The antianginal efficacy and tolerability of controlled-release metoprolol once daily

DEFF Research Database (Denmark)

Egstrup, K; Gundersen, T; Härkönen, R

1988-01-01

In a randomized, double-blind, cross-over study treatment with a new controlled-release (CR) preparation of metoprolol, given once daily, was compared with treatment with conventional metoprolol tablets, given twice daily, in 115 patients with stable effort angina pectoris. The patients were...... questionnaire. When all patients were analysed together there were no differences in antianginal efficacy between the two treatment regimens. However, when the group taking 200 mg daily was analysed separately better exercise tolerance was found during metoprolol CR therapy, as measured by onset of chest pain...... and ST-segment change, compared with conventional metoprolol therapy. The two formulations were well tolerated. When given once daily in a total daily dose of 100 mg, the CR preparation induced less adverse effects than the conventional tablets, 50 mg twice daily. It was concluded that the new metoprolol...

Evaluation the Metoprolol Effects in Controlled Hypotension and Reduction of Bleeding During Head and Neck Surgery

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P Rahimzadeh

2012-05-01

Full Text Available

Background and objectives

Intraoperative bleeding, which reduces visibility in the operative field, is one of the major problems of head and neck surgeries. Improvement of intraoperative visibility and reduction of bleeding is an important task for an anesthetist during head and neck surgery. It has been shown that preoperative beta-blockade decreases bleeding during the operation.

Methods

In a 18 month period,88 patients , who were candidate for nasal procedures in hazrat Rasul medical complex, were selected in a randomized open clinical trial study. They were divided to 4 groupes:

50 mg metoprolol at night before surgery

50 mg metoprolol in the morning of the surgery

50 mg metoprolol at night before surgery and in the morning of the surgery

placebo

Heart rate, Systolic and diastolic blood pressure was measured in a non-invasive way just both upon arrival on the operation bed and after induction of anesthesia during operation. For evaluation of the visibility of the operative field during operation the quality scale proposed by Fromm and Boezzart was used.

Results

SPSS13 was used for assessment. There was significant relationship between metoprolol administration and bleeding during the operation. All patients who received two doses of metoprolol one in the last night and another in the morning of the operation day had only mild bleeding. There was statistically significant relation between agitation and time of administration of metoprolol.

Conclution

Nowadays, there are growing evidences that not only decrease in systolic blood pressure but also a low heart rate (< 60 beats per minute can minimize surgical bleeding. Both of the above mentioned effects could be induced by beta blockers.

In this study, two

Placebo-controlled comparison of captopril, metoprolol, and hydrochlorothiazide therapy in non-insulin-dependent diabetic patients with primary hypertension

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Gall, M A; Rossing, P; Skøtt, P

1992-01-01

The antihypertensive effect of captopril, metoprolol, and hydrochlorothiazide was compared in 23 non-insulin-dependent (NIDDM) diabetic patients less than or equal to 75 years of age, with borderline to moderate primary hypertension. In a double blind, placebo-controlled cross-over trial...

TREATMENT OF CHRONIC HEART FAILURE: FOCUS ON METOPROLOL SUCCINATE

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O. D. Ostroumova

2012-01-01

Full Text Available Advantages of metoprolol succinate in patients with chronic heart failure (CHF are covered. Results of MERIT-HF study are taken as the main evidences. Patterns of the metoprolol succinate use in the treatment of different categories of patients with CHF (women, the elderly , severe CHF forms, CHF with concomitant hypertension or diabetes are considered.

TREATMENT OF CHRONIC HEART FAILURE: FOCUS ON METOPROLOL SUCCINATE

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O. D. Ostroumova

2015-12-01

Full Text Available Advantages of metoprolol succinate in patients with chronic heart failure (CHF are covered. Results of MERIT-HF study are taken as the main evidences. Patterns of the metoprolol succinate use in the treatment of different categories of patients with CHF (women, the elderly , severe CHF forms, CHF with concomitant hypertension or diabetes are considered.

Osteogenic actions of metoprolol in an ovariectomized rat model of menopause.

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Zang, Yuan; Tan, Quanchang; Ma, Xiangyu; Zhao, Xiong; Lei, Wei

2016-09-01

Osteoporosis and hypertension are age-related chronic diseases with increased morbidity rates among postmenopausal women. Clinical epidemiological investigations have demonstrated that hypertensive patients treated with β1-selective β-blockers have a higher bone mineral density (BMD) and lower fracture risk. Nevertheless, no fundamental studies have examined the relationships between β1-selective β-blockers and these effects. The present study explored the effects and mechanisms of metoprolol in the in vitro treatment of osteoblasts and the in vivo treatment of ovariectomy-induced osteoporosis in rats. Primary osteoblasts were obtained by digestion of the cranial bones of 24-hour-old Sprague-Dawley rats. After metoprolol treatment, cell proliferation and differentiation capacities were assessed at the corresponding time points. In addition, 3-month-old female Sprague-Dawley rats (200-220 g) were divided into a sham-operated group (n = 8) and three ovariectomized (OVX) (bilateral removal of ovaries) groups as follows: vehicle (OVX; n = 8), low-dose metoprolol (L-M, oral, 120 mg/kg/d; n = 8), and high-dose metoprolol (H-M, oral, 240 mg/kg/d; n = 8). After 12 weeks of metoprolol treatment, BMD, microarchitecture, and biomechanical properties were evaluated. The results indicated that the treatments with 0.01 to 0.1 μM metoprolol increased osteoblast proliferation, alkaline phosphatase activity, and calcium mineralization, and promoted the expression of osteogenic genes. The in vivo study indicated that administration of metoprolol to OVX rats resulted in maintenance of the BMDs of the L4 vertebrae. Moreover, amelioration of trabecular microarchitecture deterioration and preservation of bone biomechanical properties were detected in the trabecular bones of the OVX rats. Our findings indicate that metoprolol prevents estrogen deficiency-induced bone loss by increasing the number and enhancing the biological functions of osteoblasts, implying

Effects of Metoprolol and Nebivolol on Exercise Blood Pressure in Patients with Mild Hypertension

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Huseyin Ugur Yazici

2013-01-01

Full Text Available Objectives. We planned to compare the impact of two beta blockers, metoprolol and nebivolol, on arterial blood pressure during exercise in patients with mild hypertension. Methods. A total of 60 patients (13 males, 47 females; mean age: years were enrolled in the present study. The patients were randomly selected to receive either nebivolol 5 mg/day ( or metoprolol 50 mg/day ( for 8 weeks. At the end of the 8th week, each of the patients received exercise stress test according to Bruce protocol and their blood pressures were remeasured after rest, exercise, and recovery. Results. Blood pressures were determined to be similar between metoprolol and nebivolol groups during rest, exercise, and recovery periods. Metoprolol and nebivolol achieved similar reductions in blood pressures during rest and exercise. However, five patients in nebivolol group and four patients in metoprolol group developed exaggerated BP response to exercise but the difference between metoprolol and nebivolol was not meaningful (. Conclusion. The results of the present study showed that metoprolol and nebivolol established comparable effects on the control of blood pressures during exercise in the patients with mild hypertensions.

Rediscovering Chirality - Role of S-Metoprolol in Cardiovascular Disease Management.

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Mohan, Jagdish C; Shah, Siddharth N; Chinchansurkar, Sunny; Dey, Arindam; Jain, Rishi

2017-06-01

The process of drug discovery and development today encompass a myriad of paths for bringing a new therapeutic molecule that has minimal adverse effects and of optimal use to the patient. Chirality was proposed in the direction of providing a purer and safer form of drug [Ex- cetrizine and levocetrizine]. Decades have passed since the introduction of this concept and numerous chiral molecules are in existence in therapeutics, yet somehow this concept has been ignored. This review aims to rediscover the ignored facts about chirality, its benefits and clear some common myths considering the example of S-Metoprolol in the management of Hypertension and other cardiovascular diseases. Relevant articles from Pubmed, Embase, Medline and Google Scholar were searched using the terms "Chiral", "Chirality", "Enantiomers", "Isomers", "Isomerism", "Stereo-chemistry", and "S-Metoprolol". Out of 103 articles found 17 articles mentioning in general about the concept of chirality and articles on study of S-metoprolol in various cardiovascular diseases were then reviewed. Many articles mention about the importance of chirality yet the concept has not been highlighted much. Clear benefits with chiral molecules have been documented for various drug molecules few amongst them being anaesthetics, antihypertensives, antidepressants. Benefits of S-metoprolol over racemate are also clear in terms of responder rates, dose of administration and adverse effects profile in various cardiovascular diseases. Chirality is a good way forward in providing a new drug molecule which is safe with lesser pharmacokinetic and pharmacodynamics variability, lesser side effects and more potent action. S-metoprolol is chirally pure form of racemate metoprolol and has lesser side effects, is safer in patients of COPD and Diabetes who also have hypertension and comparable responder rates at half the doses when compared to racemate.

Development of Lecithin Nanoemulsion Based Organogels for Permeation Enhancement of Metoprolol through Rat Skin

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J. Varshosaz

2013-01-01

Full Text Available Background. Drugs with low oral bioavailability due to the first pass metabolism are good candidates for transdermal delivery. Objectives. The aim of this work was preparation of transdermal nanoemulsion of metoprolol which has high first pass metabolism. Methods. Three commercially available types of lecithin (200, 100p, and 170, three short chain alcohol (n-butanol, isopropyl alcohol, and n-propanol, and isopropyl myristate (IPM were used as surfactant, cosurfactant, and oil phase, respectively. The aqueous phase was composed of metoprolol tartrate. Nanoemulsions with different surfactant/cosurfactant weight ratio, various amounts of drug, and different types of alcohol were prepared, and their phase diagrams were studied. Drug release, permeability, and diffusion coefficient of the drug were studied using hairless rat skin. Results. A significant increase in drug solution rate was observed with increasing the metoprolol content in the nanoemulsions, while it decreased when lecithin concentration increased from 40% to 60%. Increasing the water content resulted in a significant increase in metoprolol release. N-butanol enhanced the drug flux from nanoemulsions more than n-propanol and isopropyl alcohol. The o/w nanoemulsions of metoprolol showed high flux and permeability through the skin. Conclusion. Both w/o and o/w nanoemulsions of metoprolol could enhance permeation and diffusion of metoprolol through rat skin.

EFFECTS OF AMLODIPINE, FOSINOPRIL AND METOPROLOL ON HEMODYNAMICS IN HYPERTENSIVE PATIENTS

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A. L. Hohlov

2007-01-01

Full Text Available Aim. To assess an efficacy of antihypertensive therapy with calcium antagonist, angiotensin converting enzyme inhibitor and β-blocker in patients with arterial hypertension (AH taking into account influence on central and peripheral hemodynamics.Material and methods. 60 patients with AH of I-II stage, 1-2 grade were studied. They were split in 3 groups. Patients of the first group received amlodipine (Tenox, 5-10 mg/d, the second group – fosinopril (Monopril, 10-20 mg/d and the third group – metoprolol (Metocard, 50-200 mg/d.Diuretics were added when necessary. Ambulatory blood pressure (BP monitoring, echocardiography, ultrasound investigation of brachiocephalic and main cerebral arteries, test on reactive hyperemia and nitroglycerine were conducted before and after 6 months of therapy.Results. Amlodipine, fosinopril and metoprolol had similar antihypertensive effect. Amlodipine was more effective in comparison with fosinopril and metoprolol in reduction of left ventricular (LV myocardial mass and improving of LV diastolic function. Amlodipine and fosinopril had positive effect on vascular remodeling. Metoprolol reduced in BP morning elevation and heart rate, but had no effect on systolic BP variability.Conclusion. Amlodipine, fosinopril and metoprolol have similar antihypertensive effect but different influence on the heart, arteries, BP variability and hemodinamics.

Hemodynamic effects of metoprolol and nifedipine in angina pectoris measured by isotope technique

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Bostroem, P.A.

1988-01-01

In order to evaluate the therapeutic effects of metoprolol, nifedipine, and their combination, 11 patients with secondary angina pectoris and with thallium tomographic findings indicating coronary artery disease were studied before and after these three treatment regimes in a single-blind cross-over study. The therapeutic effect was measured by standardized working test and isotope angiocardiography, which enabled evaluation of left ventricular ejection fraction, stroke volume, and phase analysis of left ventricular contraction. Treatment with metoprolol and combination therapy increased work performance. Ejection fraction did not differentiate the treatment regimes, whereas stroke volume was significantly lower at work and heart rate higher at rest and at work during nifedipine treatment compared to either metoprolol or combination treatment (p less than 0.05). Cardiac output was significantly reduced during nifedipine and metoprolol treatment during work (p less than 0.05). Phase improved after all therapeutic regimes, but reached significance only during the metoprolol treatment period at rest (p less than 0.05).

Preparation of Biological Samples Containing Metoprolol and Bisoprolol for Applying Methods for Quantitative Analysis

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Corina Mahu Ştefania

2015-12-01

Full Text Available Arterial hypertension is a complex disease with many serious complications, representing a leading cause of mortality. Selective beta-blockers such as metoprolol and bisoprolol are frequently used in the management of hypertension. Numerous analytical methods have been developed for the determination of these substances in biological fluids, such as liquid chromatography coupled with mass spectrometry, gas chromatography coupled with mass spectrometry, high performance liquid chromatography. Due to the complex composition of biological fluids a biological sample pre-treatment before the use of the method for quantitative determination is required in order to remove proteins and potential interferences. The most commonly used methods for processing biological samples containing metoprolol and bisoprolol were identified through a thorough literature search using PubMed, ScienceDirect, and Willey Journals databases. Articles published between years 2005-2015 were reviewed. Protein precipitation, liquid-liquid extraction and solid phase extraction are the main techniques for the extraction of these drugs from plasma, serum, whole blood and urine samples. In addition, numerous other techniques have been developed for the preparation of biological samples, such as dispersive liquid-liquid microextraction, carrier-mediated liquid phase microextraction, hollow fiber-protected liquid phase microextraction, on-line molecularly imprinted solid phase extraction. The analysis of metoprolol and bisoprolol in human plasma, urine and other biological fluids provides important information in clinical and toxicological trials, thus requiring the application of appropriate extraction techniques for the detection of these antihypertensive substances at nanogram and picogram levels.

Efeitos do tartarato de metoprolol em pacientes portadores de insuficiência cardíaca Effects of metoprolol tartrate therapy in patients with heart failure

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José Albuquerque de Figueiredo Neto

2006-09-01

Full Text Available OBJETIVO: Estudar os efeitos do tartarato de metoprolol em pacientes portadores de insuficiência cardíaca. MÉTODOS: Foram avaliados em estudo prospectivo, 50 pacientes (36 homens com insuficiência cardíaca, classe funcional II a IV, com 52±14,8 anos, e fração de ejeção do ventrículo esquerdo (FEVE 0,05. A freqüência cardíaca apresentou redução de 78,84±batimentos por minuto para 67,48±1,86 batimentos por minuto (pOBJECTIVE: To study the effects of metoprolol tartrate therapy in patients with heart failure. METHODS: Fifty patients (36 males aged 52±14.8 yrs, with functional class II to IV heart failure (HF and left ventricular ejection fraction (LVFE 0.05. Cardiac frequency decreased from 78.84±1.68 to 67.48±1.86 b.p.m. (p<0.001. CONCLUSION: The adding of metoprolol tartrate to the usual heart failure therapy is followed by an increase of ejection fraction, functional class improvement, and decrease of ventricular diameters and cardiac frequency. These results suggest anti-remodeling effects in patients with HF who utilize metoprolol tartrate in addition to the usual therapy.

Interaction of Palmitic Acid with Metoprolol Succinate at the Binding Sites of Bovine Serum Albumin

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Mashiur Rahman

2014-12-01

Full Text Available Purpose: The aim of this study was to characterize the binding profile as well as to notify the interaction of palmitic acid with metoprolol succinate at its binding site on albumin. Methods: The binding of metoprolol succinate to bovine serum albumin (BSA was studied by equilibrium dialysis method (ED at 27°C and pH 7.4, in order to have an insight in the binding chemistry of the drug to BSA in presence and absence of palmitic acid. The study was carried out using ranitidine as site-1 and diazepam as site-2 specific probe. Results: Different analysis of binding of metoprolol succinate to bovine serum albumin suggested two sets of association constants: high affinity association constant (k1 = 11.0 x 105 M-1 with low capacity (n1 = 2 and low affinity association (k2 = 4.0×105 M-1 constant with high capacity (n2 = 8 at pH 7.4 and 27°C. During concurrent administration of palmitic acid and metoprolol succinate in presence or absence of ranitidine or diazepam, it was found that palmitic acid displaced metoprolol succinate from its binding site on BSA resulting reduced binding of metoprolol succinate to BSA. The increment in free fraction of metoprolol succinate was from 26.27% to 55.08% upon the addition of increased concentration of palmitic acid at a concentration of 0×10-5 M to 16×10-5 M. In presence of ranitidine and diazepam, palmitic acid further increases the free fraction of metoprolol succinate from 33.05% to 66.95% and 40.68% to 72.88%, respectively. Conclusion: This data provided the evidence of interaction at higher concentration of palmitic acid at the binding sites on BSA, which might change the pharmacokinetic properties of metoprolol succinate.

Metoprolol and propranolol in essential tremor: a double-blind, controlled study.

Science.gov (United States)

Calzetti, S; Findley, L J; Gresty, M A; Perucca, E; Richens, A

1981-01-01

Single oral doses of propranolol (120 mg), metoprolol (150 mg) and placebo were given in a randomised, double-blind fashion to 23 patients with essential tremor. Both beta blockers were significantly more effective than placebo in reducing the magnitude of tremor. The decrease in tremor produced by metoprolol (47, sem 9%, n = 23) was not significantly different from that observed propranolol (55, sem 5%, n = 23). Tachycardia on standing was antagonised by both drugs to a similar extent. These findings suggest that metoprolol may represent a valuable alternative to propranolol in the treatment of essential tremor. The data is consistent with the hypothesis that the tremorolytic effect of beta blockers in these patients may be unrelated to peripheral beta-2 adreno-receptor blockade, being possibly mediated by other central or peripheral modes of action of these drugs. However, it cannot be excluded that at the dose used, metoprolol had lost its relative cardio-selectivity and that the reduction in tremor was mediated by competitive antagonism at beta-2 receptor sites in skeletal muscle. PMID:7031187

Metoprolol succinate extended release/hydrochlorothiazide combination tablets

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James W Hainer

2007-07-01

Full Text Available James W Hainer, Jennifer SuggAstraZeneca LP, Wilmington, DE, USAAbstract: Lowering elevated blood pressure (BP with drug therapy reduces the risk for catastrophic fatal and nonfatal cardiovascular events such as stroke and myocardial infarction. Given the heterogeneity of hypertension as a disease, the marked variability in an individual patient’s BP response, and low response rates with monotherapy, expert groups such as the Joint National Committee (JNC emphasize the value of combination antihypertensive regimens, noting that combinations, usually of different classes, have additive antihypertensive effects. Metoprolol succinate extended-release tablet is a beta-1 (cardio-selective adrenoceptor-blocking agent formulated to provide controlled and predictable release of metoprolol. Hydrochlorothiazide (HCT is a well-established diuretic and antihypertensive agent, which promotes natruresis by acting on the distal renal tubule. The pharmacokinetics, efficacy, and safety/tolerability of the antihypertensive combination tablet, metoprolol extended release hydrochlorothiazide, essentially reflect the well-described independent characteristics of each of the component agents. Not only is the combination product more effective than monotherapy with the individual components but the combination product allows a low-dose multidrug regimen as an alternative to high-dose monotherapy, thereby, minimizing the likelihood of dose-related side-effects.Keywords: antihypertensive, blood pressure, cardiovascular disease, combination product

Endothelial function is unaffected by changing between carvedilol and metoprolol in patients with heart failure--a randomized study

DEFF Research Database (Denmark)

Falskov, Britt; Hermann, Thomas Steffen; Raunsø, Jakob

2011-01-01

endothelial function, 24 hour ambulatory blood pressure and heart rate during treatment with carvedilol, metoprolol tartrate and metoprolol succinate in patients with HF. METHODS: Twenty-seven patients with mild HF, all initially treated with carvedilol, were randomized to a two-month treatment...... with carvedilol, metoprolol tartrate or metoprolol succinate. Venous occlusion plethysmography, 24-hour blood pressure and heart rate measurements were done before and after a two-month treatment period. RESULTS: Endothelium-dependent vasodilatation was not affected by changing from carvedilol to either...... metoprolol tartrate or metoprolol succinate. The relative forearm blood flow at the highest dose of serotonin was 2.42 ± 0.33 in the carvedilol group at baseline and 2.14 ± 0.24 after two months continuation of carvedilol (P = 0.34); 2.57 ± 0.33 before metoprolol tartrate treatment and 2.42 ± 0.55 after...

UV-C radiation based methods for aqueous metoprolol elimination

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Rivas, F.J., E-mail: fjrivas@unex.es [Departamento de Ingenieria Quimica y Quimica Fisica, Universidad de Extremadura, Facultad de Ciencias, Edificio Jose Luis Sotelo, Avenida de Elvas S/N, 06071 Badajoz (Spain); Gimeno, O.; Borralho, T.; Carbajo, M. [Departamento de Ingenieria Quimica y Quimica Fisica, Universidad de Extremadura, Facultad de Ciencias, Edificio Jose Luis Sotelo, Avenida de Elvas S/N, 06071 Badajoz (Spain)

2010-07-15

The endocrine disruptor metoprolol has been oxidised in aqueous solution by means of the systems UV-C, UV-C/H{sub 2}O{sub 2}, UV-C/percarbonate, UV-C/monopersulfate, UV-C/TiO{sub 2}, UV-C/H{sub 2}O{sub 2}/TiO{sub 2} and photo-Fenton. From simple photolysis experiments the quantum yield of metoprolol has been calculated (roughly 5 x 10{sup -3} mol Einstein{sup -1} at circumneutral pH). Addition of free radicals promoters significantly enhanced the metoprolol depletion rate. Mineralization degree was negligible when no promoter was added, while low values were achieved in the presence of either inorganic peroxides or titanium dioxide. The combination of radiation, hydrogen peroxide and TiO{sub 2} increased the mineralization level up to values in the proximity of 45-50% under the best conditions investigated. The photo-Fenton process was the best system in terms of total oxidation (mineralization degree 70%) when optimum conditions were applied.

UV-C radiation based methods for aqueous metoprolol elimination

International Nuclear Information System (INIS)

Rivas, F.J.; Gimeno, O.; Borralho, T.; Carbajo, M.

2010-01-01

The endocrine disruptor metoprolol has been oxidised in aqueous solution by means of the systems UV-C, UV-C/H 2 O 2 , UV-C/percarbonate, UV-C/monopersulfate, UV-C/TiO 2 , UV-C/H 2 O 2 /TiO 2 and photo-Fenton. From simple photolysis experiments the quantum yield of metoprolol has been calculated (roughly 5 x 10 -3 mol Einstein -1 at circumneutral pH). Addition of free radicals promoters significantly enhanced the metoprolol depletion rate. Mineralization degree was negligible when no promoter was added, while low values were achieved in the presence of either inorganic peroxides or titanium dioxide. The combination of radiation, hydrogen peroxide and TiO 2 increased the mineralization level up to values in the proximity of 45-50% under the best conditions investigated. The photo-Fenton process was the best system in terms of total oxidation (mineralization degree 70%) when optimum conditions were applied.

Combined milrinone and enteral metoprolol therapy in patients with septic myocardial depression

Science.gov (United States)

Schmittinger, Christian A; Dünser, Martin W; Haller, Maria; Ulmer, Hanno; Luckner, Günter; Torgersen, Christian; Jochberger, Stefan; Hasibeder, Walter R

2008-01-01

Introduction The multifactorial etiology of septic cardiomyopathy is not fully elucidated. Recently, high catecholamine levels have been suggested to contribute to impaired myocardial function. Methods This retrospective analysis summarizes our preliminary clinical experience with the combined use of milrinone and enteral metoprolol therapy in 40 patients with septic shock and cardiac depression. Patients with other causes of shock or cardiac failure, patients with beta-blocker therapy initiated more than 48 hours after shock onset, and patients with pre-existent decompensated congestive heart failure were excluded. In all study patients, beta blockers were initiated only after stabilization of cardiovascular function (17.7 ± 15.5 hours after shock onset or intensive care unit admission) in order to decrease the heart rate to less than 95 beats per minute (bpm). Hemodynamic data and laboratory parameters were extracted from medical charts and documented before and 6, 12, 24, 48, 72, and 96 hours after the first metoprolol dosage. Adverse cardiovascular events were documented. Descriptive statistical methods and a linear mixed-effects model were used for statistical analysis. Results Heart rate control (65 to 95 bpm) was achieved in 97.5% of patients (n = 39) within 12.2 ± 12.4 hours. Heart rate, central venous pressure, and norepinephrine, arginine vasopressin, and milrinone dosages decreased (all P milrinone dosages were increased in nine (22.5%) and six (15%) patients, respectively. pH increased (P < 0.001) whereas arterial lactate (P < 0.001), serum C-reactive protein (P = 0.001), and creatinine (P = 0.02) levels decreased during the observation period. Twenty-eight-day mortality was 33%. Conclusion Low doses of enteral metoprolol in combination with phosphodiesterase inhibitors are feasible in patients with septic shock and cardiac depression but no overt heart failure. Future prospective controlled trials on the use of beta blockers for septic cardiomyopathy

Perbandingan Pemberian Metoprolol Tartrat dengan Lidokain secara Intravena terhadap Perubahan Tekanan Darah dan Laju Nadi Akibat Tindakan Laringoskopi dan Intubasi

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Yovita Koswara

2014-08-01

Full Text Available Laryngoscopy and endotracheal intubation associated with a sudden rise in blood pressure and pulse rate due to stimulation of sympathetic activity. The aim of this study was to compare effectiveness of metoprolol 5 mg intavenously and lidocaine 1.5 mg/kgBW to attenuate hemodynamic response evoked by laryngoscopy and intubation. This was an experimental randomized double blind controlled trial study was conducted in 40 patients with American Society of Anesthesiologist (ASA physical status I or II who will have surgery with general anesthesia techniques in Hasan Sadikin Hospital Bandung from July−August 2013. Subjects were divided into two groups wich received metoprolol 5 mg intravenously or lidocaine 1.5 mg/kgBW 3 minutes before laryngoscopy and intubation. All data were analysed using t-test, with p value < 0.05 considered significant. Statistical analysis showed that on second and third minutes after intubation and laryngoscopy showed a significant differences on hemodynamic parameter between two groups with p value <0.05. The conclusions of this study are intravenous 5 mg of metoprolol found to be better than lidocaine 1.5 mg/kgBW to attenuate hemodynamic response evoked by laryngoscopy and intubation.

EFFECT OF METOPROLOL ON COGNITIVE FUNCTION IN HYPERTENSIVE PATIENTS OF YOUNG TO MIDDLE AGE

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S. A. Smakotina

2008-01-01

Full Text Available Aim. To evaluate the effect of metoprolol tartrate on blood pressure (BP and cognitive function in young to middle aged patients with essential hypertension (HT.Material and methods. 40 men (age of 49,0±1,9 y.o. with HT of I-II stage not taking antihypertensive medication regularly were enrolled into the study. All patients were given metoprolol tartrate (start dose 50-100 mg/d. Variables of 24-h BP monitoring and clinic BP, left ventricular mass index (measured by echocardiography and characteristics of cognitive function (memory, attention, thinking and neurodynamic were assessed at the start, after 1 and 6 months of therapy.Results. Good and satisfactory antihypertensive effect was achieved in 75% of hypertensive patients with metoprolol (186,6±13,4mg/d monotherapy. Metoprolol significantly decreased maximum day-time systolic and diastolic BP, maximum night-time diastolic BP, mean day-time systolic and night-time diastolic BP, time-index, load-index and variability-index for night-time diastolic BP, day-time and night-time pulse BP. Left ventricular mass index reduced significantly (p<0,0001. After 6 months of therapy significant improvement of memory, attention, thinking and neurodynamic was observedConclusion. Metoprolol had beneficial effect on cognitive function in hypertensive patients, which demonstrate its cerebroprotective properties in addition to antihypertensive action. Metoprolol can reduce the risk of dementia in young to middle aged patients with HT.

Metoprolol compared to carvedilol deteriorates insulin-stimulated endothelial function in patients with type 2 diabetes - a randomized study

DEFF Research Database (Denmark)

Kveiborg, Britt; Hermann, Thomas S; Major-Pedersen, Atheline

2010-01-01

Studies of beta blockade in patients with type 2 diabetes have shown inferiority of metoprolol treatment compared to carvedilol on indices of insulin resistance. The aim of this study was to examine the effect of metoprolol versus carvedilol on endothelial function and insulin-stimulated endothel......Studies of beta blockade in patients with type 2 diabetes have shown inferiority of metoprolol treatment compared to carvedilol on indices of insulin resistance. The aim of this study was to examine the effect of metoprolol versus carvedilol on endothelial function and insulin...

Quantification of metoprolol beta 2-adrenoceptor antagonism in asthmatic patients by pharmacokinetic-pharmacodynamic modelling

NARCIS (Netherlands)

Braat, M. C.; Jonkers, R. E.; van Boxtel, C. J.

1992-01-01

An integrated pharmacokinetic-pharmacodynamic model was used to quantify the beta 2-blocking activity of metoprolol in seven asthmatic patients. The patients received a subcutaneous dose of terbutaline on two consecutive days. On day 1 they were pretreated with placebo and on day 2 with metoprolol

The low/high BCS permeability class boundary: physicochemical comparison of metoprolol and labetalol.

Science.gov (United States)

Zur, Moran; Gasparini, Marisa; Wolk, Omri; Amidon, Gordon L; Dahan, Arik

2014-05-05

Although recognized as overly conservative, metoprolol is currently the common low/high BCS permeability class boundary reference compound, while labetalol was suggested as a potential alternative. The purpose of this study was to identify the various characteristics that the optimal marker should exhibit, and to investigate the suitability of labetalol as the permeability class reference drug. Labetalol's BCS solubility class was determined, and its physicochemical properties and intestinal permeability were thoroughly investigated, both in vitro and in vivo in rats, considering the complexity of the whole of the small intestine. Labetalol was found to be unequivocally a high-solubility compound. In the pH range throughout the small intestine (6.5-7.5), labetalol exhibited pH-dependent permeability, with higher permeability at higher pH values. While in vitro octanol-buffer partitioning (Log D) values of labetalol were significantly higher than those of metoprolol, the opposite was evident in the in vitro PAMPA permeability assay. The results of the in vivo perfusion studies in rats lay between the two contradictory in vitro studies; metoprolol was shown to have moderately higher rat intestinal permeability than labetalol. Theoretical distribution of the ionic species of the drugs was in corroboration with the experimental in vitro and the in vivo data. We propose three characteristics that the optimal permeability class reference drug should exhibit: (1) fraction dose absorbed in the range of 90%; (2) the optimal marker drug should be absorbed largely via passive transcellular permeability, with no/negligible carrier-mediated active intestinal transport (influx or efflux); and (3) the optimal marker drug should preferably be nonionizable. The data presented in this paper demonstrate that neither metoprolol nor labetalol can be regarded as optimal low/high-permeability class boundary standard. While metoprolol is too conservative due to its complete absorption

Metoprolol Dose Equivalence in Adult Men and Women Based on Gender Differences: Pharmacokinetic Modeling and Simulations

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Andy R. Eugene

2016-11-01

Full Text Available Recent meta-analyses and publications over the past 15 years have provided evidence showing there are considerable gender differences in the pharmacokinetics of metoprolol. Throughout this time, there have not been any research articles proposing a gender stratified dose-adjustment resulting in an equivalent total drug exposure. Metoprolol pharmacokinetic data was obtained from a previous publication. Data was modeled using nonlinear mixed effect modeling using the MONOLIX software package to quantify metoprolol concentration–time data. Gender-stratified dosing simulations were conducted to identify equivalent total drug exposure based on a 100 mg dose in adults. Based on the pharmacokinetic modeling and simulations, a 50 mg dose in adult women provides an approximately similar metoprolol drug exposure to a 100 mg dose in adult men.

Atenolol Is Associated with Lower Day of Surgery Heart Rate as compared to Long and Short-acting Metoprolol

Science.gov (United States)

Schonberger, Robert B.; Brandt, Cynthia; Feinleib, Jessica; Dai, Feng; Burg, Matthew M.

2012-01-01

Objectives We analyzed the association between outpatient beta-blocker type and day-of-surgery heart rate in ambulatory surgical patients. We further investigated whether differences in day of surgery heart rate between atenolol and metoprolol could be explained by once-daily versus twice-daily dosing regimens. Design Retrospective observational study. Setting VA Hospital Participants Ambulatory surgical patients on chronic atenolol or metoprolol. Interventions None. Measurements and Main Results Using a propensity-score matched cohort, we compared day of surgery heart rates of patients prescribed atenolol versus metoprolol. We then differentiated between once-daily and twice-daily metoprolol formulations and compared day of surgery heart rates within a general linear model. Day of surgery heart rates in patients prescribed atenolol vs. any metoprolol formulation were slower by a mean of 5.1 beats/min (66.6 vs. 71.7; 95% CI of difference 1.9 to 8.3, p=0.002), a difference that was not observed in preoperative primary care visits. The general linear model demonstrated that patients prescribed atenolol (typically QD dosing) had a mean day of surgery heart rate 5.6 beats/min lower compared to patients prescribed once-daily metoprolol succinate (68.9 vs. 74.5; 95% CI of difference: −8.6 to −2.6, p<0.001) and 3.8 beats/minute lower compared to patients prescribed twice-daily metoprolol tartrate (68.9 vs. 72.7; 95% CI of difference: −6.1 to −1.6, p<0.001). Day of surgery heart rates were similar between different formulations of metoprolol (95% CI of difference: −1.0 to +4.6, p=0.22). Conclusions Atenolol is associated with lower day of surgery heart rate vs. metoprolol. The heart rate difference is specific to the day of surgery and is not explained by once-daily versus twice-daily dosing regimens. PMID:22889605

Análisis de costo efectividad del uso de metoprolol succinato en el tratamiento de la hipertensión arterial y la falla cardiaca en Colombia Analysis of cost effectiveness of the use of metoprolol succinate in the treatment of hypertension and heart failure in Colombia

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Martín Romero

2012-08-01

Full Text Available Objetivo: realizar una evaluación de costo-efectividad del uso de metoprolol succinato frente a metoprolol tartrato y carvedilol en el tratamiento de pacientes con insuficiencia cardiaca congestiva e hipertensión arterial en Colombia, desde la perspectiva del tercero pagador. Métodos: el estudio se desarrolló mediante un modelo de Markov simulando la historia natural de la enfermedad para un horizonte temporal de cinco años, para lo cual se tomaron 100 pacientes con edad de 45 años. Se evaluaron como desenlaces tanto las hospitalizaciones como las muertes evitadas. Los datos de probabilidades se obtuvieron de estudios clínicos y los costos de bases de datos de instituciones y opinión de expertos, expresados en pesos colombianos de 2009. Se aplicó una tasa de descuento del 3%. Resultados: el costo del brazo tratado con metoprolol succinato fue el menor, con 299 millones de pesos frente a 364 millones y 346 millones de pesos para carvedilol y metoprolol tartrato, respectivamente. El menor número de hospitalizaciones se presentó con metoprolol succinato, y fue de 24 ingresos en el horizonte de tiempo. En el brazo con carvedilol fue donde ocurrieron menos muertes. Los índices mostraron que el metoprolol succinato fue dominante frente a los otros beta-bloqueadores en las hospitalizaciones evitadas y en las muertes en comparación con metoprolol tartrato. Conclusiones: se comprobó la escasa efectividad del metoprolol tartrato, que además generó los mayores costos de atención dentro del modelo. El carvedilol mostró ligeramente mejores resultados en mortalidad frente a metoprolol succinato aunque con costos mayores. El metoprolol succinato es la mejor opción puesto que es la menos costosa y más efectiva medida en relación con las hospitalizaciones. Para la atención de los pacientes con insuficiencia cardiaca congestiva e hipertensión arterial en Colombia, el tratamiento con metoprolol succinato es la opción más recomendable por

Comparison of metoprolol as hydrochlorothiazide and antihypertensive agents.

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Pedersen, O L

1976-01-01

A crossover comparison of metoprolol and hydrochlorothiazide has been performed in 20 patients with mild hypertension. Both drugs caused almost identical statistically significant reduction in blood pressure of about 20 mm Hg systolic and 15 mm Hg diastolic. The side effects during active therapy were few and mild, but 5 patients experienced subjective symptoms during the first few days following abrupt withdrawal of metoprolol, namely general malaise, palpitations, headache, sweating and tremor. The symptoms were more pronounced in the standing position and disappeared at once on resumption of beta-blocker therapy, or gradually over 5 - 7 days when placebo tablets were given. In 11 of the 20 patients hydrochlorothiazide produced subnormal serum potassium levels and potassium supplements were given. The serum uric acid level was also significantly increased during hydrochlorothiazide treatment.

Impact of metoprolol treatment on mental status of chronic heart failure patients with neuropsychiatric disorders

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Liu X

2017-01-01

Full Text Available Xuelu Liu,1 Xueming Lou,1 Xianliang Cheng,2 Yong Meng1 1Department of Cardiology, 2Department of Endocrinology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China Background: Metoprolol treatment is well established for chronic heart failure (CHF patients, but the central nervous system side effects are often a potential drawback.Objective: To investigate the impact of metoprolol treatment on change in mental status of CHF patients with clinical psychological disorders (such as depression, anxiety, and burnout syndrome.Methods: From February 2013 to April 2016, CHF patients with clinical mental disorders received metoprolol (23.75 or 47.5 mg, qd PO, dose escalated with 23.75 mg each time until target heart rate [HR] <70 bpm was achieved at the Second Affiliated Hospital of Kunming Medical University. Mental status was assessed by means of the Hospital Anxiety and Depression Scale (HADS and the Copenhagen Burnout Inventory (CBI scale. The primary outcome assessed was change in mental status of patients post-metoprolol treatment and the association with reduction in HR achieved by metoprolol.Results: A total of 154 patients (median age: 66.39 years; males: n=101 were divided into eight groups on the basis of their mental status. HR decreased significantly from baseline values in all the groups to <70 bpm in the 12th month, P≤0.0001. The HADS depression and CBI scores significantly increased from baseline throughout the study frame (P≤0.0001 for all groups, but a significant decrease in the HADS anxiety score was observed in patients with anxiety (P≤0.0001 for all groups. Regression analysis revealed no significant correlation in any of the groups between the HR reduction and the change in the HADS/CBI scores, except for a change in the CBI scores of CHF patients with depression (P=0.01, which was HR dependent.Conclusion: Metoprolol treatment worsens the depressive and high burnout

Final product analysis in the e-beam and gamma radiolysis of aqueous solutions of metoprolol tartrate

Energy Technology Data Exchange (ETDEWEB)

Slegers, Catherine [Universite Catholique de Louvain, Unite d' Analyse Chimique et Physico-chimique des Medicaments, CHAM 72.30, Avenue E. Mounier, 72, B-1200 Brussels (Belgium)]. E-mail: catherine.slegers@cham.ucl.ac.be; Tilquin, Bernard [Universite Catholique de Louvain, Unite d' Analyse Chimique et Physico-chimique des Medicaments, CHAM 72.30, Avenue E. Mounier, 72, B-1200 Brussels (Belgium)

2006-09-15

The radiostability of metoprolol tartrate aqueous solutions and the influence of the absorbed dose (0-50 kGy), dose rate (e-beam (EB) vs. gamma ({gamma})) and radioprotectors (pharmaceutical excipients) are investigated by HPLC-UV analyses and through computer simulations. The use of radioprotecting excipients is more promising than an increase in the dose rate to lower the degradation of metoprolol tartrate aqueous solutions for applications such as radiosterilization. The decontamination of metoprolol tartrate from waste waters by EB processing appears highly feasible.

Preparation and characterization of metoprolol tartrate containing matrix type transdermal drug delivery system.

Science.gov (United States)

Malipeddi, Venkata Ramana; Awasthi, Rajendra; Ghisleni, Daniela Dal Molim; de Souza Braga, Marina; Kikuchi, Irene Satiko; de Jesus Andreoli Pinto, Terezinha; Dua, Kamal

2017-02-01

The present study aimed to develop matrix-type transdermal drug delivery system (TDDS) of metoprolol tartrate using polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA). The transdermal films were evaluated for physical parameters, Fourier transform infrared spectroscopy analysis (FTIR), differential scanning calorimetry (DSC), in vitro drug release, in vitro skin permeability, skin irritation test and stability studies. The films were found to be tough, non-sticky, easily moldable and possess good tensile strength. As the concentration of PVA was increased, the tensile strength of the films was also increased. Results of FTIR spectroscopy and DSC revealed the absence of any drug-polymer interactions. In vitro release of metoprolol followed zero-order kinetics and the mechanism of release was found to be diffusion rate controlled. In vitro release studies of metoprolol using Keshary-Chein (vertical diffusion cell) indicated 65.5 % drug was released in 24 h. In vitro skin permeation of metoprolol transdermal films showed 58.13 % of the drug was released after 24 h. In vitro skin permeation of metoprolol followed zero-order kinetics in selected formulations. The mechanism of release was found to be diffusion rate controlled. In a 22-day skin irritation test, tested formulation of transdermal films did not exhibit any allergic reactions, inflammation, or contact dermatitis. The transdermal films showed good stability in the 180-day stability study. It can be concluded that the TDDS of MPT can help in bypassing the first-pass effect and will provide patient improved compliance, without sacrificing the therapeutic advantages of the drugs.

Endothelial function is unaffected by changing between carvedilol and metoprolol in patients with heart failure-a randomized study

DEFF Research Database (Denmark)

Falskov, Britt; Hermann, Thomas Steffen; Raunsø, Jakob

2011-01-01

Carvedilol has been shown to be superior to metoprolol tartrate to improve clinical outcomes in patients with heart failure (HF), yet the mechanisms responsible for these differences remain unclear. We examined if there were differences in endothelial function, insulin stimulated endothelial func...... function, 24 hour ambulatory blood pressure and heart rate during treatment with carvedilol, metoprolol tartrate and metoprolol succinate in patients with HF.......Carvedilol has been shown to be superior to metoprolol tartrate to improve clinical outcomes in patients with heart failure (HF), yet the mechanisms responsible for these differences remain unclear. We examined if there were differences in endothelial function, insulin stimulated endothelial...

Neurohumoral prediction of left-ventricular morphologic response to beta-blockade with metoprolol in chronic left-ventricular systolic heart failure

DEFF Research Database (Denmark)

Grønning, Bjørn Aaris; Nilsson, Jens C; Hildebrandt, Per R

2002-01-01

from metoprolol treatment in patients with chronic LV systolic heart failure. METHODS: Forty-one subjects randomised to placebo or metoprolol were studied with magnetic resonance imaging and blood samples to measure LV dimensions and ejection fraction, epinephrine, norepinephrine, plasma renin activity......LVESVI: r=-0.53, P=0.03) volumes during metoprolol treatment. Change in ANP during the study was an independent marker for deltaLVEDVI: r=0.66, P=0.004, and deltaLVESVI: r=0.69, P=0.002 in the entire metoprolol group, but at the individual patient level, results were less clear. CONCLUSION: The pre......-treatment plasma level of ANP may be a predictor of LV antiremodelling from treatment with metoprolol in patients with chronic heart failure. However, the potential for individual neurohumoral monitoring of the effects on LV dimensions during beta-blockade appears limited...

The biopharmaceutics of successful controlled release drug product: Segmental-dependent permeability of glipizide vs. metoprolol throughout the intestinal tract.

Science.gov (United States)

Zur, Moran; Cohen, Noa; Agbaria, Riad; Dahan, Arik

2015-07-15

The purpose of this work was to study the challenges and prospects of regional-dependent absorption in a controlled-release scenario, through the oral biopharmaceutics of the sulfonylurea antidiabetic drug glipizide. The BCS solubility class of glipizide was determined, and its physicochemical properties and intestinal permeability were thoroughly investigated, both in-vitro (PAMPA and Caco-2) and in-vivo in rats. Metoprolol was used as the low/high permeability class boundary marker. Glipizide was found to be a low-solubility compound. All intestinal permeability experimental methods revealed similar trend; a mirror image small intestinal permeability with opposite regional/pH-dependency was obtained, a downward trend for glipizide, and an upward trend for metoprolol. Yet the lowest permeability of glipizide (terminal Ileum) was comparable to the lowest permeability of metoprolol (proximal jejunum). At the colon, similar permeability was evident for glipizide and metoprolol, that was higher than metoprolol's jejunal permeability. We present an analysis that identifies metoprolol's jejunal permeability as the low/high permeability class benchmark anywhere throughout the intestinal tract; we show that the permeability of both glipizide and metoprolol matches/exceeds this threshold throughout the entire intestinal tract, accounting for their success as controlled-release dosage form. This represents a key biopharmaceutical characteristic for a successful controlled-release dosage form. Copyright © 2015 Elsevier B.V. All rights reserved.

Lidocaine alleviates propofol related pain much better than metoprolol and nitroglycerin

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Asutay Goktug

2015-10-01

Full Text Available ABSTRACTBACKGROUND AND OBJECTIVES: Injection pain after propofol administration is common and maydisturb patients' comfort. The aim of this study was to compare effectiveness of intravenous(iv nitroglycerin, lidocaine and metoprolol applied through the veins on the dorsum of hand orantecubital vein on eliminating propofol injection pain.METHOD: There were 147 patients and they were grouped according to the analgesic adminis-tered. Metoprolol (n = 31, Group M, lidocaine (n = 32, Group L and nitroglycerin (n = 29, GroupN were applied through iv catheter at dorsum hand vein or antecubital vein. Pain was evalu-ated by 4 point scale (0 - no pain, 1 --- light pain, 2 --- mild pain, 3 --- severe pain in 5, 10, 15and 20th seconds. ASA, BMI, patient demographics, education level and the effect of pathwaysfor injection and location of operations were analyzed for their effect on total pain score.RESULTS: There were no differences between the groups in terms of total pain score (p = 0.981.There were no differences in terms of total pain score depending on ASA, education level,location of operation. However, lidocaine was more effective when compared with metoprolol(p = 0.015 and nitroglycerin (p = 0.001 among groups. Although neither lidocaine nor metopro-lol had any difference on pain management when applied from antecubital or dorsal hand vein(p > 0.05, nitroglycerin injection from antecubital vein had demonstrated statistically lowerpain scores (p = 0.001.CONCLUSION: We found lidocaine to be the most effective analgesic in decreasing propofolrelated pain. We therefore suggest iv lidocaine for alleviating propofol related pain at operations.

Evaluation of efficacy of metoprolol in patients having heart failure with preserved ejection fraction: A randomized, double-blind, placebo-controlled pilot trial

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Niti Mittal

2017-01-01

Conclusion: Hence, this pilot study showed that metoprolol succinate possibly has some beneficial role in HFpEF as reflected by improvement in some parameters. The findings highlight the need of a larger study with longer follow-up to provide a definitive answer.

Improvement of exercise capacity and left ventricular diastolic function with metoprolol XL after acute myocardial infarction

DEFF Research Database (Denmark)

Poulsen, S H; Jensen, S E; Egstrup, K

2000-01-01

dysfunction after acute myocardial infarction were given metoprolol XL (n = 29) or placebo (n = 30). The effects of metoprolol XL on exercise capacity in relation to effects on LV diastolic filling were studied. Two-dimensional Doppler echocardiography and maximal symptom limited bicycle test were performed...

