| 1. |
- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 2. |
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| 3. |
- Müller, T D, et al.
(författare)
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Ghrelin.
- 2015
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Ingår i: Molecular metabolism. - : Elsevier BV. - 2212-8778. ; 4:6, s. 437-60
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Tidskriftsartikel (refereegranskat)abstract
- The gastrointestinal peptide hormone ghrelin was discovered in 1999 as the endogenous ligand of the growth hormone secretagogue receptor. Increasing evidence supports more complicated and nuanced roles for the hormone, which go beyond the regulation of systemic energy metabolism.
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| 4. |
- Anker, A., et al.
(författare)
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Neutrino vertex reconstruction with in-ice radio detectors using surface reflections and implications for the neutrino energy resolution
- 2019
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP PUBLISHING LTD. - 1475-7516. ; :11
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Tidskriftsartikel (refereegranskat)abstract
- Ultra high energy neutrinos (E-nu >10(16.5) eV) are efficiently measured via radio signals following a neutrino interaction in ice. An antenna placed O(15 m) below the ice surface will measure two signals for the vast majority of events (90% at E-nu = 10(18) eV): a direct pulse and a second delayed pulse from a reflection off the ice surface. This allows for a unique identification of neutrinos against backgrounds arriving from above. Furthermore, the time delay between the direct and reflected signal (D'n'R) correlates with the distance to the neutrino interaction vertex, a crucial quantity to determine the neutrino energy. In a simulation study, we derive the relation between time delay and distance and study the corresponding experimental uncertainties in estimating neutrino energies. We find that the resulting contribution to the energy resolution is well below the natural limit set by the unknown inelasticity in the initial neutrino interaction. We present an in-situ measurement that proves the experimental feasibility of this technique. Continuous monitoring of the local snow accumulation in the vicinity of the transmit and receive antennas using this technique provide a precision of O(1mm) in surface elevation, which is much better than that needed to apply the D'n'R technique to neutrinos.
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| 5. |
- Cowie, M. R., et al.
(författare)
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New medicinal products for chronic heart failure: advances in clinical trial design and efficacy assessment
- 2017
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 19:6, s. 718-727
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Tidskriftsartikel (refereegranskat)abstract
- Despite the availability of a number of different classes of therapeutic agents with proven efficacy in heart failure, the clinical course of heart failure patients is characterized by a reduction in life expectancy, a progressive decline in health-related quality of life and functional status, as well as a high risk of hospitalization. New approaches are needed to address the unmet medical needs of this patient population. The European Medicines Agency (EMA) is undertaking a revision of its Guideline on Clinical Investigation of Medicinal Products for the Treatment of Chronic Heart Failure. The draft version of the Guideline was released for public consultation in January 2016. The Cardiovascular Round Table of the European Society of Cardiology (ESC), in partnership with the Heart Failure Association of the ESC, convened a dedicated two-day workshop to discuss three main topic areas of major interest in the field and addressed in this draft EMA guideline: (i) assessment of efficacy (i.e. endpoint selection and statistical analysis); (ii) clinical trial design (i.e. issues pertaining to patient population, optimal medical therapy, run-in period); and (iii) research approaches for testing novel therapeutic principles (i.e. cell therapy). This paper summarizes the key outputs from the workshop, reviews areas of expert consensus, and identifies gaps that require further research or discussion. Collaboration between regulators, industry, clinical trialists, cardiologists, health technology assessment bodies, payers, and patient organizations is critical to address the ongoing challenge of heart failure and to ensure the development and market access of new therapeutics in a scientifically robust, practical and safe way.
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| 6. |
- Anker, A., et al.
(författare)
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Targeting ultra-high energy neutrinos with the ARIANNA experiment
- 2019
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Ingår i: Advances in Space Research. - : Elsevier BV. - 0273-1177 .- 1879-1948. ; 64:12, s. 2595-2609
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Tidskriftsartikel (refereegranskat)abstract
- The measurement of ultra-high energy (UHE) neutrinos (E > 10(16) eV) opens a new field of astronomy with the potential to reveal the sources of ultra-high energy cosmic rays especially if combined with observations in the electromagnetic spectrum and gravitational waves. The ARIANNA pilot detector explores the detection of UHE neutrinos with a surface array of independent radio detector stations in Antarctica which allows for a cost-effective instrumentation of large volumes. Twelve stations are currently operating successfully at the Moore's Bay site (Ross Ice Shelf) in Antarctica and at the South Pole. We will review the current state of ARIANNA and its main results. We report on a newly developed wind generator that successfully operates in the harsh Antarctic conditions and powers the station for a substantial time during the dark winter months. The robust ARIANNA surface architecture, combined with environmentally friendly solar and wind power generators, can be installed at any deep ice location on the planet and operated autonomously. We report on the detector capabilities to determine the neutrino direction by reconstructing the signal arrival direction of a 800 m deep calibration pulser, and the reconstruction of the signal polarization using the more abundant cosmic-ray air showers. Finally, we describe a large-scale design - ARIA - that capitalizes on the successful experience of the ARIANNA operation and is designed sensitive enough to discover the first UHF neutrino.
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| 7. |
- Bhatia, V., et al.
