| 1. |
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| 2. |
- Sprigg, N, et al.
(författare)
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Intravenous tranexamic acid for hyperacute primary intracerebral hemorrhage: Protocol for a randomized, placebo-controlled trial
- 2016
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Ingår i: International journal of stroke : official journal of the International Stroke Society. - : SAGE Publications. - 1747-4949. ; 11:6, s. 717-723
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Tidskriftsartikel (refereegranskat)abstract
- Outcome after intracerebral hemorrhage remains poor. Tranexamic acid is easy to administer, readily available, inexpensive, and effective in other hemorrhagic conditions. Aim This randomized trial aims to test the hypothesis that intravenous tranexamic acid given within 8 h of spontaneous intracerebral hemorrhage reduces death or dependency. Design Phase III prospective double-blind randomized placebo-controlled trial. Participants within 8 h of spontaneous intracerebral hemorrhage are randomized to receive either intravenous tranexamic acid 1 g 10 min bolus followed by 1 g 8 h infusion, or placebo. Sample size estimates A trial of 2000 participants (300 from start-up phase and 1700 from main phase) will have 90% power to detect an ordinal shift of the modified Rankin Scale with odds ratio 0.79. Study outcomes The primary outcome is death or dependency measured by ordinal shift analysis of the 7 level mRS at day 90. Secondary outcomes are neurological impairment at day 7 and disability, quality of life, cognition, and mood at day 90. Safety outcomes are death, serious adverse events, thromboembolic events, and seizures. Cost outcomes are length of stay in hospital, readmission, and institutionalization. Discussion This pragmatic trial is assessing efficacy of tranexamic acid after spontaneous intracerebral hemorrhage. Recruitment started in 2013; as of 15th January 2016 1355 participants have been enrolled, from 95 centers in seven countries. Recruitment is due to end in 2017. TICH-2 Trial is registered as ISRCTN93732214.
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| 3. |
- Cannon, J. A., et al.
(författare)
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Clinical outcomes according to QRS duration and morphology in the Eplerenone in Mild Patients: Hospitalization and SurvIval Study in Heart Failure (EMPHASIS-HF)
- 2015
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 17:7, s. 707-716
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Tidskriftsartikel (refereegranskat)abstract
- AimsWe examined the relationship between different degrees of QRS prolongation and different QRS morphologies and clinical outcomes in patients with heart failure, reduced ejection fraction (HF-REF), and mild symptoms in the Eplerenone in Mild Patients Hospitalization and SurvIval Study in Heart Failure trial (EMPHASIS-HF). We also evaluated the effect of eplerenone in these patients according to QRS duration/morphology. Methods and resultsPatients were categorized as: QRS duration (ms) (i) <120 (n = 1375); (ii) 120-149 (n = 517); and (iii) 150 (n = 383), and QRS morphology (i) normal (n = 1252); (ii) left bundle branch block (BBB) (n = 608); and (iii) right BBB/intraventricular conduction defect (IVCD) (n = 415). The outcomes examined were the composite of cardiovascular death or heart failure hospitalization and all-cause mortality. Both abnormal QRS duration and QRS morphology were associated with higher risk, e.g. the rates of the composite outcome were: 10.2, 17.6, and 15.5 per 100 patient-years in the <120, 120-149, and 150ms groups, respectively. Eplerenone reduced the risk of the primary outcome and mortality, compared with placebo, consistently across the QRS duration/morphology subgroups. ConclusionWe found that even moderate prolongation of QRS duration and right BBB/IVCD were associated with a high risk of adverse outcomes in HF-REF. Eplerenone was similarly effective, irrespective of QRS duration/morphology.
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| 4. |
- Carstensen, Anna-Maria, 1982, et al.