Bioanalytical method development and validation for determination of metoprolol tartarate and hydrochlorothiazide using HPTLC in human plasma

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Ambadas Ranganath Rote

2013-12-01

Full Text Available A simple, sensitive, rapid and economic chromatographic method has been developed for determination of metoprolol tartarate and hydrochlorothiazide in human plasma using paracetamol as an internal standard. The analytical technique used for method development was high-performance thin-layer chromatography. HPTLC Camag with precoated silica gel Plate 60F254 (20 cm×10 cm at 250 µm thicknesses (E. Merck, Darmstadt, Germany was used as the stationary phase. The mobile phase used consisted of chloroform: methanol: ammonia (9:1:0.5v/v/v. Densitometric analysis was carried out at a wavelength of 239 nm. The rf values for hydrochlorothiazide, paracetamol and metoprolol tartarate were 0.13±0.04, 0.28±0.05, 0.48±0.04, respectively. Plasma samples were extracted by protein precipitation with methanol. Concentration ranges of 200, 400, 600, 800, 1000, 1200 ng/mL and 2000, 4000, 6000, 8000, 10000, 12000 ng/mL of hydrochlorothiazide and metoprolol tartarate, respectively, were used with plasma for the calibration curves. The percent recovery of metoprolol tartarate and hydrochlorothiazide was found to be 77.30 and 77.02 %, respectively. The stability of metoprolol tartarate and hydrochlorothiazide in plasma were confirmed during three freeze-thaw cycles (-20 ºC on a bench for 24 hours and post-preparatively for 48 hours. The proposed method was validated statistically and proved suitable for determination of metoprolol tartarate and hydrochlorothiazide in human plasma.

Development and validation of dissolution test for Metoprolol ...

African Journals Online (AJOL)

The dissolution method which uses USP apparatus I (Basket) with rotating at 100 rpm, 900 ml of different dissolution medium, ultra violet spectroscopy for quantification was demonstrated to be robust, discriminating and transferable. Dissolution tests conditions were selected after it was demonstrated that the Metoprolol ...

Plasma C-type natriuretic peptide as a predictor for therapeutic response to metoprolol in children with postural tachycardia syndrome.

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Jing Lin

Full Text Available POTS is a global public-health disease, but predictor for therapeutic response to metoprolol in children with POTS is lacking. This study was designed to investigate predictive value of plasma C-type natriuretic peptide (CNP in the therapeutic efficacy of metoprolol on postural tachycardia syndrome (POTS in children. Totally 34 children with POTS and 27 healthy children were included in the study. The head-up test or head-up tilt test was used to check heart rate and blood pressure from supine to upright in subjects. A double antibody (competitive sandwich immunoluminometric assay was used to detect plasma CNP. Metoprolol was used to treat children with POTS. The difference in plasma concentrations of CNP between responders and non-responders was compared. An ROC curve was used to analyze plasma CNP to predict efficacy of metoprolol on POTS in children. Plasma CNP in children with POTS was significantly higher than that of healthy children [(51.9 ± 31.4 vs. (25.1 ± 19.1 pg/ml, P 32.55 pg/ml yielded a sensitivity of 95.8% and specificity of 70% in predicting therapeutic efficacy of metoprolol on POTS children. Plasma CNP might serve as a useful predictor for the therapeutic efficacy of metoprolol on POTS in children.

Metoprolol compared to carvedilol deteriorates insulin-stimulated endothelial function in patients with type 2 diabetes - a randomized study

DEFF Research Database (Denmark)

Kveiborg, Britt; Hermann, Thomas S; Major-Pedersen, Atheline

2010-01-01

-stimulated endothelial function in patients with type 2 diabetes. METHOD: 24 patients with type 2 diabetes were randomized to receive either 200 mg metoprolol succinate or 50 mg carvedilol daily. Endothelium-dependent vasodilation was assessed by using venous occlusion plethysmography with increasing doses of intra......AIM: Studies of beta blockade in patients with type 2 diabetes have shown inferiority of metoprolol treatment compared to carvedilol on indices of insulin resistance. The aim of this study was to examine the effect of metoprolol versus carvedilol on endothelial function and insulin...... with metoprolol, the percentage change in forearm blood-flow was 60.19% +/- 17.89 (at the highest serotonin dosages) before treatment and -33.80% +/- 23.38 after treatment (p = 0.007). Treatment with carvedilol did not change insulin-stimulated endothelial function. Endothelium-dependent vasodilation without...

Enantioselectively controlled release of chiral drug (metoprolol) using chiral mesoporous silica materials

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Guo Zhen; Liu Xianbin; Ng, Siu-Choon; Chen Yuan; Yang Yanhui [School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459 (Singapore); Du Yu, E-mail: du_yu@jlu.edu.cn, E-mail: yhyang@ntu.edu.sg [College of Electronic Science and Engineering, Jilin University, Changchun 130012 (China)

2010-04-23

Chiral porous materials have attracted burgeoning attention on account of their potential applications in many areas, such as enantioseparation, chiral catalysis, chemical sensors and drug delivery. In this report, chiral mesoporous silica (CMS) materials with various pore sizes and structures were prepared using conventional achiral templates (other than chiral surfactant) and a chiral cobalt complex as co-template. The synthesized CMS materials were characterized by x-ray diffraction, nitrogen physisorption, scanning electron microscope and transmission electron microscope. These CMS materials, as carriers, were demonstrated to be able to control the enantioselective release of a representative chiral drug (metoprolol). The release kinetics, as modeled by the power law equation, suggested that the release profiles of metoprolol were remarkably dependent on the pore diameter and pore structure of CMS materials. More importantly, R- and S-enantiomers of metoprolol exhibited different release kinetics on CMS compared to the corresponding achiral mesoporous silica (ACMS), attributable to the existence of local chirality on the pore wall surface of CMS materials. The chirality of CMS materials on a molecular level was further substantiated by vibrational circular dichroism measurements.

Enantioselectively controlled release of chiral drug (metoprolol) using chiral mesoporous silica materials

International Nuclear Information System (INIS)

Guo Zhen; Liu Xianbin; Ng, Siu-Choon; Chen Yuan; Yang Yanhui; Du Yu

2010-01-01

Chiral porous materials have attracted burgeoning attention on account of their potential applications in many areas, such as enantioseparation, chiral catalysis, chemical sensors and drug delivery. In this report, chiral mesoporous silica (CMS) materials with various pore sizes and structures were prepared using conventional achiral templates (other than chiral surfactant) and a chiral cobalt complex as co-template. The synthesized CMS materials were characterized by x-ray diffraction, nitrogen physisorption, scanning electron microscope and transmission electron microscope. These CMS materials, as carriers, were demonstrated to be able to control the enantioselective release of a representative chiral drug (metoprolol). The release kinetics, as modeled by the power law equation, suggested that the release profiles of metoprolol were remarkably dependent on the pore diameter and pore structure of CMS materials. More importantly, R- and S-enantiomers of metoprolol exhibited different release kinetics on CMS compared to the corresponding achiral mesoporous silica (ACMS), attributable to the existence of local chirality on the pore wall surface of CMS materials. The chirality of CMS materials on a molecular level was further substantiated by vibrational circular dichroism measurements.

APPLICATION OF KATG::LUX GENE CONSTRUCT FOR CYTOTOXICITY AND GENOTOXICITY MONITORING OF METOPROLOL IN ENVIRONMENT

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Eliza Hawrylik

2017-06-01

Full Text Available The aim of the study was the evaluation of usefulness of Escherichia coli K-12 RFM 443 katG::lux for cytotoxicity and genotoxicity monitoring of metoprolol in the environment. Metoprolol is one of the most popular cardiac drug which belongs to the group of β – blockers. The drug was applied at concentrations ranging from 10-1 mg/cm3 to 10-5 mg/cm3. Obtained data indicated the influence of metoprolol on lux gene expression and katG promotor activity in E.coli K-12. The results indicato the possibility of using of Escherichia coli K-12 RFM 443 strain with katG::lux gene construct in the monitoring of cytotoxicity and genotoxicity cardiac drug residues in the environment.

[Impact of metoprolol use in the treatment of patients with electrical-storm after cardioverter defibrillators implantation].

Science.gov (United States)

Yu, Jin-bo; Yang, Bing; Xu, Dong-jie; Chen, Ming-long; Shan, Qi-jun; Zou, Jian-gang; Chen, Chun; Zhang, Feng-xiang; Hou, Xiao-feng; Li, Wen-qi; Zhang, Rong; Cao, Ke-jiang

2011-08-01

To explore the effectiveness of the metoprolol dosage adjustment on reducing the incidence of electrical-storm (ES) in patients with Implantable Cardioverter Defibrillators (ICDs). Data from patients with ICD implantation between Jan, 2003 and Jun, 2006 in our hospital were retrospectively analyzed. ES was defined as either ≥ 3 times of ventricular tachyarrhythmias (VTAs) resulting in ICD therapy or VTAs lasting more than 30 s detected by ICD without any therapy within 24 hours. During a follow-up period of (27.5 ± 21.2) months, ES was recorded in 39 cases [34 males, average age (52.0 ± 13.1) years] out of 119 patients (32.8%) and 9 patients died after ES. During the period of storm attack, ES was successfully controlled in 25/30 patients by various interventions, including predisposing factors corrected in 5 cases, ICD reprogramming and antiarrhythmic drugs therapy optimized in 16 cases (one received intravenous injection of metoprolol), and VTAs eliminated by catheter ablation in 4 cases. ES was spontaneously resolved in the remaining 5 cases. In the chronic phase, 2 patients with Brugada syndrome were treated with Quinidine mono-therapy while the dosage of metoprolol was adjusted in the remaining 23 patients and the dosage of metoprolol was increased gradually from (26.8 ± 13.9) mg/d to (88.9 ± 53.5) mg/d without any adverse effects (9 patients received also oral amiodarone 200 mg/d). Post dosage adjustment, the total VTA episodes [(1.9 ± 1.7) times/month vs. (0.8 ± 0.6) times/month, P = 0.004], incidence of antitachycardia pacing therapies [(4.2 ± 3.8) runs/month vs. (2.3 ± 2.0) runs/month, P = 0.003], as well as electrical cardioversion or defibrillation [(1.1 ± 0.9) times/month vs. (0.4 ± 0.2) times/month, P = 0.001] were significantly decreased. ES was not controlled until a extremely high dosage [225 - 300 (255.3 ± 41.7) mg/d] of metoprolol was reached in the remaining 5 patients. Metoprolol use is essential and its dosage should be

Randomized double-blind comparison of metoprolol, nifedipine, and their combination in chronic stable angina

DEFF Research Database (Denmark)

Egstrup, K

1988-01-01

In a randomized double-blind study, treatment with either metoprolol, nifedipine, or their combination was compared for effects on ischemic variables and heart rate obtained during ambulatory monitoring in 42 patients with chronic stable angina. All patients had severe chronic stable angina...... could be detected during nifedipine monotherapy. It is concluded that metoprolol monotherapy, as well as its combination with nifedipine, effectively reduces total ischemic activity compared with placebo and nifedipine monotherapy. Control of ischemic activity in chronic stable angina may have...

The effects of changes of plasma endothelin level in patients with hypertension after medication of metoprolol tartrate combined with felodipine

International Nuclear Information System (INIS)

Tao Zhihu; Pan Quan

2011-01-01

Objective: To investigate the clinical efficacy and safety of metoprolol tartrate combined with felodipine sustained-release tablets in treatment of high blood pressure. Methods: Patients were allocated to groups of medication of metoprolol tartrate combined with felodipine (Group A, n=57) and single medication of metoprolol tartrate (Group B, n=60). All patients received daily measurement of blood pressure, heart rate, observation of adverse reactions and detection of the plasma endothelin levels before and after the medication. Results: Compared with Group B after the medication, the therapeutic effect was significant in Group A (P<0.01) and both the plasma endothelin levels and the side effects were much lower(P<0.05, P<0.01, respectively). Conclusion: Metoprolol tartrate combined with sustained release felodipine tablets appears effectively in treatment of hypertension, and the therapeutic effect may be associated with the variation of plasma endothelin levels. In addition, metoprolol in combination sustained release felodipine tablets can counteract the adverse reaction from single dose and is worthy for wide clinical use. (authors)

Effects of Flos carthami on CYP2D6 and on the Pharmacokinetics of Metoprolol in Rats

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Gaofeng Liu

2011-01-01

Full Text Available Flos carthami is a traditional Chinese herbal medicine. Clinically, the Flos carthami Injection has been used concomitantly with other Western drugs and may be used concomitantly with β-blockers, such as metoprolol, to treat cerebrovascular and coronary heart diseases, in China. Metoprolol is a CYP2D6 substrate and is predominantly metabolized by this isozyme. However, we do not know whether there is an effect of Flos carthami on CYP2D6 and the consequences of such an effect. Concern is raised regarding the possible herb-drug interaction. In this report, the effects of Flos carthami on the activity of CYP2D6 in vivo and in vitro and on the pharmacokinetics of metoprolol, in rats, are investigated. To assess the inhibitory potency of Flos carthami, the concentration associated with 50% inhibition (IC50 of dextromethorphan metabolism was determined based on the concentration-inhibition curves. The inhibitory effect of Flos carthami on CYP2D6 was also compared with cimetidine in vitro. Flos carthami could significantly inhibit CYP2D6 in rats both in vitro and in vivo (P<.05 and could slow down the metabolic rate of metoprolol as suggested by prolonged t1/2 (67.45%, by increased Cmax (74.51% and AUC0−∞ (76.89%. These results suggest that CYP2D6 is a risk factor when Flos carthami is administered concomitantly with metoprolol or other CYP2D6 substrates.

Effect of European Clinical Trials Directive on academic drug trials in Denmark: retrospective study of applications to the Danish Medicines Agency 1993-2006

DEFF Research Database (Denmark)

Berendt, Louise; Hakansson, Cecilia; Bach, Karin Ursula Friis

2008-01-01

To determine the impact of the European Union's Clinical Trials Directive on the number of academic drug trials carried out in Denmark.......To determine the impact of the European Union's Clinical Trials Directive on the number of academic drug trials carried out in Denmark....

Impact of carvedilol and metoprolol on inappropriate implantable cardioverter-defibrillator therapy

DEFF Research Database (Denmark)

Ruwald, Martin H; Abu-Zeitone, Abeer; Jons, Christian

2013-01-01

The goal of this study was to evaluate the effects of carvedilol and metoprolol on the endpoint of inappropriate implantable cardioverter-defibrillator therapy in the MADIT-CRT (Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy) study....

Effects of acute beta-adrenoceptor blockade with metoprolol on the renal response to dopamine in normal humans

DEFF Research Database (Denmark)

Olsen, Niels Vidiendal; Lang-Jensen, T; Hansen, J M

1994-01-01

outflow. Baseline values of heart rate, systolic pressure and mean arterial pressure decreased with metoprolol compared with placebo, but cardiac output, effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) were not significantly changed. Metoprolol significantly decreased baseline CLLi...... and sodium clearance (CLNa) by 19% (P rate and systolic pressure, but cardiac output increased to the same extent on both study days by 26% (placebo, P

Liquid chromatography tandem mass spectrometry method for simultaneous determination of metoprolol tartrate and ramipril in human plasma.

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Gowda, K Veeran; Mandal, Uttam; Senthamil Selvan, P; Sam Solomon, W D; Ghosh, Animesh; Sarkar, Amlan Kanti; Agarwal, Sangita; Nageswar Rao, T; Pal, Tapan Kumar

2007-10-15

A simple, rapid, sensitive and specific liquid chromatography-tandem mass spectrometry method was developed and validated for quantification of metoprolol tartrate (MT) and ramipril, in human plasma. Both the drugs were extracted by liquid-liquid extraction with diethyl ether-dichloromethane (70:30, v/v). The chromatographic separation was performed on a reversed-phase C8 column with a mobile phase of 10 mM ammonium formate-methanol (3:97, v/v). The protonated analyte was quantitated in positive ionization by multiple reaction monitoring with a mass spectrometer. The method was validated over the concentration range of 5-500 ng/ml for metoprolol and ramipril in human plasma. The precursor to product ion transitions of m/z 268.0-103.10 and m/z 417.20-117.20 were used to measure metoprolol and ramipril, respectively.

Bisoprolol compared with carvedilol and metoprolol succinate in the treatment of patients with chronic heart failure.

Science.gov (United States)

Fröhlich, Hanna; Torres, Lorella; Täger, Tobias; Schellberg, Dieter; Corletto, Anna; Kazmi, Syed; Goode, Kevin; Grundtvig, Morten; Hole, Torstein; Katus, Hugo A; Cleland, John G F; Atar, Dan; Clark, Andrew L; Agewall, Stefan; Frankenstein, Lutz

2017-09-01

Beta-blockers are recommended for the treatment of chronic heart failure (CHF). However, it is disputed whether beta-blockers exert a class effect or whether there are differences in efficacy between agents. 6010 out-patients with stable CHF and a reduced left ventricular ejection fraction prescribed either bisoprolol, carvedilol or metoprolol succinate were identified from three registries in Norway, England, and Germany. In three separate matching procedures, patients were individually matched with respect to both dose equivalents and the respective propensity scores for beta-blocker treatment. During a follow-up of 26,963 patient-years, 302 (29.5%), 637 (37.0%), and 1232 (37.7%) patients died amongst those prescribed bisoprolol, carvedilol, and metoprolol, respectively. In univariable analysis of the general sample, bisoprolol and carvedilol were both associated with lower mortality as compared with metoprolol succinate (HR 0.80, 95% CI 0.71-0.91, p < 0.01, and HR 0.86, 95% CI 0.78-0.94, p < 0.01, respectively). Patients prescribed bisoprolol or carvedilol had similar mortality (HR 0.94, 95% CI 0.82-1.08, p = 0.37). However, there was no significant association between beta-blocker choice and all-cause mortality in any of the matched samples (HR 0.90; 95% CI 0.76-1.06; p = 0.20; HR 1.10, 95% CI 0.93-1.31, p = 0.24; and HR 1.08, 95% CI 0.95-1.22, p = 0.26 for bisoprolol vs. carvedilol, bisoprolol vs. metoprolol succinate, and carvedilol vs. metoprolol succinate, respectively). Results were confirmed in a number of important subgroups. Our results suggest that the three beta-blockers investigated have similar effects on mortality amongst patients with CHF.

Differential effects of adrenergic antagonists (Carvedilol vs Metoprolol on parasympathetic and sympathetic activity: a comparison of clinical results

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Heather L. Bloom

2014-08-01

Full Text Available Background Cardiovascular autonomic neuropathy (CAN is recognized as a significant health risk, correlating with risk of heart disease, silent myocardial ischemia or sudden cardiac death. Beta-blockers are often prescribed to minimize risk. Objectives In this second of two articles, the effects on parasympathetic and sympathetic activity of the alpha/beta-adrenergic blocker, Carvedilol, are compared with those of the selective beta-adrenergic blocker, Metoprolol. Methods Retrospective, serial autonomic nervous system test data from 147 type 2 diabetes mellitus patients from eight ambulatory clinics were analyzed. Patients were grouped according to whether a beta-blocker was (1 introduced, (2 discontinued or (3 continued without adjustment. Group 3 served as the control. Results Introducing Carvedilol or Metoprolol decreased heart rate and blood pressure, and discontinuing them had the opposite effect. Parasympathetic activity increased with introducing Carvedilol. Sympathetic activity increased more after discontinuing Carvedilol, suggesting better sympathetic suppression. With ongoing treatment, resting parasympathetic activity decreased with Metoprolol but increased with Carvedilol. Conclusion Carvedilol has a more profound effect on sympathovagal balance than Metoprolol. While both suppress sympathetic activity, only Carvedilol increases parasympathetic activity. Increased parasympathetic activity may underlie the lower mortality risk with Carvedilol.

European randomized lung cancer screening trials: Post NLST

DEFF Research Database (Denmark)

Field, JK; Klaveren, R; Pedersen, JH

2013-01-01

Overview of the European randomized lung cancer CT screening trials (EUCT) is presented with regard to the implementation of CT screening in Europe; post NLST. All seven principal investigators completed a questionnaire on the epidemiological, radiological, and nodule management aspects...

Influence of competing inorganic cations on the ion exchange equilibrium of the monovalent organic cation metoprolol on natural sediment.

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Niedbala, Anne; Schaffer, Mario; Licha, Tobias; Nödler, Karsten; Börnick, Hilmar; Ruppert, Hans; Worch, Eckhard

2013-02-01

The aim of this study was to systematically investigate the influence of the mono- and divalent inorganic ions Na(+) and Ca(2+) on the sorption behavior of the monovalent organic cation metoprolol on a natural sandy sediment at pH=7. Isotherms for the beta-blocker metoprolol were obtained by sediment-water batch tests over a wide concentration range (1-100000 μg L(-1)). Concentrations of the competing inorganic ions were varied within freshwater relevant ranges. Data fitted well with the Freundlich sorption model and resulted in very similar Freundlich exponents (n=0.9), indicating slightly non-linear behavior. Results show that the influence of Ca(2+) compared to Na(+) is more pronounced. A logarithmic correlation between the Freundlich coefficient K(Fr) and the concentration or activity of the competing inorganic ions was found allowing the prediction of metoprolol sorption on the investigated sediment at different electrolyte concentrations. Additionally, the organic carbon of the sediment was completely removed for investigating the influence of organic matter on the sorption of metoprolol. The comparison between the experiments with and without organic carbon removal revealed no significant contribution of the organic carbon fraction (0.1%) to the sorption of metoprolol on the in this study investigated sediment. Results of this study will contribute to the development of predictive models for the transport of organic cations in the subsurface. Copyright © 2012 Elsevier Ltd. All rights reserved.

Neurohumoral prediction of left-ventricular morphologic response to beta-blockade with metoprolol in chronic left-ventricular systolic heart failure

DEFF Research Database (Denmark)

Groenning, Bjoern A; Nilsson, Jens C; Hildebrandt, Per R

2002-01-01

BACKGROUND: In order to tailor therapy in heart failure, a solution might be to develop sensitive and reliable markers that can predict response in individual patients or monitor effectiveness of therapy. AIMS: To evaluate neurohumoral factors as markers for left-ventricular (LV) antiremodelling...... from metoprolol treatment in patients with chronic LV systolic heart failure. METHODS: Forty-one subjects randomised to placebo or metoprolol were studied with magnetic resonance imaging and blood samples to measure LV dimensions and ejection fraction, epinephrine, norepinephrine, plasma renin activity......-treatment plasma level of ANP may be a predictor of LV antiremodelling from treatment with metoprolol in patients with chronic heart failure. However, the potential for individual neurohumoral monitoring of the effects on LV dimensions during beta-blockade appears limited....

EFFICACY AND SAFETY OF METOPROLOL SUCCINATE IN HIGH DOSES IN PATIENTS WITH STABLE COURSE OF ISCHEMIC HEART DISEASE

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S. N. Tolpygina

2008-01-01

Full Text Available Aim. To compare two initial doses (50 or 100mg/day ofmetoprolol succinate in control released presentation (Betaloc ZOK, AstraZeneca for achievement of target level of heart rate (HR in patients with stable course of ischemic heart disease (IHD.Material and methods. 50 patients (34 men and 16 women, aged 61,3 y.o., in average with IHD were involved into the open randomized comparative study. IHD duration was from 1 to 22 years (8,3 years in average. 47 patients completed study, 3 patients drop out because of side effects. Previous therapy with β-blockers or other HR reducing drugs was replaced on metoprolol. Patients were randomized in 2 groups (G1 and G2. The initial metoprolol dose was 50 mg in G1 patients and 100 mg - in G2 patients. The dose was enlarged twice if necessary. Study duration was 6 weeks. The change of HR, blood pressure, electrocardiogram parameters was evaluated. Patients filled in Seattle angina questionnaire initially and after 6 weeks treatment. Therapy tolerability was also estimated.Results. In 6 weeks of therapy 61% of G1 patients and 87,5% of G2 patients (p<0,01 reached HR target. Dependence of achievement of target HR and dose of metoprolol was observed (r=0,3; p=0,056. Improvement of the HR control was accompanied by reduction of frequency of angina attacks and increase of life quality.Conclusion. Metoprolol (Betaloc ZOK 200 mg/day provides more effective HR control in patients with IHD vs metoprolol 50-100 mg/day and has good tolerability.

Simultaneous determination of metoprolol and metabolites in urine by capillary column gas chromatography as oxazolidineone and trimethylsilyl derivatives.

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Gyllenhaal, O; Hoffmann, K J

1984-08-10

A method for the determination of metoprolol and its main metabolites in urine is presented. The method comprises derivatization of the aminopropanol side-chain with phosgene at alkaline pH and isolation in an organic phase at acidic pH. After trimethylsilylation, separation and quantification are performed by capillary column gas chromatography with flame ionization detection. The reaction is performed at pH 12 with 60 microliters of 2 M phosgene in toluene added in three portions. Diethyl ether--dichloromethane is used as extraction medium and bis(trimethylsilyl) acetamide as silylating agent. With spiked samples linear standard curves were obtained for metoprolol and three of its main metabolites with a detection limit varying between 4 and 20 mumol/l of urine. The method was applied to urine samples from a normal individual who had taken 292 mumol of metoprolol as tartrate.

Sorption of the organic cation metoprolol on silica gel from its aqueous solution considering the competition of inorganic cations.

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Kutzner, Susann; Schaffer, Mario; Börnick, Hilmar; Licha, Tobias; Worch, Eckhard

2014-05-01

Systematic batch experiments with the organic monovalent cation metoprolol as sorbate and the synthetic material silica gel as sorbent were conducted with the aim of characterizing the sorption of organic cations onto charged surfaces. Sorption isotherms for metoprolol (>99% protonated in the tested pH of around 6) in competition with mono- and divalent inorganic cations (Na(+), NH4(+), Ca(2+), and Mg(2+)) were determined in order to assess their influence on cation exchange processes and to identify the role of further sorptive interactions. The obtained sorption isotherms could be described well by an exponential function (Freundlich isotherm model) with consistent exponents (about 0.8). In general, a decreasing sorption of metoprolol with increasing concentrations in inorganic cations was observed. Competing ions of the same valence showed similar effects. A significant sorption affinity of metoprolol with ion type dependent Freundlich coefficients KF,0.77 between 234.42 and 426.58 (L/kg)(0.77) could still be observed even at very high concentrations of competing inorganic cations. Additional column experiments confirm this behavior, which suggests the existence of further relevant interactions beside cation exchange. In subsequent batch experiments, the influence of mixtures with more than one competing ion and the effect of a reduced negative surface charge at a pH below the point of zero charge (pHPZC ≈ 2.5) were also investigated. Finally, the study demonstrates that cation exchange is the most relevant but not the sole mechanism for the sorption of metoprolol on silica gel. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evaluation of poly(2-ethyl-2-oxazoline) containing copolymer networks of varied composition as sustained metoprolol tartrate delivery systems.

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Kostova, Bistra; Ivanova, Sijka; Balashev, Konstantin; Rachev, Dimitar; Christova, Darinka

2014-08-01

Segmented copolymer networks (SCN) based on poly(2-ethyl-2-oxazoline) and containing 2-hydroxyethyl methacrylate, 2-hydroxypropyl acrylate, and/or methyl methacrylate segments have been evaluated as potential sustained release systems of the water soluble cardioselective β-blocker metoprolol tartrate. The structure and properties of the drug carriers were investigated by differential scanning calorimetry, attenuated total reflectance Fourier transform infrared spectroscopy, scanning electron microscopy, and atomic force microscopy. Swelling kinetics of SCNs in various media was followed, and the conditions for effective MT loading were specified. MT-loaded SCNs with drug content up to 80 wt.% were produced. The release kinetics of metoprolol tartrate from the systems was studied and it was shown that the conetworks of different structure and composition are able to sustain the metoprolol tartrate release without additional excipients.

Análisis de costo efectividad del uso de metoprolol succinato en el tratamiento de la hipertensión arterial y la falla cardiaca en Colombia

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Martín Romero, MD., MSc.

2012-07-01

Conclusiones: se comprobó la escasa efectividad del metoprolol tartrato, que además generó los mayores costos de atención dentro del modelo. El carvedilol mostró ligeramente mejores resultados en mortalidad frente a metoprolol succinato aunque con costos mayores. El metoprolol succinato es la mejor opción puesto que es la menos costosa y más efectiva medida en relación con las hospitalizaciones. Para la atención de los pacientes con insuficiencia cardiaca congestiva e hipertensión arterial en Colombia, el tratamiento con metoprolol succinato es la opción más recomendable por su menor costo y mayor efectividad en las condiciones del caso base.

Formulation development and comparative in vitro study of metoprolol tartrate (IR) tablets.

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Husain, Tazeen; Shoaib, Muhammad Harris; Yousuf, Rabia Ismail; Maboos, Madiha; Khan, Madeeha; Bashir, Lubna; Naz, Shazia

2016-05-01

The objective of the present work was to develop Immediate Release (IR) tablets of Metoprolol Tartrate (MT) and to compare trial formulations to a reference product. Six formulations (F1-F6) were designed using central composite method and compared to a reference brand (A). Two marketed products (brands B and C) were also evaluated. F1-F6 were prepared with Avicel PH101 (filler), Crospovidone (disintegrant) and Magnesium Stearate (lubricant) by direct compression. Pharmacopoeial and non-pharmacopoeial methods were used to assess their quality. Furthermore, drug profiles were characterized using model dependent and independent (f(2)) approaches. Brands B and C and F5 and F6 did not qualify the tests for content uniformity. Moreover, brand B did not meet weight variation criteria and brand C did not satisfy requirements for single point dissolution test. Of the trial formulations, F2 failed the test for uniformity in thickness while F4 did not disintegrate within time limit. Only F1 and F3 met all quality parameters and were subjected to accelerated stability testing without significant alterations in their physicochemical characteristics. Based on AIC and r(2)(adjusted) values obtained by applying various kinetic models, drug release was determined to most closely follow Hixson-Crowell cube root law. F1 was determined to be the optimized formulation.

Influence of cilazapril on memory functions and sleep behaviour in comparison with metoprolol and placebo in healthy subjects.

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Dietrich, B; Herrmann, W M

1989-01-01

1. In a controlled, randomized, double-blind study the influence of cilazapril and metoprolol on learning and memory functions and on sleep behaviour was investigated in healthy young volunteers under steady-state conditions. Twenty-three subjects were given either 2.5 mg cilazapril, 200 mg metoprolol, or placebo for 14 days in a latin square design separated by washout periods of 7 days. 2. To test memory functions different modalities--verbal, visual, numerical associative and two dimensional spatial memory were tested for recent anterograde recall, both short-term (less than 10 s) and middle-term (up to 15 min) were selected. The test had a content similar to that used in daily life situations. The sleep behaviour was tested both by objective (all night sleep EEG) and subjective measures. 3. Neither antihypertensive drug had an observable influence on memory performance at the dosages used under steady-state conditions. However, sleep was disturbed during metoprolol, while cilazapril could not be differentiated from placebo. The effects of metoprolol on sleep behaviour were observed in the objective and subjective measures. There was more frequent awakening during the night with the subjective complaint of difficulties in sleeping through. 4. From this study it is concluded that cilazapril has no major effect on memory functions and sleep behaviour. This is only true for the dosages given and under steady-state conditions.

The burden and management of cytochrome P450 2D6 (CYP2D6)-mediated drug-drug interaction (DDI): co-medication of metoprolol and paroxetine or fluoxetine in the elderly.

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Bahar, Muh Akbar; Hak, Eelko; Bos, Jens H J; Borgsteede, Sander D; Wilffert, Bob

2017-07-01

Metoprolol and paroxetine/fluoxetine are inevitably co-prescribed because cardiovascular disorders and depression often coexist in the elderly. This leads to CYP2D6-mediated drug-drug interactions (DDI). Because systematic evaluations are lacking, we assessed the burden of metoprolol-paroxetine/fluoxetine interaction in the elderly and how these interactions are managed in Dutch community pharmacies. Dispensing data were collected from the University of Groningen pharmacy database (IADB.nl, 1999-2014) for elderly patients (≥60 years) starting beta-blockers and/or antidepressants. Based on the two main DDI alert systems (G-Standard and Pharmabase), incidences were divided between signalled (metoprolol-fluoxetine/paroxetine) and not-signalled (metoprolol-alternative antidepressants and alternative beta-blockers-paroxetine/fluoxetine) combinations. Incident users were defined as patients starting at least one signalled or a non-signalled combination. G-Standard signalled throughout the study period, whereas Pharmabase stopped after 2005. A total of 1763 patients had 2039 metoprolol-paroxetine/fluoxetine co-prescriptions, despite DDI alert systems, and about 57.3% were signalled. The number of metoprolol-alternative antidepressant combinations (incidences = 3150) was higher than alternative beta-blocker-paroxetine/fluoxetine combinations (incidences = 1872). Metoprolol users are more likely to be co-medicated with an alternative antidepressant (incidences = 2320) than paroxetine/fluoxetine users (incidences = 1232) are. The number of paroxetine/fluoxetine users co-prescribed with alternative beta-blockers was comparable to those co-medicated with metoprolol (about 50%). Less than 5% of patients received a substitute therapy after using metoprolol-paroxetine/fluoxetine. Most of the metoprolol users (90%) received a low dose (mean DDD = 0.47) regardless whether they were prescribed paroxetine/fluoxetine. Despite the signalling software, metoprolol

Design, development and in-vitro evaluation of metoprolol tartrate tablets containing xanthan-tragacanth.

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Rasul, Akhtar; Iqbal, Muhammad; Murtaza, Ghulam; Waqas, Muhammad K; Hanif, Muhammad; Khan, Shujaat A; Bhatti, Naveed S

2010-01-01

The present study was undertaken to develop oral sustained release tablets of metoprolol tartrate using natural hydrophilic matrix formers (xanthan gum and tragacanth). Sustained release matrix tablets of metoprolol tartrate were prepared by using different ratios of drug, xanthan gum and tragacanth. Microcrystalline cellulose (MCC) was used as diluent. The polymer was incorporated into a matrix system using direct compression technique. All the lubricated formulations were compressed using concave punches in compression machine. Compressed tablets were evaluated for diameter, hardness, friability, weight variation and in vitro dissolution using USP dissolution apparatus-II. Different formulations were evaluated with respect to dissolution profile in 900 mL phosphate buffer (pH 6.8), 0.1 M HCl solution and distilled water for 12 h at 37 degrees C. Increasing the amount of polymer (xanthan gum) in the formulation led to slow release of drug and decreasing the amount of polymer gave enhanced release of metoprolol tartrate. The kinetic treatment showed the best fitted different mathematical models (Zero order, First order, Higuchi's and Hixson-Crowell). Most of the solid matrix formulations followed Higuchi or zero order kinetics. The formulations F1, F2, F3 and F7, F8, F9 showed maximum linearity while the formulations F4, F5, F6 were not of linear behavior. The results showed that the formulation F9 containing 30% xanthan gum and 10% gum tragacanth is the most similar to that of the reference marketed preparation.

AAS and spectrophotometric determination of propranolol HCl and metoprolol tartrate.

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El-Ries, M A; Abou Attia, F M; Ibrahim, S A

2000-12-15

Two simple and accurate spectrophotometric methods are described for the determination of propranolol hydrochloride (I) and metoprolol tartrate (II). The methods are based on the reaction of each drug as a secondary amine: (a) with carbon disulphide, the formed complex extracted into iso-butyl methyl ketone (IBMK) after chelation with Cu(II) ions at pH 7.5, followed by measuring the absorbance at 435.4 nm or indirectly for the drug by flame atomic absorption spectrophotometry (AAS). The calibration graph is linear up to 40 and 60 microg ml(-1) with apparent molar absorptivities of 6.89 x 10(3) and 1.08 x 104 l mol(-1) cm(-1) and correlation coefficients of 0.9994 and 0.9995 for propranolol and metoprolol, respectively; (b) with pi-acceptors, tetracyanoethylene (TCNE), or chloranilic acid (CLA) to give highly coloured complex species. The coloured products are quantitated spectrophotometrically at 415 or 510 nm for the two drugs with TCNE and CLA, respectively, and obey Beer's Law with RSD less than 2.0. The methods were applied to the determination of these drugs in pharmaceutical preparation without interferences.

METOPROLOL VERSUS THIAZIDE DIURETICS IN HYPERTENSION - MORBIDITY RESULTS FROM THE MAPHY STUDY

NARCIS (Netherlands)

WIKSTRAND, J; WARNOLD, [No Value; TUOMILEHTO, J; OLSSON, G; BARBER, HJ; ELIASSON, K; ELMFELDT, D; JASTRUP, B; KARATZAS, NB; LEER, J; MARCHETTA, F; RAGNARSSON, J; ROBITAILLE, NM; VALKOVA, L; WESSELING, H; BERGLUND, G

The present study in hypertensive men (40-64 years old) with untreated diastolic blood pressure above 100 mm Hg was aimed at investigating whether metoprolol (n = 1,609) given as initial treatment would lower the risk for coronary events (sudden death and myocardial infarction) more effectively than

Cost-effectiveness of clopidogrel in myocardial infarction with ST-segment elevation: a European model based on the CLARITY and COMMIT trials.

Science.gov (United States)

Berg, Jenny; Lindgren, Peter; Spiesser, Julie; Parry, David; Jönsson, Bengt

2007-06-01

Several health economic studies have shown that the use of clopidogrel is cost-effective to prevent ischemic events in non-ST-segment elevation myocardial infarction (NSTEMI) and unstable angina. This study was designed to assess the cost-effectiveness of clopidogrel in short- and long-term treatment of ST-segment elevation myocardial infarction (STEMI) with the use of data from 2 trials in Sweden, Germany, and France: CLARITY (Clopidogrel as Adjunctive Reperfusion Therapy) and COMMIT (Clopidogrel and Metoprolol in Myocardial Infarction Trial). A combined decision tree and Markov model was constructed. Because existing evidence indicates similar long-term outcomes after STEMI and NSTEMI, data from the long-term NSTEMI CURE trial (Clopidogrel in Unstable Angina to Prevent Recurrent Events) were combined with 1-month data from CLARITY and COMMIT to model the effect of treatment up to 1 year. The risks of death, myocardial infarction, and stroke in an untreated population and long-term survival after all events were derived from the Swedish Hospital Discharge and Cause of Death register. The model was run separately for the 2 STEMI trials. A payer perspective was chosen for the comparative analysis, focusing on direct medical costs. Costs were derived from published sources and were converted to 2005 euros. Effectiveness was measured as the number of life-years gained (LYG) from clopidogrel treatment. In a patient cohort with the same characteristics and event rates as in the CLARITY population, treatment with clopidogrel for up to 1 year resulted in 0.144 LYG. In Sweden and France, this strategy was dominant with estimated cost savings of euro 111 and euro 367, respectively. In Germany, clopidogrel treatment had an incremental cost-effectiveness ratio (ICER) of euro 92/LYG. Data from the COMMIT study showed that clopidogrel treatment resulted in 0.194 LYG at an incremental cost of euro 538 in Sweden, euro 798 in Germany, and euro 545 in France. The corresponding

Development of sustained release capsules containing "coated matrix granules of metoprolol tartrate".

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Siddique, Sabahuddin; Khanam, Jasmina; Bigoniya, Papiya

2010-09-01

The objective of this investigation was to prepare sustained release capsule containing coated matrix granules of metoprolol tartrate and to study its in vitro release and in vivo absorption. The design of dosage form was performed by choosing hydrophilic hydroxypropyl methyl cellulose (HPMC K100M) and hydrophobic ethyl cellulose (EC) polymers as matrix builders and Eudragit® RL/RS as coating polymers. Granules were prepared by composing drug with HPMC K100M, EC, dicalcium phosphate by wet granulation method with subsequent coating. Optimized formulation of metoprolol tartrate was formed by using 30% HPMC K100M, 20% EC, and ratio of Eudragit® RS/RL as 97.5:2.5 at 25% coating level. Capsules were filled with free flowing optimized granules of uniform drug content. This extended the release period upto 12 h in vitro study. Similarity factor and mean dissolution time were also reported to compare various dissolution profiles. The network formed by HPMC and EC had been coupled satisfactorily with the controlled resistance offered by Eudragit® RS. The release mechanism of capsules followed Korsemeyer-Peppas model that indicated significant contribution of erosion effect of hydrophilic polymer. Biopharmaceutical study of this optimized dosage form in rabbit model showed 10 h prolonged drug release in vivo. A close correlation (R(2) = 0.9434) was established between the in vitro release and the in vivo absorption of drug. The results suggested that wet granulation with subsequent coating by fluidized bed technique, is a suitable method to formulate sustained release capsules of metoprolol tartrate and it can perform therapeutically better than conventional immediate release dosage form.

EFFECTS OF AMLODIPIN AND METOPROLOL ON AUTONOMIC SYSTEM IN EMOTIONAL AND COLD TESTS IN HYPERTENSIVE PATIENTS WITH DIFFERENT PSYCHOLOGICAL PROFILE

Directory of Open Access Journals (Sweden)

M. P. Rubanova

2006-01-01

Full Text Available Aim. To asses effects of amlodipin and metoprolol on autonomic system in emotional and cold tests in hypertensive patients with different psychological profile (PP Material and methods. 61 patients with arterial hypertension of II grade were observed. Therapy with amlodipin or metoprolol was prescribed and allowed to reach target blood pressure (BP level in all the patients. Patients were divided into 2 groups: 1-st one – patients with normal PP, 2-nd group – patients with subclinical depression. Patients were examined before and 30 days after therapy. Examination included ambulatory BP monitoring, assessment of autonomic status by variational intervalometry and spectral analysis of heart rate variability (HRV in cold and emotional tests. Depression and anxiety levels were determined with Bek’s and HADS scales.  Results. Treatment with amlodipin  and metoprolol can result in improvement, worsening or unchanging of PP.  In hypertensive patients with subclinical depression improving their PP resulted in autonomic reaction change: sympathetic activity increases and reaction on stress becomes more adequate. If subclinical depression occurred in hypertensive patients because of amlodipin and metoprolol therapy, sympathetic system stress-reaction decreased and parasympathetic influence increased. Conclusion. The study results show necessity of psychometric examination of hypertensive patients in order to reveal subclinical depression and anxiety.  

Metoprolol induces oxidative damage in common carp (Cyprinus carpio).

Science.gov (United States)

Martínez-Rodríguez, Héctor; Donkor, Kingsley; Brewer, Sharon; Galar-Martínez, Marcela; SanJuan-Reyes, Nely; Islas-Flores, Hariz; Sánchez-Aceves, Livier; Elizalde-Velázquez, Armando; Gómez-Oliván, Leobardo Manuel

2018-04-01

During the last decade, β-blockers such as metoprolol (MTP) have been frequently detected in surface water, aquatic systems and municipal water at concentrations of ng/L to μg/L. Only a small number of studies exist on the toxic effects induced by this group of pharmaceuticals on aquatic organisms. Therefore, the present study aimed to evaluate the oxidative damage induced by MTP in the common carp Cyprinus carpio, using oxidative stress biomarkers. To this end, indicators of cellular oxidation such as hydroperoxide content (HPC), lipid peroxidation (LPX) and protein carbonyl content (PCC) were determined, as well as the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). Also, concentrations of MTP and its metabolite O-desmethyl metoprolol were determined in water as well as carp gill, liver, kidney, brain and blood, along with the partial uptake pattern of these compounds. Results show that carp takes up MTP and its metabolite in the different organs evaluated, particularly liver and gill. The oxidative stress biomarkers, HPC, LPX, and PCC, as well as SOD and CAT activity all increased significantly at most exposure times in all organs evaluated. Results indicate that MTP and its metabolite induce oxidative stress on the teleost C. carpio and that the presence of these compounds may constitute a risk in water bodies for aquatic species. Copyright © 2018 Elsevier B.V. All rights reserved.

The simultaneous identification of metoprolol and its major acidic and basic metabolites in human urine by gas chromatography-mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Li, Feng; Cooper, S.F. [Universite du Quebec, Pointe-Claire (Canada)

1996-12-31

A novel gas chromatography-mass spectrometric (GC-MS) method was developed to confirm and identify metoprolol and its metabolites by double derivatization with S-(-)menthyl chloroformate [(-)-MCF] and N-methyl(trimethylsilyl-trifluoroacetamide) (MSTFA). This is the first report, which describes the simultaneous identification of metoprolol, its one major acidc and other basic metabolites in human urine based on solid-phase extraction with C{sub 18} reversed-phase cartridges. 12 refs., 4 figs.

Sotalol vs metoprolol for ventricular rate control in patients with chronic atrial fibrillation who have undergone digitalization: a single-blinded crossover study.

Science.gov (United States)

Kochiadakis, G E; Kanoupakis, E M; Kalebubas, M D; Igoumenidis, N E; Vardakis, K E; Mavrakis, H E; Vardas, P E

2001-01-01

To compare the effects of sotalol and metoprolol on heart rate, during isotonic (ITE) and isometric (IME) exercise and daily activities, in digitalized patients with chronic atrial fibrillation. The study had a randomized, single-blinded, crossover design. Twenty-three patients with chronic atrial fibrillation received placebo for 4 weeks, followed by a 4-week period of treatment with sotalol and metoprolol in random order. At the end of each period, the patients were assessed with 24-h ECG monitoring, a cardiopulmonary exercise test and a handgrip manoeuvre. Both agents produced a lower heart rate than placebo at rest and at all levels of isotonic exercise (P digitalized patients with atrial fibrillation. Sotalol is superior to metoprolol at submaximal exercise, resulting in better rate control during daily activities.

Primary HPV screening for cervical cancer prevention: results from European trials

DEFF Research Database (Denmark)

Lynge, Elsebeth; Rebolj, Matejka

2009-01-01

testing increased the detection of cervical intraepithelial neoplasia (CIN) grade 2+. Detection of CIN3+ was significantly increased in two trials (relative risks [RRs] 1.70 and 2.26), but not in three other trials (RRs 1.03, 1.09 and 1.31). In three trials, seven extra women had a false-positive test......Six European, randomized, controlled trials that will compare human papillomavirus (HPV) testing with cytological testing for cervical screening are under way. We reviewed the results published so far to compare the benefits and costs for participating women. At baseline screening, use of HPV...

COMPARISON BETAXOLOL AND METOPROLOL TARTRATE THERAPIES IN PATIENTS WITH ARTERIAL HYPERTENSION ASSOCIATED WITH STABLE ANGINA

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A. A. Anderzhanova

2009-01-01

Full Text Available Aim. To compare antihypertensive, antianginal and antiischemic efficacy of β1-selective adrenoblockers (betaxolol and metoprolol tartrate in patients with arterial hypertension (HT of 1-2 degree associated with stable angina class II.Material and methods. 100 patients (aged 23-66 y.o. with HT associated with stable angina or without angina were involved in the study. Patients were randomized into 2 groups (G1 and G2. G1 patients were treated with betaxolol, and G2 patients – with metoprolol tartrate. Ambulatory BP and electrocardiogram monitoring, exercise stress-test, echocardiography, evaluating of respiratory function, blood analysis was performed initially and in 30 and 90 days of treatment.Results. Target BP level was reached in 44 (88% patients treated with betaxolol (average daily dose 10±4 mg. 34 patients of G1 took 10 mg daily. Target BP level was reached in 41 (82% patients treated with metoprolol tartrate (average daily dose 150±27 mg. 30 patients of G2 took 150 mg daily. Exercise tolerance increased and a number of ischemic ST segment depressions reduced significantly in both groups. There were no significant differences in antihypertensive, antianginal, and antiischemic efficacy between groups.Conclusion. Betaxolol advantage is an ability to maintain target BP level more than 24 hours. A possibility to take betaxolol once a day raises patient’s compliance with therapy.

