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91.
Effects of sildenafil on cardiac structure and function,cardiopulmonary exercise testing and health‐related quality of life measures in heart failure patients with preserved ejection fraction and pulmonary hypertension
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92.
Serelaxin in addition to standard therapy in acute heart failure: rationale and design of the RELAX‐AHF‐2 study
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John R. Teerlink Adriaan A. Voors Piotr Ponikowski Peter S. Pang Barry H. Greenberg Gerasimos Filippatos G. Michael Felker Beth A. Davison Gad Cotter Claudio Gimpelewicz Leandro Boer‐Martins Margaret Wernsing Tsushung A. Hua Thomas Severin Marco Metra 《European journal of heart failure》2017,19(6):800-809
Patients admitted for acute heart failure (AHF) experience high rates of in‐hospital and post‐discharge morbidity and mortality despite current therapies. Serelaxin is recombinant human relaxin‐2, a hormone with vasodilatory and end‐organ protective effects believed to play a central role in the cardiovascular and renal adaptations of human pregnancy. In the phase 3 RELAX‐AHF trial, serelaxin met its primary endpoint of improving dyspnoea through day 5 in patients admitted for AHF. Compared to placebo, serelaxin also reduced worsening heart failure (WHF) by 47% through day 5 and both all‐cause and cardiovascular mortality by 37% through day 180. RELAX‐AHF‐2 ( ClinicalTrials.gov NCT01870778) is designed to confirm serelaxin's effect on these clinical outcomes. RELAX‐AHF‐2 is a multicentre, randomized, double‐blind, placebo‐controlled, event‐driven, phase 3 trial enrolling ~6800 patients hospitalized for AHF with dyspnoea, congestion on chest radiograph, increased natriuretic peptide levels, mild‐to‐moderate renal insufficiency, and systolic blood pressure ≥125 mmHg. Patients are randomized within 16 h of presentation to 48 h intravenous infusions of serelaxin (30 µg/kg/day) or placebo, both in addition to standard of care treatments. The primary objectives are to demonstrate that serelaxin is superior to placebo in reducing: (i) 180 day cardiovascular death, and (ii) occurrence of WHF through day 5. Key secondary endpoints include 180 day all‐cause mortality, composite of 180 day combined cardiovascular mortality or heart failure/renal failure rehospitalization, and in‐hospital length of stay during index AHF. The results from RELAX‐AHF‐2 will provide data on the potential beneficial effect of serelaxin on cardiovascular mortality and WHF in selected patients with AHF. 相似文献
93.
Satit Janwanishstaporn Siting Feng John Teerlink Marco Metra Gad Cotter Beth A. Davison G. Michael Felker Gerasimos Filippatos Peter Pang Piotr Ponikowski Thomas Severin Claudio Gimpelewicz Thomas Holbro Chien Wei Chen Iziah Sama Adriaan A. Voors Barry H. Greenberg 《European journal of heart failure》2020,22(4):726-738
94.
Lisette A.P. Krassenburg Raoel Maan Alnoor Ramji Michael P. Manns Markus Cornberg Heiner Wedemeyer Robert J. de Knegt Bettina E. Hansen Harry L.A. Janssen Robert A. de Man Jordan J. Feld Adriaan J. van der Meer 《Journal of hepatology》2021,74(5):1053-1063
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95.
Traditional and new composite endpoints in heart failure clinical trials: facilitating comprehensive efficacy assessments and improving trial efficiency
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Stefan D. Anker Stefan Schroeder Dan Atar Jeroen J. Bax Claudio Ceconi Martin R. Cowie Adam Crisp Fabienne Dominjon Ian Ford Hossein‐Ardeschir Ghofrani Savion Gropper Gerhard Hindricks Mark A. Hlatky Richard Holcomb Narimon Honarpour J. Wouter Jukema Albert M. Kim Michael Kunz Martin Lefkowitz Chantal Le Floch Ulf Landmesser Theresa A. McDonagh John J. McMurray Bela Merkely Milton Packer Krishna Prasad James Revkin Giuseppe M.C. Rosano Ransi Somaratne Wendy Gattis Stough Adriaan A. Voors Frank Ruschitzka 《European journal of heart failure》2016,18(5):482-489
Composite endpoints are commonly used as the primary measure of efficacy in heart failure clinical trials to assess the overall treatment effect and to increase the efficiency of trials. Clinical trials still must enrol large numbers of patients to accrue a sufficient number of outcome events and have adequate power to draw conclusions about the efficacy and safety of new treatments for heart failure. Additionally, the societal and health system perspectives on heart failure have raised interest in ascertaining the effects of therapy on outcomes such as repeat hospitalization and the patient's burden of disease. Thus, novel methods for using composite endpoints in clinical trials (e.g. clinical status composite endpoints, recurrent event analyses) are being applied in current and planned trials. Endpoints that measure functional status or reflect the patient experience are important but used cautiously because heart failure treatments may improve function yet have adverse effects on mortality. This paper discusses the use of traditional and new composite endpoints, identifies qualities of robust composites, and outlines opportunities for future research. 相似文献
96.
1. DNA repair was measured in 3 Gy gamma-irradiated human peripheral lymphocyte subpopulations by means of nucleoid sedimentation. 2. The influence of aphidicolin (an inhibitor of DNA polymerase) on the repair process was investigated. 3. Repair of 40-44% of the DNA lesions induced by gamma-irradiation was blocked by aphidicolin. 4. Enriched B- and T-lymphocyte fractions were affected by aphidicolin to the same extent. 相似文献
97.
