantation could reduce morbidity and maximize cost-effectiveness of ICDs. OBJECTIVE We aimed to identify baseline variables in patients with cardiomyopathy that are independently associated with a disproportionate fraction of mortality risk attributable to sudden death vs nonsudden death. METHODS We used data from 9885 patients with heart failure without ICDs, of whom 2552 died during an average follow-up of 2.3 years. Using commonly available baseline clinical and demographic variables, we developed a multivariate regression model to identify variables associated with a disproportionate risk of sudden death. RESULTS We confirmed that lower ejection fraction and better functional class were associated with a greater proportion of mortality due to sudden death. Younger age, male sex, and higher body mass index were independently associated with a greater proportional risk of sudden death, while diabetes mellitus, hyper/hypotension, higher creatinine level, and hyponatremia were associated with a disproportionately Lower risk of sudden death. The use of several heart failure medications, Left ventricular end-diastolic dimension, or NT-pro brain natriuretic peptide concentrations were not associated with a disproportionate risk of sudden death. CONCLUSION Several easily obtained baseline demographic and clinical variables, beyond ejection fraction and New York Heart Association functional class, are independently associated with a disproportionately increased risk of sudden death. Further investigation is needed to assess whether this novel predictive method can be used to target the use of lifesaving therapies to populations who will derive greatest mortality benefit
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| 13. |
- Shen, L., et al.
(författare)
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Declining Risk of Sudden Death in Heart Failure
- 2017
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 377:1, s. 41-51
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The risk of sudden death has changed over time among patients with symptomatic heart failure and reduced ejection fraction with the sequential introduction of medications including angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, and mineralocorticoid-receptor antagonists. We sought to examine this trend in detail. We analyzed data from 40,195 patients who had heart failure with reduced ejection fraction and were enrolled in any of 12 clinical trials spanning the period from 1995 through 2014. Patients who had an implantable cardioverter-defibrillator at the time of trial enrollment were excluded. Weighted multivariable regression was used to examine trends in rates of sudden death over time. Adjusted hazard ratios for sudden death in each trial group were calculated with the use of Cox regression models. The cumulative incidence rates of sudden death were assessed at different time points after randomization and according to the length of time between the diagnosis of heart failure and randomization. Sudden death was reported in 3583 patients. Such patients were older and were more often male, with an ischemic cause of heart failure and worse cardiac function, than those in whom sudden death did not occur. There was a 44% decline in the rate of sudden death across the trials (P = 0.03). The cumulative incidence of sudden death at 90 days after randomization was 2.4% in the earliest trial and 1.0% in the most recent trial. The rate of sudden death was not higher among patients with a recent diagnosis of heart failure than among those with a longer-standing diagnosis. Rates of sudden death declined substantially over time among ambulatory patients with heart failure with reduced ejection fraction who were enrolled in clinical trials, a finding that is consistent with a cumulative benefit of evidence-based medications on this cause of death. (Funded by the China Scholarship Council and the University of Glasgow.)
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| 15. |
- Ambrosy, A. P., et al.