COMPARISON BETAXOLOL AND METOPROLOL TARTRATE THERAPIES IN PATIENTS WITH ARTERIAL HYPERTENSION ASSOCIATED WITH STABLE ANGINA

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A. A. Anderzhanova

2016-01-01

Full Text Available Aim. To compare antihypertensive, antianginal and antiischemic efficacy of β1-selective adrenoblockers (betaxolol and metoprolol tartrate in patients with arterial hypertension (HT of 1-2 degree associated with stable angina class II.Material and methods. 100 patients (aged 23-66 y.o. with HT associated with stable angina or without angina were involved in the study. Patients were randomized into 2 groups (G1 and G2. G1 patients were treated with betaxolol, and G2 patients – with metoprolol tartrate. Ambulatory BP and electrocardiogram monitoring, exercise stress-test, echocardiography, evaluating of respiratory function, blood analysis was performed initially and in 30 and 90 days of treatment.Results. Target BP level was reached in 44 (88% patients treated with betaxolol (average daily dose 10±4 mg. 34 patients of G1 took 10 mg daily. Target BP level was reached in 41 (82% patients treated with metoprolol tartrate (average daily dose 150±27 mg. 30 patients of G2 took 150 mg daily. Exercise tolerance increased and a number of ischemic ST segment depressions reduced significantly in both groups. There were no significant differences in antihypertensive, antianginal, and antiischemic efficacy between groups.Conclusion. Betaxolol advantage is an ability to maintain target BP level more than 24 hours. A possibility to take betaxolol once a day raises patient’s compliance with therapy.

Drug Release Kinetics and Front Movement in Matrix Tablets Containing Diltiazem or Metoprolol/λ-Carrageenan Complexes

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Ruggero Bettini

2014-01-01

Full Text Available In this work we investigated the moving boundaries and the associated drug release kinetics in matrix tablets prepared with two complexes between λ-carrageenan and two soluble model drugs, namely, diltiazem HCl and metoprolol tartrate aiming at clarifying the role played by drug/polymer interaction on the water uptake, swelling, drug dissolution, and drug release performance of the matrix. The two studied complexes released the drug with different mechanism indicating two different drug/polymer interaction strengths. The comparison between the drug release behaviour of the complexes and the relevant physical mixtures indicates that diltiazem gave rise to a less soluble and more stable complex with carrageenan than metoprolol. The less stable metoprolol complex afforded an erodible matrix, whereas the stronger interaction between diltiazem and carrageenan resulted in a poorly soluble, slowly dissolving matrix. It was concluded that the different stability of the studied complexes affords two distinct drug delivery systems: in the case of MTP, the dissociation of the complex, as a consequence of the interaction with water, affords a classical soluble matrix type delivery system; in the case of DTZ, the dissolving/diffusing species is the complex itself because of the very strong interaction between the drug and the polymer.

Atenolol en metoprolol beide geschikt als beta-blokker voor de behandeling van hypertensie

NARCIS (Netherlands)

van den Born, B. J. H.; Brewster, L. M.; Koopmans, R. P.; van Montfrans, G. A.

2005-01-01

Recently the guideline committee of the Dutch College of General Practitioners advocated the use of metoprolol instead of atenolol in patients with an indication for beta-blockers. This recommendation was based on a recent meta-analysis in The Lancet in which no effect was observed in favour

INFLUENCE OF METOPROLOL SUCCINATE ON REGULATORY AND ADAPTIVE STATUS OF PATIENTS WITH CHRONIC HEART FAILURE FUNCTIONAL CLASS I. RESULTS OF NOT COMPARATIVE STUDY

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V. G. Tregubov

2011-01-01

Full Text Available Aim. To estimate metoprolol succinate effect on regulatory and adaptive status (RAS of patients with сhronic heart failure (CHF functional class (FC I and arterial hypertension (HT I-II stages. Material and methods. 51 patients with CHF FC I and HT I-II stage, (30 men and 21 women aged 52.6±1.4 yeas. Cardio-respiratory synchronism (CRS test, 6-minute walking test, tread-mill burden test with registration of maximal oxygen consumption, 24-hour blood pressure monitoring, echocardiography and determination of N-terminal pro-brain natriuretic peptide (NT-proBNP blood level were performed initially and after 6 months of therapy with metoprolol succinate (dose 78.1±5.7 mg/day in sustained-release presentation. Results. Metoprolol succinate therapy had no significant effect on RAS (there was no unidirectional dynamics of the basic CRS test parameters: a range of synchronization decreased significantly from 8.8±0.4 to 7.2±0.6 сardio-respiratory cycles per minute (in 18%; р<0.05, and duration of CRS development on the minimal boundary from 18.8±2.2 to 14.3±1.2 сardiocycles (in 24%; р<0,05; RAS index considerably did not change, myocardium structure, exercise tolerance and neuro-humoral activity. Metoprolol therapy only moderately improved left ventricle diastolic function. Conclusion. Metoprolol succinate therapy has no significant effect on RAS of patients with CHF FC I and HT I-II stages.

Enhanced oral bioavailability of metoprolol with gallic acid and ellagic acid in male Wistar rats: involvement of CYP2D6 inhibition.

Science.gov (United States)

Athukuri, Bhargavi Latha; Neerati, Prasad

2016-12-01

Cytochrome P450-2D6 (CYP2D6), a member of the CYP450 mixed function oxidase system, is an important CYP isoform with regard to herbal-drug interactions and is responsible for the metabolism of nearly 25% of drugs. Until now, studies on the effects of various phytochemicals on CYP2D6 activity in vivo have been very rare. Gallic acid and ellagic acid are natural polyphenols which are widely distributed in fruits and medicinal plants. In the present study, the effects of gallic acid and ellagic acid pretreatment on intestinal transport and oral bioavailability of metoprolol were investigated. The intestinal transport of metoprolol was assessed by conducting an in situ single pass intestinal perfusion (SPIP) study. The bioavailability study was conducted to evaluate the pharmacokinetic parameters of orally administered metoprolol in rats. After pretreatment with gallic acid and ellagic acid, no significant change in effective permeability of metoprolol was observed at the ileum part of rat intestine. A significant improvement in the peak plasma concentration (Cmax) and area under the serum concentration-time profile (AUC) and decrease in clearance were observed in rats pretreated with gallic acid and ellagic acid. Gallic acid and ellagic acid significantly enhanced the oral bioavailability of metoprolol by inhibiting CYP2D6-mediated metabolism in the rat liver. Hence, adverse herbal-drug interactions may result with concomitant ingestion of gallic acid and ellagic acid supplements and drugs that are CYP2D6 substrates. The clinical assessment of these interactions should be further investigated in human volunteers.

Data on administration of cyclosporine, nicorandil, metoprolol on reperfusion related outcomes in ST-segment Elevation Myocardial Infarction treated with percutaneous coronary intervention

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Gianluca Campo

2017-10-01

Full Text Available Mortality and morbidity in patients with ST elevation myocardial infarction (STEMI treated with primary percutaneous coronary intervention (PCI are still high [1]. A huge amount of the myocardial damage is related to the mitochondrial events happening during reperfusion [2]. Several drugs directly and indirectly targeting mitochondria have been administered at the time of the PCI and their effect on fatal (all-cause mortality, cardiovascular (CV death and non fatal (hospital readmission for heart failure (HF outcomes have been tested showing conflicting results [3–16]. Data from 15 trials have been pooled with the aim to analyze the effect of drug administration versus placebo on outcome [17]. Subgroup analysis are here analyzed: considering only randomized clinical trial (RCT on cyclosporine or nicorandil [3–5,9–11], excluding a trial on metoprolol [12] and comparing trial with follow-up length <12 months versus those with longer follow-up [3–16]. This article describes data related article titled “Clinical Benefit of Drugs Targeting Mitochondrial Function as an Adjunct to Reperfusion in ST-segment Elevation Myocardial Infarction: a Meta-Analysis of Randomized Clinical Trials” [17].

Ultrastructural effects of pharmaceuticals (carbamazepine, clofibric acid, metoprolol, diclofenac) in rainbow trout (Oncorhynchus mykiss) and common carp (Cyprinus carpio).

Science.gov (United States)

Triebskorn, R; Casper, H; Scheil, V; Schwaiger, J

2007-02-01

In order to assess potential effects of human pharmaceuticals in aquatic wildlife, laboratory experiments were conducted with carbamazepine, clofibric acid, metoprolol, and diclofenac using fish as test organisms. For each substance, at least one environmentally relevant concentration was tested. In liver, kidney, and gills of trout and carp exposed to carbamazepine, clofibric acid, and metoprolol, ultrastructural effects were qualitatively described and semi-quantitatively assessed. The obtained assessment values were compared with previously published data for diclofenac-induced effects in rainbow trout tissues. Quantitative analyses of protein accumulated in kidneys of diclofenac-exposed trout corroborated previously published data which indicated that diclofenac induced a severe glomerulonephritis resulting in a hyaline droplet degeneration of proximal kidney tubules. The investigations provided information on the general health status of the pharmaceutical-exposed fish, and allowed a differential diagnosis of harmful effects caused by these human pharmaceuticals in non-target species. For the different cytological effects observed, lowest observed effect concentration (LOECs) for at least three of the test substances (diclofenac, carbamazepine, metoprolol) were in the range of environmentally relevant concentrations (1 microg/L).

COMPARATIVE STUDY OF NEW DRUG OF LONG ACTING METOPROLOL TARTRATE - EGILOK RETARD AND ORIGINAL DRUG OF METOPROLOL SUCCINATE – BETALOC ZOK IN PATIENTS WITH MILD TO MODERATE ARTERIAL HYPERTENSION

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J. V. Lukina

2015-12-01

Full Text Available Aim. To study efficiency and safety of new drug of long acting metoprolol tartrate, “Egilok retard” (ER in patients with mild to moderate arterial hypertension (AH in comparison with the original drug of metoprolol succinat, “Betaloc ZOK” (BZ, possibility of reaching target blood pressure (BP level with treatment with each drug.Material and methods. 30 patients (11 men and 19 women with mild to moderate AH took part in randomized, open, cross over study. Previous antihypertensive treatment had been canceled for all the patients 10-14 days before the study started. Each patient by turns was treated during 6 weeks with ER and BZ 50-100 mg daily. After cancellation of the previous antihypertensive therapy, BZ and ER were prescribed (according to the randomization table in dose 50 mg daily. Drugs were taken once per day. 29 patients completed therapy with the first drug of randomization, 25 patients – with the second. After 2 weeks efficiency of treatment was assessed by target BP level achievement (< 140/90 mmHg. If efficiency of beta-adrenoblocker (BB was not sufficient, the dose of the drug was doubled to 100 mg daily, if target level was reached – the dose remained unchanged. Treatment with the settled dose was held within next 4 weeks. After 6-week treatment with the first randomized drug antihypertensive therapy was canceled for 10-14 days depending on the BB dose. At each visit office BP and heart rate were assessed, EKG was registered. Side-effects were registered according to the self-control diary, questionnaire results, examination and EKG data.Results. After 6-week treatment with ER and BZ average level of systolic BP reduced by 15,7 and 15,2 mmHg, of diastolic BP – by 8,0 and 4,5 mmHg, heart rate – by 4,1 and 4,3 beat/min respectively. Differences between antihypertensive and heart rate lowering effect of the studied drugs were not significant. Target BP level with treatment with both drugs was reached in approximately

COMPARATIVE STUDY OF NEW DRUG OF LONG ACTING METOPROLOL TARTRATE - EGILOK RETARD AND ORIGINAL DRUG OF METOPROLOL SUCCINATE – BETALOC ZOK IN PATIENTS WITH MILD TO MODERATE ARTERIAL HYPERTENSION

Directory of Open Access Journals (Sweden)

J. V. Lukina

2005-01-01

Full Text Available Aim. To study efficiency and safety of new drug of long acting metoprolol tartrate, “Egilok retard” (ER in patients with mild to moderate arterial hypertension (AH in comparison with the original drug of metoprolol succinat, “Betaloc ZOK” (BZ, possibility of reaching target blood pressure (BP level with treatment with each drug.Material and methods. 30 patients (11 men and 19 women with mild to moderate AH took part in randomized, open, cross over study. Previous antihypertensive treatment had been canceled for all the patients 10-14 days before the study started. Each patient by turns was treated during 6 weeks with ER and BZ 50-100 mg daily. After cancellation of the previous antihypertensive therapy, BZ and ER were prescribed (according to the randomization table in dose 50 mg daily. Drugs were taken once per day. 29 patients completed therapy with the first drug of randomization, 25 patients – with the second. After 2 weeks efficiency of treatment was assessed by target BP level achievement (< 140/90 mmHg. If efficiency of beta-adrenoblocker (BB was not sufficient, the dose of the drug was doubled to 100 mg daily, if target level was reached – the dose remained unchanged. Treatment with the settled dose was held within next 4 weeks. After 6-week treatment with the first randomized drug antihypertensive therapy was canceled for 10-14 days depending on the BB dose. At each visit office BP and heart rate were assessed, EKG was registered. Side-effects were registered according to the self-control diary, questionnaire results, examination and EKG data.Results. After 6-week treatment with ER and BZ average level of systolic BP reduced by 15,7 and 15,2 mmHg, of diastolic BP – by 8,0 and 4,5 mmHg, heart rate – by 4,1 and 4,3 beat/min respectively. Differences between antihypertensive and heart rate lowering effect of the studied drugs were not significant. Target BP level with treatment with both drugs was reached in approximately

Efficacy of antipsychotic drugs against hostility in the European First-Episode Schizophrenia Trial (EUFEST)

NARCIS (Netherlands)

Volavka, Jan; Czobor, Pal; Derks, Eske M.; Bitter, Istvan; Libiger, Jan; Kahn, René S.; Fleischhacker, W. Wolfgang; Kahn, R. S.; Fleischhacker, W. W.; Boter, H.; Keet, I. P. M.; Brugman, C.; Davidson, M.; Dollfus, S.; Gaebel, W.; Galderisi, S.; Gheorghe, M.; Gonen, I.; Grobbee, D. E.; Hranov, L. G.; Hummer, M.; Libiger, J.; Králové, Hradec; Lindefors, N.; López-Ibor, J. J.; Nijssen, K.; Peuskens, J.; Prelipceanu, D.; Riecher-Rössler, A.; Rybakowski, J. K.; Sedvall, G.; von Wilmsdorff, M.

2011-01-01

To compare the effects of haloperidol, amisulpride, olanzapine, quetiapine, and ziprasidone on hostility in first-episode schizophrenia, schizoaffective disorder, or schizophreniform disorder. We used the data acquired in the European First-Episode Schizophrenia Trial, an open, randomized trial

Debrisoquine phenotype and the pharmacokinetics and beta-2 receptor pharmacodynamics of metoprolol and its enantiomers

NARCIS (Netherlands)

Jonkers, R. E.; Koopmans, R. P.; Portier, E. J.; van Boxtel, C. J.

1991-01-01

The metabolism of the cardioselective beta-blocker metoprolol is under genetic control of the debrisoquine/sparteine type. The two metabolic phenotypes, extensive (EM) and poor metabolizers (PM), show different stereoselective metabolism, resulting in apparently higher beta-1 adrenoceptor

Comparison of the permeability of metoprolol and labetalol in rat, mouse, and Caco-2 cells: use as a reference standard for BCS classification.

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Incecayir, Tuba; Tsume, Yasuhiro; Amidon, Gordon L

2013-03-04

The purpose of this study was to investigate labetalol as a potential high permeability reference standard for the application of Biopharmaceutics Classification Systems (BCS). Permeabilities of labetalol and metoprolol were investigated in animal intestinal perfusion models and Caco-2 cell monolayers. After isolating specific intestinal segments, in situ single-pass intestinal perfusions (SPIP) were performed in rats and mice. The effective permeabilities (Peff) of labetalol and metoprolol, an FDA standard for the low/high Peff class boundary, were investigated in two different segments of rat intestine (proximal jejunum and distal ileum) and in the proximal jejunum of mouse. No significant difference was found between Peff of metoprolol and labetalol in the jejunum and ileum of rat (0.33 ± 0.11 × 10(-4) vs 0.38 ± 0.06 × 10(-4) and 0.57 ± 0.17 × 10(-4) vs 0.64 ± 0.30 × 10(-4) cm/s, respectively) and in the jejunum of mouse (0.55 ± 0.05 × 10(-4) vs 0.59 ± 0.13 × 10(-4) cm/s). However, Peff of metoprolol and labetalol were 1.7 and 1.6 times higher in the jejunum of mouse, compared to the jejunum of rat, respectively. Metoprolol and labetalol showed segmental-dependent permeability through the rat intestine, with increased Peff in the distal ileum in comparison to the proximal jejunum. Most significantly, Peff of labetalol was found to be concentration-dependent. Decreasing concentrations of labetalol in the perfusate resulted in decreased Peff compared to Peff of metoprolol. The intestinal epithelial permeability of labetalol was lower than that of metoprolol in Caco-2 cells at both apical pH 6.5 and 7.5 (5.96 ± 1.96 × 10(-6) vs 9.44 ± 3.44 × 10(-6) and 15.9 ± 2.2 × 10(-6) vs 23.2 ± 7.1 × 10(-6) cm/s, respectively). Labetalol exhibited higher permeability in basolateral to apical (BL-AP) compared to AP-BL direction in Caco-2 cells at 0.1 times the highest dose strength (HDS) (46.7 ± 6.5 × 10(-6) vs 14.2 ± 1.5 × 10(-6) cm/s). The P

IMPACT OF PREOPERATIVE METOPROLOL ON THE OCCURRENCE OF NEW-ONSET ATRIAL FIBRILLATION AFTER CORONARY ARTERY BYPASS GRAFTING

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Salla Surya Prakasarao

2016-09-01

Full Text Available BACKGROUND Postoperative Atrial fibrillation (POAF is the most frequent arrhythmia observed after Coronary artery bypass grafting (CABG. Worldwide incidence is documented to be 20-30% in patients undergoing isolated Coronary artery bypass grafting (CABG. There is no published data for Indian population so far. Hence, the objective of our study is to analyse the occurrence of newonset POAF in our Indian population and to assess whether the preoperative beta-blocker therapy has any role in its prevention. MATERIAL AND METHODS This is a retrospective and prospective observational study of coronary artery disease patients in Andhra Medical College, Visakhapatnam, who underwent coronary artery bypass grafting at various institutions between August 2013 and August 2014. The patients with documented AF during the preoperative period and patients undergoing associated cardiac procedures have been excluded from the study. Data has been collected from the patients’ medical records and the relative clinical variables were analysed. Chi-square test used for statistical analysis. RESULTS 227 patients with coronary artery disease (followed up at our centre were found to have undergone CABG during the study period. Among the 227 patients, 191 (84.14% were males and 36 (15.85% were females. The mean age of patients developing AF was 61.9±8.7 and for patients in sinus rhythm was 58.7±7.9 years (range: 37-80 years. 159 patients received preoperative Metoprolol and 68 patients were free from Metoprolol usage. The overall incidence of AF was 6.16%. 3.1% of patients with Metoprolol were noted to have AF while 13.23% of patients with no Metoprolol coverage developed new-onset AF (p<0.05. 14.28% of patients developing AF were with LV function <40%. The mean duration of ICU stay for patients who had POAF was 73.74±39.33 hours and 34.47±19.39 hours for patients in sinus rhythm. CONCLUSION The incidence of Postoperative Atrial fibrillation in Indian patients is

Ex Vivo Correlation of the Permeability of Metoprolol Across Human and Porcine Buccal Mucosa

DEFF Research Database (Denmark)

Meng-Lund, Emil; Marxen, Eva; Pedersen, Anne Marie Lynge

2014-01-01

.0. In addition, hematoxylin-eosin and Alcian blue-van Gieson were used as tissue stains to evaluate the histology and the presence of acidic polysaccharides (e.g., mucins), respectively. The permeability of metoprolol was decreased in human buccal mucosa by almost twofold when compared with porcine buccal mucosa...

EFFECTS OF CARVEDILOL AND METOPROLOL ON VEGETATIVE REGULATION OF HEART AND MICROCIRCULATION IN PATIENTS WITH HYPERTENSION AND HIGH BODY MASS

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A. R. Kiselev

2016-01-01

Full Text Available Aim. To study effects of carvedilol and metoprolol on vegetative regulation of heart and microcirculatory vessels in patients with arterial hypertension (HT of 1-2 degrees and high body mass/obesity.Material and methods. Patients with HT of 1-2 degrees (n=25; aged 51±8 y.o. were included in the study. Registration of 0,1 Hz-fluctuations in heart rhythm variability and microcirculation change was performed during passive orthostatic test at spontaneous breath (duration of each test stage 10 min. Synchronization of 0,1 Hz-rhythms was estimated by calculation of phases difference and a numerical measure of synchronization. Frequency estimations of heart rhythm variability spectrum were performed in high and low frequency ranges additionaly.Results. Carvedilol and metoprolol have the comparable antihypertensive effect and influence on vegetative regulation of cardiovascular system in patients with HT. Both drugs have negative influence on synchronization of 0,1 Hz-rhythms in initially high systolic blood pressure level (>150 mm Hg.Conclusion. Carvedilol and metoprolol have comparable influence on synchronization of 0,1 Hz-rhythms in cardiovascular system.

Stress degradation studies of Telmisartan and Metoprolol extended release tablets by a validated stability indicating reverse phase-high performance liquid chromatography method

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Kabeer Ahmed Shaikh

2014-01-01

Full Text Available Background and Aim: A sensitive reverse phase high-performance liquid chromatographic method has been developed for the simultaneous determination of Telimisartan and Metoprolol in tablet dosage form. Materials and Method: The chromatographic separation was achieved on Inertsil ODS 3V, 150 x 4.6 mm, 5μ analytical column. Mobile phase consisting of mobile phase A- 0.05M sodium dihydrogen phosphate buffer pH 3.0 and mobile phase B-Acetonitrile, with gradient program time in min /Mobile phase B% 0/22, 4/45, 6/45,18/22, 20/22. Detector was set at 222nm. Results and Conclusion: The described method shows excellent linearity over a range of 80-2 μg mL−1 for Telmisartan and 100-4 μg mL−1 for Metoprolol. The correlation coefficient for Telmisartan is 0.9998 and Metoprolol is 0.9999. The proposed method was found to be suitable for determination of Telmisartan and Metoprolol in tablet dosage form. Forced degradation of the drug product was conducted in accordance with the ICH guideline. Acidic, basic, hydrolytic, oxidative, thermal and photolytic degradation was used to assess the stability indicating power of the method. The drug product was found to be stable in acid, oxidation, thermal and photolytic stress condition and found degradation in base hydrolysis stress condition.

Complying with the European Clinical Trials directive while surviving the administrative pressure

DEFF Research Database (Denmark)

Frandsen, Thomas Leth; Heyman, Mats; Abrahamsson, Jonas

2014-01-01

The European Clinical Trials Directive of 2004 has increased the amount of paper work and reduced the number of initiated clinical trials. Particularly multinational trials have been delayed. To meet this challenge we developed a novel, simplified, fast and easy strategy for on-line toxicity......-known serious, but rarer events with focus on changes in therapy introduced in the treatment protocol. This toxicity registration strategy was approved by the relevant regulatory authorities in all seven countries involved, as compliant within the EU directive of 2004. The centre compliance to registration...

The impact of carvedilol and metoprolol on serum lipid concentrations and symptoms in patients with hyperthyroidism.

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Ozbilen, Sabahattin; Eren, Mehmet Ali; Turan, Mehmet Nuri; Sabuncu, Tevfik

2012-01-01

Hyperthyroidism is associated with unpleasant symptoms and hypertension due to increased adrenergic tone. Therefore, beta-blockers are often used in hyperthyroid patients. While some beta-blockers (such as propronolol and metoprolol) may have unwanted effects on lipid profile, carvedilol, a new alpha- and beta-blocker, has been suggested to have some metabolic advantages with respect to lipid profiles in hypertensive patients. However, this has not been shown in hyperthyroid patients. We aimed to compare the effects of two beta-blockers (metoprolol and carvedilol) on the lipid profiles of hyperthyroid patients with hypertension. Thirty patients with hyperthyroidism and hypertension were randomly assigned to receive either carvedilol (n = 15) or metoprolol (n = 15). Thyroid-stimulating hormone (TSH), free T3, free T4, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride, and total cholesterol levels were measured before and following 3 months of treatment. Systolic and diastolic blood pressure, heart rate, TSH, and free T4 improved significantly in both treatment groups. There were no statistically significant changes in the lipid parameters in either of the two treatment groups; however, triglyceride levels slightly decreased with carvedilol treatment. There were also no differences between the two groups in terms of the typical symptoms of hyperthyroidism. Carvedilol might be a preferred agent to treat hyperthyroid patients who have hypertension and dyslipidemia. This is likely due to the possible beneficial effect of carvedilol on lipid parameters, especially on triglyceride levels.

LC-MS analysis in the e-beam and gamma radiolysis of metoprolol tartrate in aqueous solution: Structure elucidation and formation mechanism of radiolytic products

Energy Technology Data Exchange (ETDEWEB)

Slegers, Catherine [Unite d' Analyse Chimique et Physico-chimique des Medicaments, Universite Catholique de Louvain, CHAM 72.30, Avenue E. Mounier, 72, B-1200, Brussels (Belgium)]. E-mail: catherine.slegers@skynet.be; Maquille, Aubert [Unite d' Analyse Chimique et Physico-chimique des Medicaments, Universite Catholique de Louvain, CHAM 72.30, Avenue E. Mounier, 72, B-1200, Brussels (Belgium); Deridder, Veronique [Unite d' Analyse Chimique et Physico-chimique des Medicaments, Universite Catholique de Louvain, CHAM 72.30, Avenue E. Mounier, 72, B-1200, Brussels (Belgium); Sonveaux, Etienne [Unite de Chimie Pharmaceutique et de Radiopharmacie, Universite Catholique de Louvain, Brussels (Belgium); Habib Jiwan, Jean-Louis [Laboratoire de Spectrometrie de Masse, Universite Catholique de Louvain, Louvain-La-Neuve (Belgium); Tilquin, Bernard [Unite d' Analyse Chimique et Physico-chimique des Medicaments, Universite Catholique de Louvain, CHAM 72.30, Avenue E. Mounier, 72, B-1200, Brussels (Belgium)

2006-09-15

E-beam and gamma products from the radiolysis of aqueous solutions of ({+-})-metoprolol tartrate, saturated in nitrogen, are analyzed by HPLC with on-line mass and UV detectors. The structures of 10 radiolytic products common to e-beam and gamma irradiations are elucidated by comparing their fragmentation pattern to that of ({+-})-metoprolol. Two of the radiolytic products are also metabolites. Different routes for the formation of the radiolytic products are proposed.

COMPARISON OF THE METABOLIC EFFECTS OF CARVEDILOL AND METОPROLOL IN HYPERTENSIVE PATIENTS WITH OVERWEIGHT AND OBESITY. THE CAMELLIA TRIAL

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S. Y. Martsevich

2009-01-01

Full Text Available Aim. To compare two therapies based on carvedilol or metoprolol in hypertensive patients with overweight and obesity.Material and methods. 320 patients with arterial hypertension (1-2 degree were involved in the study. 160 patients received carvedilol and 160 patients – metoprolol. Both randomized groups were comparable on the main clinical characteristics.Results. By the end of the study both systolic and diastolic blood pressure (SBP, DBP reduced in both groups р<0,0001. There were not differences of antihypertensive effect between investigated drugs (р=0,88 for SBP and р=0,61 for DBP. By the end of the study body mass index decreased by 0,52±0,10 kg/m2 (р<0,0001 in carvedilol group and by 0,26±0,10kg/m2 (р<0,01 in metoprolol group. Carvedilol in comparison with metoprolol had more positive effects on glucose (р<0,01 and lipid blood levels. By the end of the study urine acid blood level reduction was observed in carvedilol group (-16,6 μmol/l while an increasing tendency - in metoprolol group. Carvedilol did not have negative effect on serum potassium and creatinine levels. Adverse effects rate was 6,3% in carvedilol group and 3,8% - in metoprolol group.Conclusion. The results of open, randomized CAMELLIA trial confirmed antihypertensive effect and good tolerability of carvedilol in common clinical practice as well as demonstrated some its advantages in patients with metabolic syndrome. Carvedilol has positive metabolic effects on lipid, glucose and uric acid levels. Carvedilol therapy is more preferable in patients with arterial hypertension and metabolic risk factors.

Comparison of dynamic of autonomic control indices in cardiovascular system under the treatment by ACE inhibitor (Enalapril and beta-blocker (Metoprolol in patients with hypertension

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A.R. Kiselev

2010-03-01

Full Text Available The objective of the present research was to compare the influence of Enalapril and Metoprolol on synchronization of 0.1 Hz-regulation of heart and blood microcirculation. 42 patients aged 49±9 years old with hypertension I, II were included in the study. 0.1 Hz-oscillations in heart rate variability (HRV and blood microcirculation were registered during the passive orthostatic sign while breathing spontaneously. The duration of each test was 10 minutes. Synchronization was estimated as a phase difference between 0.1 Hz-rhythms in heart rate and in filling of blood microcirculation. Quantitative measures of synchronization were also estimated. In addition frequency values of HRV spectrum in LF- and HF-ranges were assessed. Enalapril and Metoprolol had comparable effect on blood pressure reduction. Treatment with both Enalapril and Metoprolol in patients with significant vegetative dysfunction resulted in repair of functional interaction between 0.1 Hz-regulation of heart and blood microcirculation. Enalapril was preferred in hypertensive patients with prevalence of disorders of vegetative regulation of blood microcirculation. Metoprolol influenced positively on 0,1 Hz-rhythm synchronization in patients with predominance of heart vegetative regulation dysfunction and in patients with sympathicotonia. In patients with hypertension and initially normal level of synchronization of 0.1 Hz-mechanisms treatment with Enalapril or Metoprolol caused functional dissociation. Differentiated approach to the choice of hypertensive therapy should consider individual peculiarities of system vegetative dysfunction. The level of synchronization of 0.1 Hz-rhythms in cardiovascular system should especially be evaluated initially and during the treatment

LC-MS analysis in the e-beam and gamma radiolysis of metoprolol tartrate in aqueous solution: Structure elucidation and formation mechanism of radiolytic products

International Nuclear Information System (INIS)

Slegers, Catherine; Maquille, Aubert; Deridder, Veronique; Sonveaux, Etienne; Habib Jiwan, Jean-Louis; Tilquin, Bernard

2006-01-01

E-beam and gamma products from the radiolysis of aqueous solutions of (±)-metoprolol tartrate, saturated in nitrogen, are analyzed by HPLC with on-line mass and UV detectors. The structures of 10 radiolytic products common to e-beam and gamma irradiations are elucidated by comparing their fragmentation pattern to that of (±)-metoprolol. Two of the radiolytic products are also metabolites. Different routes for the formation of the radiolytic products are proposed

Efficacy of trimetazidine combining with metoprolol on plasma BNP in coronary heart disease patients with heart failure

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Ping Li

2016-01-01

Full Text Available Objective: To explore the effect of combined application of trimetazidine and metoprolol on plasma BNP in coronary heart disease patients with heart failure and the clinical efficacy. Methods: A total of 140 cases of coronary heart disease patients with heart failure treated in Cardiology Department of our hospital from May 2012 to January 2015 were selected and divided into study group and control group by random number table method. The control group received digitalis, diuretics, ACEI (angiotensin-converting enzyme inhibitor and other conventional drugs for treatment, the study group received combined use of trimetazidine and metoprolol on the basis of routine treatment of the control group, and treatment duration was 12 weeks. Then plasma BNP, systolic blood pressure, heart rate, left ventricular end diastolic diameter (LVEDD, left ventricular end systolic end (LVESD and left ventricular ejection fraction (LVEF of two groups before and after treatment were statistically analyzed, and the overall effect was evaluated. Results: Before treatment, there were no significant differences in plasma BNP, blood pressure, heart rate, LVEDD, LVESD and LVEF between the two groups; after treatment, plasma BNP, blood pressure, heart rate, LVEDD and LVESD of both groups decreased and LVEF increased, but the changes in study group were better than those in control group. Conclusion: Trimetazidine combined with metoprolol has better application effect in plasma BNP decrease and heart function improvement in coronary heart disease patients with heart failure.

The influence of carvedilol vs. metoprolol on sympathetic activity and hemostasis in patients with heart failure

NARCIS (Netherlands)

De Peuter, O.R.; Kok, W. E.; Verberne, H.J.; Van Den Bogaard, B.; Truijen, J.; Schaap, M.C.; Nieuwland, R.; Meijers, J.C.; Verheul, J.A.; De Groot, C.A.; Bakx, A.D.; Somsen, G.A.; Brewster, L.M.; Buller, H.R.; Kamphuisen, P.W.

2011-01-01

Background: Carvedilol, a non-selective beta-blocker, may be more effective in reducing the risk of thromboembolic events in heart failure, compared to metoprolol, a selective beta-blocker (De Peuter et al., Eur J Heart Fail, in press/ISTH 2009). We hypothesized that carvedilol lowers this risk

Preparation of Biological Samples Containing Metoprolol and Bisoprolol for Applying Methods for Quantitative Analysis

OpenAIRE

Corina Mahu Ştefania; Monica Hăncianu; Luminiţa Agoroaei; Anda Cristina Coman Băbuşanu; Elena Butnaru

2015-01-01

Arterial hypertension is a complex disease with many serious complications, representing a leading cause of mortality. Selective beta-blockers such as metoprolol and bisoprolol are frequently used in the management of hypertension. Numerous analytical methods have been developed for the determination of these substances in biological fluids, such as liquid chromatography coupled with mass spectrometry, gas chromatography coupled with mass spectrometry, high performance liquid chromatography. ...

Formulation and in vitro evaluation of fast dissolving tablets of metoprolol tartrate

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Mangesh Machhindranath Satpute

2013-12-01

Full Text Available The demand for fast dissolving tablets has been growing during the last decade, especially for elderly and children who have swallowing difficulties. In the present work, fast dissolving tablets of metoprolol tartrate, were prepared using sodium starch glycolate, sodium croscarmellose and crospovidone as superdisintegrants, by the direct compression method. The tablets prepared were evaluated for various parameters including weight variation, hardness, friability, in vitro dispersion time, drug-polymer interaction, drug content water absorption ratio, wetting time, in vitro drug release, FTIR and DSC studies. The tablets prepared by the direct compression method had a weight variation in the range of 145 mg to 152 mg, which is below ± 7.5%, a hardness of 3.6 kg/cm² to 4.5 kg/cm², percentage friability of 0.46% to 0.73%, in vitro dispersion time of 18 s to 125 s, drug content uniformity of between 98.12% and 100.03%, a water absorption ratio of 67% to 87%, wetting time of 32 sec. to 64 sec., and an in vitro drug release of 53.92% - 98.82% within 15 min. The IR spectral analysis and DSC study showed no drug interaction with formulation additives of the tablet, and the formulations indicated no significant changes in hardness, friability, drug content or in vitro drug release. Fast dissolving tablets of metoprolol tartrate have enhanced dissolution and will lead to improved bioavailability and more effective therapy.

European and Developing Countries Clinical Trials Partnership (EDCTP): the path towards a true partnership.

Science.gov (United States)

Matee, Mecky I; Manyando, Christine; Ndumbe, Peter M; Corrah, Tumani; Jaoko, Walter G; Kitua, Andrew Y; Ambene, Herman Pa; Ndounga, Mathieu; Zijenah, Lynn; Ofori-Adjei, David; Agwale, Simon; Shongwe, Steven; Nyirenda, Thomas; Makanga, Michael

2009-07-20

European and Developing Countries Clinical Trials Partnership (EDCTP) was founded in 2003 by the European Parliament and Council. It is a partnership of 14 European Union (EU) member states, Norway, Switzerland, and Developing Countries, formed to fund acceleration of new clinical trial interventions to fight the human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS), malaria and tuberculosis (TB) in the sub-Saharan African region. EDCTP seeks to be synergistic with other funding bodies supporting research on these diseases. EDCTP promotes collaborative research supported by multiple funding agencies and harnesses networking expertise across different African and European countries. EDCTP is different from other similar initiatives. The organisation of EDCTP blends important aspects of partnership that includes ownership, sustainability and responds to demand-driven research. The Developing Countries Coordinating Committee (DCCC); a team of independent scientists and representatives of regional health bodies from sub-Saharan Africa provides advice to the partnership. Thus EDCTP reflects a true partnership and the active involvement and contribution of these African scientists ensures joint ownership of the EDCTP programme with European counterparts. The following have been the major achievements of the EDCTP initiative since its formation in 2003; i) increase in the number of participating African countries from two to 26 in 2008 ii) the cumulative amount of funds spent on EDCTP projects has reached 150 m euros, iii) the cumulative number of clinical trials approved has reached 40 and iv) there has been a significant increase number and diversity in capacity building activities. While we recognise that EDCTP faced enormous challenges in its first few years of existence, the strong involvement of African scientists and its new initiatives such as unconditional funding to regional networks of excellence in sub-Saharan Africa is envisaged to

Effect of permeation enhancers on the iontophoretic transport of metoprolol tartrate and the drug retention in skin.

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Nair, Anroop; Vyas, Hiral; Shah, Jigar; Kumar, Ashok

2011-01-01

Utilization of chemical penetration enhancers in conjunction with iontophoresis is regarded as the most effective method to enhance the passage of molecules across the skin barrier. A systematic approach to enhance the transdermal delivery of metoprolol tartrate and the subsequent release of the drug depot in the skin was investigated. Gel formulations with proximate viscosity were prepared and assessed for the effect of polymers (carbopol, hydroxypropyl methyl cellulose, and methyl cellulose), permeation enhancers (5% w/w, sodium lauryl sulfate (SLS), dimethyl formamide, n-methyl-2-pyrrolidone, and polyethylene glycol 400), and the combination approach (permeation enhancers with iontophoresis-0.5 mA/cm² on the drug delivery. The flux values observed in passive (4.59-5.89 µg/cm²/h) and iontophoresis (37.99-41.57 µg/cm²/h) processes revealed that the permeation of metoprolol was not influenced by the polymers studied, under similar conditions, and further studies were carried out using carbopol gel as a representative polymer. Appreciable enhancement (~5-fold) in drug delivery was observed with SLS in the passive process while the optimum iontophoretic delivery condition ensured better delivery (~7-fold). Combination of iontophoresis with SLS further enhanced the drug delivery (~9-fold) and leads to noticeable drug retention in the skin as well. Moreover, the drug retained in the cutaneous layer of the skin eventually released over a period of time (5 days) and followed a near first order profile. This study concludes that the combination of iontophoresis with SLS augmented the metoprolol delivery and rendered skin drug depot, which eventually released over a period of time.

The effects of acebutolol and metoprolol on walking distances and distal blood pressure in hypertensive patients with intermittent claudication

DEFF Research Database (Denmark)

Svendsen, T L; Jelnes, Rolf; Tønnesen, K H

1986-01-01

The effects of acebutolol (with intrinsic sympathomimetic activity (ISA] and metoprolol (without ISA) on arm blood pressure, ankle systolic blood pressure, claudication distances (CD) and maximal walking distances (MWD) were compared in patients with essential hypertension and intermittent...... claudication. Fourteen patients participated in a long-term, open, randomized cross-over study. After randomization the patients received either acebutolol, 200 mg b.i.d., or metoprolol, 100 mg b.i.d. After eight weeks the drugs were shifted and after another eight weeks they were withdrawn. Arm and ankle...... pressure there were no significant changes in ankle blood pressure, CD or MWD after the two drugs. After withdrawal of the drugs and after the arm blood pressure had returned to the control value no significant changes were seen in CD, MWD or ankle blood pressure. It is concluded that beta-blockers have...

The beta-receptor blocker metoprolol alters detoxification processes in the non-target organism Dreissena polymorpha

Energy Technology Data Exchange (ETDEWEB)

Contardo-Jara, Valeska, E-mail: contardo@igb-berlin.d [Dpt. Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Mueggelseedamm 301, 12587 Berlin (Germany); Pflugmacher, Stephan, E-mail: pflugmacher@igb-berlin.d [Dpt. Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Mueggelseedamm 301, 12587 Berlin (Germany); Nuetzmann, Gunnar, E-mail: nuetzmann@igb-berlin.d [Dpt. Ecohydrology, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Mueggelseedamm 301, 12587 Berlin (Germany); Kloas, Werner, E-mail: werner.kloas@igb-berlin.d [Dpt. Ecophysiology and Aquaculture, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Mueggelseedamm 301, 12587 Berlin (Germany); Wiegand, Claudia, E-mail: wiegand@biology.sdu.d [University of Southern Denmark Institute of Biology, Campusvej 55, 5230 Odense M (Denmark)

2010-06-15

Due to increasing amounts of pharmaceutically active compounds (PhACs) in the aquatic environment, their largely unknown effects to non-target organisms need to be assessed. This study examined physiological changes in the freshwater mussel Dreissena polymorpha exposed to increasing concentrations (0.534, 5.34, 53.4 and 534 mug L{sup -1}) of the beta-blocker metoprolol in a flow-through system for seven days. The two lower concentrations represent the environmentally relevant range. Surprisingly, metallothionein mRNA was immediately up-regulated in all treatments. For the two higher concentrations mRNA up-regulation in gills was found for P-glycoprotein after one day, and after four days for pi class glutathione S-transferase, demonstrating elimination and biotransformation processes, respectively. Additionally, catalase and superoxide dismutase were up-regulated in the digestive gland indicating oxidative stress. In all treated mussels a significant up-regulation of heat shock protein mRNA was observed in gills after four days, which suggests protein damage and the requirement for repair processes. Metoprolol was 20-fold bioaccumulated for environmentally relevant concentrations. - Evidence for significant physiological changes in an aquatic mollusc due to exposure to a pharmaceutically active compound detected by real-time PCR.

PDE3, but not PDE4, reduces β1- and β2-adrenoceptor-mediated inotropic and lusitropic effects in failing ventricle from metoprolol-treated patients

Science.gov (United States)

Molenaar, Peter; Christ, Torsten; Hussain, Rizwan I; Engel, Andreas; Berk, Emanuel; Gillette, Katherine T; Chen, Lu; Galindo-Tovar, Alejandro; Krobert, Kurt A; Ravens, Ursula; Levy, Finn Olav; Kaumann, Alberto J

2013-01-01

Background and Purpose PDE3 and/or PDE4 control ventricular effects of catecholamines in several species but their relative effects in failing human ventricle are unknown. We investigated whether the PDE3-selective inhibitor cilostamide (0.3–1 μM) or PDE4 inhibitor rolipram (1–10 μM) modified the positive inotropic and lusitropic effects of catecholamines in human failing myocardium. Experimental Approach Right and left ventricular trabeculae from freshly explanted hearts of 5 non-β-blocker-treated and 15 metoprolol-treated patients with terminal heart failure were paced to contract at 1 Hz. The effects of (-)-noradrenaline, mediated through β1 adrenoceptors (β2 adrenoceptors blocked with ICI118551), and (-)-adrenaline, mediated through β2 adrenoceptors (β1 adrenoceptors blocked with CGP20712A), were assessed in the absence and presence of PDE inhibitors. Catecholamine potencies were estimated from –logEC50s. Key Results Cilostamide did not significantly potentiate the inotropic effects of the catecholamines in non-β-blocker-treated patients. Cilostamide caused greater potentiation (P = 0.037) of the positive inotropic effects of (-)-adrenaline (0.78 ± 0.12 log units) than (-)-noradrenaline (0.47 ± 0.12 log units) in metoprolol-treated patients. Lusitropic effects of the catecholamines were also potentiated by cilostamide. Rolipram did not affect the inotropic and lusitropic potencies of (-)-noradrenaline or (-)-adrenaline on right and left ventricular trabeculae from metoprolol-treated patients. Conclusions and Implications Metoprolol induces a control by PDE3 of ventricular effects mediated through both β1 and β2 adrenoceptors, thereby further reducing sympathetic cardiostimulation in patients with terminal heart failure. Concurrent therapy with a PDE3 blocker and metoprolol could conceivably facilitate cardiostimulation evoked by adrenaline through β2 adrenoceptors. PDE4 does not appear to reduce inotropic and lusitropic effects of

A facile stereospecific synthesis of the ( sup 2 H sub 6 )-isopropyl-labelled metoprolol enantiomers from (2R)- and (2S)-glycidyl 3-nitrobenzenesulfonate

Energy Technology Data Exchange (ETDEWEB)

Murthy, S.S.; Nelson, W.L. (Washington Univ., Seattle, WA (USA). Dept. of Medicinal Chemistry)

1990-12-01

Enantiomers of metoprolol containing six deuterium atoms in the isopropyl methyl groups were prepared in two steps from the sodium salt of 4-(2-methoxyethyl)phenol (3) and the commercially available (2R)-and (2S)-glycidyl 3-nitrobenzenesulfonates ((2R)-2 and (2S)-2). The resulting (2R)- and (2S)-epoxides were opened using ({sup 2}H{sub 6})-isopropylamine. The enantiomeric excesses were 93 and 95% for the deuterated (2R)- and (2S)-enantiomers of metoprolol ((2R)-1 and (2S)-1), respectively, as determined by chiral column HPLC. (author).

Development of Sustained Release Capsules Containing “Coated Matrix Granules of Metoprolol Tartrate”

OpenAIRE

Siddique, Sabahuddin; Khanam, Jasmina; Bigoniya, Papiya

2010-01-01

The objective of this investigation was to prepare sustained release capsule containing coated matrix granules of metoprolol tartrate and to study its in vitro release and in vivo absorption. The design of dosage form was performed by choosing hydrophilic hydroxypropyl methyl cellulose (HPMC K100M) and hydrophobic ethyl cellulose (EC) polymers as matrix builders and Eudragit® RL/RS as coating polymers. Granules were prepared by composing drug with HPMC K100M, EC, dicalcium phosphate by wet gr...

Sublingual fast dissolving niosomal films for enhanced bioavailability and prolonged effect of metoprolol tartrate

OpenAIRE

Allam, Ayat; Fetih, Gihan

2016-01-01

Ayat Allam, Gihan Fetih Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt Abstract: The aim of the present work was to prepare and evaluate sublingual fast dissolving films containing metoprolol tartrate-loaded niosomes. Niosomes were utilized to allow for prolonged release of the drug, whereas the films were used to increase the drug’s bioavailability via the sublingual route. Niosomes were prepared using span 60 and cholesterol at different drug to...

Design and characterization of controlled release tablet of metoprolol

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Gautam Singhvi

2012-01-01

Full Text Available Metoprolol succinate is a selective beta-adrenergic receptor blocker useful in treatment of hypertension, angina and heart failure. The purpose of the present work was to design and evaluate controlled release matrix type tablet of Metoprolo succinate using HPMC K15M and Eudragit (RLPO and RSPO as a matrix forming agents. Effect of various polymer alone and combinations were studied in pH 1.2 buffer using USP type II paddle at 50 rpm. HPMC was used to form firm gel with Eudragit polymer. Formulation with Equal proportion (1:1 of Eudragit RSPO and RLPO showed optimum drug release t50 =7 hrs and t100 =16 hrs indicate optimum permeability for drug release from matrix. The drug release mechanism was predominantly found to be Non-Fickian diffusion controlled.