Aim
To validate plant species for hypoglycaemic activity.Materials and methods
Four plants were investigated for hypoglycaemic activity by evaluating inhibiting effects on carbohydrate-hydrolising enzymes: α-glucosidase and α-amylase. Acetone plant extracts were screened against C2C12 myocytes, 3T3-L1 preadipocytes and Chang liver cells by measuring glucose uptake. Cytotoxicity was done in preadipocytes and hepatocytes.Results
Extract of Euclea undulata rootbark exhibited highest activity, displaying a glucose uptake of 162.2% by Chang liver cells at 50 μg/ml. An inhibition concentration of 50% for Euclea undulata was found to be 49.95 μg/ml for α-glucosidase and 2.8 μg/ml for α-amylase. No cytotoxicity was recorded for Euclea undulata, while Schkuhria pinnata and Elaeodendron transvaalense exhibited cytotoxicity at 12.5 μg/ml. α-Glucosidase and α-amylase assays showed inhibitory activity on enzymes for three plant extracts.Conclusion
Euclea undulata, Schkuhria pinnata and Elaeodendron transvaalense showed in vitro hypoglycaemic activity. Schkuhria pinnata and Elaeodendron transvaalense indicated cytotoxicity on 3T3-L1 preadipocytes and Chang liver cells. Euclea undulata, Pteronia divaricata and Elaeodendron transvaalense inhibited α-glucosidase and α-amylase enzymes.Ethnopharmacological relevance
Screening of plant extracts scientifically validated traditional use of Euclea undulata for treatment of diabetes. Cytotoxicity results revealed that acetone extracts of Schkuhria pinnata and Elaeodendron transvaalense are toxic and raise concern for chronic use. 相似文献98.
99.
van Dongen H de Kroon CD van den Tillaart SA Louwé LA Trimbos-Kemper GC Jansen FW 《BJOG : an international journal of obstetrics and gynaecology》2008,115(10):1232-1237
Objective The purpose of this study was to compare patient discomfort during saline infusion sonography (SIS) and office hysteroscopy performed according to a vaginoscopic approach.
Design Randomised controlled trial.
Setting University hospital.
Population Women with an indication for further investigation of the uterine cavity.
Methods A total of 100 women randomly allocated to either SIS or vaginoscopic office hysteroscopy in an outpatient clinic.
Main outcome measures Scores on a visual analogue scale (VAS) for pain and a present pain intensity (PPI) scale, conclusiveness and success rate.
Results The patients' pain scores on both the VAS and the PPI were lower for SIS when compared with office hysteroscopy ( P < 0.05). However, in cases of severe pain (VAS > 7 or PPI > 2), there was no statistically significant difference between both groups. The success rate, defined as adequate inspection of the cervical canal and uterine cavity, was 94% for SIS compared with 92% for office hysteroscopy ( P = 0.633). SIS, multiparity, shorter procedure time and position of the uterus in anteversion decreased pain scores among women studied.
Conclusions Both SIS and office hysteroscopy are successful procedures and well tolerated by women. SIS induces significantly less discomfort than office hysteroscopy and should therefore be considered the method of choice. 相似文献
Design Randomised controlled trial.
Setting University hospital.
Population Women with an indication for further investigation of the uterine cavity.
Methods A total of 100 women randomly allocated to either SIS or vaginoscopic office hysteroscopy in an outpatient clinic.
Main outcome measures Scores on a visual analogue scale (VAS) for pain and a present pain intensity (PPI) scale, conclusiveness and success rate.
Results The patients' pain scores on both the VAS and the PPI were lower for SIS when compared with office hysteroscopy ( P < 0.05). However, in cases of severe pain (VAS > 7 or PPI > 2), there was no statistically significant difference between both groups. The success rate, defined as adequate inspection of the cervical canal and uterine cavity, was 94% for SIS compared with 92% for office hysteroscopy ( P = 0.633). SIS, multiparity, shorter procedure time and position of the uterus in anteversion decreased pain scores among women studied.
Conclusions Both SIS and office hysteroscopy are successful procedures and well tolerated by women. SIS induces significantly less discomfort than office hysteroscopy and should therefore be considered the method of choice. 相似文献
100.
Rooibos (Aspalathus linearis (Brum.f) Dahlg.) and honeybush (Cyclopia Vent. species) are popular indigenous South African herbal teas enjoyed for their taste and aroma. Traditional medicinal uses of rooibos in South Africa include alleviation of infantile colic, allergies, asthma and dermatological problems, while a decoction of honeybush was used as a restorative and as an expectorant in chronic catarrh and pulmonary tuberculosis. Traditional medicinal uses of Athrixia phylicoides DC., or bush tea, another indigenous South African plant with very limited localised use as herbal tea, include treatment of boils, acne, infected wounds and infected throats. Currently rooibos and honeybush are produced for the herbal tea market, while bush tea has potential for commercialisation. A summary of the historical and modern uses, botany, distribution, industry and chemical composition of these herbal teas is presented. A comprehensive discussion of in vitro, ex vivo and in vivo biological properties, required to expand their applications as nutraceutical and cosmeceutical products, is included, with the main emphasis on rooibos. Future research needs include more comprehensive chemical characterisation of extracts, identification of marker compounds for extract standardisation and quality control, bioavailability and identification of bio-markers of dietary exposure, investigation of possible herb-drug interactions and plant improvement with regards to composition and bioactivity. 相似文献