(författare)
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Changes in Dyspnea Status During Hospitalization and Postdischarge Health-Related Quality of Life in Patients Hospitalized for Heart Failure: Findings From the EVEREST Trial
- 2016
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Ingår i: Circulation-Heart Failure. - : Ovid Technologies (Wolters Kluwer Health). - 1941-3289 .- 1941-3297. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- Background-Dyspnea is the most common symptom among hospitalized patients with heart failure and represents a therapeutic target. However, the association between short-term dyspnea relief and postdischarge clinical outcomes and health-related quality of life (HRQOL) remains uncertain. Methods and Results-A post hoc analysis was performed of the Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan (EVEREST) trial, which enrolled 4133 patients within 48 hours of admission for heart failure with an ejection fraction <= 40%. Physician-assessed dyspnea was recorded on a daily basis from baseline until discharge or day 7 as none, seldom, frequent, or continuous. Patient-reported dyspnea was measured using a 7-point Likert scale, and patients experiencing moderate or marked dyspnea improvement on day 1 were classified as early responders. The Kansas City Cardiomyopathy Questionnaire summary score, which ranges from 0 to 100, was collected postdischarge at week 1. The primary outcome was unfavorable HRQOL, defined a priori as a Kansas City Cardiomyopathy Questionnaire score <45. Secondary outcomes included 30-day all-cause mortality, and all-cause and cause-specific hospitalizations. The final analytic cohort included 1567 patients discharged alive with complete HRQOL data. Patients were 66.0 +/- 12.7 years old and had a mean ejection fraction of 25 +/- 8%. Physician-assessed dyspnea was rated as frequent or continuous in 1399 patients (90%) at baseline, which decreased to 250 patients (16%) by discharge, whereas patient-reported early dyspnea relief was reported by 610 patients (40%). The median Kansas City Cardiomyopathy Questionnaire score at week 1 was 50 (35, 65). All-cause mortality was 3.0%, and all-cause hospitalization was 20.5% within 30 days of discharge. Physician-assessed and patient-reported dyspnea was not independently associated with HRQOL, all-cause mortality, or all-cause or cause-specific hospitalization. Conclusions-In-hospital physician-assessed, and patient-reported dyspnea was not independently associated with postdischarge HRQOL, survival, or readmissions. Although dyspnea relief remains a goal of therapy for hospitalized patients with heart failure with reduced ejection fraction, this measure may not be a reliable surrogate for long-term patient-centered or hard clinical outcomes.
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| 18. |
- Bilchick, K. C., et al.
(författare)
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Seattle Heart Failure and Proportional Risk Models Predict Benefit From Implantable Cardioverter-Defibrillators
- 2017
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 69:21, s. 2606-2618
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Recent clinical trials highlight the need for better models to identify patients at higher risk of sudden death. OBJECTIVES The authors hypothesized that the Seattle Heart Failure Model (SHFM) for overall survival and the Seattle Proportional Risk Model (SPRM) for proportional risk of sudden death, including death from ventricular arrhythmias, would predict the survival benefit with an implantable cardioverter-defibrillator (ICD). METHODS Patients with primary prevention ICDs from the National Cardiovascular Data Registry (NCDR) were compared with control patients with heart failure (HF) without ICDs with respect to 5-year survival using multivariable Cox proportional hazards regression. RESULTS Among 98,846 patients with HF (87,914 with ICDs and 10,932 without ICDs), the SHFM was strongly associated with all-cause mortality (p < 0.0001). The ICD-SPRM interaction was significant (p < 0.0001), such that SPRM quintile 5 patients had approximately twice the reduction in mortality with the ICD versus SPRM quintile 1 patients (adjusted hazard ratios [HR]: 0.602; 95% confidence interval [CI]: 0.537 to 0.675 vs. 0.793; 95% CI: 0.736 to 0.855, respectively). Among patients with SHFM-predicted annual mortality <= 5.7%, those with a SPRM-predicted risk of sudden death below the median had no reduction in mortality with the ICD (adjusted ICD HR: 0.921; 95% CI: 0.787 to 1.08; p = 0.31), whereas those with SPRM above the median derived the greatest benefit (adjusted HR: 0.599; 95% CI: 0.530 to 0.677; p < 0.0001). CONCLUSIONS The SHFM predicted all-cause mortality in a large cohort with and without ICDs, and the SPRM discriminated and calibrated the potential ICD benefit. Together, the models identified patients less likely to derive a survival benefit from primary prevention ICDs. (J Am Coll Cardiol 2017;69:2606-18) (C) 2017 by the American College of Cardiology Foundation.
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| 19. |
- Bonapace, Stefano, et al.