Combination therapy with metoprolol and nifedipine versus monotherapy in patients with stable angina pectoris. Results of the International Multicenter Angina Exercise (IMAGE) Study

DEFF Research Database (Denmark)

Savonitto, S; Ardissiono, D; Egstrup, K

1996-01-01

was then added for a further 4 weeks. Exercise tests were performed at weeks 0, 6 and 10. RESULTS: At week 6, both metoprolol and nifedipine increased the mean exercise time to 1-mm ST segment depression in comparison with week 0 (both p ... 10, the groups randomized to combination therapy had a further increase in time to 1-mm ST segment depression (p ... metoprolol to nifedipine showed an increase in exercise tolerance that was greater than the 90th percentile of the distribution of the changes observed in the corresponding monotherapy + placebo groups. However, among these patients, an additive effect was observed only in 1 (14%) of the 7 patients treated...

Moving the boundaries of international collaboration on clinical trials and QoL: experiences in oncology and legislation within the European Parliament.

Science.gov (United States)

Bottomley, Andrew; Kirby, Tony; Bean, John; Walker, Julie

2013-02-01

The European Organisation for Research and Treatment of Cancer undertook another successful event with their third annual conference addressing quality of life matters in cancer clinical trials. More than 40 presentations were made over a 3-day period hosted at the European Parliament on 17-20 October 2012, in Brussels. The conference managed to get speakers and policy makers together to debate all the key issues in cancer clinical trials, design and reporting, including future policy and regulatory concerns. This meeting set the stage for future research and policy meetings to give greater visibility to quality of life as an outcome in clinical trials within the world of EU legislators.

ANTIHYPERTENSIVE AND ANTIOXIDATIVE EFFECTS OF CARVEDILOL AND METOPROLOL IN HYPERTENSIVE PATIENTS WITH OVERWEIGHT/OBESITY

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V. A. Nevzorova

2010-01-01

Full Text Available Aim. To evaluate an efficacy of the 24-week antihypertensive therapy based on the carvedilol or metoprolol and its influence on markers of blood oxidative status in hypertensive patients with overweight/obesity.Material and methods. The observation data of 20 hypertensive patients (aged 40-65 y.o. with overweight/obesity were analyzed. Blood pressure (BP dynamics at each visit and a rate of target BP achievement were evaluated. Blood oxidative status was evaluated by plasma malondialdehyde (MDA level and erythrocyte superoxide dismutase (SOD activity. Therapy safety was evaluated by adverse events registration.Results. Significant reduction in both systolic and diastolic BP compared with baseline values was found. BP targets were achieved in all patients in both groups. The therapy based on carvedilol had a greater effect on blood oxidative status in comparison with metoprolol therapy. Plasma MDA level reduced from 7.03 [6.49;7.41] to 3.23 [2.88;3.57] μM/l (p<0.05 vs from 6.95 [6.51;7.39] to 6.08 [5.46;6.71] μM/l, respectively, and erythrocyte SOD activity increased from 27,89 [25.29;30.49] to 40.18 [35.89;44.45]% (p<0.05 vs from 28.41 [25.18;31.64] to 33.45 [30.65;36.23]%, respectively.Conclusion. The high antihypertensive efficacy, positive effect on blood oxidative status and well tolerability of therapy based on carvedilol in everyday clinical practice is presented.

Sentinel European Node Trial (SENT)

DEFF Research Database (Denmark)

Schilling, Clare; Stoeckli, Sandro J; Haerle, Stephan K

2015-01-01

in patients with early-stage oral squamous cell carcinoma. METHODS: An European Organisation for Research and Treatment of Cancer-approved prospective, observational study commenced in 2005. Fourteen European centres recruited 415 patients with radiologically staged T1-T2N0 squamous cell carcinoma. SNB...

LEADER 7: cardiovascular risk profiles of US and European participants in the LEADER diabetes trial differ

NARCIS (Netherlands)

Rutten, G.E.; Tack, C.J.J.; Pieber, T.R.; Comlekci, A.; Orsted, D.D.; Baeres, F.M.; Marso, S.P.; Buse, J.B.

2016-01-01

AIMS: To determine whether US and European participants in the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial differ regarding risk factors for cardiovascular mortality and morbidity. METHODS: Baseline data, stratified for prior cardiovascular

LEADER 7 : Cardiovascular risk profiles of US and European participants in the LEADER diabetes trial differ

NARCIS (Netherlands)

Rutten, Guy E H M; Tack, Cees J.; Pieber, Thomas R.; Comlekci, Abdurrahman; Ørsted, David Dynnes; Baeres, Florian M M; Marso, Steven P.; Buse, John B.

2016-01-01

Aims: To determine whether US and European participants in the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial differ regarding risk factors for cardiovascular mortality and morbidity. Methods: Baseline data, stratified for prior cardiovascular

EFFECTS OF BETA-BLOCKER METOPROLOL ON QUALITY OF LIFE IN ELDERLY PATIENTS WITH CHRONIC HEART FAILURE

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I. V. Vologdina

2007-01-01

Full Text Available Aim. To study effect of cardioselective β-adrenoblocker metoprolol tartrate (in retarded formulation on quality of life in elderly patients with chronic heart failure (CHF of ischemic etiology.Material and methods. 78 patients with CHF class III (NYHA were involved in the study. Patients were 81,6±0,25 y.o. in average. All patients had clinical signs of mild-to-moderate depressive disorders. Patients were split on 2 groups comparable in sex and age. Patients of the 1st group (n=43 received metoprolol tartrate (Egilok Retard, 50-100 mg/d additionally to standard therapy. Patients of the 2nd group (n=35 received only standard therapy. The somatic status was assessed before and after 1 and 3 months of therapy by clinical condition evaluated scale (CCES, 6-minute walking test, left ventricular ejection fraction (Echocardiography as well as mental status by special tests (SMSP, BDI, Hamilton scale, C.D.Spilberger-Y.L.Hanin scale and qualities of life (MLHFQ, SF-36.Results. Reduction of CHF class from III to II was observed in 31 (76,7% patients of the 1st group and in 23 (65,7% patients of the 2nd group. Tolerability of Egilok Retard was good and there were not cessations because of side effects. In 3 months of therapy severity of the somatic status according to CCES reduced more significantly in the 1st group in comparison with the 2nd group (29,5 % vs 11,5 %, p <0,001. The exercise tolerance increased higher in the 1st group comparing with the 2nd one (34 % vs 17 %, respectively, p<0,001. The severity of depression reduced (according to SMSP, Hamilton scale more significantly in the 1st group in comparison with this in the 2nd one. Quality of life also improved more significantly in the 1st group according to MLHFQ and SF-36 (physical functions, role physical functions, social function scales at the end of therapy.Conclusion. Metoprolol tartrate (in retarded formulation improves somatic and mental status as well as quality of life in elderly

The selective beta 1-blocking agent metoprolol compared with antithyroid drug and thyroxine as preoperative treatment of patients with hyperthyroidism. Results from a prospective, randomized study.

Science.gov (United States)

Adlerberth, A; Stenström, G; Hasselgren, P O

1987-01-01

Despite the increasing use of beta-blocking agents alone as preoperative treatment of patients with hyperthyroidism, there are no controlled clinical studies in which this regimen has been compared with a more conventional preoperative treatment. Thirty patients with newly diagnosed and untreated hyperthyroidism were randomized to preoperative treatment with methimazole in combination with thyroxine (Group I) or the beta 1-blocking agent metoprolol (Group II). Metoprolol was used since it has been demonstrated that the beneficial effect of beta-blockade in hyperthyroidism is mainly due to beta 1-blockade. The preoperative, intraoperative, and postoperative courses in the two groups were compared, and patients were followed up for 1 year after thyroidectomy. At the time of diagnosis, serum concentration of triiodothyronine (T3) was 6.1 +/- 0.59 nmol/L in Group I and 5.7 +/- 0.66 nmol/L in Group II (reference interval 1.5-3.0 nmol/L). Clinical improvement during preoperative treatment was similar in the two groups of patients, but serum T3 was normalized only in Group I. The median length of preoperative treatment was 12 weeks in Group I and 5 weeks in Group II (p less than 0.01). There were no serious adverse effects of the drugs during preoperative preparation in either treatment group. Operating time, consistency and vascularity of the thyroid gland, and intraoperative blood loss were similar in the two groups. No anesthesiologic or cardiovascular complications occurred during operation in either group. One patient in Group I (7%) and three patients in Group II (20%) had clinical signs of hyperthyroid function during the first postoperative day. These symptoms were abolished by the administration of small doses of metoprolol, and no case of thyroid storm occurred. Postoperative hypocalcemia or recurrent laryngeal nerve paralysis did not occur in either group. During the first postoperative year, hypothyroidism developed in two patients in Group I (13%) and in six

Formulation and Characterization of Matrix and Triple-Layer matrix tablets for Controlled Delivery of Metoprolol tartrate

OpenAIRE

Izhar Ahmed Syed; Lakshmi Narsu Mangamoori; Yamsani Madhusudan Rao

2011-01-01

In the present study matrix and triple layer matrix tablets of metoprolol tartrate were formulated by using xanthan gum as the matrix forming agent and Sodium Carboxy Methyl Cellulose (Na CMC) as barrier layers. The prepared tablets were analysed for their hardness, friability, drug content and in-vitro drug release studies. Marked differences in dissolution characteristics of (M3) and (M3L3) were observed and showed a significant difference statistically. Mean dissolution time (MDT) for M3 a...

Predictors of discontinuation of antipsychotic medication and subsequent outcomes in the European First Episode Schizophrenia Trial (EUFEST)

NARCIS (Netherlands)

Landolt, Karin; Rössler, Wulf; Ajdacic-Gross, Vladeta; Derks, Eske M.; Libiger, Jan; Kahn, René S.; Fleischhacker, W. Wolfgang

2016-01-01

This study had two aims: to describe patients suffering from first-episode schizophrenia who had stopped taking any antipsychotic medication, and to gain information on the predictors of successful discontinuation. We investigated data from the European First Episode Schizophrenia Trial (EUFEST).

European Marketing Authorizations Granted Based on a Single Pivotal Clinical Trial: The Rule or the Exception?

Science.gov (United States)

Morant, Anne Vinther; Vestergaard, Henrik Tang

2018-07-01

A minimum of two positive, adequate, and well-controlled clinical trials has historically been the gold standard for providing substantial evidence to support regulatory approval of a new medicine. Nevertheless, the present analysis of European Marketing Authorizations granted between 2012 and 2016 showed that 45% of new active substances were approved based on a single pivotal clinical trial. For therapeutic areas such as oncology and cardiovascular diseases, approvals based on a single pivotal trial are the rule rather than the exception, whereas new medicines within the nervous system area were generally supported by two or more pivotal trials. While overall similar trends have been observed in the US, the recent US Food and Drug Administration approvals of nervous system medicines based on a single pivotal trial suggest that a case-by-case scientific evaluation of the totality of evidence is increasingly applied to facilitate faster access of new medicines to patients suffering from serious diseases. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Evaluation of Poly(2-Ethyl-2-Oxazoline) Containing Copolymer Networks of Varied Composition as Sustained Metoprolol Tartrate Delivery Systems

OpenAIRE

Kostova, Bistra; Ivanova, Sijka; Balashev, Konstantin; Rachev, Dimitar; Christova, Darinka

2014-01-01

Segmented copolymer networks (SCN) based on poly(2-ethyl-2-oxazoline) and containing 2-hydroxyethyl methacrylate, 2-hydroxypropyl acrylate, and/or methyl methacrylate segments have been evaluated as potential sustained release systems of the water soluble cardioselective β-blocker metoprolol tartrate. The structure and properties of the drug carriers were investigated by differential scanning calorimetry, attenuated total reflectance Fourier transform infrared spectroscopy, scanning electron ...

European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP): a randomized trial.

Science.gov (United States)

Landolfi, R; Marchioli, R

1997-01-01

Thrombotic complications characterize the clinical course of polycythemia vera (PV) and represent the main cause of morbidity and mortality. However, uncertainty still exists as to the benefit/risk ratio of aspirin prophylaxis in this setting. In vivo platelet biosynthesis of thromboxane A2 is enhanced and can be suppressed by low-dose aspirin in PV, thus providing a rationale for assessing the efficacy and safety of a low-dose aspirin regimen in these patients. The Gruppo Italiano Studio Policitemia Vera has recently performed a pilot study on 112 patients randomized to receive aspirin, 40 mg daily, or placebo and followed for 16 +/- 6 months (mean +/- SD). This study showed that low-dose aspirin is well tolerated in PV patients, and that a large-scale efficacy trial is feasible in this setting. In this article we report the protocol of the European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP) study, which is a randomized trial designed to assess the risk/benefit ratio of low-dose aspirin in PV. To estimate the size and the follow-up duration required for the ECLAP trial, a retrospective analysis of the clinical epidemiology of a large PV population has recently been completed by the Gruppo Italiano Studio Policitemia Vera. On this basis, approximately 3500 patients will be enrolled in the ECLAP study with a follow-up of 3 to 4 years. The uncertainty principle will be used as the main eligibility criterion: Polycythemic patients of any age, having no clear indication for or contraindication to aspirin treatment, will be randomized in a double-blind fashion to receive oral aspirin (100 mg daily) or placebo. According to current therapeutic recommendations, the basic treatment of randomized patients should be aimed at maintaining the hematocrit value 50. Randomization will be stratified by participating center. The study is funded by the European Union BIOMED 2 program.

Beta 1 versus nonselective blockade in therapy of essential tremor.

Science.gov (United States)

Larsen, T A; Teräväinen, H

1983-01-01

The beta 1-selective blocker metoprolol was compared to propranolol and a placebo in a double-blind crossover trial in 24 patients with essential tremor. Both beta blockers suppressed the essential tremor, but metoprolol, which caused a mean reduction of 32.0% in tremor intensity from the base-line value, was less effective than propranolol, which reduced mean tremor intensity by 41.3%. Subjective benefit for their tremor was found by 15 of the patients taking propranolol and by one taking metoprolol. The tremor frequency was not affected. No serious side effects were observed. Metoprolol may offer an alternative for those essential tremor patients who cannot tolerate propranolol.

Pediatric Clinical Trials Conducted in South Korea from 2006 to 2015: An Analysis of the South Korean Clinical Research Information Service, US ClinicalTrials.gov and European Clinical Trials Registries.

Science.gov (United States)

Choi, Sheung-Nyoung; Lee, Ji-Hyun; Song, In-Kyung; Kim, Eun-Hee; Kim, Jin-Tae; Kim, Hee-Soo

2017-12-01

The status of pediatric clinical trials performed in South Korea in the last decade, including clinical trials of drugs with unapproved indications for children, has not been previously examined. The aim was to provide information regarding the current state of pediatric clinical trials and create a basis for future trials performed in South Korea by reviewing three databases of clinical trials registrations. We searched for pediatric clinical studies (participants South Korea between 2006 and 2015 registered on the Clinical Research Information Service (CRIS), ClinicalTrials.gov, and the European Clinical Trials Registry (EuCTR). Additionally, we reviewed whether unapproved indications were involved in each trial by comparing the trials with a list of authorized trials provided by the Ministry of Food and Drug Safety (MFDS). The primary and secondary outcomes were to determine the change in number of pediatric clinical trials with unapproved indications over time and to assess the status of unauthorized pediatric clinical trials from the MFDS and the publication of articles after these clinical trials, respectively. We identified 342 clinical studies registered in the CRIS (n = 81), ClinicalTrials.gov (n = 225), and EuCTR (n = 36), of which 306 were reviewed after excluding duplicate registrations. Among them, 181 studies were interventional trials dealing with drugs and biological agents, of which 129 (71.3%) involved unapproved drugs. Of these 129 trials, 107 (82.9%) were authorized by the MFDS. Pediatric clinical trials in South Korea aiming to establish the safety and efficacy of drugs in children are increasing; however, non-MFDS-authorized studies remain an issue.

A Step Forward in Molecular Diagnostics of Lyssaviruses – Results of a Ring Trial among European Laboratories

DEFF Research Database (Denmark)

Fischer, Melina; Wernike, Kerstin; Freuling, Conrad M.

2013-01-01

Rabies is a lethal and notifiable zoonotic disease for which diagnostics have to meet the highest standards. In recent years, an evolution was especially seen in molecular diagnostics with a wide variety of different detection methods published. Therefore, a first international ring trial...... participants were asked to investigate a panel of defined lyssavirus RNAs, consisting of Rabies virus (RABV) and European bat lyssavirus 1 and 2 (EBLV-1 and -2) RNA samples, with systems available in their laboratory. The ring trial allowed the important conclusion that conventional RT-PCR assays were really...

Sublingual fast dissolving niosomal films for enhanced bioavailability and prolonged effect of metoprolol tartrate.

Science.gov (United States)

Allam, Ayat; Fetih, Gihan

2016-01-01

The aim of the present work was to prepare and evaluate sublingual fast dissolving films containing metoprolol tartrate-loaded niosomes. Niosomes were utilized to allow for prolonged release of the drug, whereas the films were used to increase the drug's bioavailability via the sublingual route. Niosomes were prepared using span 60 and cholesterol at different drug to surfactant ratios. The niosomes were characterized for size, zeta-potential, and entrapment efficiency. The selected niosomal formulation was incorporated into polymeric films using hydroxypropyl methyl cellulose E15 and methyl cellulose as film-forming polymers and Avicel as superdisintegrant. The physical characteristics (appearance, texture, pH, uniformity of weight and thickness, disintegration time, and palatability) of the prepared films were studied, in addition to evaluating the in vitro drug release, stability, and in vivo pharmacokinetics in rabbits. The release of the drug from the medicated film was fast (99.9% of the drug was released within 30 minutes), while the drug loaded into the niosomes, either incorporated into the film or not, showed only 22.85% drug release within the same time. The selected sublingual film showed significantly higher rate of drug absorption and higher drug plasma levels compared with that of commercial oral tablet. The plasma levels remained detectable for 24 hours following sublingual administration, compared with only 12 hours after administration of the oral tablet. In addition, the absolute bioavailability of the drug (ie, relative to intravenous administration) following sublingual administration was found to be significantly higher (91.06%±13.28%), as compared with that after oral tablet administration (39.37%±11.4%). These results indicate that the fast dissolving niosomal film could be a promising delivery system to enhance the bioavailability and prolong the therapeutic effect of metoprolol tartrate.

Supercritical fluid chromatography of metoprolol and analogues on aminopropyl and ethylpyridine silica without any additives.

Science.gov (United States)

Lundgren, Johanna; Salomonsson, John; Gyllenhaal, Olle; Johansson, Erik

2007-06-22

Metoprolol and a number of related amino alcohols and similar analytes have been chromatographed on aminopropyl (APS) and ethylpyridine (EPS) silica columns. The mobile phase was carbon dioxide with methanol as modifier and no amine additive was present. Optimal isocratic conditions for the selectivity were evaluated based on experiments using design of experiments. A central composite circumscribed model for each column was used. Factors were column temperature, back-pressure and % (v/v) of modifier. The responses were retention and selectivity versus metoprolol. The % of modifier mainly controlled the retention on both columns but pressure and temperature could also be important for optimizing the selectivity between the amino alcohols. The compounds could be divided into four and five groups on both columns, with respect to the selectivity. Furthermore, on the aminopropyl silica the analytes were more spread out whereas on the ethylpyridine silica, due to its aromaticity, retention and selectivity were closer. For optimal conditions the column temperature and back-pressure should be high and the modifier concentration low. A comparison of the selectivity using optimized conditions show a few switches of retention order between the two columns. On aminopropyl silica an aldehyde failed to be eluted owing to Schiff-base formation. Peak symmetry and column efficiency were briefly studied for some structurally close analogues. This revealed some activity from the columns that affected analytes that had less protected amino groups, a methyl group instead of isopropyl. The tailing was more marked with the ethylpyridine column even with the more bulky alkyl substituents. Plate number N was a better measure than the asymmetry factor since some analyte peaks broadened without serious deterioration of symmetry compared to homologues.

Conscious and anaesthetised Göttingen mini-pigs as an in-vivo model for buccal absorption - pH-dependent absorption of metoprolol from bioadhesive tablets.

Science.gov (United States)

Meng-Lund, Emil; Jacobsen, Jette; Andersen, Morten B; Jespersen, Mads L; Karlsson, Jens-Jacob; Garmer, Mats; Jørgensen, Erling B; Holm, René

2014-05-01

The potential of buccal mucosa as a site for systemic absorption has attracted increased attention in recent years creating a need for new predictive in-vivo models. The aim of this study was to evaluate anaesthetised and conscious Göttingen mini-pigs as a model for buccal drug absorption by testing pH-dependent absorption of metoprolol from a solid dosage form. Buccal tablets buffered to pH 6.2 and pH 8.9, oral liquid and intravenous injection were tested in four conscious and anaesthetised Göttingen mini-pigs in a non-randomised cross-over study. Blood samples were collected and processed before analysis by ultra-performance liquid chromatography with tandem mass spectrometry detection. An ex-vivo flow retention model was applied to study release and retention of the bioadhesive buccal tablets. The Tmax obtained from the two buccal conscious groups (55 ± 5 and 35 ± 5 min) were significantly different to the buccal anaesthetised groups (120 ± 0 and 165 ± 15 min) for buccal tablet pH 6.2 and pH 8.9, respectively. Also, the absolute bioavailability from the anaesthetised buccal tablet pH 8.9 (20.7 ± 4.0%) had a significant increase compared to all other buccal tablet groups. In conclusion, this study showed a pH-dependent absolute bioavailability of metoprolol when administrated as bioadhesive buccal tablets to anaesthetised mini-pigs. The anaesthesia was found to delay the time to reach maximal plasma concentration of metoprolol as compared to the conscious pig model when administrated as buccal tablets.

NILVAD protocol: a European multicentre double-blind placebo-controlled trial of nilvadipine in mild-to-moderate Alzheimer's disease

NARCIS (Netherlands)

Lawlor, B.; Kennelly, S.; O'Dwyer, S.; Cregg, F.; Walsh, C.; Coen, R.; Kenny, R.A.; Howard, R.; Murphy, C.; Adams, J.; Daly, L.; Segurado, R.; Gaynor, S.; Crawford, F.; Mullan, M.; Lucca, U.; Banzi, R.; Pasquier, F.; Breuilh, L.; Riepe, M.; Kalman, J.; Wallin, A.; Borjesson, A.; Molloy, W.; Tsolaki, M.; Olde Rikkert, M.G.M.

2014-01-01

INTRODUCTION: This study is a European multicentre, randomised, double-blind, placebo-controlled trial investigating the efficacy and safety of nilvadipine as a disease course modifying treatment for mild-to-moderate Alzheimer's disease (AD) in a phase III study that will run for a period of 82

Stereospecific synthesis of specifically deuterated metoprolol enantiomers from chiral starting materials

Energy Technology Data Exchange (ETDEWEB)

Shetty, H.U.; Murthy, S.S.; Nelson, W.L. (Washington Univ., Seattle, WA (USA). Dept. of Medicinal Chemistry)

1989-10-01

Enantiomers of metoprolol (1) containing six deuterium atoms in the isopropyl methyl groups ((2R)), two deuterium atoms at C-2 and C-6 of the aromatic ring ((2S)), and two deuterium atoms at C-3 of the propanolamine side chain ((2S)) were prepared. Chiral 2,2-dimethyl-1,3-dioxolane-4-methanols ((4R) and (4S)) were key synthons. Sources of deuterium were ({sup 2}H{sub 6})-isopropyl-amine, 4-(2-methoxyethyl)-2,6-({sup 2}H{sub 2})-phenol, prepared by {sup 2}HCl/{sup 2}H{sub 2}O exchange, and (4S)-2,2-dimethyl-1,3-dioxolane-4-({sup 2}H{sub 2})-4-methanol, prepared by LiAl{sup 2}H{sub 4} reduction of (4S)-methyl 2,2-dimethyl-1,3-dioxolane-4-carboxylate. Enantiomeric excess was greater than 94% for each of the prepared enantiomers, as determined independently by {sup 1}H NMR spectroscopy on diastereomeric derivatives and by chiral column HPLC. (author).

The Bolton Treovance abdominal stent-graft: European clinical trial design.

Science.gov (United States)

Chiesa, R; Riambau, V; Coppi, G; Zipfel, B; Llagostera, S; Marone, E M; Kahlberg, A

2012-10-01

Endovascular aortic repair (EVAR) has emerged as a promising, less invasive alternative to conventional open surgery for the treatment of infrarenal abdominal aortic aneurysms (AAAs). In the last 20 years, the application rate of EVAR and its clinical results have significantly improved thanks to the evolution of stent-grafts and endovascular delivery systems. However, further development is still needed to reduce the incidence of complications and secondary re-interventions. The Treovance abdominal aortic stent-graft (Bolton Medical, Barcelona, Spain) is a new-generation endovascular device, developed to increase flexibility, lower profile, improve deployment and sealing mechanisms. In particular, it is provided with some innovative features as a double layer of proximal barbs (suprarenal and infrarenal) for supplemental fixation, dull barbs between modules to avoid potential leg disconnections, detachable outer sheath provided with a new-design hemostatic valve, and a double improved mechanism (slow motion and "pin and pull") for precise stent-graft deployment. A European prospective, non-randomized, multi-institutional, "first-in-human" trial (the ADVANCE trial) was conducted from March to December 2011 to assess the safety and performance of the Treovance stent-graft system before commercialization. Thirty patients with anatomically suitable non-ruptured AAAs were enrolled at five clinical sites in Italy, Spain, and Germany. EVAR was completed successfully in all patients. The stent-graft was delivered and deployed safely even in heavily angulated or calcified anatomies. No 30-day device-related complications nor deaths were observed. Preliminary experience with the Treovance abdominal stent-graft within the ADVANCE trial was satisfactory with regard to technical success and perioperative clinical results. Follow-up data are needed to assess mid- and long-term clinical outcomes, along with durability of this new-generation endovascular device.

RANDOMIZED EUROPEAN MULTICENTER TRIAL OF SURFACTANT REPLACEMENT THERAPY FOR SEVERE NEONATAL RESPIRATORY-DISTRESS SYNDROME - SINGLE VERSUS MULTIPLE DOSES OF CUROSURF

NARCIS (Netherlands)

SPEER, CP; ROBERTSON, B; CURSTEDT, T; HALLIDAY, HL; COMPAGNONE, D; GEFELLER, O; HARMS, K; HERTING, E; MCCLURE, G; REID, M; TUBMAN, R; HERIN, P; NOACK, G; KOK, J; KOPPE, J; VANSONDEREN, L; LAUFKOTTER, E; KOHLER, W; BOENISCH, H; ALBRECHT, K; HANSSLER, L; HAIM, M; OETOMO, SB; Okken, Albert; ALTFELD, PC; GRONECK, P; KACHEL, W; RELIER, JP; WALTI, H

There is now convincing evidence that the severity of neonatal respiratory distress syndrome can be reduced by surfactant replacement therapy; however, the optimal therapeutic regimen has not been defined. This randomized European multicenter trial was designed to determine whether the beneficial

Sublingual fast dissolving niosomal films for enhanced bioavailability and prolonged effect of metoprolol tartrate

Directory of Open Access Journals (Sweden)

Allam A

2016-08-01

Full Text Available Ayat Allam, Gihan Fetih Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt Abstract: The aim of the present work was to prepare and evaluate sublingual fast dissolving films containing metoprolol tartrate-loaded niosomes. Niosomes were utilized to allow for prolonged release of the drug, whereas the films were used to increase the drug’s bioavailability via the sublingual route. Niosomes were prepared using span 60 and cholesterol at different drug to surfactant ratios. The niosomes were characterized for size, zeta-potential, and entrapment efficiency. The selected niosomal formulation was incorporated into polymeric films using hydroxypropyl methyl cellulose E15 and methyl cellulose as film-forming polymers and Avicel as superdisintegrant. The physical characteristics (appearance, texture, pH, uniformity of weight and thickness, disintegration time, and palatability of the prepared films were studied, in addition to evaluating the in vitro drug release, stability, and in vivo pharmacokinetics in rabbits. The release of the drug from the medicated film was fast (99.9% of the drug was released within 30 minutes, while the drug loaded into the niosomes, either incorporated into the film or not, showed only 22.85% drug release within the same time. The selected sublingual film showed significantly higher rate of drug absorption and higher drug plasma levels compared with that of commercial oral tablet. The plasma levels remained detectable for 24 hours following sublingual administration, compared with only 12 hours after administration of the oral tablet. In addition, the absolute bioavailability of the drug (ie, relative to intravenous administration following sublingual administration was found to be significantly higher (91.06%±13.28%, as compared with that after oral tablet administration (39.37%±11.4%. These results indicate that the fast dissolving niosomal film could be a promising delivery system to

Predictors of weight loss and maintenance during 2 years of treatment by sibutramine in obesity. Results from the European multi-centre STORM trial. Sibutramine Trial of Obesity Reduction and Maintenance

DEFF Research Database (Denmark)

Hansen, D; Astrup, A; Toubro, S

2001-01-01

In this report we assess pre-treatment determinants of weight loss and maintenance outcome in The Sibutramine Trial of Obesity Reduction and Maintenance (STORM), a 2 y randomized, double-blind, placebo-controlled, European multicenter study examining the effect of sibutramine (Sib) on inducing...

Synovial sarcoma in children and adolescents: the European Pediatric Soft Tissue Sarcoma Study Group prospective trial (EpSSG NRSTS 2005)

NARCIS (Netherlands)

Ferrari, A.; de Salvo, G. L.; Brennan, B.; van Noesel, M. M.; de Paoli, A.; Casanova, M.; Francotte, N.; Kelsey, A.; Alaggio, R.; Oberlin, O.; Carli, M.; Ben-Arush, M.; Bergeron, C.; Merks, J. H. M.; Jenney, M.; Stevens, M. C.; Bisogno, G.; Orbach, D.

2015-01-01

To report the results of the first European prospective nonrandomized trial dedicated to pediatric synovial sarcoma. From August 2005 to August 2012, 138 patients <21 years old with nonmetastatic synovial sarcoma were registered in 9 different countries (and 60 centers). Patients were treated with a

Economic evaluation of the randomized European Achalasia trial comparing pneumodilation with Laparoscopic Heller myotomy.

Science.gov (United States)

Moonen, A; Busch, O; Costantini, M; Finotti, E; Tack, J; Salvador, R; Boeckxstaens, G; Zaninotto, G

2017-11-01

A recent multicenter randomized trial in achalasia patients has shown that pneumatic dilation resulted in equivalent relief of symptoms compared to laparoscopic Heller myotomy. Additionally, the cost of each treatment should be also taken in consideration. Therefore, the aim of the present study was to perform an economic analysis of the European achalasia trial. Patients with newly diagnosed achalasia were enrolled from to 2003 to 2008 in 14 centers in five European countries and were randomly assigned to either pneumatic dilation (PD) or laparoscopic Heller (LHM). The economic analysis was performed in the three centers in three different countries where most patients were enrolled (Amsterdam [NL], Leuven, [B] and Padova [I]) and then applied to all patients included in the study. The total raw costs of the two treatments per patient include the initial costs, the costs of complications, and the costs of retreatments. Two hundred and one patients, 107 (57 males and 50 females, mean age 46 CI: 43-49 years) were randomized to LHM and 94 (59 males and 34 females, mean age 46 CI 43-50 years) to PD. The total cost of PD per patient was quite comparable in the three different centers; €3397 in Padova, €3259 in Amsterdam and €3792 in Leuven. For LHM, the total costs per patient were highest in Amsterdam: €4488 in Padova, €6720 in Amsterdam, and €5856 in Leuven. In conclusion, the strategy of treating achalasia starting with PD appears the most economic approach, independent of the health system. © 2017 John Wiley & Sons Ltd.

CYP2D6 Genetic Variation and Beta-Blocker Maintenance Dose in Patients with Heart Failure.

Science.gov (United States)

Luzum, Jasmine A; Sweet, Kevin M; Binkley, Philip F; Schmidlen, Tara J; Jarvis, Joseph P; Christman, Michael F; Sadee, Wolfgang; Kitzmiller, Joseph P

2017-08-01

This study examined whether a CYP2D6 polymorphism (CYP2D6*4) was related to beta-blocker maintenance dose in patients with heart failure. Logistic regression modeling was utilized in a retrospective chart-review analysis of heart-failure patients (60% Male, 90% of European descent) to assess whether CYP2D6*4 (non-functional CYP2D6 allele present in 1 of 5 individuals of European descent) is associated with maintenance dose of carvedilol (n = 65) or metoprolol (n = 33). CYP2D6*4 was associated with lower maintenance dose of metoprolol (OR 0.13 [95% CI 0.02-0.75] p = 0.023), and a trend was observed between CYP2D6*4 and higher maintenance dose of carvedilol (OR 2.94 [95% CI 0.84-10.30] p = 0.093). None of the patients that carried CYP2D6*4 achieved the recommended target dose of metoprolol (200 mg/day). Consistent with the role of CYP2D6 in the metabolism of metoprolol, the tolerated maintenance dose of metoprolol was lower in CYP2D6*4 carriers compared to non-carriers. Consistent with the role of CYP2D6 in activation of carvedilol, tolerated maintenance dose of carvedilol was higher in CYP2D6*4 carriers compared to non-carriers. Further investigation is warranted to ascertain the potential of CYP2D6 as a potential predictive biomarker of beta-blocker maintenance dose in heart failure patients.

Impact assessment of the European Clinical Trials Directive: a longitudinal, prospective, observational study analyzing patterns and trends in clinical drug trial applications submitted since 2001 to regulatory agencies in six EU countries

Directory of Open Access Journals (Sweden)

Hartmann Markus

2012-04-01

Full Text Available Abstract Background Shifts in clinical trial application rates over time indicate if the attractiveness of a country or region for the conduct of clinical trials is growing or decreasing. The purpose of this observational study was to track changes in drug trial application patterns across several EU countries in order to analyze the medium-term impact of the EU Clinical Trials Directive 2001/20/EC on the conduct of drug trials. Methods Rates of Clinical Trial Applications (CTA for studies with medicinal products in those six countries in the EU, which authorize on average more than 500 trials per year, were analyzed. Publicly available figures on the number of annually submitted CTA, the distribution of trials per phase and the type of sponsorship were tracked; missing data were provided by national drug agencies. Results Since 2001, the number of CTA in Italy and Spain increased significantly (5.0 and 2.5% average annual growth. For Italy, the gain was driven by a strong increase of applications from academic trial sponsors; Spain's growth was due to a rise in trials run by commercial sponsors. The Netherlands, Germany, France and the UK saw a decline (1.9, 2.3, 3.0 and 5.3% average annual diminution; significant (P Conclusions The EU Clinical Trials Directive 2001/20/EC did not achieve the harmonization of clinical trial requirements across Europe. Rather, it resulted in the leveling of clinical trial activities caused by a continuing decrease in CTA rates in the Netherlands, Germany, France and the UK. Southern European countries, Italy and Spain, benefited to some extent from policy changes introduced by the Directive. In Italy's case, national funding measures helped to considerably promote the conduct of non-commercial trials. On the other hand, the EU Directive-driven transition from liberal policy environments, based on non-explicit trial approval through notifications, towards red-taped processes of trial authorization, contributed to

Notification of suspected and unexpected serious adverse reactions according to the Clinical Trials Directive - A descriptive analysis of the legislation and the requirements in a European context

DEFF Research Database (Denmark)

Larsen, Ellen Moseholm; Grarup, Jesper; Gey, Daniela Christine

2010-01-01

The European Clinical Trials Directive (CTD) came into force on May 1st 2004. The CTD provides the legal basis for monitoring the safety of clinical trials and covers the requirements for notification of SUSAR. Implementation of the CTD into national legislation in each Member State has resulted...... in various interpretations of CTD requirements. The objective of this paper is to investigate how the European Member States administer the safety reporting requirements of the CTD and to clarify the requirements for SUSAR notification in the different Member States. Data was collected through publicly...

Determination of beta-adrenergic receptor blocking pharmaceuticals in united states wastewater effluent

Energy Technology Data Exchange (ETDEWEB)

Huggett, D.B.; Khan, I.A.; Foran, C.M.; Schlenk, D

2003-02-01

This is the first report of beta-adrenergic receptor antagonist pharmaceuticals in United States wastewater effluent. - Beta adrenergic receptor antagonists ({beta}-Blockers) are frequently prescribed medications in the United States and have been identified in European municipal wastewater effluent, however no studies to date have investigated these compounds in United States wastewater effluent. Municipal wastewater effluent was collected from treatment facilities in Mississippi, Texas, and New York to investigate the occurrence of metoprolol, nadolol, and propranolol. Propranolol was identified in all wastewater samples analyzed (n=34) at concentrations {<=}1.9 {mu}g/l. Metoprolol and nadolol were identified in {>=}71% of the samples with concentrations of metoprolol {<=}1.2 {mu}g/l and nadolol {<=}0.36 {mu}g/l. Time course studies at both Mississippi plants and the Texas plant indicate that concentrations of propranolol, metoprolol, and nadolol remain relatively constant at each sampling period. This study indicates that {beta}-Blockers are present in United States wastewater effluent in the ng/l to {mu}g/l range.

Synthesis of the sup 11 C-labelled. beta. -adrenergic receptor ligands atenolol, metoprolol and propanolol

Energy Technology Data Exchange (ETDEWEB)

Antoni, G.; Ulin, J.; Laangstroem, B. (Uppsala Univ. (Sweden). Dept. of Organic Chemistry)

1989-01-01

The {sup 11}C-labelled {beta}-adrenergic receptor ligands atenolol 1, metoprolol 2 and propranolol 3 have been synthesized by an N-alkylation reaction using (2-{sup 11}C)isopropyl iodide. The labelled isopropyl iodide was prepared in a one-pot reactor system from ({sup 11}C)carbon dioxide and obtained in 40% radiochemical yield within 14 min reaction time. The total reaction times for compounds 1-3, counted from the start of the isopropyl iodide synthesis and including purification were 45-55 min. The products were obtained in 5-15% radiochemical yields and with radiochemical purities higher than 98%. The specific activity ranged from 0.4 to 4 GBq/{mu}mol. In a typical experiment starting with 4 GBq around 75 MBq of product was obtained. (author).

The burden and management of cytochrome P450 2D6 (CYP2D6)-mediated drug–drug interaction (DDI) : Co-medication of metoprolol and paroxetine or fluoxetine in the elderly

NARCIS (Netherlands)

Bahar, Muh Akbar; Hak, Eelko; Bos, Jens H. J.; Borgsteede, Sander D.; Wilffert, Bob

Purpose: Metoprolol and paroxetine/fluoxetine are inevitably co-prescribed because cardiovascular disorders and depression often coexist in the elderly. This leads to CYP2D6-mediated drug-drug interactions (DDI). Because systematic evaluations are lacking, we assessed the burden of

Industry Perspective of Pediatric Drug Development in the United States: Involvement of the European Union Countries.

Science.gov (United States)

Onishi, Taku; Tsukamoto, Katsura; Matsumaru, Naoki; Waki, Takashi

2018-01-01

Efforts to promote the development of pediatric pharmacotherapy include regulatory frameworks and close collaboration between the US Food and Drug Administration and the European Medicines Agency. We characterized the current status of pediatric clinical trials conducted in the United States by the pharmaceutical industry, focusing on the involvement of the European Union member countries, to clarify the industry perspective. Data on US pediatric clinical trials were obtained from ClinicalTrials.gov . Binary regression analysis was performed to identify what factors influence the likelihood of involvement of European Union countries. A total of 633 US pediatric clinical trials that met inclusion criteria were extracted and surveyed. Of these, 206 (32.5%) involved a European Union country site(s). The results of binary regression analysis indicated that attribution of industry, phase, disease area, and age of pediatric participants influenced the likelihood of the involvement of European Union countries in US pediatric clinical trials. Relatively complicated or large pediatric clinical trials, such as phase II and III trials and those that included a broad age range of participants, had a significantly greater likelihood of the involvement of European Union countries ( P European Union countries, and (3) feasibility of clinical trials is mainly concerned by pharmaceutical industry for pediatric drug development. Additional incentives for high marketability may further motivate pharmaceutical industry to develop pediatric drugs.

Spectrophotometric Determination of Metoprolol Tartrate in Pharmaceutical Dosage Forms on Complex Formation with Cu(II

Directory of Open Access Journals (Sweden)

Mustafa Cesme

2011-06-01

Full Text Available A new, simple, sensitive and accurate spectrophotometric method has been developed for the assay of metoprolol tartrate (MPT, which is based on the complexation of drug with copper(II [Cu(II] at pH 6.0, using Britton-Robinson buffer solution, to produce a blue adduct. The latter has a maximum absorbance at 675 nm and obeys Beer’s law within the concentration range 8.5-70 mg/mL. Regression analysis of the calibration data showed a good correlation coefficient (r = 0.998 with a limit of detection of 5.56 mg/mL. The proposed procedure has been successfully applied to the determination of this drug in its tablets. In addition, the spectral data and stability constant for the binuclear copper(II complex of MPT (Cu2MPT2Cl2 have been reported.

The duty to give reasons as a guarantee for a fair trial under the sight of the European Court of Human Rights

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Marcella Alves Mascarenhas Nardelli

2015-06-01

Full Text Available This paper aims to define the outlines of the judicial duty to provide reasons for their decisions in its theoretical aspect - according to contemporary procedural knowledge -, as well as to establish its importance for the concretion of a fair trial. At the same time, the duty to give reasons will be analyzed in a practical perspective according to the case-law of the European Court of Human Rights, with a special emphasis in the case Taxquet v. Belgium and its impact on Jury Trials.

A feasibility trial to examine the social norms approach for the prevention and reduction of licit and illicit drug use in European University and college students

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Pischke Claudia R

2012-10-01

Full Text Available Abstract Background Incorrect perceptions of high rates of peer alcohol and tobacco use are predictive of increased personal use in student populations. Correcting misperceptions by providing feedback has been shown to be an effective intervention for reducing licit drug use. It is currently unknown if social norms interventions are effective in preventing and reducing illicit drug use in European students. The purpose of this paper is to describe the design of a multi-site cluster controlled trial of a web-based social norms intervention aimed at reducing licit and preventing illicit drug use in European university students. Methods/Design An online questionnaire to assess rates of drug use will be developed and translated based on existing social norms surveys. Students from sixteen universities in seven participating European countries will be invited to complete the questionnaire. Both intervention and control sites will be chosen by convenience. In each country, the intervention site will be the university that the local principal investigator is affiliated with. We aim to recruit 1000 students per site (baseline assessment. All participants will complete the online questionnaire at baseline. Baseline data will be used to develop social norms messages that will be included in a web-based intervention. The intervention group will receive individualized social norms feedback. The website will remain online during the following 5 months. After five months, a second survey will be conducted and effects of the intervention on social norms and drug use will be measured in comparison to the control site. Discussion This project is the first cross-national European collaboration to investigate the feasibility of a social norms intervention to reduce licit and prevent illicit drug use among European university students. Final trial registration number DRKS00004375 on the ‘German Clinical Trials Register’.

A European multi-language initiative to make the general population aware of independent clinical research: the European Communication on Research Awareness Need project

OpenAIRE

Mosconi, Paola; Antes, Gerd; Barbareschi, Giorgio; Burls, Amanda; Demotes-Mainard, Jacques; Chalmers, Iain; Colombo, Cinzia; Garattini, Silvio; Gluud, Christian; Gyte, Gill; Mcllwain, Catherine; Penfold, Matt; Post, Nils; Satolli, Roberto; Valetto, Maria Rosa

2016-01-01

BACKGROUND: The ECRAN (European Communication on Research Awareness Needs) project was initiated in 2012, with support from the European Commission, to improve public knowledge about the importance of independent, multinational, clinical trials in Europe. \\ud \\ud METHODS: Participants in the ECRAN consortium included clinicians and methodologists directly involved in clinical trials; researchers working in partnership with the public and patients; representatives of patients; and experts in s...

The influence of Metolose structure on the free volume and the consequent metoprolol tartrate release of patches.

Science.gov (United States)

Papp, József; Marton, Sylvia; Süvegh, Károly; Zelkó, Romána

2009-01-01

Matrix-type patches containing Metoprolol tartrate were prepared from two types of Metolose and acrylate polymers. Metolose SM 4000 and Metolose 90SH 100.000SR were applied in different proportions in the patches where the total polymer content was kept constant in each sample. The purpose of the study was to investigate the effect of Metolose structure on the free volume of the patches and the consequent drug release profile. The drug release profiles were characterized by zero-order and first-order models. The results indicate that Metolose, containing hydroxypropyl ether groups and methyl ether groups, enables the formation of H-bonds, thus increasing the free volume holes and the consequent extent and rate of drug release of patches.

Doxycycline in the treatment of respiratory tract infections. Results of a pan-European multi-centre trial.

Science.gov (United States)

Pestel, M

1975-01-01

In the winter of 1973-4, general practitioners from seven European countries took part in a multi-centre trial of doxycycline in the treatment of infections of the respiratory tract. The carefully designed protocol was observed by all participants. A total of 1,747 patients were admitted to the trial; their ages ranged from 6 years to over 80. The commonest diagnoses (50%) were acute bronchitis and acute exacerbations of chronic bronchitis. On the recommended dosage of 200 mg doxycycline on the first day, followed by 100 mg daily thereafter (though 200 mg could be continued daily in severe cases), 87% of patients achieved good or very good results. Both subjective (pain) and objective (sputum volume and viscosity, temperature, cough) measures showed rapid improvement, usually by the third to fifth days. Side-effects were minimal and mainly gastrointestinal and caused only 4 patients to discontinue treatment. Overall, doxycycline proved its effectiveness and rapidity of action.

A step forward in molecular diagnostics of lyssaviruses--results of a ring trial among European laboratories.

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Melina Fischer

Full Text Available Rabies is a lethal and notifiable zoonotic disease for which diagnostics have to meet the highest standards. In recent years, an evolution was especially seen in molecular diagnostics with a wide variety of different detection methods published. Therefore, a first international ring trial specifically designed on the use of reverse transcription polymerase chain reaction (RT-PCR for detection of lyssavirus genomic RNA was organized. The trial focussed on assessment and comparison of the performance of conventional and real-time assays. In total, 16 European laboratories participated. All participants were asked to investigate a panel of defined lyssavirus RNAs, consisting of Rabies virus (RABV and European bat lyssavirus 1 and 2 (EBLV-1 and -2 RNA samples, with systems available in their laboratory. The ring trial allowed the important conclusion that conventional RT-PCR assays were really robust assays tested with a high concordance between different laboratories and assays. The real-time RT-PCR system by Wakeley et al. (2005 in combination with an intercalating dye, and the combined version by Hoffmann and co-workers (2010 showed good sensitivity for the detection of all RABV samples included in this test panel. Furthermore, all used EBLV-specific assays, real-time RT-PCRs as well as conventional RT-PCR systems, were shown to be suitable for a reliable detection of EBLVs. It has to be mentioned that differences were seen in the performance between both the individual RT-PCR systems and the laboratories. Laboratories which used more than one molecular assay for testing the sample panel always concluded a correct sample result. Due to the markedly high genetic diversity of lyssaviruses, the application of different assays in diagnostics is needed to achieve a maximum of diagnostic accuracy. To improve the knowledge about the diagnostic performance proficiency testing at an international level is recommended before using lyssavirus molecular

Determination of beta-adrenergic receptor blocking pharmaceuticals in united states wastewater effluent

International Nuclear Information System (INIS)

Huggett, D.B.; Khan, I.A.; Foran, C.M.; Schlenk, D.