(författare)
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Exploring the dynamics of remotely detected fluorescence transients from basil as a potential feedback for lighting control in greenhouses
- 2016
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Ingår i: Acta Horticulturae. - 0567-7572. - 9789462611092 ; 1134, s. 375-383
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Tidskriftsartikel (refereegranskat)abstract
- Optimizing artificial lighting control in industrial scale greenhouses has a potential for increased crop yields, energy savings and production timing. One possible component in controlling greenhouse lighting is continuous and accurate measurement of plant photosynthetic performance. A widely used tool for measuring photosynthetic performance non-invasively is chlorophyll fluorescence. For the purpose of automatic control, remote sensing of fluorescence is favourable, since it provides an aggregated measure for a large canopy area. However, adaptation of traditional fluorescence methodologies to remote sensing is problematic since they are based on the analysis of fluorescence intensities and therefore sensitive to distance and morphology. Other problems with using traditional methods remotely in a greenhouse are a need for dark adaption and use of saturating light. This paper presents a novel concept for the detection of photosynthetic performance based on the dynamics of remotely sensed light induced fluorescence signals. The dynamics of the fluorescence signal is insensitive to distance and morphology and hence provide a good basis for remote detection of photosynthetic performance. Through experiments we have explored how the dynamics of the time-varying fluorescence signal from basil plants was affected by light intensity, light acclimation and light induced stress. This was done by first identifying a dynamic model by transient analysis and then applying frequency analysis on the model. We conclude that the capacity of basil plants to use a certain light intensity was reflected by how fast and how complex the dynamics are. These results show that an identified resonance peak frequency is a potential indicator of plants' ability to adapt to light, which could be a valuable feedback signal for lighting control in greenhouses.
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| 5. |
- Carstensen, Anna-Maria, 1982, et al.
(författare)
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Remote detection of light tolerance in Basil through frequency and transient analysis of light induced fluorescence
- 2016
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Ingår i: Computers and Electronics in Agriculture. - : Elsevier BV. - 0168-1699. ; 127, s. 289-301
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Tidskriftsartikel (refereegranskat)abstract
- © 2016 Elsevier B.V.Artificial lighting control in industrial scale greenhouses has a large potential for increased crop yields, energy savings and timing in greenhouse production. One key component in controlling greenhouse lighting is continuous and accurate measurement of plant performance. This paper presents a novel concept for remote detection of plant performance based on the dynamics of chlorophyll fluorescence (CF) signals induced by a LED-lamp. The dynamic properties of the CF is studied through fitting a linear dynamic model to CF data. The hypothesis is that changes in photochemistry affects the fluorescence dynamics and can therefore be detected as changes in the model parameters and properties. The dynamics was studied in experiments using a sinusoidal varying light intensity (period 60 s) or step changes (step length 300 s). Experiments were performed in a controlled light environment on Basil plants acclimated to different light intensities. It is concluded that the capacity to use a certain light intensity is reflected by how fast and how complex the dynamics are. In particular, the results show that optimal model order is a potential indicator of light tolerance in plants that could be a valuable feedback signal for lighting control in greenhouses.
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| 6. |
- Chin, K. L., et al.
(författare)
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Aspirin does not reduce the clinical benefits of the mineralocorticoid receptor antagonist eplerenone in patients with systolic heart failure and mild symptoms: an analysis of the EMPHASIS-HF study
- 2016
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Ingår i: European journal of heart failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 18:9, s. 1175-1181
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: It is not known whether concomitant use of aspirin might attenuate the beneficial effects of mineralocorticoid receptor antagonists (MRAs). The purpose of this subgroup analysis was to explore the interaction between baseline aspirin treatment and the effect of eplerenone on the primary efficacy outcomes (composite of hospitalization for heart failure or cardiovascular mortality), its components, and safety markers [estimated glomerular filtration rate (eGFR), systolic blood pressure (SBP), and serum potassium >5.5 mmol/L] in the Eplerenone in Mild Patients Hospitalization and SurvIval Study in Heart Failure trial (EMPHASIS-HF). METHODS AND RESULTS: Patients with chronic heart failure, reduced ejection fraction (HFREF), and mild symptoms were enrolled in EMPHASIS-HF. We evaluated baseline characteristics according to aspirin use. We explored the interaction between aspirin and eplerenone, using Cox proportional hazards models providing adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) and P-values for interaction. Of the 2737 patients randomized, 1605 patients (58.6%) were taking aspirin. The beneficial effects of eplerenone on the primary endpoint were similar in patients not treated (adjusted HR 0.59, 95% CI 0.46-0.75) or treated (adjusted HR 0.71, 95% CI 0.59-0.87) with aspirin at baseline (interaction P-value = 0.19). We did not observe any significant modification of the safety markers by aspirin that was clinically meaningful. CONCLUSION: Aspirin use in patients with chronic systolic heart failure and mild symptoms did not substantially reduce the overall beneficial effects of the MRA eplerenone contrary to what has been described in some studies with ACE inhibitors.