(författare)
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Brachial pulse pressure in acute heart failure. Results of the Heart Failure Registry
- 2019
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Ingår i: ESC Heart Failure. - : WILEY PERIODICALS, INC. - 2055-5822. ; 6:6, s. 1167-1177
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Tidskriftsartikel (refereegranskat)abstract
- Aims To investigate the still uncertain independent prognostic impact of pulse pressure (PP) in acute heart failure (HF), in particular across the left ventricular ejection fraction (EF) phenotypes, and the potential contribution of PP in outlining the individual phenotypes. Methods and results We prospectively evaluated 1-year death and rehospitalization in 4314 patients admitted for acute HF grouped by EF and stratified by their PP level on admission. In HF with reduced (amp;lt; 40%) EF (HFrEF), the highest quartiles of PP had the lowest unadjusted [hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.61-0.98] and adjusted (HR 0.64 0.50-0.82) risk of 1 year all cause death compared to the lowest quartile. Its prognostic impact was partially mediated by systolic blood pressure (SBP). In HF with preserved (amp;gt;= 50%) EF (HFpEF), the intermediate quartile of PP showed the lowest 1 year all cause mortality in unadjusted (HR 0.598, CI 0.416-0.858) and adjusted (HR 0.55, 95% CI 0.388-0.801) models with no relationship with SBP. In a receiver operating characteristic analysis, a combination of PP amp;gt; 60 mmHg and SBP amp;gt; 140 mmHg was associated to a preserved EF with a high performance value. No prognostic significance of PP was found in the HF with mid-range EF subgroup. Conclusions In acute HFrEF, there is an almost linear inverse relation between mortality and PP, partly mediated by SBP. In HFpEF, a J-shaped relationship between mortality and PP was present with a better prognosis at the nadir. A combination of PP amp;gt; 60 mmHg with SBP amp;gt; 140 mmHg may be clinically helpful as marker of a preserved left ventricular EF.
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| 23. |
- Cook, T. D., et al.
(författare)
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Temporal Changes in Postdischarge Mortality Risk After Hospitalization for Heart Failure (from the EVEREST Trial)
- 2016
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149. ; 117:4, s. 611-616
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Tidskriftsartikel (refereegranskat)abstract
- In observational studies of patients hospitalized for heart failure (HHF), risk of death is highest immediately after discharge and decreases over time. It is unclear whether this population risk trajectory reflects (1) lowering of individual patient mortality risk with increasing time from index hospitalization or (2) temporal changes in population case-mix with earlier postdischarge death for "sicker" patients. Survival rate and longitudinal models were used to estimate temporal changes in postdischarge all-cause mortality risk in 3,993 HHF patients discharged alive in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with, Tolvaptan (EVEREST) trial. After median 'follow-up of 9.9 months, 971 patients died (24.2%). Predicted mortality rate decreased from 15.9 per 100 patient-years immediately after discharge to 13.4 at 30 days and 12.8 at 90 days; mortality rate increased steadily thereafter. Risk variation between quintiles of risk was considerably larger than the temporal variation within risk strata. In a longitudinal model serially reassessing predicted patient mortality risk after each follow-up visit using data collected at these visits, predicted mortality risk increased during the 90 days preceding subsequent heart failure readmission and then followed' a postdischarge trajectory similar to the index admission. In conclusion, although there is transiently elevated individual patient risk in the 90 days before and after discharge, the patient's individual risk profile, rather than temporal change in risk relative to hospitalization, remains the main determinant of mortality. For purposes of reducing all-cause mortality in HF patients, preventative and therapeutic measures may be best implemented as long-term interventions for high mortality risk patients based on serial risk assessments, irrespective of recent hospitalization. (C) 2016 Elsevier Inc. All rights reserved.
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| 24. |
- Crespo-Leiro, Maria G., et al.
(författare)
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European Society of Cardiology Heart Failure Long-Term Registry (ESC-HF-LT): 1-year follow-up outcomes and differences across regions
- 2016
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Ingår i: European Journal of Heart Failure. - : WILEY-BLACKWELL. - 1388-9842 .- 1879-0844. ; 18:6, s. 613-625
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Tidskriftsartikel (refereegranskat)abstract
- AimsThe European Society of Cardiology Heart Failure Long-Term Registry (ESC-HF-LT-R) was set up with the aim of describing the clinical epidemiology and the 1-year outcomes of patients with heart failure (HF) with the added intention of comparing differences between participating countries. Methods and resultsThe ESC-HF-LT-R is a prospective, observational registry contributed to by 211 cardiology centres in 21 European and/or Mediterranean countries, all being member countries of the ESC. Between May 2011 and April 2013 it collected data on 12440 patients, 40.5% of them hospitalized with acute HF (AHF) and 59.5% outpatients with chronic HF (CHF). The all-cause 1-year mortality rate was 23.6% for AHF and 6.4% for CHF. The combined endpoint of mortality or HF hospitalization within 1year had a rate of 36% for AHF and 14.5% for CHF. All-cause mortality rates in the different regions ranged from 21.6% to 36.5% in patients with AHF, and from 6.9% to 15.6% in those with CHF. These differences in mortality between regions are thought reflect differences in the characteristics and/or management of these patients. ConclusionThe ESC-HF-LT-R shows that 1-year all-cause mortality of patients with AHF is still high while the mortality of CHF is lower. This registry provides the opportunity to evaluate the management and outcomes of patients with HF and identify areas for improvement.