2003-01-01

This is the first report of beta-adrenergic receptor antagonist pharmaceuticals in United States wastewater effluent. - Beta adrenergic receptor antagonists (β-Blockers) are frequently prescribed medications in the United States and have been identified in European municipal wastewater effluent, however no studies to date have investigated these compounds in United States wastewater effluent. Municipal wastewater effluent was collected from treatment facilities in Mississippi, Texas, and New York to investigate the occurrence of metoprolol, nadolol, and propranolol. Propranolol was identified in all wastewater samples analyzed (n=34) at concentrations ≤1.9 μg/l. Metoprolol and nadolol were identified in ≥71% of the samples with concentrations of metoprolol ≤1.2 μg/l and nadolol ≤0.36 μg/l. Time course studies at both Mississippi plants and the Texas plant indicate that concentrations of propranolol, metoprolol, and nadolol remain relatively constant at each sampling period. This study indicates that β-Blockers are present in United States wastewater effluent in the ng/l to μg/l range

Report of the 1st meeting of the "Vienna Initiative to Save European Academic Research (VISAER)".

Science.gov (United States)

Druml, Christiane; Singer, Ernst A; Wolzt, Michael

2006-04-01

The European Directive 2001/20/EC ("Clinical Trials Directive") was aimed at simplifying and harmonising European clinical research. The directive's attempt represents an important step because many European Member States lack national laws that specifically address details of research, but the goal has been only partly achieved. For academic investigators doing national or multi-national research the new European law and the requirements following its implementation are likely to have the opposite effect. Some areas seem to be of particular concern: trial sponsorship, the ethical review process, the participation of patients who are temporarily not able to consent in clinical trials, in particular the informed consent process, an accepted European registry for all clinical trials, insurance and pharmacovigilance. Furthermore there are fundamental problems of the conduct of clinical trials that could have been foreseen at the time of implementation of the new law, which are impeding academic basic clinical research. The bureaucratic burden for academic investigators has tremendously increased without representing any contribution to patients' safety or to the scientific value of research. Furthermore some large European academic trials cannot be conducted anymore due to the new regulations. This result in a reduction in the number of trials and additionally in a reduction in the number of patients enrolled in a study. European research and thus European patients will suffer from the loss of potential benefits of research. The Vienna Initiative to Save European Academic Research (VISEAR) brings together leading stakeholders from academic research groups and interested parties from industry, international organisations and regulatory authorities to focus on the issues of concern regarding the organisational and funding of academic clinical research in order to improve the development and use of medicines in Europe. The first step of the initiative was a meeting held

Differential effects of antipsychotic drugs on insight in first episode schizophrenia: Data from the European First-Episode Schizophrenia Trial (EUFEST).

Science.gov (United States)

Pijnenborg, G H M; Timmerman, M E; Derks, E M; Fleischhacker, W W; Kahn, R S; Aleman, A

2015-06-01

Although antipsychotics are widely prescribed, their effect of on improving poor illness insight in schizophrenia has seldom been investigated and therefore remains uncertain. This paper examines the effects of low dose haloperidol, amisulpride, olanzapine, quetiapine, and ziprasidone on insight in first-episode schizophrenia, schizoaffective disorder, or schizophreniform disorder. The effects of five antipsychotic drugs in first episode psychosis on insight were compared in a large scale open randomized controlled trial conducted in 14 European countries: the European First-Episode Schizophrenia Trial (EUFEST). Patients with at least minimal impairments in insight were included in the present study (n=455). Insight was assessed with item G12 of the Positive and Negative Syndrome Scale (PANSS), administered at baseline and at 1, 3, 6, 9, and 12 months after randomization. The use of antipsychotics was associated with clear improvements in insight over and above improvements in other symptoms. This effect was most pronounced in the first three months of treatment, with quetiapine being significantly less effective than other drugs. Effects of spontaneous improvement cannot be ruled out due to the lack of a placebo control group, although such a large spontaneous improvement of insight would seem unlikely. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Superior outcome of women with stage I/II cutaneous melanoma: Pooled analysis of four European organisation for research and treatment of cancer phase III trials

NARCIS (Netherlands)

A. Joosse (Arjen); S. Collette (Sandra); S. Suciu (Stefan); T.E.C. Nijsten (Tamar); F.J. Lejeune (Ferdy); U.R. Kleeberg (Ulrich); J.W.W. Coebergh (Jan Willem); A.M.M. Eggermont (Alexander); E.G.E. de Vries (Elisabeth)

2012-01-01

textabstractPurpose: Several studies observed a female advantage in the prognosis of cutaneous melanoma, for which behavioral factors or an underlying biologic mechanism might be responsible. Using complete and reliable follow-up data from four phase III trials of the European Organisation for

COMPARISON OF THERAPIES BASED ON CARVEDILOL AND METOPROLOL IN HYPERTENSIVE PATIENTS WITH OVERWEIGHT OR OBESITY. THE FIRST RESULTS OF CAMELLIA TRIAL

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S. Y. Martsevich

2009-01-01

Full Text Available Aim. To evaluate antihypertensive and metabolic effects of the therapy based on carvedilol (C in comparison with metoprolol (M in hypertensive patients with overweight or obesity.Material and methods. 320 patients were involved in multicenter, randomized open parallel study. One part of the patients received C 12,5 mg BID (Vedicardol, “Sintez”, another part – M 25 mg/day BID. Doubling dose of β-blockers (BB and switching patients to combined therapy with AML 5-10 mg OD (Amlorus, “Sintez” and hydrochlorothiazide (HCT 12,5-25 mg OD was performed if necessary. The study duration was 24 weeks.Results. Significant reduction of systolic and diastolic blood pressure was revealed in both groups, there was no difference between groups (р=0,88 and p=0,61 respectively. Switching patients to combined therapy with AML and HCT was made more often in M group than in C group (p>0,05. Prescription of BB resulted in significant reduction of the heart rate, there was no difference between groups (p=0,61. 96,2% patients of group C and 95,5% of group M reached target levels of BP. Significant reduction of glucose (p<0,01 and uric acid levels were registered in group C as well as tendency to lowering of total cholesterol (TC and low density lipoprotein cholesterol (LDLC levels. 34 adverse effects were registered during observation period: 24 in group C and 10 in group M (p>0.05, half of them were not related to BB taking.Conclusion: Controlled antihypertensive therapy, based on С and M, allows reaching target levels of BP in majority of patients with overweight or obesity. Switching to combined therapy was made more seldom in group of С than in M group. Both drugs demonstrated metabolic neutrality, however significant lowering of glucose and uric acid levels and tendency to lowering of TC an LDLC levels was observed only in group С.

New developments in secondary stroke prevention: impact of the European/Australasian Stroke Prevention in Reversible Ischemia Trial (ESPRIT) on clinical management.

Science.gov (United States)

Lutsep, Helmi L

2007-01-01

Secondary stroke prevention is an important goal of poststroke patient treatment. Various pharmacologic approaches have been advocated, but the relative efficacy and safety of these regimens has remained the subject of much debate. Recently released data from the European/Australasian Stroke Prevention in Reversible Ischemia Trial (ESPRIT) indicated that combination therapy with aspirin and extended-release dipyridamole was more effective than aspirin monotherapy, and probably more effective than anticoagulants, for the prevention of cerebrovascular events after a stroke or transient ischemic attack. When viewed in light of results of earlier trials, these findings confirmed that combination aspirin plus extended-release dipyridamole therapy improved outcomes in these patients and is a recommended option for poststroke patient treatment.

Piloting the European Unified Patient Identity Management (EUPID) Concept to Facilitate Secondary Use of Neuroblastoma Data from Clinical Trials and Biobanking.

Science.gov (United States)

Ebner, Hubert; Hayn, Dieter; Falgenhauer, Markus; Nitzlnader, Michael; Schleiermacher, Gudrun; Haupt, Riccardo; Erminio, Giovanni; Defferrari, Raffaella; Mazzocco, Katia; Kohler, Jan; Tonini, Gian Paolo; Ladenstein, Ruth; Schreier, Guenter

2016-01-01

Data from two contexts, i.e. the European Unresectable Neuroblastoma (EUNB) clinical trial and results from comparative genomic hybridisation (CGH) analyses from corresponding tumour samples shall be provided to existing repositories for secondary use. Utilizing the European Unified Patient IDentity Management (EUPID) as developed in the course of the ENCCA project, the following processes were applied to the data: standardization (providing interoperability), pseudonymization (generating distinct but linkable pseudonyms for both contexts), and linking both data sources. The applied procedures resulted in a joined dataset that did not contain any identifiers that would allow to backtrack the records to either data sources. This provided a high degree of privacy to the involved patients as required by data protection regulations, without preventing proper analysis.

European multicentre double-blind placebo-controlled trial of Nilvadipine in mild-to-moderate Alzheimer's disease-the substudy protocols: NILVAD frailty; NILVAD blood and genetic biomarkers; NILVAD cerebrospinal fluid biomarkers; NILVAD cerebral blood flow

NARCIS (Netherlands)

Meulenbroek, O.V.; O'Dwyer, S.; Jong, D. de; Spijker, G.J. van; Kennelly, S.; Cregg, F.; Olde Rikkert, M.G.M.; Abdullah, L.; Wallin, A.; Walsh, C.; Coen, R.; Kenny, R.A.; Daly, L.; Segurado, R.; Borjesson-Hanson, A.; Crawford, F.; Mullan, M.; Lucca, U.; Banzi, R.; Pasquier, F.; Breuilh, L.; Riepe, M.; Kalman, J.; Molloy, W.; Tsolaki, M.; Howard, R.; Adams, J.; Gaynor, S.; Lawlor, B.

2016-01-01

INTRODUCTION: In conjunction with the NILVAD trial, a European Multicentre Double-Blind Placebo Controlled trial of Nilvadipine in Mild-to-Moderate Alzheimer's disease (AD), there are four NILVAD substudies in which eligible NILVAD patients are also invited to participate. The main NILVAD protocol

Predictors of discontinuation of antipsychotic medication and subsequent outcomes in the European First Episode Schizophrenia Trial (EUFEST).

Science.gov (United States)

Landolt, Karin; Rössler, Wulf; Ajdacic-Gross, Vladeta; Derks, Eske M; Libiger, Jan; Kahn, René S; Fleischhacker, W Wolfgang

2016-04-01

This study had two aims: to describe patients suffering from first-episode schizophrenia who had stopped taking any antipsychotic medication, and to gain information on the predictors of successful discontinuation. We investigated data from the European First Episode Schizophrenia Trial (EUFEST). From the 325 patients included, 15.7% discontinued all antipsychotic medication. In a first analysis, clinical and sociodemographical predictors of discontinuing any antipsychotic medication were identified, using Cox regression. In the second analysis, logistic regression was used to determine variables associated with those patients who had stopped taking antipsychotic medication and had a favourable outcome, i.e., successful discontinuation. A good outcome was defined as a) having had no relapse within the whole observation period (80.6%), and b) having had no relapse and symptomatic remission at 12-month-follow-up (37.2%). Cox regression revealed that a higher proportion of patients from Western European countries and Israel stopped antipsychotic medication than from Central and Eastern European countries, that relapse was associated with discontinuation, and that discontinuers had lower compliance and higher quality of life. Predictors of successful discontinuation differed with the outcome definition used. Using definition b), successful discontinuers had a better baseline prognosis and better baseline social integration. Using definition a), successful discontinuers more often were from Western European countries. Region and clinical factors were associated with discontinuation. Prognosis and social integration played an important role in predicting successful discontinuation. As this study had several limitations, for example the observational design regarding discontinuation, further studies are needed to identify predictors of successful discontinuation. Copyright © 2016 Elsevier B.V. All rights reserved.

Recruiting long-term survivors of European Organisation for Research and Treatment of Cancer phase III clinical trials into quality of life studies : Challenges and opportunities

NARCIS (Netherlands)

van Leeuwen, M.L.; Efficace, F.; Fosså, S.D.; Bolla, M.; de Giorgi, U.; De Wit, R.; Holzner, B.; van de Poll-Franse, L.; White, J.; Collette, L.; Osanto, S.; Aaronson, N.K.; European Organisation for Research and Treatment of Cancer Quality of Life Group; Genito-Urinary Cancers Group, The

2014-01-01

Objectives In this pilot study we evaluated the feasibility of and methods for assessing the quality of life of long term survivors of European Organisation for Research and Treatment of Cancer (EORTC) phase III clinical trials. Here we report the results pertaining to the feasibility of conducting

Recruiting long-term survivors of European Organisation for Research and Treatment of Cancer phase III clinical trials into quality of life studies: Challenges and opportunities

NARCIS (Netherlands)

van Leeuwen, M.; Efficace, F.; Fosså, S.D.; Bolla, M.; De Giorgi, U.; de Wit, R; Holzner, B.; van de Poll-Franse, L.V.; van Poppel, H.; White, J.; Collette, L.; Osanto, S.; Aaronson, N.K.

2014-01-01

Objectives: In this pilot study we evaluated the feasibility of and methods for assessing the quality of life of long term survivors of European Organisation for Research and Treatment of Cancer (EORTC) phase III clinical trials. Here we report the results pertaining to the feasibility of conducting

The European Narcolepsy Network (EU-NN) database

DEFF Research Database (Denmark)

Khatami, Ramin; Luca, Gianina; Baumann, Christian R

2016-01-01

Narcolepsy with cataplexy is a rare disease with an estimated prevalence of 0.02% in European populations. Narcolepsy shares many features of rare disorders, in particular the lack of awareness of the disease with serious consequences for healthcare supply. Similar to other rare diseases, only a ......, identification of post-marketing medication side-effects, and will contribute to improve clinical trial designs and provide facilities to further develop phase III trials....... Narcolepsy Network is introduced. The database structure, standardization of data acquisition and quality control procedures are described, and an overview provided of the first 1079 patients from 18 European specialized centres. Due to its standardization this continuously increasing data pool is most...

GUARANTEES OF THE RIGHT TO A FAIR CIVIL TRIAL

Directory of Open Access Journals (Sweden)

Diana-Loredana Jalbă

2015-11-01

Full Text Available In order to ensure the effective protection of human rights and provide for more than theoretical and illusory substantive rights, the need to define the right to a fair trial is emerging, along with the necessity that litigants become aware of the guarantees established by article 6 of the European Convention on Human Rights. Thus, the article aims to approach the ample issue regarding the litigants’ right to a fair civil trial in light of current legal regulations, and in particular, in light of the jurisprudence of the European Court of Human Rights. Given the fact that the right to a fair civil trial involves establishing, throughout the trial, a set of rules of procedure aimed at creating a balance between the parties in the process - the so-called guarantees of a fair trial - in her scientific pursuits, the author analyzes both explicit and implicit guarantees of fair trial, highlighting relevant European standards as well as their degree of implementation in the national (procedural law.

EAP viewpoint on unpublished data from paediatric clinical trials.

Science.gov (United States)

Schrier, L; Illy, K; Valiulis, A; Wyder, C; Stiris, T

2018-02-01

European children and paediatricians rely heavily on the fair, complete and timely publication of data obtained from paediatric randomised controlled trials (RCTs). Selective publication and reporting of paediatric RCTs is common practice. Industry-sponsored trials are more likely to remain unpublished, and take longer to get published compared with trials sponsored by others. However, also academic sponsors contribute to inefficiencies in publishing clinical data. Publication bias violates the ethical obligation that investigators have towards study participants, leads to considerable inefficiencies in research and a waste of financial and human resources, and has the potential to distort evidence for treatment approaches. The European Academy of Paediatrics (EAP) therefore actively supports initiatives that increase the public dissemination of paediatric clinical trial data. The EAP will raise awareness about the guidelines for Good Publication Practice among European paediatricians and subspecialty societies.

Cost effectiveness of eptifibatide in acute coronary syndromes; an economic analysis of Western European patients enrolled in the PURSUIT trial. The Platelet IIa/IIb in unstable Angina: Receptor Suppression Using Integrilin Therapy.

Science.gov (United States)

Brown, R E; Henderson, R A; Koster, D; Hutton, J; Simoons, M L

2002-01-01

To assess the direct medical costs and cost effectiveness of routine eptifibatide use amongst patients with unstable angina and myocardial infarction without persistent ST-segment elevation in the Western European subgroup of the PURSUIT trial. Health care resources were collected for the Western European PURSUIT trial patients (n=3697). Unit costs for major resources were developed within six countries using a consistent bottom-up methodology. Resource consumption from the Western European population was used to calculate the average direct medical costs per patient in the eptifibatide and placebo arms of the trial. Eptifibatide was estimated to cost 524 Euros per treatment. Long-term survival estimated from the 6-month trial survival data and combined with the cost data was used to calculate cost-effectiveness ratios. Additionally, cost per death and non-fatal myocardial infarction at 30 days was calculated. Sensitivity analyses were conducted on the discount rate and resource consumption. Cost-effectiveness ratios ranged from 9603 Euros to 18 115 Euros per year of life saved with 3% discount. Using resource consumption based on countries with low coronary arteriography rates, the cost per year of life saved was between 3329 Euros and 10 079 Euros. Using resource consumption based on high coronary arteriography rate countries, the cost per year of life saved was between 17 089 Euros and 24 099 Euros. Assuming no difference in treatment costs except for the addition of eptifibatide, the incremental cost per year of life saved was 23 818 Euros. Routine eptifibatide use was associated with a reduction in the combined end-point of death and myocardial infarction at 30 days, which was sustained at 6 months. Long-term projections indicate a modest increase in survival in eptifibatide patients. These data translate into cost-effectiveness ratios that compare favourably with other new technologies that are currently in use. Copyright 2001 The European Society of

Successful treatment of polymedicamentous poisoning with metoprolol, diltiazem and cilazapril

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Radovanović Milan R.

2009-01-01

Full Text Available Introduction. Poisoning caused by drugs with cardiodepressive effects is an urgent condition in medicine which is associated with high mortality rate regardless of modern therapeutic methods. Accidental or intentional poisoning whit these drugs produces heart activity depression and cardiovascular collapse as consequences. Current therapy for severe poisoning caused by beta-blockers and calcium channel blockers includes both unspecific and specific antidote therapy whit glucagon, as well as application of adrenergic drugs, calcium, phosphodiesterase inhibitors and hyperinsulinemia/euglycemia therapy. However, even whit the application of these drugs, prompt measures of unspecific detoxication therapy and cardiopulmonary reanimation are crucial for survival of patients with severe poisoning. Case report. A 28-year-old female patient was hospitalized for cardiogenic shock and altered state of conscioussnes (Glasgow coma score = 4, caused by acute poisoning with 2 g of metoprolol (Presolol®, 1.8 g of diltiazem (Cortiazem® and 50 mg of cilazapril (Zobox®. Prolonged cardiopulmonary resuscitation was applied during the first 16 hours of hospitalization, including administration of crystaline solutions (8 L, 17 mg of adrenaline, 4 mg of atropine, 4 mg of glucagone and 1.6 g of dopamine, with electro-stimulation by temporary pacemaker and mechanical ventilation. In a defined time period, normalized state of consciousness was registered, mechanical ventilation was stopped and normal heart activity and hemodynamic stability were accomplished. During hospitalization the patient was treated for mild pneumonia and after ten days, completely recovered, was released and sent to home treatment. Conclusion. Prompt measures of cardiopulmonary resuscitation and multidisciplinary treatment in intensive care units significantly increase the chances of complete recovery of a patient with severe poisoning caused by drugs with cardiodepressive efects.

Can harmonized regulation overcome intra-European differences? Insights from a European Phase III stem cell trial.

Science.gov (United States)

Hauskeller, Christine

2017-09-01

Harmonized regulation of research with human stem cells in Europe has shaped innovation in regenerative medicine. Findings from a Phase III academic clinical trial of an autologous cell procedure illustrate the obstacles that a multinational trial faces. A typology of the obstacles encountered, may help other teams embarking upon trials. The findings throw light on the situation of clinician-scientists in clinical innovation, as the expertise to run scientific trials is very complex. The innovation route of clinical translation takes insufficient account of the interdependencies between multiple social and cultural factors from outside the laboratory and the clinic. For ethical reasons, however, academic and business routes to stem cell treatments ought to be enabled by the regulators. Suggestions arise, how academics can prepare for trials, that academic research needs better institutional support and that new models of medical innovation may need to be developed for regenerative medicine.

Geographic differences in heart failure trials.

Science.gov (United States)

Ferreira, João Pedro; Girerd, Nicolas; Rossignol, Patrick; Zannad, Faiez

2015-09-01

Randomized controlled trials (RCTs) are essential to develop advances in heart failure (HF). The need for increasing numbers of patients (without substantial cost increase) and generalization of results led to the disappearance of international boundaries in large RCTs. The significant geographic differences in patients' characteristics, outcomes, and, most importantly, treatment effect observed in HF trials have recently been highlighted. Whether the observed regional discrepancies in HF trials are due to trial-specific issues, patient heterogeneity, structural differences in countries, or a complex interaction between factors are the questions we propose to debate in this review. To do so, we will analyse and review data from HF trials conducted in different world regions, from heart failure with preserved ejection fraction (HF-PEF), heart failure with reduced ejection fraction (HF-REF), and acute heart failure (AHF). Finally, we will suggest objective and actionable measures in order to mitigate regional discrepancies in future trials, particularly in HF-PEF where prognostic modifying treatments are urgently needed and in which trials are more prone to selection bias, due to a larger patient heterogeneity. © 2015 The Authors European Journal of Heart Failure © 2015 European Society of Cardiology.

Ophthalmic epidemiology in Europe : the "European Eye Epidemiology" (E3) consortium

NARCIS (Netherlands)

Delcourt, Cecile; Korobelnik, Jean-Francois; Buitendijk, Gabrielle H. S.; Foster, Paul J.; Hammond, Christopher J.; Piermarocchi, Stefano; Peto, Tunde; Jansonius, Nomdo; Mirshahi, Alireza; Hogg, Ruth E.; Bretillon, Lionel; Topouzis, Fotis; Deak, Gabor; Grauslund, Jakob; Broe, Rebecca; Souied, Eric H.; Creuzot-Garcher, Catherine; Sahel, Jose; Daien, Vincent; Lehtimaki, Terho; Hense, Hans-Werner; Prokofyeva, Elena; Oexle, Konrad; Rahi, Jugnoo S.; Cumberland, Phillippa M.; Schmitz-Valckenberg, Steffen; Fauser, Sascha; Bertelsen, Geir; Hoyng, Carel; Bergen, Arthur; Silva, Rufino; Wolf, Sebastian; Lotery, Andrew; Chakravarthy, Usha; Fletcher, Astrid; Klaver, Caroline C. W.

The European Eye Epidemiology (E3) consortium is a recently formed consortium of 29 groups from 12 European countries. It already comprises 21 population-based studies and 20 other studies (case-control, cases only, randomized trials), providing ophthalmological data on approximately 170,000

Optimization of bilayer floating tablet containing metoprolol tartrate as a model drug for gastric retention.

Science.gov (United States)

Narendra, C; Srinath, M S; Babu, Ganesh

2006-04-07

The purpose of the present study was to develop an optimized gastric floating drug delivery system (GFDDS) containing metoprolol tartrate (MT) as a model drug by the optimization technique. A 2(3) factorial design was employed in formulating the GFDDS with total polymer content-to-drug ratio (X1), polymer-to-polymer ratio (X2), and different viscosity grades of hydroxypropyl methyl cellulose (HPMC) (X3) as independent variables. Four dependent variables were considered: percentage of MT release at 8 hours, T50%, diffusion coefficient, and floating time. The main effect and interaction terms were quantitatively evaluated using a mathematical model. The results indicate that X1 and X2 significantly affected the floating time and release properties, but the effect of different viscosity grades of HPMC (K4M and K10M) was nonsignificant. Regression analysis and numerical optimization were performed to identify the best formulation. Fickian release transport was confirmed as the release mechanism from the optimized formulation. The predicted values agreed well with the experimental values, and the results demonstrate the feasibility of the model in the development of GFDDS.

'Cloud computing' and clinical trials: report from an ECRIN workshop.

Science.gov (United States)

Ohmann, Christian; Canham, Steve; Danielyan, Edgar; Robertshaw, Steve; Legré, Yannick; Clivio, Luca; Demotes, Jacques

2015-07-29

Growing use of cloud computing in clinical trials prompted the European Clinical Research Infrastructures Network, a European non-profit organisation established to support multinational clinical research, to organise a one-day workshop on the topic to clarify potential benefits and risks. The issues that arose in that workshop are summarised and include the following: the nature of cloud computing and the cloud computing industry; the risks in using cloud computing services now; the lack of explicit guidance on this subject, both generally and with reference to clinical trials; and some possible ways of reducing risks. There was particular interest in developing and using a European 'community cloud' specifically for academic clinical trial data. It was recognised that the day-long workshop was only the start of an ongoing process. Future discussion needs to include clarification of trial-specific regulatory requirements for cloud computing and involve representatives from the relevant regulatory bodies.

Tapioca starch blended alginate mucoadhesive-floating beads for intragastric delivery of Metoprolol Tartrate.

Science.gov (United States)

Biswas, Nikhil; Sahoo, Ranjan Kumar

2016-02-01

The objective of the study was to develop tapioca starch blended alginate mucoadhesive-floating beads for the intragastric delivery of Metoprolol Tartrate (MT). The beads were prepared by ionotropic gelation method using calcium chloride as crosslinker and gas forming calcium carbonate (CaCO3) as floating inducer. The alginate gel beads having 51-58% entrapped MT showed 90% release within 45 min in gastric medium (pH 1.2). Tapioca starch blending markedly improved the entrapment efficiency (88%) and sustained the release for 3-4 h. A 12% w/w HPMC coating on these beads extended the release upto 9-11 h. In vitro wash off and buoyancy test in gastric media revealed that the beads containing CaCO3 has gastric residence of more than 12 h. In vitro optimized multi-unit formulation consisting of immediate and sustained release mucoadhesive-floating beads (40:60) showed good initial release of 42% MT within 1h followed by a sustained release of over 90% for 11 h. Pharmacokinetic study performed in rabbit model showed that the relative oral bioavailability of MT after administration of oral solution, sustain release and optimized formulation was 51%, 67% and 87%, respectively. Optimized formulation showed a higher percent inhibition of isoprenaline induced heart rate in rabbits for almost 12 h. Copyright © 2015 Elsevier B.V. All rights reserved.

Improving clinical trials for cardiovascular diseases: a position paper from the Cardiovascular Round Table of the European Society of Cardiology.

Science.gov (United States)

Jackson, Neville; Atar, Dan; Borentain, Maria; Breithardt, Günter; van Eickels, Martin; Endres, Matthias; Fraass, Uwe; Friede, Tim; Hannachi, Hakima; Janmohamed, Salim; Kreuzer, Jörg; Landray, Martin; Lautsch, Dominik; Le Floch, Chantal; Mol, Peter; Naci, Huseyin; Samani, Nilesh J; Svensson, Anders; Thorstensen, Cathrine; Tijssen, Jan; Vandzhura, Victoria; Zalewski, Andrew; Kirchhof, Paulus

2016-03-01

Cardiovascular disease is the most common cause of mortality and morbidity in the world, but the pharmaceutical industry's willingness to invest in this field has declined because of the many challenges involved with bringing new cardiovascular drugs to market, including late-stage failures, escalating regulatory requirements, bureaucracy of the clinical trial business enterprise, and limited patient access after approval. This contrasts with the remaining burden of cardiovascular disease in Europe and in the world. Thus, clinical cardiovascular research needs to adapt to address the impact of these challenges in order to ensure development of new cardiovascular medicines. The present paper is the outcome of a two-day workshop held by the Cardiovascular Round Table of the European Society of Cardiology. We propose strategies to improve development of effective new cardiovascular therapies. These can include (i) the use of biomarkers to describe patients who will benefit from new therapies more precisely, achieving better human target validation; (ii) targeted, mechanism-based approaches to drug development for defined populations; (iii) the use of information technology to simplify data collection and follow-up in clinical trials; (iv) streamlining adverse event collection and reducing monitoring; (v) extended patent protection or limited rapid approval of new agents to motivate investment in early phase development; and (vi) collecting data needed for health technology assessment continuously throughout the drug development process (before and after approval) to minimize delays in patient access. Collaboration across industry, academia, regulators, and payers will be necessary to enact change and to unlock the existing potential for cardiovascular clinical drug development. A coordinated effort involving academia, regulators, industry, and payors will help to foster better and more effective conduct of clinical cardiovascular trials, supporting earlier

A harmonized and efficient clinical research environment would benefit patients and enhance European competitiveness. Commentary.

Science.gov (United States)

Amato, Antonino; Aringhieri, Eugenio; Boccia, Stefania; Buccella, Filippo; Gorini, Barbara; Gramaglia, Donatella; Masetti, Riccardo; Rossi, Paolo; Pelicci, Pier Giuseppe

2017-01-01

The forthcoming implementation of the European Clinical Trial Regulation (Regulation (EU) No. 536/2014), which is expected to facilitate the conduct of clinical trials across the European Union, will require National Authorities to create the best conditions for the implementation of the new Regulation through national guidelines, so that sponsors may reconsider Europe as a prime location for planning clinical trials. During a meeting titled "Innovation in Clinical Research", an expert panel discussed potential local advances fostering competitiveness of European clinical research with representatives of the pharmaceutical industry, patient organisations and Italian regulatory agency in view of the forthcoming implementation of (EU) No. 536/2014 on clinical trials of medicinal products. In this article we summarise the findings of the meeting, describe features characterising clinical research patterns and offer some suggestions on the possible involvement of all stakeholders in order to foster research innovation and allow the timely access to novel medicines for patients.

Scintimammography with technetium-99m methoxyisobutylisonitrile: results of a prospective European multicentre trial

Energy Technology Data Exchange (ETDEWEB)

Palmedo, H.; Biersack, H.J. [Bonn Univ. (Germany). Dept. of Nucl. Med.; Lastoria, S. [Department of Nuclear Medicine, National Cancer Institute of Naples (Italy); Maublant, J. [Department of Nuclear Medicine, Centre Jean Perrin in Clermont Ferrand (France); Prats, E. [Department of Nuclear Medicine, University Hospital of Zaragoza (Spain); Stegner, H.E. [Department of Gynecology, University of Hamburg (Germany); Bourgeois, P. [Department of Nuclear Medicine, Hospital St. Pierre in Bruxelles (Belgium); Hustinx, R. [Department of Nuclear Medicine, University Hospital in Liege (Belgium); Hilson, A.J.W. [Department of Nuclear Medicine, NHS Trust Hospital in London (United Kingdom); Bischof-Delaloye, A. [Department of Nuclear Medicine, University of Lausanne (Switzerland)

1998-04-01

The aim of the trial was to determine the diagnostic accuracy of scintimmammography with technetium-99m methoxyisobutylisonitrile ({sup 99m}Tc-MIBI) in the detection of primary breast cancer and to verify its clinical usefulness. A total of 246 patients with a suspicious breast mass or positive mammogram were included in this prospective European multicentre trial. At 5 min and 60 min (optional) p.i. two lateral prone images were acquired for 10 min each; 30 min p.i. one anterior image was acquired for 10 min. There were 253 lesions (195 palpable and 58 non-palpable), in respect of which histology revealed 165 cancers and 88 benign lesions. Institutional and blinded read results were correlated to core laboratory histopathology results obtained during excisional biopsy. Diagnostic accuracy for the detection of breast cancer was calculated per lesion. The overall sensitivity and specificity of blinded read scintimammography were 71% and 69%, respectively. For palpable lesions, the sensitivity of blinded read and institutional read scintimammography was 83% and 91%, respectively. Sensitivity was not dependent on the density of the breast tissue. Invasive ductal and invasive lobular cancers showed similar sensitivity. The sensitivity and specificity of mammography were 91% and 42%, respectively, and did not depend on the tumour size. In 60% of false-negative mammograms, {sup 99m}Tc-MIBI was able to diagnose malignancy (true-positive). High-quality imaging with {sup 99m}Tc-MIBI has a high diagnostic accuracy for the detection of primary breast cancer. Used as a complementary method, scintimammography with {sup 99m}Tc-MIBI can help to diagnose breast cancer at an earlier stage in patients with dense breasts. (orig.) With 6 figs., 12 tabs., 55 refs.

Origin of a Jury Trial in the European Countries

Directory of Open Access Journals (Sweden)

Radik N. Hamitov

2017-11-01

Full Text Available Traditionally it is believed that the birthplace of the jury trial creation is England, but the issue of the birthplace location of this particular form of popular participation in the criminal justice administration is not yet fully resolved by the historical science. The continental lawyers were particularly interested in the jury trial among other institutions of English law, in which the English themselves identified the stronghold of the country's law and order, its political and civil freedom. It is not difficult to see that the main role was not played by the judges, but by the community representatives in this form of justice administration. Since then the community has been gaining more and more importance in England as a state body in the matter of justice administration, and the initial forms of its activity have being further developed in this direction. This works investigates roots of jury trial by basing on such methods as historical, systemic, formally logical, concrete-historical, comparative legal analysis method.­ The authors, in turn, come to the conclusion that the jury trial has its roots still in the Ancient States, but the classical modern model owes its origin to England.

Randomized controlled trial of relaxation music to reduce heart rate in patients undergoing cardiac CT

Energy Technology Data Exchange (ETDEWEB)

Ng, Ming Yen [University of Toronto, Department of Medical Imaging, Toronto General Hospital, Toronto, ON (Canada); The University of Hong Kong, Queen Mary Hospital, Department of Diagnostic Radiology, Hong Kong (China); Karimzad, Yasser; Menezes, Ravi J.; Wintersperger, Bernd J.; Li, Qin; Forero, Julian; Paul, Narinder S.; Nguyen, Elsie T. [University of Toronto, Department of Medical Imaging, Toronto General Hospital, Toronto, ON (Canada)

2016-10-15

To evaluate the heart rate lowering effect of relaxation music in patients undergoing coronary CT angiography (CCTA), pulmonary vein CT (PVCT) and coronary calcium score CT (CCS). Patients were randomised to a control group (i.e. standard of care protocol) or to a relaxation music group (ie. standard of care protocol with music). The groups were compared for heart rate, radiation dose, image quality and dose of IV metoprolol. Both groups completed State-Trait Anxiety Inventory anxiety questionnaires to assess patient experience. One hundred and ninety-seven patients were recruited (61.9 % males); mean age 56y (19-86 y); 127 CCTA, 17 PVCT, 53 CCS. No significant difference in heart rate, radiation dose, image quality, metoprolol dose and anxiety scores. 86 % of patients enjoyed the music. 90 % of patients in the music group expressed a strong preference to have music for future examinations. The patient cohort demonstrated low anxiety levels prior to CT. Relaxation music in CCTA, PVCT and CCS does not reduce heart rate or IV metoprolol use. Patients showed low levels of anxiety indicating that anxiolytics may not have a significant role in lowering heart rate. Music can be used in cardiac CT to improve patient experience. (orig.)

Randomized controlled trial of relaxation music to reduce heart rate in patients undergoing cardiac CT

International Nuclear Information System (INIS)

Ng, Ming Yen; Karimzad, Yasser; Menezes, Ravi J.; Wintersperger, Bernd J.; Li, Qin; Forero, Julian; Paul, Narinder S.; Nguyen, Elsie T.

2016-01-01

To evaluate the heart rate lowering effect of relaxation music in patients undergoing coronary CT angiography (CCTA), pulmonary vein CT (PVCT) and coronary calcium score CT (CCS). Patients were randomised to a control group (i.e. standard of care protocol) or to a relaxation music group (ie. standard of care protocol with music). The groups were compared for heart rate, radiation dose, image quality and dose of IV metoprolol. Both groups completed State-Trait Anxiety Inventory anxiety questionnaires to assess patient experience. One hundred and ninety-seven patients were recruited (61.9 % males); mean age 56y (19-86 y); 127 CCTA, 17 PVCT, 53 CCS. No significant difference in heart rate, radiation dose, image quality, metoprolol dose and anxiety scores. 86 % of patients enjoyed the music. 90 % of patients in the music group expressed a strong preference to have music for future examinations. The patient cohort demonstrated low anxiety levels prior to CT. Relaxation music in CCTA, PVCT and CCS does not reduce heart rate or IV metoprolol use. Patients showed low levels of anxiety indicating that anxiolytics may not have a significant role in lowering heart rate. Music can be used in cardiac CT to improve patient experience. (orig.)

American College of Rheumatology/European League against Rheumatism Preliminary Definition of Remission in Rheumatoid Arthritis for Clinical Trials

Science.gov (United States)

Felson, David T.; Smolen, Josef S.; Wells, George; Zhang, Bin; van Tuyl, Lilian H. D.; Funovits, Julia; Aletaha, Daniel; Allaart, Renée; Bathon, Joan; Bombardieri, Stefano; Brooks, Peter; Brown, Andrew; Matucci-Cerinic, Marco; Choi, Hyon; Combe, Bernard; de Wit, Maarten; Dougados, Maxime; Emery, Paul; Furst, Dan; Gomez-Reino, Juan; Hawker , Gillian; Keystone, Edward; Khanna, Dinesh; Kirwan, John; Kvien, Tore; Landewé, Robert; Listing, Joachim; Michaud, Kaleb; Mola, Emilio Martin; Montie, Pam; Pincus, Ted; Richards, Pam; Siegel, Jeff; Simon, Lee; Sokka, Tuulikki; Strand, Vibeke; Tugwell, Peter; Tyndall, Alan; van der Heijde, Desirée; Verstappen, Suzan; White, Barbara; Wolfe, Fred; Zink, Angela; Boers, Maarten

2010-01-01

Background With remission in rheumatoid arthritis (RA) an increasingly attainable goal, there is no widely used definition of remission that is stringent but achievable and could be applied uniformly as an outcome in clinical trials. Methods A committee consisting of members of the American College of Rheumatology, the European League Against Rheumatism and the Outcome Measures in Rheumatology Initiative (OMERACT) met to guide the process and review prespecified analyses from clinical trials of patients with RA. The committee requested a stringent definition (little, if any, active disease) and decided to use core set measures to define remission including at least joint counts and an acute phase reactant. Members were surveyed to select the level of each core set measure consistent with remission. Candidate definitions of remission were tested including those that constituted a number of individual measures in remission (Boolean approach) as well as definitions using disease activity indexes. To select a definition of remission, trial data were analyzed to examine the added contribution of patient reported outcomes and the ability of candidate measures to predict later good x-ray and functional outcomes. Results Survey results for the definition of remission pointed to indexes at published thresholds and to a count of core set measures with each measure scored as 1 or less (e.g. tender and swollen joint counts, CRP and global assessments on 0-10 scale). Analyses suggested the need to include a patient reported measure. Examination of 2 year follow-up data suggested that many candidate definitions performed comparably in terms of predicting later good x-ray and functional outcomes, although DAS28 based measures of remission did not predict good radiographic outcomes as well as did the other candidate definitions. Given these and other considerations, we propose that a patient be defined as in remission based on one of two definitions : 1: When their scores on the

Future trials of endovascular mechanical recanalisation therapy in acute ischemic stroke patients - A position paper endorsed by ESMINT and ESNR. Pt. 2. Methodology of future trials

Energy Technology Data Exchange (ETDEWEB)

Fiehler, Jens [University Medical Centre Hamburg-Eppendorf, Department of Neuroradiology, Hamburg (Germany); Soederman, Michael [Karolinska University Hospital, Department of Neuroradiology, Stockholm (Sweden); Turjman, Francis [Hopital neurologique, Centre de Neurosciences Cognitives, Department of Neuroradiology, Lyon (France); White, Philip M. [University of Edinburgh, Department of Clinical Neurosciences, Western General Hospital, Edinburgh (United Kingdom); Bakke, Soeren Jacob [Oslo University Hospital, Department of Neuroradiology, Oslo (Norway); Mangiafico, Salvatore [University Hospital Careggi, Interventional Neuroradiology Unit, Florence (Italy); Kummer, Ruediger von [University of Dresden, Department of Neuroradiology, Dresden (Germany); Muto, Mario [University of Naples, Department of Neuroradiology, Naples (Italy); Cognard, Christophe [Hopital Purpan, Service de Neuroradiologie, Toulouse (France); Gralla, Jan [Inselspital Bern, Department of Neuroradiology, Bern (Switzerland)

2012-12-15

Based on current data and experience, the joint working group of the European Society of Minimally Invasive Neurological Therapy (ESMINT) and the European Society of Neuroradiology (ESNR) make suggestions on trial design and conduct aimed to investigate therapeutic effects of mechanical thrombectomy (MT). We anticipate that this roadmap will facilitate the setting up and conduct of successful trials in close collaboration with our neighbouring disciplines. (orig.)

Future trials of endovascular mechanical recanalisation therapy in acute ischemic stroke patients - a position paper endorsed by ESMINT and ESNR : part II: methodology of future trials.

Science.gov (United States)

Fiehler, Jens; Söderman, Michael; Turjman, Francis; White, Philip M; Bakke, Søren Jacob; Mangiafico, Salvatore; von Kummer, Rüdiger; Muto, Mario; Cognard, Christophe; Gralla, Jan

2012-12-01

Based on current data and experience, the joint working group of the European Society of Minimally Invasive Neurological Therapy (ESMINT) and the European Society of Neuroradiology (ESNR) make suggestions on trial design and conduct aimed to investigate therapeutic effects of mechanical thrombectomy (MT). We anticipate that this roadmap will facilitate the setting up and conduct of successful trials in close collaboration with our neighbouring disciplines.

Progression to type 1 diabetes in islet cell antibody-positive relatives in the European Nicotinamide Diabetes Intervention Trial

DEFF Research Database (Denmark)

Bingley, P J; Gale, E A M; Reimers, Jesper Irving

2006-01-01

of development of diabetes within 5 years varied according to age, relationship to the proband, positivity for IAA, IA-2A and GADA, number and combination of islet antibodies, HLA class II genotype, baseline glucose tolerance, and first-phase insulin secretion, but not gender or incidence of childhood type 1...... of additional antibody markers, but not antibody type or genotype. Individuals diabetes within 5 years and these combined criteria identified 81% of the cases in the whole cohort. CONCLUSIONS/INTERPRETATION: We suggest that screening......AIMS/HYPOTHESIS: To examine the role of additional immune, genetic and metabolic risk markers in determining risk of diabetes in islet cell antibody (ICA)-positive individuals with a family history of type 1 diabetes recruited into the European Nicotinamide Diabetes Intervention Trial. METHODS...

The influence of socioeconomic environment on the effectiveness of alcohol prevention among European students: a cluster randomized controlled trial

Directory of Open Access Journals (Sweden)

Faggiano Fabrizio

2011-05-01

Full Text Available Abstract Background Although social environments may influence alcohol-related behaviours in youth, the relationship between neighbourhood socioeconomic context and effectiveness of school-based prevention against underage drinking has been insufficiently investigated. We study whether the social environment affects the impact of a new school-based prevention programme on alcohol use among European students. Methods During the school year 2004-2005, 7079 students 12-14 years of age from 143 schools in nine European centres participated in this cluster randomised controlled trial. Schools were randomly assigned to either control or a 12-session standardised curriculum based on the comprehensive social influence model. Randomisation was blocked within socioeconomic levels of the school environment. Alcohol use and alcohol-related problem behaviours were investigated through a self-completed anonymous questionnaire at baseline and 18 months thereafter. Data were analysed using multilevel models, separately by socioeconomic level. Results At baseline, adolescents in schools of low socioeconomic level were more likely to report problem drinking than other students. Participation in the programme was associated in this group with a decreased odds of reporting episodes of drunkenness (OR = 0.60, 95% CI = 0.44-0.83, intention to get drunk (OR = 0.60, 95% CI = 0.45-0.79, and marginally alcohol-related problem behaviours (OR = 0.70, 95% CI = 0.46-1.06. No significant programme's effects emerged for students in schools of medium or high socioeconomic level. Effects on frequency of alcohol consumption were also stronger among students in disadvantaged schools, although the estimates did not attain statistical significance in any subgroup. Conclusions It is plausible that comprehensive social influence programmes have a more favourable effect on problematic drinking among students in underprivileged social environments. Trial registration ISRCTN: ISRCTN

Regulation of Clinical Trials with Advanced Therapy Medicinal Products in Germany.

Science.gov (United States)

Renner, Matthias; Anliker, Brigitte; Sanzenbacher, Ralf; Schuele, Silke

2015-01-01

In the European Union, clinical trials for Advanced Therapy Medicinal Products are regulated at the national level, in contrast to the situation for a Marketing Authorisation Application, in which a centralised procedure is foreseen for these medicinal products. Although based on a common understanding regarding the regulatory requirement to be fulfilled before conduct of a clinical trial with an Advanced Therapy Investigational Medicinal Product, the procedures and partly the scientific requirements for approval of a clinical trial application differ between the European Union Member States. This chapter will thus give an overview about the path to be followed for a clinical trial application and the subsequent approval process for an Advanced Therapy Investigational Medicinal Product in Germany and will describe the role of the stakeholders that are involved. In addition, important aspects of manufacturing, quality control and non-clinical testing of Advanced Therapy Medicinal Products in the clinical development phase are discussed. Finally, current and future approaches for harmonisation of clinical trial authorisation between European Union Member States are summarised.

Herbicide Trials on European Larch in Northern Wisconsin

Science.gov (United States)

Daniel A. Netzer

1984-01-01

Herbicides of 17 different rates and formulations were oversprayed on newly planted 1-0 European larch seedlings in teh spring of 1983 at the recommended rates. Simazine, bifenox, oxyfluorfen, promamide, and oryzalin provided adequate weed control with no damage to the larch. Height growth at the end of the first growing season was one-and-a-half times greater in the...

Exercise and coronary heart disease risk markers in South Asian and European men.

Science.gov (United States)

Arjunan, Saravana Pillai; Bishop, Nicolette Claire; Reischak-Oliveira, Alvaro; Stensel, David John

2013-07-01

South Asians have a higher-than-average risk of CHD. The reasons for this are unclear, but physical inactivity and/or poor responsiveness to exercise may play a role. This study compared the effect of prior exercise on postprandial triacylglycerol (TAG), glucose, insulin, interleukin-6, and soluble intercellular adhesion molecule-1 concentrations in South Asian and European men. Ten healthy South Asian men (i.e., nine Indian men and one Pakistani man) and 10 healthy European men age 20 to 28 yr completed two 2-d trials (exercise and control) in a randomized crossover design. On the afternoon of day 1 of the exercise trial, participants ran on a treadmill for 60 min at approximately 70% of maximal oxygen uptake. Participants rested on day 1 of the control trial. On day 2 of both trials, participants rested and consumed high-fat (57% of energy content) test meals for breakfast (0 h) and lunch (4 h). Fourteen venous blood samples were collected from a cannula between 0 and 9 h for metabolic measurements. Three-way ANOVA identified higher (P < 0.05) postprandial TAG and insulin concentrations in South Asian versus European men. Exercise lowered postprandial TAG and interleukin-6 and elevated soluble intercellular adhesion molecule-1 concentrations. An interaction effect indicated a greater decrease (22% vs 10%) in TAG area under the concentration versus time curve after exercise in South Asian than in European men. Postprandial TAG and insulin responses to high-fat meals were elevated in these South Asian men, but acute exercise was equally, if not more, effective for reducing postprandial lipemia in South Asian than in European men.