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| 7. |
- Chin, K. L., et al.
(författare)
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Impact of eplerenone on major cardiovascular outcomes in patients with systolic heart failure according to baseline heart rate
- 2019
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Ingår i: Clinical Research in Cardiology. - : Springer Science and Business Media LLC. - 1861-0684 .- 1861-0692. ; 108:7, s. 806-814
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIncreased resting heart rate is a risk factor for cardiovascular mortality and morbidity. Mineralocorticoid receptor antagonists (MRAs) have been shown to improve cardiac sympathetic nerve activity, reduce heart rate and attenuate left ventricular remodelling. Whether or not the beneficial effects of MRA are affected by heart rate in heart failure patients with reduced ejection fraction (HFREF) is unclear.MethodsWe undertook a secondary analysis of data from the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure study to assess if clinical outcomes, as well as the efficacy of eplerenone, varied according to heart rate at baseline.ResultsHigh resting heart rate of 80bpm and above predisposed patients to greater risk of all outcomes in the trial, regardless of treatment allocation. The beneficial effects of eplerenone were observed across all categories of heart rate. Eplerenone reduced the risk of primary endpoint, the composite of cardiovascular death and hospitalisation for heart failure, by 30% (aHR 0.70; 95% CI 0.54-0.91) in subjects with heart rate80bpm, and by 48% (aHR 0.52; 95% CI 0.33-0.81) in subjects with heart rate60bpm. Eplerenone also reduced the risks of hospitalisation for heart failure, cardiovascular deaths and all-cause deaths independently of baseline heart rate.ConclusionsBaseline heart rate appears to be an important predictor of major clinical outcome events in patients with HFREF, as has been previously reported. The benefits of eplerenone were preserved across all categories of baseline heart rate, without observed heterogeneity in the responses.
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| 8. |
- Collier, T. J., et al.
(författare)
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The impact of eplerenone at different levels of risk in patients with systolic heart failure and mild symptoms: insight from a novel risk score for prognosis derived from the EMPHASIS-HF trial
- 2013
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 34:36, s. 2823-2829
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Our objective was to create a simple prognostic risk score for patients with systolic heart failure and mild symptoms. We then assessed the efficacy of eplerenone across different categories of risk. METHODS AND RESULTS: The Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure trial (EMPHASIS-HF) was an international randomized trial, comparing eplerenone with placebo in 2737 patients with systolic heart failure and mild symptoms. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure, over a median 2.1 years follow-up. Using multivariable Cox modelling age, sex, systolic blood pressure, estimated glomerular filtration rate, diabetes, BMI, haemoglobin, prior heart failure (HF) hospitalization, prior myocardial infarction/coronary artery bypass surgery (CABG), and heart rate were identified as strong independent risk factors. Estimates from the model were converted into a simple integer risk score which was categorized into three groups of low-, medium-, and high risk. In placebo patients, the rates (per 100 patient-years) for the primary outcome were 7.6, 19.0, and 39.4 in the low-, medium-, and high-risk groups, respectively. On eplerenone, these rates were reduced to 5.6, 12.2, and 24.2, respectively. Eplerenone was beneficial across all risk categories and the hazard ratios were similar. The absolute treatment benefit was greatest among those at highest risk. Similar patterns emerged for all-cause mortality and for all HF hospitalizations. CONCLUSION: This easy-to-use integer risk score should be of value in quantifying individual patient risk in patients with systolic HF and mild symptoms. The relative benefits of eplerenone appeared consistent across the whole spectrum of risk, including those at lower risk.