(författare)
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Beta-blocker Use and 30-day All-cause Readmission in Medicare Beneficiaries with Systolic Heart Failure
- 2015
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Ingår i: American Journal of Medicine. - : Elsevier BV. - 0002-9343. ; 128:7, s. 715-721
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Beta-blockers improve outcomes in patients with systolic heart failure. However, it is unknown whether their initial negative inotropic effect may increase 30-day all-cause readmission, a target outcome for Medicare cost reduction and financial penalty for hospitals under the Affordable Care Act. METHODS: Of the 3067 Medicare beneficiaries discharged alive from 106 Alabama hospitals (1998-2001) with a primary discharge diagnosis of heart failure and ejection fraction <45%, 2202 were not previously on beta-blocker therapy, of which 383 received new discharge prescriptions for beta-blockers. Propensity scores for beta-blocker use, estimated for each of the 2202 patients, were used to assemble a matched cohort of 380 pairs of patients receiving and not receiving beta-blockers who were balanced on 36 baseline characteristics (mean age 73 years, mean ejection fraction 27%, 45% women, 33% African American). RESULTS: Beta-blocker use was not associated with 30-day all-cause readmission (hazard ratio [HR] 0.87; 95% confidence interval [CI], 0.64-1.18) or heart failure readmission (HR 0.95; 95% CI, 0.57-1.58), but was significantly associated with lower 30-day all-cause mortality (HR 0.29; 95% CI, 0.12-0.73). During 4-year postdischarge, those in the beta-blocker group had lower mortality (HR 0.81; 95% CI, 0.67-0.98) and combined outcome of all-cause mortality or all-cause readmission (HR 0.87; 95% CI, 0.74-0.97), but not with all-cause readmission (HR 0.89; 95% CI, 0.76-1.04). CONCLUSIONS: Among hospitalized older patients with systolic heart failure, discharge prescription of beta-blockers was associated with lower 30-day all-cause mortality and 4-year combined death or readmission outcomes without higher 30-day readmission. Published by Elsevier Inc.
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| 8. |
- Dent, E., et al.
(författare)
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International Clinical Practice Guidelines for Sarcopenia (ICFSR) : Screening, Diagnosis and Management
- 2018
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Ingår i: The Journal of Nutrition, Health & Aging. - : Springer Science and Business Media LLC. - 1279-7707 .- 1760-4788. ; 22:10, s. 1148-1161
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Sarcopenia, defined as an age-associated loss of skeletal muscle function and muscle mass, occurs in approximately 6 - 22 % of older adults. This paper presents evidence-based clinical practice guidelines for screening, diagnosis and management of sarcopenia from the task force of the International Conference on Sarcopenia and Frailty Research (ICSFR).Methods: To develop the guidelines, we drew upon the best available evidence from two systematic reviews paired with consensus statements by international working groups on sarcopenia. Eight topics were selected for the recommendations: (i) defining sarcopenia; (ii) screening and diagnosis; (iii) physical activity prescription; (iv) protein supplementation; (v) vitamin D supplementation; (vi) anabolic hormone prescription; (vii) medications under development; and (viii) research. The ICSFR task force evaluated the evidence behind each topic including the quality of evidence, the benefit harm balance of treatment, patient preferences/values, and cost-effectiveness. Recommendations were graded as either strong or conditional (weak) as per the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Consensus was achieved via one face-to-face workshop and a modified Delphi process.Recommendations: We make a conditional recommendation for the use of an internationally accepted measurement tool for the diagnosis of sarcopenia including the EWGSOP and FNIH definitions, and advocate for rapid screening using gait speed or the SARC-F. To treat sarcopenia, we strongly recommend the prescription of resistance-based physical activity, and conditionally recommend protein supplementation/a protein-rich diet. No recommendation is given for Vitamin D supplementation or for anabolic hormone prescription. There is a lack of robust evidence to assess the strength of other treatment options.
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| 9. |
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| 10. |
- Seferovic, Petar M., et al.
(författare)
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Clinical practice update on heart failure 2019: pharmacotherapy, procedures, devices and patient management. An expert consensus meeting report of the Heart Failure Association of the European Society of Cardiology
- 2019
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Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 21:10, s. 1169-1186
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Tidskriftsartikel (refereegranskat)abstract
- The European Society of Cardiology (ESC) has published a series of guidelines on heart failure (HF) over the last 25 years, most recently in 2016. Given the amount of new information that has become available since then, the Heart Failure Association (HFA) of the ESC recognized the need to review and summarise recent developments in a consensus document. Here we report from the HFA workshop that was held in January 2019 in Frankfurt, Germany. This expert consensus report is neither a guideline update nor a position statement, but rather a summary and consensus view in the form of consensus recommendations. The report describes how these guidance statements are supported by evidence, it makes some practical comments, and it highlights new research areas and how progress might change the clinical management of HF. We have avoided re-interpretation of information already considered in the 2016 ESC/HFA guidelines. Specific new recommendations have been made based on the evidence from major trials published since 2016, including sodium-glucose co-transporter 2 inhibitors in type 2 diabetes mellitus, MitraClip for functional mitral regurgitation, atrial fibrillation ablation in HF, tafamidis in cardiac transthyretin amyloidosis, rivaroxaban in HF, implantable cardioverter-defibrillators in non-ischaemic HF, and telemedicine for HF. In addition, new trial evidence from smaller trials and updated meta-analyses have given us the chance to provide refined recommendations in selected other areas. Further, new trial evidence is due in many of these areas and others over the next 2 years, in time for the planned 2021 ESC guidelines on the diagnosis and treatment of acute and chronic heart failure.
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