Photocatalytic degradation of metoprolol tartrate in suspensions of two TiO2-based photocatalysts with different surface area. Identification of intermediates and proposal of degradation pathways

International Nuclear Information System (INIS)

Abramović, Biljana; Kler, Sanja; Šojić, Daniela; Laušević, Mila; Radović, Tanja; Vione, Davide

2011-01-01

Highlights: ► Kinetics and efficiency of photocatalytic degradation of the β 1 -blocker metoprolol tartrate (MET). ► Two TiO 2 specimens employed. ► Faster degradation of MET, but slower mineralization, obtained with the TiO 2 specimen having lower surface area. ► Photocatalytic transformation pathways of MET including mineralization. - Abstract: This study investigates the efficiency of the photocatalytic degradation of metoprolol tartrate (MET), a widely used β 1 -blocker, in TiO 2 suspensions of Wackherr's “Oxyde de titane standard” and Degussa P25. The study encompasses transformation kinetics and efficiency, identification of intermediates and reaction pathways. In the investigated range of initial concentrations (0.01–0.1 mM), the photocatalytic degradation of MET in the first stage of the reaction followed approximately a pseudo-first order kinetics. The TiO 2 Wackherr induced a significantly faster MET degradation compared to TiO 2 Degussa P25 when relatively high substrate concentrations were used. By examining the effect of ethanol as a scavenger of hydroxyl radicals (·OH), it was shown that the reaction with ·OH played the main role in the photocatalytic degradation of MET. After 240 min of irradiation the reaction intermediates were almost completely mineralized to CO 2 and H 2 O, while the nitrogen was predominantly present as NH 4 + . Reaction intermediates were studied in detail and a number of them were identified using LC–MS/MS (ESI+), which allowed the proposal of a tentative pathway for the photocatalytic transformation of MET as a function of the TiO 2 specimen.

Effect of chronic metoprolol and coronary occlusion (CO) on cardiac beta receptor density in cats

Energy Technology Data Exchange (ETDEWEB)

Lathers, C.M.; Spivey, W.H.; Levin, R.M.

1986-03-05

The effect of metoprolol (M) on beta receptor density (BRD) was examined. M (5 mg/kg, p.o., b.i.d.) was given for 2 and 8 wks prior to CO of the left anterior descending artery (LAD) at its origin. BRD, determined by binding of /sup 3/H-dihydroalprenol, was examined in the myocardium (LA = left atrium, RA = right atrium, LV1 = proximal LAD distribution, LV = 2 distal LAD distribution, LV3 = posterior left ventricle, RV = right ventricle, and S = septum. A 2 factor ANOVA followed by simple effect and Newman-Keuls post hoc tests revealed that M produced no effect in BRD in LA, RA, LV2, or S. M increased BRD in LV1, LV3, and RV after 2 wk when compared to no M. In addition, BRD in LV3 and RV were also greater at 2 wk than after 8 wk M. The data indicate that there are regional differences in the beta adrenergic receptor densities among the areas of the heart and within the left ventricle. Chronic dosing with M produced increased BRD in only some of the areas of the heart. These differences may be related to functional differences in the various areas of the heart after CO.

[Clinical trials in nursing journals].

Science.gov (United States)

Di Giulio, Paola; Campagna, Sara; Dimonte, Valerio

2014-01-01

Clinical trials are pivotal for the development of nursing knowledge. To describe the clinical trials published in nursing journals in the last two years and propose some general reflections on nursing research. A search with the key-word trial was done on PubMed (2009-2013) on Cancer Nursing, European Journal of Oncology Nursing, International Journal of Nursing Studies, Journal of Advanced Nursing, Journal of Clinical Nursing and Nursing Research. Of 228 trials identified, 104 (45.8%) were published in the last 2 years. Nurses from Asian countries published the larger number of trials. Educational and supportive interventions were the most studied (61/104 trials), followed by clinical interventions (33/104). Samples were limited and most trials are monocentric. A growing number of trials is published, on issues relevant for the nursing profession, however larger samples and multicentric studies would be necessary.

Sharing and reuse of individual participant data from clinical trials

DEFF Research Database (Denmark)

Ohmann, Christian; Banzi, Rita; Canham, Steve

2017-01-01

: The adoption of the recommendations in this document would help to promote and support data sharing and reuse among researchers, adequately inform trial participants and protect their rights, and provide effective and efficient systems for preparing, storing and accessing data. The recommendations now need......OBJECTIVES: We examined major issues associated with sharing of individual clinical trial data and developed a consensus document on providing access to individual participant data from clinical trials, using a broad interdisciplinary approach. DESIGN AND METHODS: This was a consensus...... Research Infrastructures Building Enduring Life-science Services) and coordinated by the European Clinical Research Infrastructure Network. Thus, the focus was on non-commercial trials and the perspective mainly European. OUTCOME: We developed principles and practical recommendations on how to share data...

Study protocol, rationale and recruitment in a European multi-centre randomized controlled trial to determine the efficacy and safety of azithromycin maintenance therapy for 6 months in primary ciliary dyskinesia

DEFF Research Database (Denmark)

Kobbernagel, Helene Elgaard; Buchvald, Frederik F; Haarman, Eric G

2016-01-01

maintenance therapy in PCD. METHODS: The BESTCILIA trial is a European multi-centre, double-blind, randomized, placebo-controlled, parallel group study. The intervention is tablets of azithromycin 250/500 mg according to body weight or placebo administered three times a week for 6 months. Subjects...... prescribed in other chronic respiratory disorders. Furthermore, the trial will utilize the Lung clearance index and new, PCD-specific quality of life instruments as outcome measures for PCD. Recruitment is hampered by frequent occurrence of Pseudomonas aeruginosa infection, exacerbations at enrolment...

Towards a single European electricity market : A structured approach to regulatory mode decision-making

NARCIS (Netherlands)

De Jong, H.M.

2009-01-01

This study focuses on the processes through which the rules and regulations that govern European electricity markets - and inherently, their integration process - are established. So far, European policy makers have largely followed a 'trial-and-error' approach to finding an appropriate regulatory

First direct comparison of clinical outcomes between European and Asian cohorts in transcatheter aortic valve implantation: the Massy study group vs. the PREVAIL JAPAN trial.

Science.gov (United States)

Watanabe, Yusuke; Hayashida, Kentaro; Takayama, Morimasa; Mitsudo, Kazuaki; Nanto, Shinsuke; Takanashi, Shuichiro; Komiya, Tatsuhiko; Kuratani, Toru; Tobaru, Tetsuya; Goto, Tsuyoshi; Lefèvre, Thierry; Sawa, Yoshiki; Morice, Marie-Claude

2015-02-01

The efficacy and safety of transcatheter aortic valve implantation (TAVI) in Asian populations were unknown. The purpose of this study was to compare directly the clinical outcomes of the first Japanese trial and a European single-center experience after TAVI. Between April 2010 and October 2011, 64 patients were included in the PREVAIL JAPAN multicenter trial which was set up to evaluate the safety and efficacy of the Edwards SAPIEN XT™ (Edwards Lifesciences, Irvine, CA, USA) in high-risk Japanese patients with severe aortic stenosis. Between March 2010 and January 2012, 237 consecutive patients treated with TAVI using the Edwards SAPIEN XT™ prosthesis at Institut Cardiovasculaire Paris Sud were prospectively included in the Massy cohort. We compared the clinical outcomes of these two cohorts. Patients were of similar age (83.4±6.6 years vs. 84.5±6.1 years, p=0.25), but logistic EuroSCORE was higher in the Massy cohort (20.2±11.7% vs. 15.6±8.0%, pPREVAIL JAPAN cohort (1.41±0.14m(2) vs. 1.72±0.18m(2); pPREVAIL JAPAN cohort (12.7±11.4mmHg vs. 10.1±3.6mmHg, p=0.01), but satisfactory improvement in 6-month functional status was obtained in both cohorts (76.5% vs. 77.2%, p=0.91). Clinical outcomes after TAVI in the patients included in the PREVAIL JAPAN trial were acceptable and as safe as that of a single-center European cohort. Copyright © 2014 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Twenty Years of European Union Support to Gene Therapy and Gene Transfer.

Science.gov (United States)

Gancberg, David

2017-11-01

For 20 years and throughout its research programmes, the European Union has supported the entire innovation chain for gene transfer and gene therapy. The fruits of this investment are ripening as gene therapy products are reaching the European market and as clinical trials are demonstrating the safety of this approach to treat previously untreatable diseases.

Miscanthus: A Review of European Experience with a Novel Energy Crop

Energy Technology Data Exchange (ETDEWEB)

Scurlock, J.M.O.

1999-02-01

Miscanthus is a tall perennial grass which has been evaluated in Europe over the past 5-10 years as a new bioenergy crop. The sustained European interest in miscanthus suggests that this novel energy crop deserves serious investigation as a possible candidate biofuel crop for the US alongside switchgrass. To date, no agronomic trials or trial results for miscanthus are known from the conterminous US, so its performance under US conditions is virtually unknown. Speculating from European data, under typical agricultural practices over large areas, an average of about 8t/ha (3t/acre dry weight) may be expected at harvest time. As with most of the new bioenergy crops, there seems to be a steep ''learning curve.'' Establishment costs appear to be fairly high at present (a wide range is reported from different European countries), although these may be expected to fall as improved management techniques are developed.

The Implications of Ranaviruses to European farmed and wild freshwater fish

DEFF Research Database (Denmark)

Jensen, Ann Britt Bang

The present thesis explores the implications of ranaviruses to European farmed and wild freshwater fish. The work presented was carried out as a part of the EU project “Risk assessment of new and emerging systemic iridoviral diseases for European fish and aquatic ecosystems” which was initiated...... in 2005 as a reaction to the speculation that ranaviruses might pose a serious threat to both farmed and wild-living freshwater fish and amphibians within the European community. In the present thesis, the purpose is to determine the implications of ranaviruses to European freshwater farmed and wild...... describing the risk of introduction and spread of exotic ranaviruses in European wild and farmed aquatic ecosystems Objectives 1 and 2 have been addressed by experimental trials involving bath challenges of both European farmed and wild fish species and ornamental fish species. The results showed that some...

Toxicity assessment of metoprolol and its photodegradation mixtures obtained by using different type of TiO{sub 2} catalysts in the mammalian cell lines

Energy Technology Data Exchange (ETDEWEB)

Četojević-Simin, Dragana D., E-mail: ddaaggeerr@gmail.com [University of Novi Sad, Faculty of Medicine, Oncology Institute of Vojvodina, Dr Goldmana 4, 21204 Sremska Kamenica (Serbia); Armaković, Sanja J., E-mail: sanja.armakovic@dh.uns.ac.rs [University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Trg D. Obradovića 3, 21000 Novi Sad (Serbia); Šojić, Daniela V., E-mail: daniela.sojic@dh.uns.ac.rs [University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Trg D. Obradovića 3, 21000 Novi Sad (Serbia); Abramović, Biljana F., E-mail: biljana.abramovic@dh.uns.ac.rs [University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Trg D. Obradovića 3, 21000 Novi Sad (Serbia)

2013-10-01

Toxicity of metoprolol (MET) alone and in mixtures with its photocatalytic degradation intermediates obtained by using TiO{sub 2} Wackherr and Degussa P25 under UV irradiation in the presence of O{sub 2} was evaluated in vitro in a panel of three histologically different cell lines: rat hepatoma (H-4-II-E), human colon adenocarcinoma (HT-29) and human fetal lung (MRC-5). Both catalysts promoted a time-dependent increase in the toxicity of the photodegradation products, and those obtained using Degussa P25 photocatalyst were more toxic. The most pronounced and selective toxic action of MET and products of its photodegradation was observed in the hepatic cell line. The higher toxicity of the mixtures obtained using Degussa P25 catalyst could be explained by a different mechanism of MET degradation, i.e. by the presence or higher concentrations of some intermediates. Although the concentrations of intermediates obtained using TiO{sub 2} Wackherr catalyst were higher, they did not affect significantly the growth of the examined cell lines, indicating their lower toxicity. This suggests that a treatment aiming at complete mineralization should be performed bearing in mind that the type of catalyst, the concentration of target molecule, and the duration of the process are significant factors that determine the nature and toxicity of the resulting mixtures. Although the EC{sub 50} values of MET obtained in mammalian cell lines were higher compared to the bioassays for lower trophic levels, the time-dependent promotion of toxicity of degradation mixtures should be attributed to the higher sensitivity of mammalian cell bioassays. - Highlights: • Toxicity study of metoprolol and its photocatalytic degradation mixtures • Toxicity evaluation in vitro in H-4-II-E, HT-29 and MRC-5 cell lines • TiO{sub 2} Wackherr and Degussa P25 promoted a time-dependent increase in toxicity. • The higher toxicity of degradation mixtures obtained using Degussa P25 • Most pronounced and

European Nicotinamide Diabetes Intervention Trial (ENDIT)

DEFF Research Database (Denmark)

Gale, E A M; Bingley, P J; Emmett, C L

2004-01-01

with a pseudorandom number generator and we used size balanced blocks of four and stratified by age and national group. Primary outcome was development of diabetes, as defined by WHO criteria. Analysis was done on an intention-to-treat basis. FINDINGS: There was no difference in the development of diabetes between...... secretion. INTERPRETATION: Large-scale controlled trials of interventions designed to prevent the onset of type 1 diabetes are feasible, but nicotinamide was ineffective at the dose we used.......BACKGROUND: Results of studies in animals and human beings suggest that type 1 diabetes is preventable. Nicotinamide prevents autoimmune diabetes in animal models, possibly through inhibition of the DNA repair enzyme poly-ADP-ribose polymerase and prevention of beta-cell NAD depletion. We aimed...

Photocatalytic degradation of metoprolol tartrate in suspensions of two TiO{sub 2}-based photocatalysts with different surface area. Identification of intermediates and proposal of degradation pathways

Energy Technology Data Exchange (ETDEWEB)

Abramovic, Biljana, E-mail: biljana.abramovic@dh.uns.ac.rs [Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg D. Obradovica 3, 21000 Novi Sad (Serbia); Kler, Sanja, E-mail: sanja.kler@dh.uns.ac.rs [Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg D. Obradovica 3, 21000 Novi Sad (Serbia); Sojic, Daniela, E-mail: daniela.sojic@dh.uns.ac.rs [Department of Chemistry, Biochemistry and Environmental Protection, Faculty of Sciences, University of Novi Sad, Trg D. Obradovica 3, 21000 Novi Sad (Serbia); Lausevic, Mila, E-mail: milal@tmf.bg.ac.rs [Faculty of Technology and Metallurgy, University of Belgrade, Karnegijeva 4, 11120 Belgrade (Serbia); Radovic, Tanja, E-mail: tradovic@tmf.bg.ac.rs [Faculty of Technology and Metallurgy, University of Belgrade, Karnegijeva 4, 11120 Belgrade (Serbia); Vione, Davide, E-mail: davide.vione@unito.it [Dipartimento di Chimica Analitica, Universita di Torino, Via Pietro Giuria 5, 10125 Torino (Italy)

2011-12-30

Highlights: Black-Right-Pointing-Pointer Kinetics and efficiency of photocatalytic degradation of the {beta}{sub 1}-blocker metoprolol tartrate (MET). Black-Right-Pointing-Pointer Two TiO{sub 2} specimens employed. Black-Right-Pointing-Pointer Faster degradation of MET, but slower mineralization, obtained with the TiO{sub 2} specimen having lower surface area. Black-Right-Pointing-Pointer Photocatalytic transformation pathways of MET including mineralization. - Abstract: This study investigates the efficiency of the photocatalytic degradation of metoprolol tartrate (MET), a widely used {beta}{sub 1}-blocker, in TiO{sub 2} suspensions of Wackherr's 'Oxyde de titane standard' and Degussa P25. The study encompasses transformation kinetics and efficiency, identification of intermediates and reaction pathways. In the investigated range of initial concentrations (0.01-0.1 mM), the photocatalytic degradation of MET in the first stage of the reaction followed approximately a pseudo-first order kinetics. The TiO{sub 2} Wackherr induced a significantly faster MET degradation compared to TiO{sub 2} Degussa P25 when relatively high substrate concentrations were used. By examining the effect of ethanol as a scavenger of hydroxyl radicals ({center_dot}OH), it was shown that the reaction with {center_dot}OH played the main role in the photocatalytic degradation of MET. After 240 min of irradiation the reaction intermediates were almost completely mineralized to CO{sub 2} and H{sub 2}O, while the nitrogen was predominantly present as NH{sub 4}{sup +}. Reaction intermediates were studied in detail and a number of them were identified using LC-MS/MS (ESI+), which allowed the proposal of a tentative pathway for the photocatalytic transformation of MET as a function of the TiO{sub 2} specimen.

Barriers towards the publication of academic drug trials. Follow-up of trials approved by the Danish Medicines Agency

DEFF Research Database (Denmark)

Berendt, Louise; Petersen, Lene Grejs; Bach, Karin Friis

2017-01-01

OBJECTIVE: To characterize and quantify barriers towards the publication of academic drug trials. STUDY DESIGN: We identified academic drug trials approved during a 3-year period (2004-2007) by the Danish Medicines Agency. We conducted a survey among the trial sponsors to describe the rates...... of initiation, completion, and publication, and the reasons for the failure to reach each of these milestones. Information on size and methodological characteristics of the trials was extracted from the EudraCT database, a prospective register of all approved clinical drug trials submitted to European medicines...... agencies since 2004. RESULTS: A total of 181 academic drug trials were eligible for inclusion, 139 of which participated in our survey (response rate: 77%). Follow-up time ranged from 5.1 to 7.9 years. Most trials were randomized controlled trials (73%, 95% CI 65-81%). Initiation and completion rates were...

Transparency Policies of the European Medicines Agency: Has the Paradigm Shifted?

Science.gov (United States)

Kim, Daria

2017-08-01

This article reflects on the state of play as regards access to non-summary clinical trial data in the European Union (EU). In particular, it examines the scope of access under the recent transparency policies of the European Medicines Agency (EMA) that attempt to break away from the presumptively confidential treatment of clinical trial data. In light of the emerging case law of the Court of Justice of the European Union on clinical trial data disclosure, it remains highly uncertain what data, and under what conditions, can be lawfully released by the EMA. Under the applicable regulations, the scope of the accessible data depends on the interpretation of commercially confidential information-the notion derived from the exception to the fundamental right of access to documents. Accordingly, the analysis focuses on the application of this exception, taking into account the specifics of clinical data, the context in which disclosure occurs, and the interests that are at stake. The main complexity is found in defining the scope of the relevant and legitimate interests to be balanced when applying the exception. Overall, it is argued that the current regulatory framework does not provide a sufficient legal basis to support the objectives pursued by the EMA's policies. © The Author 2017. Published by Oxford University Press; all rights reserved. For Permissions, please email: journals.permissions@oup.com.

A European multi-language initiative to make the general population aware of independent clinical research

DEFF Research Database (Denmark)

Mosconi, Paola; Antes, Gerd; Barbareschi, Giorgio

2016-01-01

2. An animated film about clinical trials, dubbed in the 23 official languages of the European Community, and an interactive tutorial 3. An inventory of resources, available in 23 languages, searchable by topic, author, and media type 4. Two educational games for young people, developed in six......BACKGROUND: The ECRAN (European Communication on Research Awareness Needs) project was initiated in 2012, with support from the European Commission, to improve public knowledge about the importance of independent, multinational, clinical trials in Europe. METHODS: Participants in the ECRAN...... materials and tools, making them freely available under a Creative Commons licence. RESULTS: The principal communication materials developed were: 1. A website ( http://ecranproject.eu ) in six languages, including a Media centre section to help journalists to disseminate information about the ECRAN project...

Two biomarker-directed randomized trials in European and Chinese patients with nonsmall-cell lung cancer: the BRCA1-RAP80 Expression Customization (BREC) studies.

Science.gov (United States)

Moran, T; Wei, J; Cobo, M; Qian, X; Domine, M; Zou, Z; Bover, I; Wang, L; Provencio, M; Yu, L; Chaib, I; You, C; Massuti, B; Song, Y; Vergnenegre, A; Lu, H; Lopez-Vivanco, G; Hu, W; Robinet, G; Yan, J; Insa, A; Xu, X; Majem, M; Chen, X; de Las Peñas, R; Karachaliou, N; Sala, M A; Wu, Q; Isla, D; Zhou, Y; Baize, N; Zhang, F; Garde, J; Germonpre, P; Rauh, S; ALHusaini, H; Sanchez-Ronco, M; Drozdowskyj, A; Sanchez, J J; Camps, C; Liu, B; Rosell, R

2014-11-01

In a Spanish Lung Cancer Group (SLCG) phase II trial, the combination of BRCA1 and receptor-associated protein 80 (RAP80) expression was significantly associated with outcome in Caucasian patients with nonsmall-cell lung cancer (NSCLC). The SLCG therefore undertook an industry-independent collaborative randomized phase III trial comparing nonselected cisplatin-based chemotherapy with therapy customized according to BRCA1/RAP80 expression. An analogous randomized phase II trial was carried out in China under the auspices of the SLCG to evaluate the effect of BRCA1/RAP80 expression in Asian patients. Eligibility criteria included stage IIIB-IV NSCLC and sufficient tumor specimen for molecular analysis. Randomization to the control or experimental arm was 1 : 1 in the SLCG trial and 1 : 3 in the Chinese trial. In both trials, patients in the control arm received docetaxel/cisplatin; in the experimental arm, patients with low RAP80 expression received gemcitabine/cisplatin, those with intermediate/high RAP80 expression and low/intermediate BRCA1 expression received docetaxel/cisplatin, and those with intermediate/high RAP80 expression and high BRCA1 expression received docetaxel alone. The primary end point was progression-free survival (PFS). Two hundred and seventy-nine patients in the SLCG trial and 124 in the Chinese trial were assessable for PFS. PFS in the control and experimental arms in the SLCG trial was 5.49 and 4.38 months, respectively [log rank P = 0.07; hazard ratio (HR) 1.28; P = 0.03]. In the Chinese trial, PFS was 4.74 and 3.78 months, respectively (log rank P = 0.82; HR 0.95; P = 0.82). Accrual was prematurely closed on the SLCG trial due to the absence of clinical benefit in the experimental over the control arm. However, the BREC studies provide proof of concept that an international, nonindustry, biomarker-directed trial is feasible. Thanks to the groundwork laid by these studies, we expect that ongoing further research on alternative biomarkers to

Development in the number of clinical trial applications in Western Europe from 2007 to 2015

DEFF Research Database (Denmark)

Dombernowsky, Tilde; Hædersdal, Merete; Lassen, Ulrik

2017-01-01

OBJECTIVE: To investigate the development in the number of applications for authorisation of clinical trials of medicines (CTAs) submitted annually to national competent authorities in 10 Western European member states of the European Union from 2007 to 2015. DESIGN: Registry study. SETTING: Data...... from national competent authorities. PARTICIPANTS: Germany, Italy, Spain, France, the UK, Belgium, the Netherlands, Austria, Denmark and Sweden. Inclusion criteria were Western European member states of the European Union, receiving more than 200 CTAs per year. OUTCOME MEASURES: Summarised number...... of CTAs and distribution of CTAs by type of sponsor (commercial or non-commercial) and trial phase (I-IV). Average annual growth rates (AAGRs) based on linear regressions. Data were evaluated 2007-2011 and 2012-2015 to compare findings with the European Commission's statement of a 25% decrease in CTAs...

Alcolocks : factors influencing implementation, participation and compliance : literature review contributed to the EU project Alcolock Implementation in the European Union.

NARCIS (Netherlands)

Mathijssen, M.P.M.

2007-01-01

In 2004-2005, a series of alcolock field trials were conducted in four European countries, in the framework of the EU research project Alcolock Implementation in the European Union. This project was granted by the European Commission, Directorate-General for Energy and Transport (DG-TREN). As part

Randomized controlled trial of relaxation music to reduce heart rate in patients undergoing cardiac CT.

Science.gov (United States)

Ng, Ming Yen; Karimzad, Yasser; Menezes, Ravi J; Wintersperger, Bernd J; Li, Qin; Forero, Julian; Paul, Narinder S; Nguyen, Elsie T

2016-10-01

To evaluate the heart rate lowering effect of relaxation music in patients undergoing coronary CT angiography (CCTA), pulmonary vein CT (PVCT) and coronary calcium score CT (CCS). Patients were randomised to a control group (i.e. standard of care protocol) or to a relaxation music group (ie. standard of care protocol with music). The groups were compared for heart rate, radiation dose, image quality and dose of IV metoprolol. Both groups completed State-Trait Anxiety Inventory anxiety questionnaires to assess patient experience. One hundred and ninety-seven patients were recruited (61.9 % males); mean age 56y (19-86 y); 127 CCTA, 17 PVCT, 53 CCS. No significant difference in heart rate, radiation dose, image quality, metoprolol dose and anxiety scores. 86 % of patients enjoyed the music. 90 % of patients in the music group expressed a strong preference to have music for future examinations. The patient cohort demonstrated low anxiety levels prior to CT. Relaxation music in CCTA, PVCT and CCS does not reduce heart rate or IV metoprolol use. Patients showed low levels of anxiety indicating that anxiolytics may not have a significant role in lowering heart rate. Music can be used in cardiac CT to improve patient experience. • Relaxation music does not reduce heart rate in cardiac CT • Relaxation music does not reduce beta-blocker use in cardiac CT • Relaxation music has no effect on cardiac CT image quality • Low levels of anxiety are present in patients prior to cardiac CT • Patients enjoyed the relaxation music and this results in improved patient experience.

Mechanical Ventilation, Weaning Practices, and Decision Making in European PICUs

NARCIS (Netherlands)

Tume, Lyvonne N.; Kneyber, Martin C. J.; Blackwood, Bronagh; Rose, Louise

2017-01-01

Objectives: This survey had three key objectives: 1) To describe responsibility for key ventilation and weaning decisions in European PICUs and explore variations across Europe; 2) To describe the use of protocols, spontaneous breathing trials, noninvasive ventilation, high-flow nasal cannula use,

Abatement of CO2 emissions in the European Union

International Nuclear Information System (INIS)

Lesourne, J.; Keppler, J.H.; Jaureguy-Naudin, Maite; Smeers, Yves; Bouttes, Jean-Paul; Trochet, Jean-Michel; Dassa, Francois; Neuhoff, Karsten

2008-01-01

This first monograph of the Ifri program on European Governance and Geopolitics of Energy is devoted to the control of carbon dioxide emissions within the European Union. Since it is almost unanimously accepted that Greenhouse Gas emissions constitute the main cause of the observed increase of the world average temperature, the system implemented by the European Union to limit and decrease the CO 2 emissions is a significant pillar of the EU energy policy, the two others being the acceptance by the Member States of long-term commitments (for instance on the future share of renewable energy sources in their energy balance sheet) and the establishment of an internal market for electricity and gas. Though simple in principle, the European Union Greenhouse Gas Emission Trading Scheme (EU ETS) is in fact rather complex, and only experts really understand its merits and its deficiencies. These deficiencies are real and will have to be corrected in the future for the system to be effective. At this moment, when the 2005-2007 trial phase of the EU ETS is ending, the monograph has the purpose to stimulate the discussion between experts and to enable all those interested in the topic to understand the issues and to take part in the public debates on the subject. The monograph contains five papers: - 'An Overview of the CO 2 Emission Control System in the European Union' by Jacques Lesourne and Maite Jaureguy-Naudin. - 'Description and Assessment of EU CO 2 Regulations' by Yves Smeers. - 'Assessment of EU CO 2 Regulations' by Jean-Paul Bouttes, Jean-Michel Trochet and Francois Dassa. - 'Investment in Low Carbon Technologies, Policies for the Power Sector' by Karsten Neuhoff. - 'Lessons Learned from the 2005-2007 Trial Phase of the EU Emission Trading System' by Jan Horst Keppler

The Effect of Nebivolol versus Metoprolol Succinate Extended Release on Asymmetric Dimethylarginine in Hypertension

Science.gov (United States)

Kandavar, Ramprasad; Higashi, Yusuke; Chen, Wei; Blackstock, Christopher; Vaughn, Charlotte; Sukhanov, Sergiy; Sander, Gary E.; Roffidal, Louise E.; Delafontaine, Patrice; Giles, Thomas D.

2011-01-01

Objectives This study sought to determine if metoprolol succinate ER (MET), and nebivolol (NEB), a β1-AR with increased bioavailability of nitric oxide (NO), would have differing effects on plasma asymmetric dimethylarginine concentration in hypertensives. Background It was hypothesized that NEB, a β1-AR antagonist and β3-AR agonist with NO- releasing properties and MET, only a β1-AR antagonist, would have different effects on plasma ADMA concentration. Methods Forty-one hypertensive subjects randomly received either 50 mg of MET (n = 19) or 5 mg of NEB (n = 22) for 4 weeks followed by 100 mg MET and 10 mg NEB for 4 weeks. ADMA and IGF-1 were measured by ELISA kit; endothelial progenitor cells were estimated using fluorescein-labeled monoclonal antibody to KDR and CD133 receptors; arterial augmentation index was measured by radial tonometry. Results Baseline systolic/diastolic blood pressure was 155.1 ± 18.7/85.3 ± 12.5 mm Hg for MET subjects and 157.6 ± 20.7/87.1 ± 14.0 mm Hg for NEB subjects. Baseline ADMA was 0.32 ± 0.123 μmol/L in the MET group and 0.4035 ± 0.1378 in the NEB group. ADMA increased 44.78% and 72% in the MET group at weeks 4 and 8 (p < 0.05 for both), respectively, without increase in the NEB group. At week 8 augmentation index was increased in the MET group (p<0.05). IGF-1 and EPC were unchanged by treatment. Conclusions Plasma ADMA and augmentation index are increased in a dose-dependent fashion by MET but not with NEB. PMID:21251896

Influence of nifedipine on left ventricular perfusion and function in patients with unstable angina: Evaluation with radionuclide techniques

Energy Technology Data Exchange (ETDEWEB)

Wall, E.E. van der; Kerkkamp, H.J.; Simoons, M.L.; Rijk, P.P. van; Reiber, J.H.C.; Bom, N.; Lubsen, J.C.; Lie, K.I.

1986-04-01

In 1981, a large, double-blind, randomized trial was started in The Netherlands to evaluate the therapeutic effects of nifedipine and/or metoprolol in patients with unstable angina. This study has been called the Holland Interuniversity Nifedipine/metoprolol Trial (HINT) and required several hundred patients to establish potential therapeutic effects. From December 1982 to January 1984 the effects of nifedipine on left ventricular (LV) performance in a subgroup of 52 HINT patients were studied using radionuclide techniques. All patients (23 on nifedipine, 29 controls) underwent thallium-201 scintigraphy or radionuclide angiography just before and 48 h after the start of experimental medication. The radionuclide angiographic studies were also performed at 1 and 4 h after treatment. Nifedipine did not influence the incidence of disapperance of perfusion defects on the 48-h thallium images. No significant differences in overall LV ejections fraction (EF) were seen at any time between nifedipine-treated patients and controls. However, paired observations in 37 patients showed improvement of LVEF after 48 h in 8 patients on nifedipine and in only 1 control patient. Scintigraphic measurements on admission were not related to clinical outcome after 48 h. Concomitant administration of metoprolol did not influence LVEF in either group. It is concluded that nifedipine improves LVEF after 48 h in a subset of patients with unstable angina without affecting myocardial perfusion. This finding indicates that nifedipine has a predominant effect on afterload reduction in patients with unstable angina. Also, early scintigraphic measurements had no significant predictive value for subsequent cardiac events.

Features of calculation of reasonable time of the trial in civil cases in the context of the practice of the European court of human rights

Directory of Open Access Journals (Sweden)

Т. Цувіна

2015-11-01

Full Text Available Problem setting. European Convention of Human Rights (ECHR guarantees right to a fair trial within a reasonable time for everyone (par. 1 art. 6 ECHR. Reasonable time of the trial is an element of the right to a fair trial. One of the main directions for development of civil procedure in Ukraine is the implementation of international standards of fair trial, in particular standards of reasonable time of the trial. Recent research and publications analyses. Foreign and Ukrainian scientists such as Komarov V. V., Neshataeva T. M., Sakara N. U. and others in their works paid attention to different aspects of problems connected with the right to a fair trial within a reasonable time, but a comprehensive study devoted to a features of calculation of reasonable time of the trial taking into account the practice of the ECHR on this issue wasn’t conducted. Paper objective. Main objective of the article is to study decisions of the ECHR concerning the interpretation of Par. 1, Art. 6 ECHR and analyze features of calculation of reasonable time of the trial to make recommendations on implementation of such national level. Paper main body. As a rule, according to a practice of ECHR reasonable time of civil proceedings begins on the date on which the case is referred to a judicial authority. Thus ECHR can take as the starting point the date of a preliminary application to an administrative authority, especially when this is a prerequisite for commencement of proceedings. The end of reasonable time of the trial connected with the moment when the court decision become final or its execution. Conclusions of the research. Calculation of reasonable time of the trial in civil cases in circumstances when an application to the court was preceded by a seeking for protection from the authorities and public servants of executive power has features. In such situations a calculation of reasonable time of the trial doesn’t begin from the moment of seeking for

Advances in Clinical Cardiology 2016: A Summary of the Key Clinical Trials.

Science.gov (United States)

Gray, Alastair; McQuillan, Conor; Menown, Ian B A

2017-07-01

The findings of many new cardiology clinical trials over the last year have been published or presented at major international meetings. This paper aims to describe and place in context a summary of the key clinical trials in cardiology presented between January and December 2016. The authors reviewed clinical trials presented at major cardiology conferences during 2016 including the American College of Cardiology (ACC), European Association for Percutaneous Cardiovascular Interventions (EuroPCR), European Society of Cardiology (ESC), European Association for the Study of Diabetes (EASD), Transcatheter Cardiovascular Therapeutics (TCT), and the American Heart Association (AHA). Selection criteria were trials with a broad relevance to the cardiology community and those with potential to change current practice. A total of 57 key cardiology clinical trials were identified for inclusion. Here we describe and place in clinical context the key findings of new data relating to interventional and structural cardiology including delayed stenting following primary angioplasty, contrast-induced nephropathy, management of jailed wires, optimal duration of dual antiplatelet therapy (DAPT), stenting vs bypass for left main disease, new generation stents (BioFreedom, Orsiro, Absorb), transcatheter aortic valve implantation (Edwards Sapien XT, transcatheter embolic protection), and closure devices (Watchman, Amplatzer). New preventative cardiology data include trials of bariatric surgery, empagliflozin, liraglutide, semaglutide, PCSK9 inhibitors (evolocumab and alirocumab), and inclisiran. Antiplatelet therapy trials include platelet function monitoring and ticagrelor vs clopidogrel for peripheral vascular disease. New data are also presented in fields of heart failure (sacubitril/valsartan, aliskiren, spironolactone), atrial fibrillation (rivaroxaban in patients undergoing coronary intervention, edoxaban in DC cardioversion), cardiac devices (implantable cardioverter

Miniaturized membrane sensors for potentiometric determination of metoprolol tartrate and hydrochlorothiazide.

Science.gov (United States)

Ramadan, Nesrin K; Mohamed, Heba M; Mostafa, Azza A

2012-06-01

Four microsized graphite and platinum wire poly(vinyl chloride) matrix membrane electrodes responsive to some drugs affecting cardiovascular system, Metoprolol tartrate (MT) and Hydrochlorothiazide (HZ) were developed, described and characterized. These sensors were constructed by using (2-Hydroxypropyl)-β-cyclodextrin (2HP β-CD) as an ionophore which has a significant influence on increasing both membrane sensitivity and selectivity. The four sensors were fabricated in a polymeric matrix of carboxylated polyvinyl chloride (PVC-COOH) and dioctylphthalate (DOP) as a plasticizer, based on the interaction between the drugs and the dissociated COOH groups in the PVC-COOH. Fast and stable Nernstian responses of 1.0 × 10-6-1.0 × 10-2 M for MT (sensors 1 and 2) and of 1.0 × 10-7-1.0 × 10-3 M for HZ (sensors 3 and 4) over pH range 3.0-9.0 and 3.0-7.0 for the MT and HZ sensors respectively were obtained. Nernstian slopes of 56.2, 54.6, 19.0 and 20.8 mV/decade for electrodes 1-4 respectively were observed. The proposed method displayed useful analytical characteristics for the determination of MT and HZ in their pure powder forms with average recoveries of 99.11 ± 0.357, 99.21 ± 0.389, 100.08 ± 0.459 and 100.28 ± 0.438% for sensors 1-4 respectively. The lower limit of detection (LOD) were 5.5 × 10-6, 4.5 × 10-6, 4.8 × 10-8 and 5.0 × 10-8 M for sensors 1-4 respectively indicated high sensitivity. The four sensors displayed a good stability over a period of 6 weeks. The selectivity coefficients of the developed sensors indicated excellent selectivity. Results obtained by the four electrodes revealed the performance characteristics of these electrodes which evaluated according to IUPAC recommendations. The method was successively applied for the determination of MT and HZ in presence of each other, in presence of Salamide (SA), the main degradation product of HZ, in their pharmaceutical formulations and in human plasma samples. Statistical comparison between the

European Practice for CDI Treatment.

Science.gov (United States)

Fitzpatrick, Fidelma; Skally, Mairead; Brady, Melissa; Burns, Karen; Rooney, Christopher; Wilcox, Mark H

2018-01-01

Clostridium difficile infection (CDI) remains a significant cause of morbidity and mortality worldwide. Historically, two antibiotics (metronidazole and vancomycin) and a recent third (fidaxomicin) have been used routinely for CDI treatment; convincing data are now available showing that metronidazole is the least efficacious agent. The European Society of Clinical Microbiology and Infectious Diseases CDI treatment guidelines outline the treatment options for a variety of CDI clinical scenarios, including use of the more traditional anti-CDI therapies (e.g., metronidazole, vancomycin), the role of newer anti-CDI agents (e.g., fidaxomicin), indications for surgical intervention and for non-antimicrobial management (e.g., faecal microbiota transplantation, FMT). A 2017 survey of 20 European countries found that while the majority (n = 14) have national CDI guidelines that provide a variety of recommendations for CDI treatment, only five have audited guideline implementation. A variety of restrictions are in place in 13 (65%) countries prior to use of new anti-CDI treatments, including committee/infection specialist approval or economic review/restrictions. Novel anti-CDI agents are being evaluated in Phase III trials; it is not yet clear what will be the roles of these agents. Prophylaxis is an optimum approach to reduce the impact of CDI especially in high-risk populations; monoclonal antibodies, antibiotic blocking approaches and multiple vaccines are currently in advanced clinical trials. The treatment of recurrent CDI is particularly troublesome, and several different live bio therapeutics are being developed, in addition to FMT.

Towards a single European electricity market. A structured approach to regulatory mode decision-making

International Nuclear Information System (INIS)

De Jong, H.M.

2009-01-01

This study focuses on the processes through which the rules and regulations that govern European electricity markets - and inherently, their integration process - are established. So far, European policy makers have largely followed a 'trial-and-error' approach to finding an appropriate regulatory mode (process) for dealing effectively with market integration issues. This unstructured approach to regulatory mode selection leads to several problems: - Today's trial-and-error strategy of shifting from one regulatory mode to another is time-consuming. - In the regulatory mode selection process, certain key principles of good governance are insufficiently considered. - European regulatory processes are experienced as vague, intransparent, and illegitimate by 'outside' stakeholders. This study develops a 'structured approach to regulatory mode decision-making' (STARMODE) based on the theory of decision modelling in policy management and a case study exploring three key market integration issues in the field of electricity markets: interconnector investment, congestion management and market transparency. The main objective is to present a systematic and comprehensive framework for analysing and improving regulatory mode decision-making in the context of the European Union, focusing on electricity market integration. The STARMODE approach is generally applicable to (and relevant for) European market integration issues in industries characterized by a natural monopoly and/or an essential service. The approach may also contribute to national regulatory mode decision-making and multi-state decision-making in other continents.

Abatement of CO{sub 2} emissions in the European Union

Energy Technology Data Exchange (ETDEWEB)

Lesourne, J.; Keppler, J.H.; Jaureguy-Naudin, Maite; Smeers, Yves; Bouttes, Jean-Paul; Trochet, Jean-Michel; Dassa, Francois; Neuhoff, Karsten

2008-07-01

This first monograph of the Ifri program on European Governance and Geopolitics of Energy is devoted to the control of carbon dioxide emissions within the European Union. Since it is almost unanimously accepted that Greenhouse Gas emissions constitute the main cause of the observed increase of the world average temperature, the system implemented by the European Union to limit and decrease the CO{sub 2} emissions is a significant pillar of the EU energy policy, the two others being the acceptance by the Member States of long-term commitments (for instance on the future share of renewable energy sources in their energy balance sheet) and the establishment of an internal market for electricity and gas. Though simple in principle, the European Union Greenhouse Gas Emission Trading Scheme (EU ETS) is in fact rather complex, and only experts really understand its merits and its deficiencies. These deficiencies are real and will have to be corrected in the future for the system to be effective. At this moment, when the 2005-2007 trial phase of the EU ETS is ending, the monograph has the purpose to stimulate the discussion between experts and to enable all those interested in the topic to understand the issues and to take part in the public debates on the subject. The monograph contains five papers: - 'An Overview of the CO{sub 2} Emission Control System in the European Union' by Jacques Lesourne and Maite Jaureguy-Naudin. - 'Description and Assessment of EU CO{sub 2} Regulations' by Yves Smeers. - 'Assessment of EU CO{sub 2} Regulations' by Jean-Paul Bouttes, Jean-Michel Trochet and Francois Dassa. - 'Investment in Low Carbon Technologies, Policies for the Power Sector' by Karsten Neuhoff. - 'Lessons Learned from the 2005-2007 Trial Phase of the EU Emission Trading System' by Jan Horst Keppler

Correlates of poor mental health in early pregnancy in obese European women

DEFF Research Database (Denmark)

Sattler, Matteo C; Jelsma, Judith G M; Bogaerts, Annick

2017-01-01

health, in a group of overweight/obese pregnant women in nine European countries, and thus, to contribute to better recognition and intervention for maternal depression. METHODS: In this cross-sectional observational study, baseline data from early pregnancy (... in European overweight/obese pregnant women. The identified correlates might help in early recognition and subsequent treatment of poor mental health problems during pregnancy. This is important to reduce the unfavorable effects of poor mental health on pregnancy outcomes. TRIAL REGISTRATION: ISRCTN70595832...

Sea trials of MARTIN - a European survey AUV

DEFF Research Database (Denmark)

Henriksen, Lars; Bjerrum, A.; Ishoy, A.

1995-01-01

are currently being performed. A new navigation system has been developed for MARTIN. The low-drag flat-fish shaped, modular designed hull has been thoroughly tested in a towing tank and in the open sea. The hydrodynamic parameters were used in computer simulations of the vehicle dynamics. An autopilot based...... software was developed by the Institute of Automation, Danish Technical University in co-operation with Reson AS and Maridan ApS. The paper includes a description of the navigation system, results from simulations and preliminary results from the first sea trials...

Why we need easy access to all data from all clinical trials and how to accomplish it

DEFF Research Database (Denmark)

Gotzsche, Peter C

2011-01-01

ABSTRACT: International calls for registering all trials involving humans and for sharing the results, and sometimes also the raw data and the trial protocols, have increased in recent years. Such calls have come, for example, from the Organization for Economic Cooperation and Development (OECD......), the World Health Organization (WHO), the US National Institutes of Heath, the US Congress, the European Commission, the European ombudsman, journal editors, The Cochrane Collaboration, and several funders, for example the UK Medical Research Council, the Wellcome Trust, the Bill and Melinda Gates Foundation...... why it is a moral imperative to render all results from all trials involving humans, also healthy volunteers, publicly available. Respect for trial participants who often run a personal and unknown risk by participating in trials requires that they - and therefore also the society at large...

Boron Neutron Capture Therapy at European research reactors - Status and perspectives

International Nuclear Information System (INIS)

Moss, R.L.

2004-01-01

Over the last decade. there has been a significant revival in the development of Boron Neutron Capture Therapy (BNCT) as a treatment modality for curing cancerous tumours, especially glioblastoma multiforme and subcutaneous malignant melanoma. In 1987 a European Collaboration on BNCT was formed, with the prime task to identify suitable research reactors in Europe where BNCT could be applied. Due to reasons discussed in this paper, the HFR Petten was chosen as the test-bed for demonstrating BNCT. Currently, the European Collaboration is approaching the start of clinical trials, using epithermal neutrons and borocaptate sodium (BSH) as the 10 B delivery agent. The treatment is planned to start in the first half of 1996. The paper here presents an overview on the principle of BNCT, the requirements imposed on a research reactor in order to be considered for BNCT, and the perspectives for other European materials testing reactors. A brief summary on the current status of the work at Petten is given, including: the design, construction and characterisation of the epithermal neutron beam: performance and results of the healthy tissue tolerance study; the development of a treatment planning programme based on the Monte Carlo code MCNP; the design of an irradiation room; and on the clinical trials themselves. (author)

Development of EULAR recommendations for the reporting of clinical trial extension studies in rheumatology

NARCIS (Netherlands)

Buch, Maya H.; Silva-Fernandez, Lucia; Carmona, Loreto; Aletaha, Daniel; Christensen, Robin; Combe, Bernard; Emery, Paul; Ferraccioli, Gianfranco; Guillemin, Francis; Kvien, Tore K.; Landewe, Robert; Pavelka, Karel; Saag, Kenneth; Smolen, Josef S.; Symmons, Deborah; van der Heijde, Désirée; Welling, Joep; Wells, George; Westhovens, Rene; Zink, Angela; Boers, Maarten

2015-01-01

Our initiative aimed to produce recommendations on post-randomised controlled trial (RCT) trial extension studies (TES) reporting using European League Against Rheumatism (EULAR) standard operating procedures in order to achieve more meaningful output and standardisation of reports. We formed a task

Carvedilol for prevention of atrial fibrillation after cardiac surgery: a meta-analysis.

Directory of Open Access Journals (Sweden)

Hui-Shan Wang

Full Text Available BACKGROUND: Postoperative atrial fibrillation (POAF remains the most common complication after cardiac surgery. Current guidelines recommend β-blockers to prevent POAF. Carvedilol is a non-selective β-adrenergic blocker with anti-inflammatory, antioxidant, and multiple cationic channel blocking properties. These unique properties of carvedilol have generated interest in its use as a prophylaxis for POAF. OBJECTIVE: To investigate the efficacy of carvedilol in preventing POAF. METHODS: PubMed from the inception to September 2013 was searched for studies assessing the effect of carvedilol on POAF occurrence. Pooled relative risk (RR with 95% confidence interval (CI was calculated using random- or fixed-effect models when appropriate. Six comparative trials (three randomized controlled trials and three nonrandomized controlled trials including 765 participants met the inclusion criteria. RESULTS: Carvedilol was associated with a significant reduction in POAF (relative risk [RR] 0.49, 95% confidence interval [CI] 0.37 to 0.64, p<0.001. Subgroup analyses yielded similar results. In a subgroup analysis, carvedilol appeared to be superior to metoprolol for the prevention of POAF (RR 0.51, 95% CI 0.37 to 0.70, p<0.001. No evidence of heterogeneity was observed. CONCLUSIONS: In conclusion, carvedilol may effectively reduce the incidence of POAF in patients undergoing cardiac surgery. It appeared to be superior to metoprolol. A large-scale, well-designed randomized controlled trial is needed to conclusively answer the question regarding the utility of carvedilol in the prevention of POAF.