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| 9. |
- Damman, P., et al.
(författare)
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Effects of age on long-term outcomes after a routine invasive or selective invasive strategy in patients presenting with non-ST segment elevation acute coronary syndromes : A collaborative analysis of individual data from the FRISC II - ICTUS - RITA-3 (FIR) trials
- 2012
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Ingår i: Heart. - : BMJ Publishing Group. - 1355-6037 .- 1468-201X. ; 98:3, s. 207-213
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To perform a patient-pooled analysis of a routine invasive versus a selective invasive strategy in elderly patients with non-ST segment elevation acute coronary syndrome. Methods: A meta-analysis was performed of patientpooled data from the FRISC IIeICTUSeRITA-3 (FIR) studies. (Un)adjusted HRs were calculated by Cox regression, with adjustments for variables associated with age and outcomes. The main outcome was 5-year cardiovascular death or myocardial infarction (MI) following routine invasive versus selective invasive management. Results: Regarding the 5-year composite of cardiovascular death or MI, the routine invasive strategy was associated with a lower hazard in patients aged 65-74 years (HR 0.72, 95% CI 0.58 to 0.90) and those aged ≥75 years (HR 0.71, 95% CI 0.55 to 0.91), but not in those aged less than65 years (HR 1.11, 95% CI 0.90 to 1.38), p=0.001 for interaction between treatment strategy and age. The interaction was driven by an excess of early MIs in patients less than65 years of age; there was no heterogeneity between age groups concerning cardiovascular death. The benefits were smaller for women than for men (p=0.009 for interaction). After adjustment for other clinical risk factors the HRs remained similar. Conclusion: The current analysis of the FIR dataset shows that the long-term benefit of the routine invasive strategy over the selective invasive strategy is attenuated in younger patients aged less than65 years and in women by the increased risk of early events which seem to have no consequences for long-term cardiovascular mortality. No other clinical risk factors were able to identify patients with differential responses to a routine invasive strategy. Trial registration: http://www.controlled-trials.com/ISRCTN82153174 (ICTUS), http://www.controlled-trials.com/ISRCTN07752711 (RITA-3).
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| 10. |
- Garcia-Reitboeck, P., et al.
(författare)
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Human Induced Pluripotent Stem Cell-Derived Microglia-Like Cells Harboring TREM2 Missense Mutations Show Specific Deficits in Phagocytosis
- 2018
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 24:9, s. 2300-2311
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Tidskriftsartikel (refereegranskat)abstract
- Dysfunction of microglia, the brain's immune cells, is linked to neurodegeneration. Homozygous missense mutations in TREM2 cause Nasu-Hakola disease (NHD), an early-onset dementia. To study the consequences of these TREM2 variants, we generated induced pluripotent stem cell-derived microglia-like cells (iPSC-MGLCs) from patients with NHD caused by homozygous T66M or W50C missense mutations. iPSC-MGLCs expressed microglial markers and secreted higher levels of TREM2 than primary macrophages. TREM2 expression and secretion were reduced in variant lines. LPS-mediated cytokine secretion was comparable between control and TREM2 variant iPSC-MGLCs, whereas survival was markedly reduced in cells harboring missense mutations when compared with controls. Furthermore, TREM2 missense mutations caused a marked impairment in the phagocytosis of apoptotic bodies, but not in Escherichia coli or zymosan substrates. Coupled with changes in apoptotic cell-induced cytokine release and migration, these data identify specific deficits in the ability of iPSC-MGLCs harboring TREM2 missense mutations to respond to specific pathogenic signals.
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