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| 25. |
- Holman, Rury R, et al.
(författare)
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Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.
- 2017
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 377:13, s. 1228-1239
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown.METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy.RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups.CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .).
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| 26. |
- Khan, H., et al.
(författare)
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Length of hospital stay and 30-day readmission following heart failure hospitalization: insights from the EVEREST trial
- 2015
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 17:10, s. 1022-31
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Previous reports have provided conflicting data regarding the relationship between length of stay (LOS) and subsequent readmission risk among patients hospitalized for heart failure (HF). METHODS AND RESULTS: We performed a post-hoc analysis of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial to evaluate the differences in LOS overall and between geographic regions (North America, South America, Western Europe, and Eastern Europe) in association with all-cause and cause-specific [HF, cardiovascular (CV) non-HF, and non-CV] readmissions within 30 days of discharge after HF hospitalization. The present analysis included 4020 patients enrolled from 20 countries who were alive at discharge. Median [interquartile range (IQR)] LOS was 8 (4-11) days. The 30-day readmission rates were 15.7% [95% confidence interval (CI) 14.6-16.8] for all-cause; 5.6% (95% CI 4.9-6.3) for HF; 4.4% (95% CI 3.8-5.1) for CV non-HF; and 5.8% (95% CI 5.1-6.6) for non-CV readmissions. There was a positive correlation between LOS and all-cause readmissions (r = 0.09, 95% CI 0.06-0.12). The adjusted odds ratio for the top (>/=14 days) vs. the bottom (
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| 27. |
- Khan, S. S., et al.
(författare)
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Changes in Serum Potassium Levels During Hospitalization in Patients With Worsening Heart Failure and Reduced Ejection Fraction (from the EVEREST Trial)
- 2015
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149. ; 115:6, s. 790-796
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Tidskriftsartikel (refereegranskat)abstract
- Both hyperkalemia and hypokalemia may be related to heart failure (HF) therapy and are associated with adverse outcomes. Abnormalities in serum potassium levels in hospitalized patients with HF and reduced ejection fraction (EF) have not been previously investigated. A post hoc analysis was performed in 1,907 hospitalized patients with worsening HF and reduced EF in the placebo arm of the Efficacy of Vasopressin Antagonism in HF Outcome Study with Tolvaptan (EVEREST) trial. Serum potassium was measured at randomization and at discharge or day 7. The co-primary end points were all-cause mortality (ACM) and cardiovascular mortality or the first HF hospitalization (CVM + HFH). The association between inhospital change in potassium levels and time to outcomes was evaluated using multivariate Cox regression models. Study participants had a mean age of 65.6 +/- 12.0 years and were on optimal guideline-directed medical therapies, including beta blockers (77%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (85%), and aldosterone antagonists (55%). Baseline potassium concentration was 4.3 +/- 0.6 mEq/l, and hyperkalemia or hypokalemia was seen in 6.5% of the participants. On average, serum potassium level increased by 0.21 +/- 0.66 mEq/l, p < 0.0001, during hospitalization. Inhospital potassium change was not associated with either the primary or the secondary end point over a median follow-up of 9.9 months. In conclusion, in patients with reduced EF hospitalized for worsening HF, serum potassium abnormalities are common at baseline (within 48 hours of admission) and potassium levels increase during hospitalization, despite aggressive diuretic therapy. However, they are not associated with all-cause or CVM or HFH. Inhospital changes in potassium may limit the implementation of evidence-based therapies such as mineralocorticoid receptor antagonists. (C) 2015 Elsevier Inc. All rights reserved.
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| 28. |
- Komajda, M, et al.