A parallel randomized trial on the effect of a healthful diet on inflammageing and its consequences in European elderly people: design of the NU-AGE dietary intervention study.

Science.gov (United States)

Berendsen, Agnes; Santoro, Aurelia; Pini, Elisa; Cevenini, Elisa; Ostan, Rita; Pietruszka, Barbara; Rolf, Katarzyna; Cano, Noël; Caille, Aurélie; Lyon-Belgy, Noëlle; Fairweather-Tait, Susan; Feskens, Edith; Franceschi, Claudio; de Groot, C P G M

2013-01-01

The proportion of European elderly is expected to increase to 30% in 2060. Combining dietary components may modulate many processes involved in ageing. So, it is likely that a healthful diet approach might have greater favourable impact on age-related decline than individual dietary components. This paper describes the design of a healthful diet intervention on inflammageing and its consequences in the elderly. The NU-AGE study is a parallel randomized one-year trial in 1250 apparently healthy, independently living European participants aged 65-80 years. Participants are randomised into either the diet group or control group. Participants in the diet group received dietary advice aimed at meeting the nutritional requirements of the ageing population. Special attention was paid to nutrients that may be inadequate or limiting in diets of elderly, such as vitamin D, vitamin B12, and calcium. C-reactive protein is measured as primary outcome. The NU-AGE study is the first dietary intervention investigating the effect of a healthful diet providing targeted nutritional recommendations for optimal health and quality of life in apparently healthy European elderly. Results of this intervention will provide evidence on the effect of a healthful diet on the prevention of age related decline. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Common definition for categories of clinical research: a prerequisite for a survey on regulatory requirements by the European Clinical Research Infrastructures Network (ECRIN)

DEFF Research Database (Denmark)

Kubiak, Christine; de Andres-Trelles, Fernando; Kuchinke, Wolfgang

2009-01-01

in relation to the wide spectrum of clinical research, the European Clinical Research Infrastructures Network (ECRIN) developed a multinational survey in ten European countries. However a lack of common classification framework for major categories of clinical research was identified, and therefore reaching...... with cell therapy, etc.); diagnostic studies; clinical research on nutrition; other interventional clinical research (including trials in complementary and alternative medicine, trials with collection of blood or tissue samples, physiology studies, etc.); and epidemiology studies. Our classification...

Comparative decline in funding of European Commission malaria vaccine projects: what next for the European scientists working in this field?

Directory of Open Access Journals (Sweden)

Imoukhuede Egeruan B

2011-09-01

Full Text Available Abstract Since 2000, under the Fifth and subsequent Framework Programmes, the European Commission has funded research to spur the development of a malaria vaccine. This funding has contributed to the promotion of an integrated infrastructure consisting of European basic, applied and clinical scientists in academia and small and medium enterprises, together with partners in Africa. Research has added basic understanding of what is required of a malaria vaccine, allowing selected candidates to be prioritized and some to be moved forward into clinical trials. To end the health burden of malaria, and its economic and social impact on development, the international community has now essentially committed itself to the eventual eradication of malaria. Given the current tentative advances towards elimination or eradication of malaria in many endemic areas, malaria vaccines constitute an additional and almost certainly essential component of any strategic plan to interrupt transmission of malaria. However, funding for malaria vaccines has been substantially reduced in the Seventh Framework Programme compared with earlier Framework Programmes, and without further support the gains made by earlier European investment will be lost.

Antivenom for European Vipera species envenoming.

Science.gov (United States)

Lamb, Thomas; de Haro, Luc; Lonati, Davide; Brvar, Miran; Eddleston, Michael

2017-07-01

randomized controlled trials comparing any European Vipera antivenom with either placebo or another antivenom. 25 reports were of retrospective hospital- (n = 13) or poison center-based (n = 12) case series including five or more patients; a further 12 reports were either case reports or case series with less than five patients and one paper was a limited literature review. An additional nine papers reported prospective data; seven collected data remotely through poison service telephone communication with the attending physicians. Antivenoms available in Europe: Eight antivenoms are available for European Vipera spp envenoming; a material safety data sheet providing information on manufacture was available for seven. Six are raised against V. berus or V. ammodytes venom; the seventh is raised against a mixture of V. ammodytes, V. aspis and V. berus venom and the eighth is raised against V. ammodytes, Macrovipera lebetina and Montivipera xanthina venom. Six manufacturers recommended intramuscular administration while two recommended intravenous administration. No randomized control trials comparing the effectiveness of antivenoms were identified. Pre-clinical data: We found two papers presenting comparative preclinical data. Clinical data: Clinical studies were predominantly retrospective and contained clinical data on antivenom used in 2602 patients; where the antivenom was identified (n = 2174), 2061 (94.8%) received Zagreb, ViperFAV or ViperaTAb antivenoms. There were few published data on the other antivenoms. Repeated use of antivenom: Repeat doses were reported in 230/1491 of cases (15.4%) where this information was recorded. Outcome and length of hospital stay: Intravenous administration of antivenom was associated with shorter length of hospital stay (median length of hospital stay in studies of intravenous ViperFAV or ViperaTAb ranged from 1 to 4.8 days versus 2 to 18 days for intramuscular Bulbio or Zagreb antivenoms). Antivenom versus no antivenom

Higher dosage nicotine patches increase one-year smoking cessation rates : results from the European CEASE trial

NARCIS (Netherlands)

Tonnesen, P; Paoletti, P; Gustavsson, G; Russell, MA; Saracci, R; Gulsvik, A; Rijcken, B

The Collaborative European Anti-Smoking Evaluation (CEASE) was a European multicentre, randomized, double-blind placebo controlled smoking cessation study, The objectives were to determine whether higher dosage and longer duration of nicotine patch therapy would increase the success rate. Thirty-six

European Utility Requirements: European nuclear energy

International Nuclear Information System (INIS)

Komsi, M.; Patrakka, E.

1997-01-01

The work procedure and the content of the European Utility Requirements (EUR) concerning the future LWRs is described in the article. European Utility Requirements, produced by utilities in a number of European countries, is a document specifying the details relating to engineered safety, operating performance, reliability and economics of the reactors to be built by manufacturers for the European market

Eurados trial performance test for neutron personal dosimetry

DEFF Research Database (Denmark)

Bordy, J.M.; Stadtmann, H.; Ambrosi, P.

2001-01-01

This paper reports on the results of a neutron trial performance test sponsored by the European Commission and organised by EURADOS. As anticipated, neutron dosimetry results were very dependent on the dosemeter type and the dose calculation algorithm. Fast neutron fields were generally well...

ENLIGHT: European network for Light ion hadron therapy.

Science.gov (United States)

Dosanjh, Manjit; Amaldi, Ugo; Mayer, Ramona; Poetter, Richard

2018-04-03

The European Network for Light Ion Hadron Therapy (ENLIGHT) was established in 2002 following various European particle therapy network initiatives during the 1980s and 1990s (e.g. EORTC task group, EULIMA/PIMMS accelerator design). ENLIGHT started its work on major topics related to hadron therapy (HT), such as patient selection, clinical trials, technology, radiobiology, imaging and health economics. It was initiated through CERN and ESTRO and dealt with various disciplines such as (medical) physics and engineering, radiation biology and radiation oncology. ENLIGHT was funded until 2005 through the EC FP5 programme. A regular annual meeting structure was started in 2002 and continues until today bringing together the various disciplines and projects and institutions in the field of HT at different European places for regular exchange of information on best practices and research and development. Starting in 2006 ENLIGHT coordination was continued through CERN in collaboration with ESTRO and other partners involved in HT. Major projects within the EC FP7 programme (2008-2014) were launched for R&D and transnational access (ULICE, ENVISION) and education and training networks (Marie Curie ITNs: PARTNER, ENTERVISION). These projects were instrumental for the strengthening of the field of hadron therapy. With the start of 4 European carbon ion and proton centres and the upcoming numerous European proton therapy centres, the future scope of ENLIGHT will focus on strengthening current and developing European particle therapy research, multidisciplinary education and training and general R&D in technology and biology with annual meetings and a continuously strong CERN support. Collaboration with the European Particle Therapy Network (EPTN) and other similar networks will be pursued. Copyright © 2018 CERN. Published by Elsevier B.V. All rights reserved.

Execution of the European Arrest Warrant by the Romanian Judicial Authorities

Directory of Open Access Journals (Sweden)

Ion Rusu

2009-06-01

Full Text Available The unprecedented development of criminality at the social and economical levels, the tendency toglobalize some categories of crimes, of maximum gravity, as terrorism, armament traffic, drug traffic orhuman traffic, have determined the world states to undertake specific measures to prevent, combat and finallyreduce it. The first and most important measure taken by the Europe’s Council, regarding the intensificationof judicial cooperation in criminal matters was the adoption of the European Convention on extradition, inParis on 13 December 1957, completed by the two Additional Protocols in Strasbourg, on 15 October 1975and 17 March 1978. In this context, the release of the Council’s Framework Decision on 13 June 2002 on theEuropean arrest warrant and the procedures of delivery among the member states (2002/584/JAI representeda natural decision, with the purpose of contributing at ensuring a free, secure and just European space. TheEuropean arrest warrant is a judicial decision through which a competent judicial authority of a EuropeanUnion member state solicits the arrest and delivery by another member state, in order to proceed to theprosecution, trial or execution of a penalty or safety measure that is privative of freedom.

Organisation and management of the first clinical trial of BNCT in Europe (EORTC Protocol 11961)

International Nuclear Information System (INIS)

Sauerwein, W.; Rassow, J.; Hideghety, K.; Sack, H.; Moss, R.; Stecher-Rasmussen, F.; Wolbers, J.G.

1999-01-01

Boron Neutron Capture Therapy is based on the ability of the isotope 10 B to capture thermal neutrons and to disintegrate instantaneously producing high LET particles. The only neutron beam available in Europe for such a treatment is based at the European High Flux Reactor HFR at Petten (The Netherlands). The European Commission, owners of the reactor, decided that the potential benefit of the facility should be opened to all European citizens and therefore insisted on a multinational approach to perform the first clinical trial in Europe on BNCT. This precondition had to be respected as well as the national laws and regulations. Together with the Dutch authorities actions were undertaken to overcome the obvious legal problems. Furthermore, the clinical trial at Petten takes place in a nuclear research reactor, which apart from being conducted in a non-hospital environment, is per se known to be dangerous. It was therefore of the utmost importance that special attention is given to safety, beyond normal rules, and to the training of staff. In itself, the trial is an unusual Phase I study, introducing a new drug with a new irradiation modality, with really an unknown dose-effect relationship. This trial must follow optimal procedures, which underscore the quality and qualified manner of performance. (orig.)

A EUropean study on effectiveness and sustainability of current Cardiac Rehabilitation programmes in the Elderly: Design of the EU-CaRE randomised controlled trial.

Science.gov (United States)

Prescott, Eva; Meindersma, Esther P; van der Velde, Astrid E; Gonzalez-Juanatey, Jose R; Iliou, Marie Christine; Ardissino, Diego; Zoccai, Giuseppe Biondi; Zeymer, Uwe; Prins, Leonie F; Van't Hof, Arnoud Wj; Wilhelm, Matthias; de Kluiver, Ed P

2016-10-01

Cardiac rehabilitation (CR) is an evidence-based intervention to increase survival and quality of life. Yet studies consistently show that elderly patients are less frequently referred to CR, show less uptake and more often drop out of CR programmes. The European study on effectiveness and sustainability of current cardiac rehabilitation programmes in the elderly (EU-CaRE) project consists of an observational study and an open prospective, investigator-initiated multicentre randomised controlled trial (RCT) involving mobile telemonitoring guided CR (mCR). The aim of EU-CaRE is to map the efficiency of current CR of the elderly in Europe, and to investigate whether mCR is an effective alternative in terms of efficacy, adherence and sustainability. The EU-CaRE study includes patients aged 65 years or older with ischaemic heart disease or who have undergone heart valve surgery. A total of 1760 patients participating in existing CR programmes in eight regions of Europe will be included. Of patients declining regular CR, 238 will be included in the RCT and randomised in two study arms. The experimental group (mCR) will receive a personalised home-based programme while the control group will receive no advice or coaching throughout the study period. Outcomes will be assessed after the end of CR and at 12 months follow-up. The primary outcome is VO 2peak and secondary outcomes include variables describing CR uptake, adherence, efficacy and sustainability. The study will provide important information to improve CR in the elderly. The EU-CaRE RCT is the first European multicentre study of mCR as an alternative for elderly patients not attending usual CR. © The European Society of Cardiology 2016.

Sensitivity of European wheat to extreme weather

DEFF Research Database (Denmark)

Mäkinen, H; Kaseva, J; Trnka, M

2018-01-01

The frequency and intensity of extreme weather is increasing concomitant with changes in the global climate change. Although wheat is the most important food crop in Europe, there is currently no comprehensive empirical information available regarding the sensitivity of European wheat to extreme...... weather. In this study, we assessed the sensitivity of European wheat yields to extreme weather related to phenology (sowing, heading) in cultivar trials across Europe (latitudes 37.21° to 61.34° and longitudes −6.02° to 26.24°) during the period 1991–2014. All the observed agro-climatic extremes (≥31 °C...... wheat cultivars that responded positively (+10%) to drought after sowing, or frost during winter (−15 °C and −20 °C). Positive responses to extremes were often shown by cultivars associated with specific regions, such as good performance under high temperatures by southern-origin cultivars. Consequently...

Application of a Bayesian model for the quantification of the European methodology for qualification of non-destructive testing

International Nuclear Information System (INIS)

Gandossi, Luca; Simola, Kaisa; Shepherd, Barrie

2010-01-01

The European methodology for qualification of non-destructive testing is a well-established approach adopted by nuclear utilities in many European countries. According to this methodology, qualification is based on a combination of technical justification and practical trials. The methodology is qualitative in nature, and it does not give explicit guidance on how the evidence from the technical justification and results from trials should be weighted. A Bayesian model for the quantification process was presented in a previous paper, proposing a way to combine the 'soft' evidence contained in a technical justification with the 'hard' evidence obtained from practical trials. This paper describes the results of a pilot study in which such a Bayesian model was applied to two realistic Qualification Dossiers by experienced NDT qualification specialists. At the end of the study, recommendations were made and a set of guidelines was developed for the application of the Bayesian model.

Impact assessment of emission management strategies of the pharmaceuticals Metformin and Metoprolol to the aquatic environment using Bayesian networks.

Science.gov (United States)

Brandmayr, Caterina; Kerber, Heide; Winker, Martina; Schramm, Engelbert

2015-11-01

The issue of pharmaceuticals in the environment has caused increasing concern in the recent years and various strategies have been proposed to tackle this problem. This work describes a Bayesian network (BN)-based socio-ecological impact assessment of a set of measures aimed at reducing the entry of pharmaceuticals in the aquatic environment. The measures investigated were selected across three sectors: public health market, environmental politics and drug design innovation. The BN model was developed for two drugs, Metformin and Metoprolol, and it models the distribution of the Predicted Environmental Concentration (PEC) values as a function of different measures. Results show that the sensitivity of the PEC for the two drugs to the measures investigated reflects the distinct drug characteristics, suggesting that in order to ensure the successful reduction of a broad range of substances, a spectrum of measures targeting the entire lifecycle of a pharmaceutical should be implemented. Furthermore, evaluation of two scenarios reflecting different emission management strategies highlights that the integrated implementation of a comprehensive set of measures across the three sectors results in a more extensive reduction of the contamination. Finally, the BN provides an initial forecasting tool to model the PEC of a drug as a function of a combination of measures in a context-specific manner and possible adaptations of the model are proposed. Copyright © 2015 Elsevier B.V. All rights reserved.

Adsorption and Photocatalytic Decomposition of the β-Blocker Metoprolol in Aqueous Titanium Dioxide Suspensions: Kinetics, Intermediates, and Degradation Pathways

Directory of Open Access Journals (Sweden)

Violette Romero

2013-01-01

Full Text Available This study reports the photocatalytic degradation of the β-blocker metoprolol (MET using TiO2 suspended as catalyst. A series of photoexperiments were carried out by a UV lamp, emitting in the 250–400 nm range, providing information about the absorption of radiation in the photoreactor wall. The influence of the radiation wavelength on the MET photooxidation rate was investigated using a filter cutting out wavelengths shorter than 280 nm. Effects of photolysis and adsorption at different initial pH were studied to evaluate noncatalytic degradation for this pharmaceutical. MET adsorption onto titania was fitted to two-parameter Langmuir isotherm. From adsorption results it appears that the photocatalytic degradation can occur mainly on the surface of TiO2. MET removed by photocatalysis was 100% conditions within 300 min, while only 26% was achieved by photolysis at the same time. TiO2 photocatalysis degradation of MET in the first stage of the reaction followed approximately a pseudo-first-order model. The major reaction intermediates were identified by LC/MS analysis such as 3-(propan-2-ylaminopropane-1,2-diol or 3-aminoprop-1-en-2-ol. Based on the identified intermediates, a photocatalytic degradation pathway was proposed, including the cleavage of side chain and the hydroxylation addition to the parent compounds.

New EORTC clinical trials for BNCT

International Nuclear Information System (INIS)

Hideghety, K.; Moss, R.; Vries, M. de

2000-01-01

Due to ethical reasons, a separated optimization of the two components of BNCT in the frame of clinical investigations can only be performed applying the whole binary system. The ongoing trial at HFR (High Flux Reactor Petten) has proven the feasibility of BNCT under defined conditions. On that basis the European Commission supported a comprehensive research project on boron imaging including three further clinical studies. In the first trial the boron uptake related to the blood boron concentration and surrounding normal tissue in various solid tumours will be examined using BSH (Sodiumborocaptate), BPA (Boronophenylalanine) or both in order to explore tumour entities, which may gain benefit from BNCT. The major objectives of the second trial are to define the maximum tolerated single and cumulative dose, and the dose limiting toxicity of BSH. The third clinical trial, a phase II study is designed to evaluate the anti-tumour effect of fractionated BNCT at the Petten treatment facility against cerebral metastasis of malignant melanoma using BPA. (author)

Design and rationale of the Procalcitonin Antibiotic Consensus Trial (ProACT), a multicenter randomized trial of procalcitonin antibiotic guidance in lower respiratory tract infection.

Science.gov (United States)

Huang, David T; Angus, Derek C; Chang, Chung-Chou H; Doi, Yohei; Fine, Michael J; Kellum, John A; Peck-Palmer, Octavia M; Pike, Francis; Weissfeld, Lisa A; Yabes, Jonathan; Yealy, Donald M

2017-08-29

Overuse of antibiotics is a major public health problem, contributing to growing antibiotic resistance. Procalcitonin has been reported to be commonly elevated in bacterial, but not viral infection. Multiple European trials found procalcitonin-guided care reduced antibiotic use in lower respiratory tract infection, with no apparent harm. However, applicability to US practice is limited due to trial design features impractical in the US, between-country differences, and residual safety concerns. The Procalcitonin Antibiotic Consensus Trial (ProACT) is a multicenter randomized trial to determine the impact of a procalcitonin antibiotic prescribing guideline, implemented with basic reproducible strategies, in US patients with lower respiratory tract infection. We describe the trial methods using the Consolidated Standards of Reporting Trials (CONSORT) framework, and the rationale for key design decisions, including choice of eligibility criteria, choice of control arm, and approach to guideline implementation. ClinicalTrials.gov NCT02130986 . Registered May 1, 2014.

Common definition for categories of clinical research: a prerequisite for a survey on regulatory requirements by the European Clinical Research Infrastructures Network (ECRIN)

LENUS (Irish Health Repository)

Kubiak, Christine

2009-10-16

Abstract Background Thorough knowledge of the regulatory requirements is a challenging prerequisite for conducting multinational clinical studies in Europe given their complexity and heterogeneity in regulation and perception across the EU member states. Methods In order to summarise the current situation in relation to the wide spectrum of clinical research, the European Clinical Research Infrastructures Network (ECRIN) developed a multinational survey in ten European countries. However a lack of common classification framework for major categories of clinical research was identified, and therefore reaching an agreement on a common classification was the initial step in the development of the survey. Results The ECRIN transnational working group on regulation, composed of experts in the field of clinical research from ten European countries, defined seven major categories of clinical research that seem relevant from both the regulatory and the scientific points of view, and correspond to congruent definitions in all countries: clinical trials on medicinal products; clinical trials on medical devices; other therapeutic trials (including surgery trials, transplantation trials, transfusion trials, trials with cell therapy, etc.); diagnostic studies; clinical research on nutrition; other interventional clinical research (including trials in complementary and alternative medicine, trials with collection of blood or tissue samples, physiology studies, etc.); and epidemiology studies. Our classification was essential to develop a survey focused on protocol submission to ethics committees and competent authorities, procedures for amendments, requirements for sponsor and insurance, and adverse event reporting following five main phases: drafting, consensus, data collection, validation, and finalising. Conclusion The list of clinical research categories as used for the survey could serve as a contribution to the, much needed, task of harmonisation and simplification of the

Common definition for categories of clinical research: a prerequisite for a survey on regulatory requirements by the European Clinical Research Infrastructures Network (ECRIN

Directory of Open Access Journals (Sweden)

Sanz Nuria

2009-10-01

Full Text Available Abstract Background Thorough knowledge of the regulatory requirements is a challenging prerequisite for conducting multinational clinical studies in Europe given their complexity and heterogeneity in regulation and perception across the EU member states. Methods In order to summarise the current situation in relation to the wide spectrum of clinical research, the European Clinical Research Infrastructures Network (ECRIN developed a multinational survey in ten European countries. However a lack of common classification framework for major categories of clinical research was identified, and therefore reaching an agreement on a common classification was the initial step in the development of the survey. Results The ECRIN transnational working group on regulation, composed of experts in the field of clinical research from ten European countries, defined seven major categories of clinical research that seem relevant from both the regulatory and the scientific points of view, and correspond to congruent definitions in all countries: clinical trials on medicinal products; clinical trials on medical devices; other therapeutic trials (including surgery trials, transplantation trials, transfusion trials, trials with cell therapy, etc.; diagnostic studies; clinical research on nutrition; other interventional clinical research (including trials in complementary and alternative medicine, trials with collection of blood or tissue samples, physiology studies, etc.; and epidemiology studies. Our classification was essential to develop a survey focused on protocol submission to ethics committees and competent authorities, procedures for amendments, requirements for sponsor and insurance, and adverse event reporting following five main phases: drafting, consensus, data collection, validation, and finalising. Conclusion The list of clinical research categories as used for the survey could serve as a contribution to the, much needed, task of harmonisation and

Guidelines for the conduct of pharmacological clinical trials in hand osteoarthritis: Consensus of a Working Group of the European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

Science.gov (United States)

Reginster, Jean-Yves L; Arden, Nigel K; Haugen, Ida K; Rannou, Francois; Cavalier, Etienne; Bruyère, Olivier; Branco, Jaime; Chapurlat, Roland; Collaud Basset, Sabine; Al-Daghri, Nasser M; Dennison, Elaine M; Herrero-Beaumont, Gabriel; Laslop, Andrea; Leeb, Burkhard F; Maggi, Stefania; Mkinsi, Ouafa; Povzun, Anton S; Prieto-Alhambra, Daniel; Thomas, Thierry; Uebelhart, Daniel; Veronese, Nicola; Cooper, Cyrus

2017-12-07

To gather expert opinion on the conduct of clinical trials that will facilitate regulatory review and approval of appropriate efficacious pharmacological treatments for hand osteoarthritis (OA), an area of high unmet clinical need. The European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal diseases (ESCEO) organized a working group under the auspices of the International Osteoporosis Foundation (IOF) and the World Health Organization (WHO). This consensus guideline is intended to provide a reference tool for practice, and should allow for better standardization of the conduct of clinical trials in hand OA. Hand OA is a heterogeneous disease affecting different, and often multiple, joints of the thumb and fingers. It was recognized that the various phenotypes and limitations of diagnostic criteria may make the results of hand OA trials difficult to interpret. Nonetheless, practical recommendations for the conduct of clinical trials of both symptom and structure modifying drugs are outlined in this consensus statement, including guidance on study design, execution, and analysis. While the working group acknowledges that the methodology for performing clinical trials in hand OA will evolve as knowledge of the disease increases, it is hoped that this guidance will support the development of new pharmacological treatments targeting hand OA. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Designing green derivatives of β-blocker Metoprolol: a tiered approach for green and sustainable pharmacy and chemistry.

Science.gov (United States)

Rastogi, Tushar; Leder, Christoph; Kümmerer, Klaus

2014-09-01

The presences of micro-pollutants (active pharmaceutical ingredients, APIs) are increasingly seen as a challenge of the sustainable management of water resources worldwide due to ineffective effluent treatment and other measures for their input prevention. Therefore, novel approaches are needed like designing greener pharmaceuticals, i.e. better biodegradability in the environment. This study addresses a tiered approach of implementing green and sustainable chemistry principles for theoretically designing better biodegradable and pharmacologically improved pharmaceuticals. Photodegradation process coupled with LC-MS(n) analysis and in silico tools such as quantitative structure-activity relationships (QSAR) analysis and molecular docking proved to be a very significant approach for the preliminary stages of designing chemical structures that would fit into the "benign by design" concept in the direction of green and sustainable pharmacy. Metoprolol (MTL) was used as an example, which itself is not readily biodegradable under conditions found in sewage treatment and the aquatic environment. The study provides the theoretical design of new derivatives of MTL which might have the same or improved pharmacological activity and are more degradable in the environment than MTL. However, the in silico toxicity prediction by QSAR of those photo-TPs indicated few of them might be possibly mutagenic and require further testing. This novel approach of theoretically designing 'green' pharmaceuticals can be considered as a step forward towards the green and sustainable pharmacy field. However, more knowledge and further experience have to be collected on the full scope, opportunities and limitations of this approach. Copyright © 2014 Elsevier Ltd. All rights reserved.

Barriers towards the publication of academic drug trials. Follow-up of trials approved by the Danish Medicines Agency.

Science.gov (United States)

Berendt, Louise; Petersen, Lene Grejs; Bach, Karin Friis; Poulsen, Henrik Enghusen; Dalhoff, Kim

2017-01-01

To characterize and quantify barriers towards the publication of academic drug trials. We identified academic drug trials approved during a 3-year period (2004-2007) by the Danish Medicines Agency. We conducted a survey among the trial sponsors to describe the rates of initiation, completion, and publication, and the reasons for the failure to reach each of these milestones. Information on size and methodological characteristics of the trials was extracted from the EudraCT database, a prospective register of all approved clinical drug trials submitted to European medicines agencies since 2004. A total of 181 academic drug trials were eligible for inclusion, 139 of which participated in our survey (response rate: 77%). Follow-up time ranged from 5.1 to 7.9 years. Most trials were randomized controlled trials (73%, 95% CI 65-81%). Initiation and completion rates were 92% (95% CI: 88-97%) and 93% (95% CI: 89-97%) respectively. The publication rate of completed trials was 73% (95% CI: 62-79%). RCTs were published faster than non-RCTs (quartile time to publication 2.9 vs. 3.1 years, p = 0.0412). Many academic drug trials are left unpublished. Main barriers towards publication were related to the process from completion to publication. Hence, there is much to gain by facilitating the process from analysis to publication. Research institutions and funders should actively influence this process, e.g. by requiring the publication of trial results within a given time after completion.

NEWS FROM THE ANNUAL CONGRESS OF EUROPEAN SOCIETY OF CARDIOLOGY (BARCELONA 2014: REALIZED AND UNREALIZED EXPECTATIONS

Directory of Open Access Journals (Sweden)

S. Y. Martsevich

2014-01-01

Full Text Available News from Congress of the European Society of Cardiology (Barcelona, 2014 is highlighted. Results of recent controlled clinical trials, new clinical recommendations and registers data that were presented at the Congress are discussed.

NEWS FROM THE ANNUAL CONGRESS OF EUROPEAN SOCIETY OF CARDIOLOGY (BARCELONA 2014: REALIZED AND UNREALIZED EXPECTATIONS

Directory of Open Access Journals (Sweden)

S. Y. Martsevich

2015-09-01

Full Text Available News from Congress of the European Society of Cardiology (Barcelona, 2014 is highlighted. Results of recent controlled clinical trials, new clinical recommendations and registers data that were presented at the Congress are discussed.

Relationship between heart failure, concurrent chronic obstructive pulmonary disease and beta-blocker use

DEFF Research Database (Denmark)

Sessa, Maurizio; Mascolo, Annamaria; Mortensen, Rikke Nørmark

2018-01-01

Aims: To compare the hazard of all-cause, chronic obstructive pulmonary disease (COPD) and heart failure (HF) hospitalization in carvedilol vs. metoprolol/bisoprolol/nebivolol users with COPD and concurrent HF from 2009 to 2012, and to evaluate the use and persistence in treatment of these β-blockers...... with COPD and concurrent HF. Additionally, we found a widespread phenomenon of carvedilol prescription at variance with the European Society of Cardiology guidelines and potential for improving the proportion of patients treated with β-blockers....

What Will Be the Benefits of Biotech Wheat for European Agriculture?

Science.gov (United States)

Ricroch, Agnès E

2017-01-01

In European countries, wheat occupies the largest crop area with high yielding production. France, a major producer and exporter in Europe, ranks the fifth producer worldwide. Biotic stresses are European farmers' major challenges (fungal and viral diseases, and insect pests) followed by abiotic ones such as drought and grain protein composition. During the last 40 years, 1136 scientific articles on biotech wheat were published by USA followed by China, Australia, Canada, and European Union with the UK. European research focuses on pests and diseases resistances using widely marker-assisted selection (MAS). Transgenesis is used in basic research to develop resistance against some fungi (Fusarium head blight) while RNA interference (RNAi) silencing is used against some fungi and virus. Transgenic plants were also transformed with genes from various species for drought tolerance. The UK (mostly with transgenesis and site-specific nucleases) and France (with no transgenic tools but with MAS and site-specific nucleases) are the main countries carrying out research programs for both biotic stress and drought tolerance. Thus, few European countries used transgenesis for gluten protein composition and RNAi-mediated silencing in celiac disease. Because of vandalism field trials of transgenics dropped since 2000. No transgenic wheat is cultivated in Europe for political reasons.

Clinical trial transparency update: an assessment of the disclosure of results of company-sponsored trials associated with new medicines approved in Europe in 2014.

Science.gov (United States)

Deane, Bryan R; Porkess, Sheuli

2018-07-01

The objective of this study was to assess the timely disclosure of results of company-sponsored clinical trials related to all new medicines approved by the European Medicines Agency (EMA) during 2014. This is the final extension of three previously reported studies of trials related to all new medicines approved in Europe in 2009, 2010 and 2011, and in 2012 and 2013. The original study found that over a three-year period over three-quarters of all trials were disclosed within 12 months and almost 90% were disclosed by the end of the study (31 January 2013). The extension studies (2012 and 2013 approvals) both showed an improvement in results disclosure within 12 months to 90%, and an overall disclosure rate of 92% and 93% respectively by the end of the studies. The methodology used was exactly as previously reported. Various publicly available information sources were searched for both clinical trial registration and disclosure of results. All completed company-sponsored trials related to each new medicine approved for marketing by the EMA in 2014, carried out in patients and recorded on a clinical trials registry and/or included in an EMA European Public Assessment Report (EPAR), were included. Information sources were searched between 1 May and 31 July 2016. The main outcome measure was the proportion of trials for which results had been disclosed on a registry or in the scientific literature either within 12 months of the later of either first regulatory approval or trial completion, or by 31 July 2016 (end of survey). Of the completed trials associated with 32 new medicines licensed to 22 different companies in 2014, results of 93% (505/542) had been disclosed within 12 months, and results of 96% (518/542) had been disclosed by 31 July 2016. The disclosure rate within 12 months of 93% suggests that industry is continuing to achieve disclosure in a timely manner. The overall disclosure rate at study end of 96% indicates that the improvement in transparency

A randomised controlled trial evaluating IGF1 titration in contrast to current GH dosing strategies in children born small for gestational age: the North European Small-for-Gestational-Age Study.

Science.gov (United States)

Jensen, Rikke Beck; Thankamony, Ajay; O'Connell, Susan M; Kirk, Jeremy; Donaldson, Malcolm; Ivarsson, Sten-A; Söder, Olle; Roche, Edna; Hoey, Hilary; Dunger, David B; Juul, Anders

2014-10-01

Short children born small for gestational age (SGA) are treated with a GH dose based on body size, but treatment may lead to high levels of IGF1. The objective was to evaluate IGF1 titration of GH dose in contrast to current dosing strategies. In the North European Small-for-Gestational-Age Study (NESGAS), 92 short pre-pubertal children born SGA were randomised after 1 year of high-dose GH treatment (67 μg/kg per day) to three different regimens: high dose (67 μg/kg per day), low dose (35 μg/kg per day) or IGF1 titration. The average dose during the second year of the randomised trial did not differ between the IGF1 titration group (38 μg/kg per day, s.d. 0.019) and the low-dose group (35 μg/kg per day, s.d. 0.002; P=0.46), but there was a wide variation in the IGF1 titration group (range 10-80 μg/kg per day). The IGF1 titration group had significantly lower height gain (0.17 SDS, s.d. 0.18) during the second year of the randomised trial compared with the high-dose group (0.46 SDS, s.d. 0.25), but not significantly lower than the low-dose group (0.23 SDS, s.d. 0.15; P=0.17). The IGF1 titration group had lower IGF1 levels after 2 years of the trial (mean 1.16, s.d. 1.24) compared with both the low-dose (mean 1.76, s.d. 1.48) and the high-dose (mean 2.97, s.d. 1.63) groups. IGF1 titration of GH dose in SGA children proved less effective than current dosing strategies. IGF1 titration resulted in physiological IGF1 levels with a wide range of GH dose and a poorer growth response, which indicates the role of IGF1 resistance and highlights the heterogeneity of short SGA children. © 2014 European Society of Endocrinology.

Re-Engineering Alzheimer Clinical Trials: Global Alzheimer's Platform Network.

Science.gov (United States)

Cummings, J; Aisen, P; Barton, R; Bork, J; Doody, R; Dwyer, J; Egan, J C; Feldman, H; Lappin, D; Truyen, L; Salloway, S; Sperling, R; Vradenburg, G

2016-06-01

Alzheimer's disease (AD) drug development is costly, time-consuming, and inefficient. Trial site functions, trial design, and patient recruitment for trials all require improvement. The Global Alzheimer Platform (GAP) was initiated in response to these challenges. Four GAP work streams evolved in the US to address different trial challenges: 1) registry-to-cohort web-based recruitment; 2) clinical trial site activation and site network construction (GAP-NET); 3) adaptive proof-of-concept clinical trial design; and 4) finance and fund raising. GAP-NET proposes to establish a standardized network of continuously funded trial sites that are highly qualified to perform trials (with established clinical, biomarker, imaging capability; certified raters; sophisticated management system. GAP-NET will conduct trials for academic and biopharma industry partners using standardized instrument versions and administration. Collaboration with the Innovative Medicines Initiative (IMI) European Prevention of Alzheimer's Disease (EPAD) program, the Canadian Consortium on Neurodegeneration in Aging (CCNA) and other similar international initiatives will allow conduct of global trials. GAP-NET aims to increase trial efficiency and quality, decrease trial redundancy, accelerate cohort development and trial recruitment, and decrease trial costs. The value proposition for sites includes stable funding and uniform training and trial execution; the value to trial sponsors is decreased trial costs, reduced time to execute trials, and enhanced data quality. The value for patients and society is the more rapid availability of new treatments for AD.

A European multicenter randomized double-blind placebo-controlled monotherapy clinical trial of milnacipran in treatment of fibromyalgia

DEFF Research Database (Denmark)

Branco, Jaime C; Zachrisson, Olof; Perrot, Serge

2010-01-01

This randomized, double-blind, placebo-controlled, multicenter study investigated the efficacy and safety of milnacipran in the treatment of fibromyalgia (FM) in a European population.......This randomized, double-blind, placebo-controlled, multicenter study investigated the efficacy and safety of milnacipran in the treatment of fibromyalgia (FM) in a European population....

The European Social Survey and European research policy

DEFF Research Database (Denmark)

Kropp, Kristoffer

2017-01-01

This article analyses the history of the European Social Survey (ESS) and its relationship to changes in European research policy, using Bourdieu’s field-analytical approach. It argues that the success of the ESS relied on three interwoven processes that we can understand theoretically in terms...... of the establishment of homological structures and the formation of conjunctural alliances between the field of European social-scientific research and the field of European policy. The three interwoven processes that I depict are: first, the production of a European field of social research, connected to both...... European and national scientific institutions; second, the establishment of European Union (EU) institutions and organisations that were able to identify and link up with social researchers; and third, the formation of conjunctural alliances between the two fields (social science and EU research policy...

Participation of older people in preauthorization trials of recently approved medicines

NARCIS (Netherlands)

Beers, Erna; Moerkerken, Dineke C; Leufkens, Hubert G M; Egberts, Toine C G; Jansen, Paul A F

2014-01-01

OBJECTIVES: To investigate the inclusion of older people in clinical trials of recently authorized medicines, evaluating adherence to the 20-year-old International Conference of Harmonisation (ICH) guideline on geriatrics (E7). DESIGN: Observational. SETTING: European public assessment reports,

BETA-ADRENOBLOCKERS IN XXI CENTURY: EPOCH END OR IMMORTALITY BEGINNING? A VIEW OF ORDINARY CARDIOLOGIST

Directory of Open Access Journals (Sweden)

L. N. Malaj

2008-01-01

Full Text Available Usage of β-blockers (BB for treatment of patients with cardiovascular diseases is discussed. Results of the basic clinical trials with BB (LIFE, ASCOT, etc. are analyzed. The role of sympathetic system in different stages of cardiovascular continuum as well as forecast of BB clinical efficacy is surveyed. Author presents a review of data about selective β1-blocker, metoprolol succinate (Betalok ZОК, in patients with cardiovascular diseases.

Blood pressure and LDL-cholesterol targets for prevention of recurrent strokes and cognitive decline in the hypertensive patient: design of the European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment randomized trial.

Science.gov (United States)

Zanchetti, Alberto; Liu, Lisheng; Mancia, Giuseppe; Parati, Gianfranco; Grassi, Guido; Stramba-Badiale, Marco; Silani, Vincenzo; Bilo, Grzegorz; Corrao, Giovanni; Zambon, Antonella; Scotti, Lorenza; Zhang, Xinhua; Wang, HayYan; Zhang, Yuqing; Zhang, Xuezhong; Guan, Ting Rui; Berge, Eivind; Redon, Josep; Narkiewicz, Krzysztof; Dominiczak, Anna; Nilsson, Peter; Viigimaa, Margus; Laurent, Stéphane; Agabiti-Rosei, Enrico; Wu, Zhaosu; Zhu, Dingliang; Rodicio, José Luis; Ruilope, Luis Miguel; Martell-Claros, Nieves; Pinto, Fernando; Schmieder, Roland E; Burnier, Michel; Banach, Maciej; Cifkova, Renata; Farsang, Csaba; Konradi, Alexandra; Lazareva, Irina; Sirenko, Yuriy; Dorobantu, Maria; Postadzhiyan, Arman; Accetto, Rok; Jelakovic, Bojan; Lovic, Dragan; Manolis, Athanasios J; Stylianou, Philippos; Erdine, Serap; Dicker, Dror; Wei, Gangzhi; Xu, Chengbin; Xie, Hengge; Coca, Antonio; O'Brien, John; Ford, Gary

2014-09-01

The SBP values to be achieved by antihypertensive therapy in order to maximize reduction of cardiovascular outcomes are unknown; neither is it clear whether in patients with a previous cardiovascular event, the optimal values are lower than in the low-to-moderate risk hypertensive patients, or a more cautious blood pressure (BP) reduction should be obtained. Because of the uncertainty whether 'the lower the better' or the 'J-curve' hypothesis is correct, the European Society of Hypertension and the Chinese Hypertension League have promoted a randomized trial comparing antihypertensive treatment strategies aiming at three different SBP targets in hypertensive patients with a recent stroke or transient ischaemic attack. As the optimal level of low-density lipoprotein cholesterol (LDL-C) level is also unknown in these patients, LDL-C-lowering has been included in the design. The European Society of Hypertension-Chinese Hypertension League Stroke in Hypertension Optimal Treatment trial is a prospective multinational, randomized trial with a 3 × 2 factorial design comparing: three different SBP targets (1, hypertension and a stroke or transient ischaemic attack 1-6 months before randomization. Antihypertensive and statin treatments will be initiated or modified using suitable registered agents chosen by the investigators, in order to maintain patients within the randomized SBP and LDL-C windows. All patients will be followed up every 3 months for BP and every 6 months for LDL-C. Ambulatory BP will be measured yearly. Primary outcome is time to stroke (fatal and non-fatal). Important secondary outcomes are: time to first major cardiovascular event; cognitive decline (Montreal Cognitive Assessment) and dementia. All major outcomes will be adjudicated by committees blind to randomized allocation. A Data and Safety Monitoring Board has open access to data and can recommend trial interruption for safety. It has been calculated that 925 patients would reach the primary

The effects of anti-hypertensives and type 2 diabetes on salivary flow and total antioxidant capacity.

Science.gov (United States)

Djukić, L J; Roganović, J; Brajović, M D; Bokonjić, D; Stojić, D

2015-07-01

The present cross-sectional study aimed to determine the effect of first-line anti-hypertensive drugs (enalapril, metoprolol, and combinations of enalapril with metoprolol and/or hydrochlorothiazide) on salivary gland function and salivary total antioxidant capacity (TAC) in hypertensive patients with/without diabetes mellitus (DM) type 2. Salivary gland function was measured as xerostomia (interview) and unstimulated whole saliva flow rate (UWSFR) in 447 subjects (387 hypertensive and 60 healthy). Salivary TAC was evaluated by spectrophotometric assay. Enalapril is not xerogenic, while metoprolol and drug combinations are. In the presence of DM type 2, all drugs, except metoprolol, had pronounced xerogenic effect. Binary logistic regression analysis found enalapril to be significantly associated with decreased risk of xerogenic effect development, while DM type 2 with increased risk. In the presence of enalapril in hypertensive patients with/without DM type 2 salivary TAC was similar to that in healthy subjects, while for metoprolol was reduced. Enalapril is not xerogenic but is antioxidant, which moderately reduces the risk of xerogenic effect development even in the presence of DM type 2. However, metoprolol and drug combinations exhibit xerogenic effect. In DM type 2, xerogenic effect of all drugs was pronounced except of metoprolol. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

THE ORGANIZATION OF JURISDICTION IN EUROPEAN UNION PERSPECTIVE

Directory of Open Access Journals (Sweden)

Mihaela Agheniţei

2014-11-01

Full Text Available Nowadays, universal jurisdiction is the favorite technique used to prevent impunity for international crimes and it is one of the most effective methods to deter and prevent international crimes by increasing the like hood of prosecution and punishment of its propagators. In regard to the defendants’ rights, the European Union states consider applicable all the rights that are necessary to assure that the trial is equitable and expeditious. There is no exception to the right to a fair trial. So, a defendant who is being prosecuted on the basis of the universality principle can rely on all the procedural rights provided for the Convention on Human Rights and the domestic code of criminal procedure without any restrictions. In Germany, the Federal Constitutional Court, in a case concerning genocide committed abroad, declared expressly that no special criminal proceedings must be provided for specific crimes.

Intestinal permeability study of minoxidil: assessment of minoxidil as a high permeability reference drug for biopharmaceutics classification.

Science.gov (United States)

Ozawa, Makoto; Tsume, Yasuhiro; Zur, Moran; Dahan, Arik; Amidon, Gordon L

2015-01-05

The purpose of this study was to evaluate minoxidil as a high permeability reference drug for Biopharmaceutics Classification System (BCS). The permeability of minoxidil was determined in in situ intestinal perfusion studies in rodents and permeability studies across Caco-2 cell monolayers. The permeability of minoxidil was compared with that of metoprolol, an FDA reference drug for BCS classification. In rat perfusion studies, the permeability of minoxidil was somewhat higher than that of metoprolol in the jejunum, while minoxidil showed lower permeability than metoprolol in the ileum. The permeability of minoxidil was independent of intestinal segment, while the permeability of metoprolol was region-dependent. Similarly, in mouse perfusion study, the jejunal permeability of minoxidil was 2.5-fold higher than that of metoprolol. Minoxidil and metoprolol showed similar permeability in Caco-2 study at apical pH of 6.5 and basolateral pH of 7.4. The permeability of minoxidil was independent of pH, while metoprolol showed pH-dependent transport in Caco-2 study. Minoxidil exhibited similar permeability in the absorptive direction (AP-BL) in comparison with secretory direction (BL-AP), while metoprolol had higher efflux ratio (ER > 2) at apical pH of 6.5 and basolateral pH of 7.4. No concentration-dependent transport was observed for either minoxidil or metoprolol transport in Caco-2 study. Verapamil did not alter the transport of either compounds across Caco-2 cell monolayers. The permeability of minoxidil was independent of both pH and intestinal segment in intestinal perfusion studies and Caco-2 studies. Caco-2 studies also showed no involvement of carrier mediated transport in the absorption process of minoxidil. These results suggest that minoxidil may be an acceptable reference drug for BCS high permeability classification. However, minoxidil exhibited higher jejunal permeability than metoprolol and thus to use minoxidil as a reference drug would raise the

The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC): experiences from a successful ERS Clinical Research Collaboration.

Science.gov (United States)

Chalmers, James D; Crichton, Megan; Goeminne, Pieter C; Loebinger, Michael R; Haworth, Charles; Almagro, Marta; Vendrell, Montse; De Soyza, Anthony; Dhar, Raja; Morgan, Lucy; Blasi, Francesco; Aliberti, Stefano; Boyd, Jeanette; Polverino, Eva

2017-09-01

In contrast to airway diseases like chronic obstructive pulmonary disease or asthma, and rare diseases such as cystic fibrosis, there has been little research and few clinical trials in bronchiectasis. Guidelines are primarily based on expert opinion and treatment is challenging because of the heterogeneous nature of the disease. In an effort to address decades of underinvestment in bronchiectasis research, education and clinical care, the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) was established in 2012 as a collaborative pan-European network to bring together bronchiectasis researchers. The European Respiratory Society officially funded EMBARC in 2013 as a Clinical Research Collaboration, providing support and infrastructure to allow the project to grow. EMBARC has now established an international bronchiectasis registry that is active in more than 30 countries both within and outside Europe. Beyond the registry, the network participates in designing and facilitating clinical trials, has set international research priorities, promotes education and has participated in producing the first international bronchiectasis guidelines. This manuscript article the development, structure and achievements of EMBARC from 2012 to 2017. To understand the role of Clinical Research Collaborations as the major way in which the European Respiratory Society can stimulate clinical research in different disease areasTo understand some of the key features of successful disease registriesTo review key epidemiological, clinical and translational studies of bronchiectasis contributed by the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) project in the past 5 yearsTo understand the key research priorities identified by EMBARC for the next 5 years.