(författare)
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The chronic ischaemic cardiovascular disease ESC Pilot Registry: Results of the six-month follow-up
- 2018
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Ingår i: European journal of preventive cardiology. - : Oxford University Press (OUP). - 2047-4881 .- 2047-4873. ; 25:4, s. 377-387
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Tidskriftsartikel (refereegranskat)abstract
- Chronic ischaemic cardiovascular disease (CICD) remains a leading cause of morbidity and mortality worldwide. The CICD Pilot Registry enrolled 2420 patients across 10 European Society of Cardiology countries prospectively to describe characteristics, management strategies and clinical outcomes in this setting. We report here the six-month outcomes. Methods and results From the overall population, 2203 patients were analysed at six months. Fifty-eight patients (2.6%) died after inclusion; 522 patients (23.7%) experienced all-cause hospitalisation or death. The rate of prescription of angiotensin-converting enzyme inhibitors, beta-blockers and aspirin was mildly decreased at six months (all P < 0.02). Patients who experienced all-cause hospitalisation or death were older, more often had a history of non-ST-segment elevation myocardial infarction, of chronic kidney disease, peripheral revascularisation and/or chronic obstructive pulmonary disease than those without events. Independent predictors of all-cause mortality/hospitalisation were age (hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.07–1.27) per 10 years, and a history of previous peripheral revascularisation (HR 1.45, 95% CI 1.03–2.03), chronic kidney disease (HR 1.31, 95% CI 1.0–1.68) or chronic obstructive pulmonary disease (HR 1.42, 95% CI 1.06–1.91, all P < 0.05). We observed a higher rate of events in eastern, western and northern countries compared to southern countries and in cohort 1. Conclusion In this contemporary European registry of CICD patients, the rate of severe clinical outcomes at six months was high and was influenced by age, heart rate and comorbidities. The medical management of this condition remains suboptimal, emphasising the need for larger registries with long-term follow-up. Ad-hoc programmes aimed at implementing guidelines adherence and follow-up procedures are necessary, in order to improve quality of care and patient outcomes.
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| 31. |
- Milano, M., et al.
(författare)
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Transmembrane 6 superfamily member 2 gene E167K variant impacts on steatosis and liver damage in chronic hepatitis C patients
- 2015
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Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 62:1, s. 111-117
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Tidskriftsartikel (refereegranskat)abstract
- Steatosis and inherited host factors influence liver damage progression in chronic hepatitis C (CHC). The transmembrane 6 superfamily member 2 (TM6SF2) gene E167K variant increases liver fat and risk of progressive steatohepatitis by interfering with lipoprotein secretion. Our aim was to determine whether the E167K variant affects histological severity of steatosis, necroinflammation, and fibrosis in a cross-sectional cohort of 815 Italian therapy-naive CHC patients. The association with clinically significant fibrosis was replicated in 645 Swiss/German patients. The TM6SF2 E167K variant was genotyped by TaqMan assays, steatosis graded according to the nonalcoholic fatty liver disease activity score, and necroinflammation and fibrosis graded and staged according to Ishak in Italian, and to Metavir in Swiss/German patients. The E167K variant was detected in 69 (9%) Italian patients and was associated with more severe steatosis, independently of confounders (P=0.038). The association between E167K and steatosis severity was present in patients not infected by genotype 3 (G3) HCV (P=0.031), but not in those infected by G3 HCV (P=0.58). Furthermore, the E167K variant was associated with more severe necroinflammation (Ishak grade; adjusted P=0.037) and nearly associated with more severe fibrosis (Ishak stage; adjusted P=0.058). At multivariate logistic regression analysis, the E167K variant was independently associated with histologically probable or definite cirrhosis (Ishak stage S6; odds ratio [OR]: 2.19; 95% confidence interval [CI]: 1.18-3.93; P=0.010). After further conditioning for steatosis and necroinflammation, the E167K variant remained associated with cirrhosis (OR, 3.15; 95% CI: 1.60-5.99; P<0.001). In Swiss/German patients, the E167K variant was independently associated with clinically significant fibrosis Metavir stage F2-F4 (OR, 1.81; 95% CI: 1.12-3.02; P=0.016). Conclusion: TM6SF2 E167K variant impacts on steatosis severity and is associated with liver damage and fibrosis in patients with CHC. (Hepatology 2015;62:111-117)
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| 34. |
- Sharma, M, et al.
(författare)
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Rationale, design, and baseline participant characteristics in the MRI and cognitive substudy of the cardiovascular outcomes for people using anticoagulation strategies trial
- 2019
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Ingår i: International journal of stroke : official journal of the International Stroke Society. - : SAGE Publications. - 1747-4949. ; 14:3, s. 270-281
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Tidskriftsartikel (refereegranskat)abstract
- Covert vascular disease of the brain manifests as infarcts, white matter hyperintensities, and microbleeds on MRI. Their cumulative effect is often a decline in cognition, motor impairment, and psychiatric disorders. Preventive therapies for covert brain ischemia have not been established but represent a huge unmet clinical need. Aims The MRI substudy examines the effects of the antithrombotic regimens in COMPASS on incident covert brain infarcts (the primary outcome), white matter hyperintensities, and cognitive and functional status in a sample of consenting COMPASS participants without contraindications to MRI. Methods COMPASS is a randomized superiority trial testing rivaroxaban 2.5 mg bid plus acetylsalicylic acid 100 mg and rivaroxaban 5 mg bid against acetylsalicylic acid 100 mg per day for the combined endpoint of MI, stroke, and cardiovascular death in individuals with stable coronary artery disease or peripheral artery disease. T1-weighted, T2-weighted, T2*-weighted, and FLAIR images were obtained close to randomization and near the termination of assigned antithrombotic therapy; biomarker and genetic samples at randomization and one month, and cognitive and functional assessment at randomization, after two years and at the end of study. Results Between March 2013 and May 2016, 1905 participants were recruited from 86 centers in 16 countries. Of these participants, 1760 underwent baseline MRI scans that were deemed technically adequate for interpretation. The mean age at entry of participants with interpretable MRI was 71 years and 23.5% were women. Coronary artery disease was present in 90.4% and 28.1% had peripheral artery disease. Brain infarcts were present in 34.8%, 29.3% had cerebral microbleeds, and 93.0% had white matter hyperintensities. The median Montreal Cognitive Assessment score was 26 (interquartile range 23–28). Conclusions The COMPASS MRI substudy will examine the effect of the antithrombotic interventions on MRI-determined covert brain infarcts and cognition. Demonstration of a therapeutic effect of the antithrombotic regimens on brain infarcts would have implications for prevention of cognitive decline and provide insight into the pathogenesis of vascular cognitive decline.
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| 35. |
- Vaduganathan, M, et al.
(författare)
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Sudden Death After Hospitalization for Heart Failure With Reduced Ejection Fraction (from the EVEREST Trial)
- 2018
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Ingår i: Am J Cardiol. - : Elsevier BV. - 1879-1913. ; 122:2, s. 255-260
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Tidskriftsartikel (refereegranskat)abstract
- Patients with chronic heart failure with reduced ejection fraction (HFrEF) benefit from medical and device therapies targeting sudden cardiac death (SCD). Contemporary estimates of SCD risk after hospitalization for heart failure are limited. We describe the incidence, timing, and clinical predictors of SCD after hospitalization for HFrEF (30 baseline covariates (including treatment randomization, demographics, comorbid conditions, natriuretic peptides, ejection fraction, and medical and device therapies) to identify predictors of 1-year SCD. Of the 4,024 trial patients discharged alive (97%), there were 268 who experienced SCD (7%) and 703 who experienced non-SCD (17%) during median follow-up of 9.9 months. Implantable cardioverter defibrillator use at baseline was 14.5%. Estimates of SCD at 1, 3, 6, and 12 months were 0.8%, 2.3%, 4.1%, and 7.4%, respectively. Most patients were readmitted before SCD (n = 147, 55%). Male gender, black race, diabetes mellitus, and angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use were potential predictors of 1-year SCD after hospitalization for HFrEF (all p <0.10); however, this final model demonstrated poor discrimination (C-statistic 0.57). In conclusion, in the EVEREST trial, patients hospitalized for HFrEF faced risks of 1-year postdischarge SCD of 7%, which accrued gradually over time, and were balanced with high competing risks of nonsudden death (17%). Traditional clinical characteristics fail to adequately predict SCD risk. Further data are needed to identify patients at greatest relative risk for SCD (compared with non-SCD) after hospitalization for HFrEF.
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