For an alliance between science, ethics and politics in promoting paediatric trials. Commentary.

Science.gov (United States)

Petrini, Carlo; Rana, Ippolita; Alleva, Enrico

2016-01-01

After several decades during which children tended to be excluded from clinical trials, provisions to encourage trials with children have been in place for some years both at international level and in individual countries. The Nuffield Council on Bioethics has published a broad-ranging report on the subject, which makes concrete proposals for decision-makers and comes at a crucial moment in the definition of European Union regulations on this topic.

Classical swine fever virus detection: results of a real-time reverse transcription polymerase chain reaction ring trial conducted in the framework of the European network of excellence for epizootic disease diagnosis and control

DEFF Research Database (Denmark)

Hoffmann, Bernd; Blome, Sandra; Bonilauri, Paolo

2011-01-01

and specificity values. Nevertheless, some in-house systems had unspecific reactions or suboptimal sensitivity with only a single CSFV genotype. Follow-up actions involved either improvement of suboptimal assays or replacement of specific laboratory assays with the FLI protocol, with or without modifications......The current study reports on a real-time reverse transcription polymerase chain reaction (real-time RT-PCR) ring trial for the detection of Classical swine fever virus (CSFV) genomic RNA undertaken by 10 European laboratories. All laboratories were asked to use their routine in-house real-time RT...

In vitro, ex vivo and in vivo examination of buccal absorption of metoprolol with varying pH in TR146 cell culture, porcine buccal mucosa and Göttingen minipigs

DEFF Research Database (Denmark)

Holm, René; Meng-Lund, Emil; Andersen, Morten B.

2013-01-01

This work studied the buccal absorption of metoprolol in vitro, ex vivo and in vivo as a function of buffered pH at 7.4, 8.5, 9.0 and 9.5. Permeability studies showed a correlation (r(2)=0.92) between in vitro TR146 cell culture and ex vivo porcine buccal mucosa in a modified Ussing chamber...... was obtained after buccal dosing (58-107%) compared to oral (3%) administration, ranging 58-107% and 3%, respectively. Macroscopically, no local toxic effects were observed by visual inspection of mini-pig cheeks. A very clear level C in vitro in vivo correlation (r(2)=0.98) was obtained between the observed....... A higher apparent permeability was observed at higher pH values, i.e. the more compound that was unionised the higher the permeability. In vivo studies were conducted in anaesthetised Göttingen mini-pigs. A clear influence of pH on the absorption was seen and a significant higher absolute bioavailability...

A tale of three labels: translating the JUPITER trial data into regulatory claims.

Science.gov (United States)

Ridker, Paul M

2011-08-01

Whether a pivotal randomized trial will be interpreted in a similar and consistent manner by different regulatory agencies is uncertain as policy perspectives may play a role in data interpretation and the translation of trial results into clinical practice. Using a contemporary example, to compare and contrast regulatory claims in the United States, Europe, and Canada that derive from a pivotal clinical trial. The recently completed JUPITER trial of rosuvastatin as compared to placebo conducted among 17,802 men and women with LDL-C JUPITER trial provides an opportunity to compare and contrast how regulatory agencies in the United States, Canada, and Europe chose to interpret an identical database. Labeling indications based on earlier statin trials of primary and secondary prevention were also reviewed. JUPITER demonstrated a 44% reduction (p JUPITER trial population by stipulating that those eligible for treatment should be older men and women with hsCRP >2 mg/L, plus one additional risk factor for heart disease. The Canadian label is silent on age and hsCRP (the major trial inclusion criterion), stipulating instead that treatment can be considered for those with 'at least two conventional risk factors for cardiovascular disease,' a group more inclusive than that studied. In contrast, the European Medicines Agency label limits treatment only to 'high risk individuals' ignoring hsCRP and using instead a post hoc definition of 'high risk' that comprised a subgroup of less than 10% of the study population who contributed but 67 events to the study total and did not show statistical significance when compared to placebo. None of the regulatory labels included the trial primary endpoint; instead, each focused on separate and different components of the primary endpoint. Similar discrepancies were found between European and North American regulatory agencies with regard to earlier pivotal trials of statins for primary prevention, but not for secondary prevention. The

Computed tomography versus invasive coronary angiography: design and methods of the pragmatic randomised multicentre DISCHARGE trial

International Nuclear Information System (INIS)

Napp, Adriane E.; Haase, Robert; Schuetz, Georg M.; Rief, Matthias; Katzer, Christoph; Dewey, Marc; Laule, Michael; Dreger, Henryk; Feuchtner, Gudrun; Friedrich, Guy; Spacek, Miloslav; Suchanek, Vojtech; Fuglsang Kofoed, Klaus; Engstroem, Thomas; Schroeder, Stephen; Drosch, Tanja; Gutberlet, Matthias; Woinke, Michael; Maurovich-Horvat, Pal; Merkely, Bela; Donnelly, Patrick; Ball, Peter; Dodd, Jonathan D.; Quinn, Martin; Saba, Luca; Porcu, Maurizio; Francone, Marco; Mancone, Massimo; Erglis, Andrejs; Zvaigzne, Ligita; Jankauskas, Antanas; Sakalyte, Gintare; Haran, Tomasz; Ilnicka-Suckiel, Malgorzata; Bettencourt, Nuno; Gama-Ribeiro, Vasco; Condrea, Sebastian; Benedek, Imre; Cemerlic Adjic, Nada; Adjic, Oto; Rodriguez-Palomares, Jose; Garcia del Blanco, Bruno; Roditi, Giles; Berry, Colin; Davis, Gershan; Thwaite, Erica; Knuuti, Juhani; Pietilae, Mikko; Kepka, Cezary; Kruk, Mariusz; Vidakovic, Radosav; Neskovic, Aleksandar N.; Diez, Ignacio; Lecumberri, Inigo; Geleijns, Jacob; Kubiak, Christine; Strenge-Hesse, Anke; Do, The-Hoang; Froemel, Felix; Gutierrez-Ibarluzea, Inaki; Benguria-Arrate, Gaizka; Keiding, Hans; Mueller-Nordhorn, Jacqueline; Rieckmann, Nina; Walther, Mario; Schlattmann, Peter

2017-01-01

More than 3.5 million invasive coronary angiographies (ICA) are performed in Europe annually. Approximately 2 million of these invasive procedures might be reduced by noninvasive tests because no coronary intervention is performed. Computed tomography (CT) is the most accurate noninvasive test for detection and exclusion of coronary artery disease (CAD). To investigate the comparative effectiveness of CT and ICA, we designed the European pragmatic multicentre DISCHARGE trial funded by the 7th Framework Programme of the European Union (EC-GA 603266). In this trial, patients with a low-to-intermediate pretest probability (10-60 %) of suspected CAD and a clinical indication for ICA because of stable chest pain will be randomised in a 1-to-1 ratio to CT or ICA. CT and ICA findings guide subsequent management decisions by the local heart teams according to current evidence and European guidelines. Major adverse cardiovascular events (MACE) defined as cardiovascular death, myocardial infarction and stroke as a composite endpoint will be the primary outcome measure. Secondary and other outcomes include cost-effectiveness, radiation exposure, health-related quality of life (HRQoL), socioeconomic status, lifestyle, adverse events related to CT/ICA, and gender differences. The DISCHARGE trial will assess the comparative effectiveness of CT and ICA. (orig.)

Computed tomography versus invasive coronary angiography: design and methods of the pragmatic randomised multicentre DISCHARGE trial

Energy Technology Data Exchange (ETDEWEB)

Napp, Adriane E.; Haase, Robert; Schuetz, Georg M.; Rief, Matthias; Katzer, Christoph; Dewey, Marc [Charite - Universitaetsmedizin Berlin, Department of Radiology, Berlin (Germany); Laule, Michael; Dreger, Henryk [Charite - Universitaetsmedizin Berlin, Department of Cardiology, Berlin (Germany); Feuchtner, Gudrun [Medical University Innsbruck, Department of Radiology, Innsbruck (Austria); Friedrich, Guy [Medical University Innsbruck, Department of Cardiology, Innsbruck (Austria); Spacek, Miloslav [University Hospital Motol, Department of Cardiology, Prague (Czech Republic); Suchanek, Vojtech [University Hospital Motol, Department of Radiology, Prague (Czech Republic); Fuglsang Kofoed, Klaus [Rigshospitalet Region Hovedstaden, Department of Radiology and Department of Cardiology, Copenhagen (Denmark); Engstroem, Thomas [Rigshospitalet Region Hovedstaden, Department of Cardiology, Copenhagen (Denmark); Schroeder, Stephen; Drosch, Tanja [ALB FILS KLINIKEN GmbH, Department of Cardiology, Goeppingen (Germany); Gutberlet, Matthias [University of Leipzig Heart Centre, Department of Radiology, Leipzig (Germany); Woinke, Michael [University of Leipzig Heart Centre, Department of Cardiology, Leipzig (Germany); Maurovich-Horvat, Pal; Merkely, Bela [Semmelweis University, MTA-SE Cardiovascular Imaging Center, Heart and Vascular Center, Budapest (Hungary); Donnelly, Patrick [Southeastern Health and Social Care Trust, Department of Cardiology, Belfast (United Kingdom); Ball, Peter [Southeastern Health and Social Care Trust, Department of Radiology, Belfast (United Kingdom); Dodd, Jonathan D. [St. Vincent' s University Hospital and National University of Ireland, Department of Radiology, Dublin (Ireland); Quinn, Martin [St. Vincent' s University Hospital, Department of Cardiology, Dublin (Ireland); Saba, Luca [Azienda Ospedaliero Universitaria di Cagliari, Department of Radiology, Monserrato (Italy); Porcu, Maurizio [Azienda Ospedaliera Brotzu, Department of Cardiology, Cagliari (Italy); Francone, Marco [Sapienza University of Rome, Department of Radiology, Rome (Italy); Mancone, Massimo [Sapienza University of Rome, Department of Cardiovascular, Respiratory, Nephrology, Anesthesiology and Geriatric Sciences, Rome (Italy); Erglis, Andrejs [Paul Stradins Clinical University Hospital, Department of Cardiology, Riga (Latvia); Zvaigzne, Ligita [Paul Stradins Clinical University Hospital, Department of Radiology, Riga (Latvia); Jankauskas, Antanas [Lithuanian University of Health Sciences, Department of Radiology, Kaunas (Lithuania); Sakalyte, Gintare [Lithuanian University of Health Sciences, Department of Cardiology, Kaunas (Lithuania); Haran, Tomasz [Wojewodzki Szpital Specjalistyczny We Wroclawiu, Department of Radiology, Wroclaw (Poland); Ilnicka-Suckiel, Malgorzata [Wojewodzki Szpital Specjalistyczny We Wroclawiu, Department of Cardiology, Wroclaw (Poland); Bettencourt, Nuno; Gama-Ribeiro, Vasco [Centro Hospitalar de Vila Nova de Gaia, Department of Cardiology, Vila Nova de Gaia (Portugal); Condrea, Sebastian; Benedek, Imre [Cardio Med Medical Center, Department of Cardiology, Targu-Mures (Romania); Cemerlic Adjic, Nada [Institute of Cardiovascular Diseases of Vojvodina, Department of Cardiology, Novi Sad, Sremska Kamenica (Serbia); Adjic, Oto [Institute of Cardiovascular Diseases of Vojvodina, Radiology Department Imaging Center, Novi Sad, Sremska Kamenica (Serbia); Rodriguez-Palomares, Jose; Garcia del Blanco, Bruno [Universitat Autonoma de Barcelona, Department of Cardiology (Barcelona Spain), Hospital Universitari Vall d' Hebron, Institut de Recerca (VHIR), Barcelona (ES); Roditi, Giles; Berry, Colin [University of Glasgow, Institute of Cardiovascular and Medical Sciences, Glasgow (GB); Davis, Gershan [Aintree University Hospital, Department of Cardiology, Liverpool (GB); Thwaite, Erica [Aintree University Hospital, Department of Radiology, Liverpool (GB); Knuuti, Juhani [Turku University Hospital and University of Turku, Turku PET Centre, Turku (FI); Pietilae, Mikko [Turku University Hospital, Heart Centre, Turku (FI); Kepka, Cezary [The Institute of Cardiology in Warsaw, Department of Radiology, Warsaw (PL); Kruk, Mariusz [The Institute of Cardiology in Warsaw, Department of Cardiology, Warsaw (PL); Vidakovic, Radosav; Neskovic, Aleksandar N. [Clinical Hospital Center Zemun, Department of Cardiology, Belgrade-Zemun (RS); Diez, Ignacio [Basurto University Hospital, Department of Cardiology, Bilbao (ES); Lecumberri, Inigo [Basurto University Hospital, Department of Radiology, Bilbao (ES); Geleijns, Jacob [Leiden University Medical Center, Department of Radiology, Leiden (NL); Kubiak, Christine [European Clinical Research Infrastructure Network (ECRIN-ERIC), Management Office, Paris (FR); Strenge-Hesse, Anke [University Cologne, European Clinical Research Infrastructure Network (ECRIN-ERIC), National ECRIN office/KKS Network, Cologne (DE); Do, The-Hoang; Froemel, Felix [Charite - Universitaetsmedizin Berlin, Clinical Coordinating Centre, Berlin (DE); Gutierrez-Ibarluzea, Inaki; Benguria-Arrate, Gaizka [Basque Office for Health Technology Assessment, Vitoria-Gasteiz (ES); Keiding, Hans [University of Copenhagen, Department of Economics, Department of Economics, Copenhagen (DK); Mueller-Nordhorn, Jacqueline; Rieckmann, Nina [Charite - Universitaetsmedizin Berlin, Institute of Public Health, Berlin (DE); Walther, Mario; Schlattmann, Peter [Jena University Hospital, Friedrich Schiller University Jena, Institute of Medical Statistics, Computer Sciences and Documentation, Jena (DE); Collaboration: The DISCHARGE Trial Group

2017-07-15

More than 3.5 million invasive coronary angiographies (ICA) are performed in Europe annually. Approximately 2 million of these invasive procedures might be reduced by noninvasive tests because no coronary intervention is performed. Computed tomography (CT) is the most accurate noninvasive test for detection and exclusion of coronary artery disease (CAD). To investigate the comparative effectiveness of CT and ICA, we designed the European pragmatic multicentre DISCHARGE trial funded by the 7th Framework Programme of the European Union (EC-GA 603266). In this trial, patients with a low-to-intermediate pretest probability (10-60 %) of suspected CAD and a clinical indication for ICA because of stable chest pain will be randomised in a 1-to-1 ratio to CT or ICA. CT and ICA findings guide subsequent management decisions by the local heart teams according to current evidence and European guidelines. Major adverse cardiovascular events (MACE) defined as cardiovascular death, myocardial infarction and stroke as a composite endpoint will be the primary outcome measure. Secondary and other outcomes include cost-effectiveness, radiation exposure, health-related quality of life (HRQoL), socioeconomic status, lifestyle, adverse events related to CT/ICA, and gender differences. The DISCHARGE trial will assess the comparative effectiveness of CT and ICA. (orig.)

Barriers to the conduct of randomised clinical trials within all disease areas

DEFF Research Database (Denmark)

Djurisic, Snezana; Rath, Ana; Gaber, Sabrina

2017-01-01

BACKGROUND: Randomised clinical trials are key to advancing medical knowledge and to enhancing patient care, but major barriers to their conduct exist. The present paper presents some of these barriers. METHODS: We performed systematic literature searches and internal European Clinical Research I...

European communion

DEFF Research Database (Denmark)

Manners, Ian James

2013-01-01

Political theory of European union, through an engagement between political concepts and theoretical understandings, provides a means of identifying the EU as a political object. It is argued that understanding the projects, processes and products of European union, based on ‘sharing’ or ‘communion......’, provides a better means of perceiving the EU as a political object rather than terms such as ‘integration’ or ‘co-operation’. The concept of ‘European communion’ is defined as the ‘subjective sharing of relationships’, understood as the extent to which individuals or groups believe themselves to be sharing...... relations (or not), and the consequences of these beliefs for European political projects, processes and products. By exploring European communion through an engagement with contemporary political theory, using very brief illustrations from the Treaty of Lisbon, the article also suggests that European...

European Union pediatric legislation jeopardizes worldwide, timely future advances in the care of children with cancer.

Science.gov (United States)

Rose, Klaus

2014-02-01

Diagnosis of childhood cancer is no longer an automatic death sentence, but it has not lost all of its horror. Drugs, surgery, radiation, and clinical trials have advanced our capacity to handle these cancers, but pediatric cancers still face challenges. Pediatric pharmaceutical legislation was introduced in the United States in 1997 and has triggered many clinical trials that have helped us better understand what drugs do to a child's body and vice versa. Following the US precedence, the European Union introduced its own legislation. The US legislation was designed to generate additional pediatric data and balances between mandatory requirements and voluntary incentives. The US legislation was designed to mandate full registration of all new drugs for children whenever there is any potential pediatric use. The purpose of this article is to discuss unintended negative consequences of the legislation of the European Medicines Agency (EMA). We analyzed the effects of the EU pediatric legislation with respect to the history of the emergence of modern drugs, pediatric clinical pharmacology, and the development of drugs for pediatric malignancies. No new drug can be registered in the European Union without a detailed pediatric investigation plan (PIP) approved by the EMA's Pediatric Committee (PDCO). This has moved the discussion of the pediatric aspects of drug development to an earlier stage and has increased public awareness. It also has brought industry and pediatric oncologists closer together. However, in a review of >100 PDCO PIP decisions in childhood cancer, we found a lack of balance between the legitimate desire to include children in drug development and the common sense needed in the complex worlds of drug development and pediatric oncology. Many decisions appeared to have been based on both exaggerated assumptions about the frequency of childhood malignancies and the feasibility of the clinical trials proposed. Pharmaceutical companies are being forced

The European Hematology Association Roadmap for European Hematology Research

DEFF Research Database (Denmark)

Engert, Andreas; Balduini, Carlo; Brand, Anneke

2016-01-01

The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology...... research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness...... of the burden of blood disorders on European society, which purely in economic terms is estimated at €23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology...

Eastern Dimension of the European Neighbourhood Policy: Europeanization Mutual Trap

Directory of Open Access Journals (Sweden)

V. A. Latkina

2014-01-01

Full Text Available The article analyses the Europeanization policy of the European Union towards the Eastern Partnership participant countries. Suffering from the lack of clear strategy and ultimate goal in the European Neighbourhood Policy the European Union enhances external democratization and its governance in post soviet states without immediate Union's membership perspective. Underestimation of common neighbourhood geopolitical duality in the context of growing rivalry between European (EU and Eurasian (Custom Union/Eurasian Economic Union integration gravitation centers presents the Eastern partners of the EU with a fierce dilemma of externally forced immediate geopolitical and civilizational choice while not all of them are well prepared to such a choice. The mutual Europeanization trap here to be studied both for the EU and its Eastern partners (involving Russia is a deficiency of regulating cooperation mechanism in the situation of European and Eurasian free trades zones overlapping. Vilnius Summit 2013 results test the "European aspirations" of the New Independent States and upset the ongoing process of the European Neighbourhood Policy in the context of growing economic interdependence in Wider Europe. Besides, the Ukrainian crisis escalation during 2014 as a new seat of tension provokes unbalance of the whole European security system and creates new dividing lines in Europe from Vancouver to Vladivostok.

The right to information within the criminal proceedings in the European Union. Comparative examination. Critical opinions

Directory of Open Access Journals (Sweden)

Ioana-Minodora Rusu

2016-10-01

Full Text Available In the present study we have examined the provisions of Directive 2012/13 / EU of the European Parliament and the Council on the right to information in criminal proceedings and a compared examination relating to the provisions of Romanian law regarding ensuring the right to information within the Romanian criminal proceedings. The innovations and the value of the work consist of the examination of the European legal instrument, the comparative examination and the critical opinions and the proposals of de lege ferenda. As recognized in the jurisprudence of the ECHR, the right to information of the person suspected or accused of committing a crime or arrested for committing a crime on the territory of another Member State is part of the right to a fair trial, being necessary its compliance throughout the criminal trial, on the territory of each Member State. At the same time the European legislative act establishes a general procedure that needs to be respected by each Member State, which entails the obligation for Member States to ensure at least the same rights as for the citizen or the conditions under which a national of another Member State is suspected, accused or arrested for the commission of a crime. This paper continues the research conducted in the field of International and European judicial cooperation in criminal matters, which have resulted in the publication of papers in wellknown publishing houses in the country and abroad, in national and international specialized journals or conference proceedings. The work can be useful to both theorists and practitioners in the field of judicial cooperation in criminal matters regarding the rights of certain categories of people and to the Romanian or European legislator for amending and supplementing the legislation.

Prevalence of potentially inappropriate prescribing in a subpopulation of older European clinical trial participants: a cross-sectional study.

Science.gov (United States)

O Riordan, David; Aubert, Carole Elodie; Walsh, Kieran A; Van Dorland, Anette; Rodondi, Nicolas; Du Puy, Robert S; Poortvliet, Rosalinde K E; Gussekloo, Jacobijn; Sinnott, Carol; Byrne, Stephen; Galvin, Rose; Jukema, J Wouter; Mooijaart, Simon P; Baumgartner, Christine; McCarthy, Vera; Walsh, Elaine K; Collet, Tinh-Hai; Dekkers, Olaf M; Blum, Manuel R; Kearney, Patricia M

2018-03-22

To estimate and compare the prevalence and type of potentially inappropriate prescribing (PIP) and potential prescribing omissions (PPOs) among community-dwelling older adults (≥65 years) enrolled to a clinical trial in three European countries. A secondary analysis of the Thyroid Hormone Replacement for Subclinical Hypothyroidism Trial dataset. A subset of 48/80 PIP and 22/34 PPOs indicators from the Screening Tool of Older Persons Prescriptions/Screening Tool to Alert doctors to Right Treatment (STOPP/START) V2 criteria were applied to prescribed medication data for 532/737 trial participants in Ireland, Switzerland and the Netherlands. The overall prevalence of PIP was lower in the Irish participants (8.7%) compared with the Swiss (16.7%) and Dutch (12.5%) participants (P=0.15) and was not statistically significant. The overall prevalence of PPOs was approximately one-quarter in the Swiss (25.3%) and Dutch (24%) participants and lower in the Irish (14%) participants (P=0.04) and the difference was statistically significant. The hypnotic Z-drugs were the most frequent PIP in Irish participants, (3.5%, n=4), while it was non-steroidal anti-inflammatory drug and oral anticoagulant combination, sulfonylureas with a long duration of action, and benzodiazepines (all 4.3%, n=7) in Swiss, and benzodiazepines (7.1%, n=18) in Dutch participants. The most frequent PPOs in Irish participants were vitamin D and calcium in osteoporosis (3.5%, n=4). In the Swiss and Dutch participants, they were bone antiresorptive/anabolic therapy in osteoporosis (9.9%, n=16, 8.6%, n=22) respectively. The odds of any PIP after adjusting for age, sex, multimorbidity and polypharmacy were (adjusted OR (aOR)) 3.04 (95% CI 1.33 to 6.95, P<0.01) for Swiss participants and aOR 1.74 (95% CI 0.79 to 3.85, P=0.17) for Dutch participants compared with Irish participants. The odds of any PPOs were aOR 2.48 (95% CI 1.27 to 4.85, P<0.01) for Swiss participants and aOR 2.10 (95% CI 1.11 to 3.96, P=0

Controlled categorisation processing in brand extension evaluation by Indo-European language speakers. An ERP study.

Science.gov (United States)

Fudali-Czyż, Agnieszka; Ratomska, Marta; Cudo, Andrzej; Francuz, Piotr; Kopiś, Natalia; Tużnik, Przemysław

2016-08-15

The purpose of our experiment was to test event-related potentials (ERP) accompanying the process of brand extension evaluation in people speaking Indo-European languages. The experimental procedure consisted of sequential presentations of pairs of stimuli; namely, a beverage brand name and a product name. The products fell into the category of beverages (congruent trials) or clothes (incongruent trials). In the response condition (RC), the participants decided whether they accepted the product as an extension of the brand. In the no-response condition (NRC), the participants' task was to attend the stimuli and try to remember them. In the response condition, the amplitudes of the N270, P300 and N400 components were sensitive to incongruence between the product category and the previously presented brand. However, in the no-response condition, differences emerged only at the level of early P1 and P2 components. Our results suggest that, in people speaking one of the Indo-European languages, the process of categorisation in brand extension evaluation is not automatic. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Standard requirements for GCP-compliant data management in multinational clinical trials

LENUS (Irish Health Repository)

Ohmann, Christian

2011-03-22

Abstract Background A recent survey has shown that data management in clinical trials performed by academic trial units still faces many difficulties (e.g. heterogeneity of software products, deficits in quality management, limited human and financial resources and the complexity of running a local computer centre). Unfortunately, no specific, practical and open standard for both GCP-compliant data management and the underlying IT-infrastructure is available to improve the situation. For that reason the "Working Group on Data Centres" of the European Clinical Research Infrastructures Network (ECRIN) has developed a standard specifying the requirements for high quality GCP-compliant data management in multinational clinical trials. Methods International, European and national regulations and guidelines relevant to GCP, data security and IT infrastructures, as well as ECRIN documents produced previously, were evaluated to provide a starting point for the development of standard requirements. The requirements were produced by expert consensus of the ECRIN Working group on Data Centres, using a structured and standardised process. The requirements were divided into two main parts: an IT part covering standards for the underlying IT infrastructure and computer systems in general, and a Data Management (DM) part covering requirements for data management applications in clinical trials. Results The standard developed includes 115 IT requirements, split into 15 separate sections, 107 DM requirements (in 12 sections) and 13 other requirements (2 sections). Sections IT01 to IT05 deal with the basic IT infrastructure while IT06 and IT07 cover validation and local software development. IT08 to IT015 concern the aspects of IT systems that directly support clinical trial management. Sections DM01 to DM03 cover the implementation of a specific clinical data management application, i.e. for a specific trial, whilst DM04 to DM12 address the data management of trials across the unit

Angiotensin receptor blockade in acute stroke. The Scandinavian Candesartan Acute Stroke Trial: rationale, methods and design of a multicentre, randomised- and placebo-controlled clinical trial (NCT00120003)

DEFF Research Database (Denmark)

Sandset, Else Charlotte; Murray, Gordon; Boysen, Gudrun Margrethe

2010-01-01

AND DESIGN: The Scandinavian Candesartan Acute Stroke Trial is an international randomised, placebo-controlled, double-blind trial of candesartan in acute stroke. We plan to recruit 2500 patients presenting within 30 h of stroke (ischaemic or haemorrhagic) and with systolic blood pressure =140 mm......Hg. The recruited patients are randomly assigned to candesartan or placebo for 7-days (doses increasing from 4 to 16 mg once daily). Randomisation is performed centrally via a secure web interface. The follow-up period is 6-months. Patients are included from the following nine North-European countries: Norway...

European Research Reloaded : Cooperation and Integration Among Europeanized States

NARCIS (Netherlands)

Holzhacker, Ron; Haverland, Markus

2006-01-01

European integration has had an ever deepening impact on the member states. The first wave of research concerned the process of institution building and policy developments at the European Union (EU) level. The second wave, on Europeanization used the resulting integration as an explanatory factor

High dose melphalan in the treatment of advanced neuroblastoma: results of a randomised trial (ENSG-1) by the European Neuroblastoma Study Group.

Science.gov (United States)

Pritchard, Jon; Cotterill, Simon J; Germond, Shirley M; Imeson, John; de Kraker, Jan; Jones, David R

2005-04-01

High dose myeloablative chemotherapy ("megatherapy"), with haematopoietic stem cell support, is now widely used to consolidate response to induction chemotherapy in patients with advanced neuroblastoma. In this study (European Neuroblastoma Study Group, ENSG1), the value of melphalan myeloablative "megatherapy" was evaluated in a randomised, multi-centre trial. Between 1982 and 1985, 167 children with stages IV and III neuroblastoma (123 stage IV > 1 year old at diagnosis and 44 stage III and stage IV from 6 to 12 months old at diagnosis) were treated with oncovin, cisplatin, epipodophyllotoxin, and cyclophosphamide (OPEC) induction chemotherapy every 3 weeks. After surgical excision of primary tumour, the 90 patients (69% of the total) who achieved complete response (CR) or good partial response (GPR) were eligible for randomisation either to high dose melphalan (180 mg per square meter) with autologous bone marrow support or to no further treatment. Sixty-five (72%) of eligible children were actually randomised and 21 of these patients were surviving at time of this analysis, with median follow-up from randomisation of 14.3 years. Five year event-free survival (EFS) was 38% (95% confidence interval (CI) 21-54%) in the melphalan-treated group and 27% (95% CI 12-42%) in the "no-melphalan" group. This difference was not statistically significant (P = 0.08, log rank test) but for the 48 randomised stage IV patients aged >1 year at diagnosis outcome was significantly better in the melphalan-treated group-5 year EFS 33% versus 17% (P = 0.01, log rank test). In this trial, high dose melphalan improved the length of EFS and overall survival of children with stage IV neuroblastoma >1 year of age who achieved CR or GPR after OPEC induction therapy and surgery. Multi-agent myeloablative regimens are now widely used as consolidation therapy for children with stage IV disease and in those with other disease stages when the MYCN gene copy number in tumour cells is amplified

European Society of Cardiology (ESC) Annual Congress Report From Barcelona 2017.

Science.gov (United States)

Satoh, Kimio; Takahashi, Jun; Matsumoto, Yasuharu; Tatebe, Shunsuke; Aoki, Tatsuo; Kikuchi, Yoku; Hao, Kiyotaka; Ohyama, Kazuma; Nogi, Masamichi; Suda, Akira; Kasahara, Shintaro; Sato, Koichi; Ichijo, Sadamitsu; Shimokawa, Hiroaki

2017-11-24

From August 26th to 30th, the 2017 Annual Congress of the European Society of Cardiology (ESC 2017) was held in Barcelona, Spain. Despite the terrorism tradegy just before the ESC congress, the congress attracted many medical professionals from all over the world to discuss the recent topics in cardiovascular medicine in more than 500 sessions, including COMPASS (Cardiovascular OutcoMes for People using Anticoagulation StrategieS Trial), CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study), and ORION (which assessed the effect of a novel siRNA inhibitor to PCSK9 on reductions in low-density lipoprotein cholesterol). Japanese cardiologists and the Japanese Circulation Society greatly contributed to the congress. This report briefly introduces some late-breaking registry results, late-breaking clinical trials, and ESC Guidelines from the ESC 2017 Congress.

News of the European Society of Cardiology Congress (London, 28 August - 2 September 2015: old drugs may be better than the new ones

Directory of Open Access Journals (Sweden)

S. Yu. Martsevich

2015-11-01

Full Text Available News of the European Society of Cardiology Congress (London, 2015 is presented. The results of recent randomized controlled trials and observational studies (registers data are discussed.

News of the European Society of Cardiology Congress (London, 28 August - 2 September 2015: old drugs may be better than the new ones

Directory of Open Access Journals (Sweden)

S. Yu. Martsevich

2015-01-01

Full Text Available News of the European Society of Cardiology Congress (London, 2015 is presented. The results of recent randomized controlled trials and observational studies (registers data are discussed.

Trimodality therapy for malignant pleural mesothelioma: Results from an EORTC phase II multicentre trial

NARCIS (Netherlands)

P.E.Y. van Schil (Paul); P. Baas (Paul); R.M. Gaafar (Rabab); A.W.P.M. Maat (Alex); F. Van De Pol (Francien); B. Hasane (B.); H.M. Klomp (Houke); A.M. Abdelrahman (A.); J. Welche (J.); J.P. van Meerbeeck (Jan)

2010-01-01

textabstractThe European Organisation for Research and Treatment of Cancer (EORTC; protocol 08031) phase II trial investigated the feasibility of trimodality therapy consisting of induction chemotherapy followed by extrapleural pneumonectomy and post-operative radiotherapy in patients with malignant

The importance of international collaboration for rare diseases research: a European perspective.

Science.gov (United States)

Julkowska, D; Austin, C P; Cutillo, C M; Gancberg, D; Hager, C; Halftermeyer, J; Jonker, A H; Lau, L P L; Norstedt, I; Rath, A; Schuster, R; Simelyte, E; van Weely, S

2017-09-01

Over the last two decades, important contributions were made at national, European and international levels to foster collaboration into rare diseases research. The European Union (EU) has put much effort into funding rare diseases research, encouraging national funding organizations to collaborate together in the E-Rare program, setting up European Reference Networks for rare diseases and complex conditions, and initiating the International Rare Diseases Research Consortium (IRDiRC) together with the National Institutes of Health in the USA. Co-ordination of the activities of funding agencies, academic researchers, companies, regulatory bodies, and patient advocacy organizations and partnerships with, for example, the European Research Infrastructures maximizes the collective impact of global investments in rare diseases research. This contributes to accelerating progress, for example, in faster diagnosis through enhanced discovery of causative genes, better understanding of natural history of rare diseases through creation of common registries and databases and boosting of innovative therapeutic approaches. Several examples of funded pre-clinical and clinical gene therapy projects show that integration of multinational and multidisciplinary expertize generates new knowledge and can result in multicentre gene therapy trials. International collaboration in rare diseases research is key to improve the life of people living with a rare disease.

Methodological challenges in designing dementia prevention trials - The European Dementia Prevention Initiative (EDPI)

NARCIS (Netherlands)

Richard, Edo; Andrieu, Sandrine; Solomon, Alina; Mangialasche, Francesca; Ahtiluoto, Satu; Moll van Charante, Eric P.; Coley, Nicola; Fratiglioni, Laura; Neely, Anna Stigsdotter; Vellas, Bruno; van Gool, Willem A.; Kivipelto, Miia

2012-01-01

Recent epidemiological studies have indicated numerous associations between vascular and lifestyle related risk factors and incident dementia. However, evidence from randomised controlled trials (RCT) showing effectiveness of interventions aimed at these risk factors in preventing or postponing

{2-Hydroxy-3-[4-(2-methoxyethylphenoxy]propyl}isopropylammonium hemisuccinate

Directory of Open Access Journals (Sweden)

Gianluca Bartolucci

2009-06-01

Full Text Available Metoprolol, a widely used adrenoreceptor blocking drug, is commonly administered as the succinate or tartrate salt. The structure of metoprolol succinate, C15H26NO3+·0.5C4H4O42−, is characterized by the presence of ribbons in which cations, generated by N-protonation of the metoprolol molecules, are hydrogen bonded to succinate anions. The dicarboxylic acid transfers its H atoms to two metoprolol molecules; the asymmetric unit contains one cation and half an anion, the latter possessing twofold rotational symmetry. There are localized nets of O—H...O and N—H...O hydrogen bonds along a ribbon, within centrosymmetric arrangements formed by pairs of metoprolol cations and pairs of anions, each of the latter contributing with one of its carboxyl groups to the localized net. This arrangement is repeated along the ribbon by the operation of the twofold axis bisecting the anion, as well as by the lattice translation.

The EMBARC European Bronchiectasis Registry: protocol for an international observational study

Directory of Open Access Journals (Sweden)

James D. Chalmers

2016-01-01

Full Text Available Bronchiectasis is one of the most neglected diseases in respiratory medicine. There are no approved therapies and few large-scale, representative epidemiological studies. The EMBARC (European Multicentre Bronchiectasis Audit and Research Collaboration registry is a prospective, pan-European observational study of patients with bronchiectasis. The inclusion criterion is a primary clinical diagnosis of bronchiectasis consisting of: 1 a clinical history consistent with bronchiectasis; and 2 computed tomography demonstrating bronchiectasis. Core exclusion criteria are: 1 bronchiectasis due to known cystic fibrosis; 2 age <18 years; and 3 patients who are unable or unwilling to provide informed consent. The study aims to enrol 1000 patients by April 2016 across at least 20 European countries, and 10 000 patients by March 2020. Patients will undergo a comprehensive baseline assessment and will be followed up annually for up to 5 years with the goal of providing high-quality longitudinal data on outcomes, treatment patterns and quality of life. Data from the registry will be available in the form of annual reports. and will be disseminated in conference presentations and peer-reviewed publications. The European Bronchiectasis Registry aims to make a major contribution to understanding the natural history of the disease, as well as guiding evidence-based decision making and facilitating large randomised controlled trials.

Methods to improve patient recruitment and retention in stroke trials

DEFF Research Database (Denmark)

Berge, Eivind; Stapf, Christian; Al-Shahi Salman, Rustam

2016-01-01

Background: The success of randomized-controlled stroke trials is dependent on the recruitment and retention of a sufficient number of patients, but fewer than half of all trials meet their target number of patients. Methods: We performed a search and review of the literature, and conducted...... a survey and workshop among 56 European stroke trialists, to identify barriers, suggest methods to improve recruitment and retention, and make a priority list of interventions that merit further evaluation. Results: The survey and workshop identified a number of barriers to patient recruitment...... and retention, from patients’ incapacity to consent, to handicaps that prevent patients from participation in trial-specific follow-up. Methods to improve recruitment and retention may include simple interventions with individual participants, funding of research networks, and reimbursement of new treatments...

European Research on Electrochemotherapy in Head and Neck Cancer (EURECA) project

DEFF Research Database (Denmark)

Plaschke, Christina Caroline; Bertino, Giulia; McCaul, James A.

2017-01-01

Aim Electrochemotherapy is an effective local treatment for cutaneous tumours and metastases. In this prospective trial, six European institutions investigated electrochemotherapy in recurrent, mucosal head and neck tumours. Patient and methods Forty-three patients with recurrent mucosal head....... Primary end-point was local tumour response. Secondary end-points were safety and toxicity, overall and progression free survival, and quality-of-life. Results Thirty-seven patients were evaluable for tumour response, pain score, side-effects and quality of life questionnaires. Six patients were...

Medical research in emergency research in the European Union member states: tensions between theory and practice.

Science.gov (United States)

Kompanje, Erwin J O; Maas, Andrew I R; Menon, David K; Kesecioglu, Jozef

2014-04-01

In almost all of the European Union member states, prior consent by a legal representative is used as a substitute for informed patient consent for non-urgent medical research. Deferred (patient and/or proxy) consent is accepted as a substitute in acute emergency research in approximately half of the member states. In 12 European Union member states emergency research is not mentioned in national law. Medical research in the European Union is covered by the Clinical Trial Directive 2001/20/EC. A proposal for a regulation by the European Commission is currently being examined by the European Parliament and the Council and will replace Directive 2001/20/EC. Deferred patient and/or proxy consent is allowed in the proposed regulation, but does not fit completely in the practice of emergency research. For example, deferred consent is only possible when legal representatives are not available. This criterion will delay inclusion of patients in acute life-threatening conditions in short time frames. As the regulation shall be binding in its entirety in all member states, emergency research in acute situations is still not possible as it should be.

How campaigns enhance European issues voting during European Parliament elections

DEFF Research Database (Denmark)

Beach, Derek; Møller Hansen, Kasper; Larsen, Martin Vinæs

2017-01-01

Based on findings from the literature on campaign effects on the one hand, and the literature on European Parliament elections on the other, we propose a model of European Parliamentary elections in which the campaign shift the calculus of electoral support, making differences in national political...... allegiances less important and attitudes about the European project more important by informing voters of and getting them interested in European politics. In effect, we argue that the political campaign leading up to the election makes European Parliament elections less second-order. While previous studies...... have demonstrated that EU attitudes can matter for voting behavior in European Parliament elections, existing research has drawn on post-election surveys that do not enable us to capture campaign effects. Our contribution is to assess the impact of a campaign by utilizing a rolling cross sectional...

Design and baseline characteristics of the Food4Me study: a web-based randomised controlled trial of personalised nutrition in seven European countries.

Science.gov (United States)

Celis-Morales, Carlos; Livingstone, Katherine M; Marsaux, Cyril F M; Forster, Hannah; O'Donovan, Clare B; Woolhead, Clara; Macready, Anna L; Fallaize, Rosalind; Navas-Carretero, Santiago; San-Cristobal, Rodrigo; Kolossa, Silvia; Hartwig, Kai; Tsirigoti, Lydia; Lambrinou, Christina P; Moschonis, George; Godlewska, Magdalena; Surwiłło, Agnieszka; Grimaldi, Keith; Bouwman, Jildau; Daly, E J; Akujobi, Victor; O'Riordan, Rick; Hoonhout, Jettie; Claassen, Arjan; Hoeller, Ulrich; Gundersen, Thomas E; Kaland, Siv E; Matthews, John N S; Manios, Yannis; Traczyk, Iwona; Drevon, Christian A; Gibney, Eileen R; Brennan, Lorraine; Walsh, Marianne C; Lovegrove, Julie A; Alfredo Martinez, J; Saris, Wim H M; Daniel, Hannelore; Gibney, Mike; Mathers, John C

2015-01-01

Improving lifestyle behaviours has considerable potential for reducing the global burden of non-communicable diseases, promoting better health across the life-course and increasing well-being. However, realising this potential will require the development, testing and implementation of much more effective behaviour change interventions than are used conventionally. Therefore, the aim of this study was to conduct a multi-centre, web-based, proof-of-principle study of personalised nutrition (PN) to determine whether providing more personalised dietary advice leads to greater improvements in eating patterns and health outcomes compared to conventional population-based advice. A total of 5,562 volunteers were screened across seven European countries; the first 1,607 participants who fulfilled the inclusion criteria were recruited into the trial. Participants were randomly assigned to one of the following intervention groups for a 6-month period: Level 0-control group-receiving conventional, non-PN advice; Level 1-receiving PN advice based on dietary intake data alone; Level 2-receiving PN advice based on dietary intake and phenotypic data; and Level 3-receiving PN advice based on dietary intake, phenotypic and genotypic data. A total of 1,607 participants had a mean age of 39.8 years (ranging from 18 to 79 years). Of these participants, 60.9 % were women and 96.7 % were from white-European background. The mean BMI for all randomised participants was 25.5 kg m(-2), and 44.8 % of the participants had a BMI ≥ 25.0 kg m(-2). Food4Me is the first large multi-centre RCT of web-based PN. The main outcomes from the Food4Me study will be submitted for publication during 2015.

Quantity and quality assessment of randomized controlled trials on orthodontic practice in PubMed.

Science.gov (United States)

Shimada, Tatsuo; Takayama, Hisako; Nakamura, Yoshiki

2010-07-01

To find current high-quality evidence for orthodontic practice within a reasonable time, we tested the performance of a PubMed search. PubMed was searched using publication type randomized controlled trial and medical subject heading term "orthodontics" for articles published between 2003 and 2007. The PubMed search results were compared with those from a hand search of four orthodontic journals to determine the sensitivity of PubMed search. We evaluated the precision of the PubMed search result and assessed the quality of individual randomized controlled trials using the Jadad scale. Sensitivity and precision were 97.46% and 58.12%, respectively. In PubMed, of the 277 articles retrieved, 161 (58.12%) were randomized controlled trials on orthodontic practice, and 115 of the 161 articles (71.42%) were published in four orthodontic journals: American Journal of Orthodontics and Dentofacial Orthopedics, The Angle Orthodontist, the European Journal of Orthodontics, and the Journal of Orthodontics. Assessment by the Jadad scale revealed 60 high-quality randomized controlled trials on orthodontic practice, of which 45 (75%) were published in these four journals. PubMed is a highly desirable search engine for evidence-based orthodontic practice. To stay current and get high-quality evidence, it is reasonable to look through four orthodontic journals: American Journal of Orthodontics and Dentofacial Orthopedics, The Angle Orthodontist, the European Journal of Orthodontics, and the Journal of Orthodontics.

Perioperative Beta Blockade - A Case Report

Directory of Open Access Journals (Sweden)

Sunitha K. Zachariah

2009-10-01

Full Text Available Continuation of antihypertensives preoperatively and their influence on intraoperative hemodynamics is a big concern among anesthesiologists. The Peri Operative Ischaemia Study Evaluation (POISE trial showed a significant reduction of myocardial infarction, need for coronary revascularization and the incidence of atrial fibrillation with metoprolol started 2-4 hours prior to surgery but a significant increase in total mortality and clinically significant hypotension and bradycardia. This is a case report of intraoperative severe bradycardia in a young patient on recently started beta blocker.

The European Parliament and the European future of Albania

Directory of Open Access Journals (Sweden)

Skerdilajd Bajramaj

2015-07-01

Full Text Available On 06.24.2014 Albania was granted the status of candidate country. The foreign ministers of the 28 European Union member states decided unanimously to grant the candidate status for Albania. After receiving the status of “candidate country” for EU membership, the institutional relations with European international bodies are becoming stronger. One of these institutions, which during this time has increased its authority with Albania, is the European Parliament. In this paper will be analyzed the composition, competences and functioning of this particular institution, which is not only important for the future of the European Union and its Member States, but also for those who aim to join in. The study will be based on decisions made by this legislative body, as the only direct representative of the citizens of the European Union, and the impact they have on the performance and functioning of the Member States and the EU itself. In order to verify the validity of these claims, the analysis aims to assess the scope of the legislative function of the European Parliament post-Lisbon, examining its participation in the EU lawmaking both from the point of view of quantity and quality in over the past legislatures. Particular attention has been given to the examination of the changes that have taken place with the entry into force of the Lisbon Treaty, and the areas most affected. We will finally look at the work and contribution of the European Parliament, through the instruments at his disposal, on behalf of Albania’s progress towards full accession in the European Union.

Centre of the European gas market. The European Autumn Gas Conference

International Nuclear Information System (INIS)

Van Hasselt, F.; Van der Wal, W.; Ruinen, H.

1998-01-01

From the results of the 1997 European Autumn Gas Conference in Barcelona, Spain, it appears that the European gas industry is mainly focused on the liberalization of the European energy market. The main topic of the Conference was 'dealing with surplus'. A brief overview is given of the natural gas trade developments in the European countries. 1 ill., 1 tab. 2 ills

European Community.

Science.gov (United States)

1987-05-01

The European Community was established in 1951 to reconcile France and Germany after World War II and to make possible the eventual federation of Europe. By 1986, there were 12 member countries: France, Italy, Belgium, the Federal Republic of Germany, Luxembourg, the Netherlands, Denmark, Ireland, the United Kingdom, Greece, Spain, and Portugal. Principal areas of concern are internal and external trade, agriculture, monetary coordination, fisheries, common industrial and commercial policies, assistance, science and research, and common social and regional policies. The European Community has a budget of US$34.035 billion/year, funded by customs duties and 1.4% of each member's value-added tax. The treaties establishing the European Community call for members to form a common market, a common customs tariff, and common agricultural, transport, economic, and nuclear policies. Major European Community institutions include the Commission, Council of Ministers, European Parliament, Court of Justice, and Economic and Social Committee. The Community is the world's largest trading unit, accounting for 15% of world trade. The 2 main goals of the Community's industrial policy are to create an open internal market and to promote technological innovation in order to improve international competitiveness. The European Community aims to contribute to the economic and social development of Third World countries as well.

Ethical, legal, and social implications (ELSI) of microdose clinical trials.

Science.gov (United States)

Kurihara, Chieko

2011-06-19

A "microdose clinical trial" (microdosing) is one kind of early phase exploratory clinical trial, administering the compound at doses estimated to have no pharmacological or toxicological effects, aimed at screening candidates for further clinical development. This article's objective is to clarify the ethical, legal, and social implications (ELSI) of such an exploratory minimum-risk human trial. The definition and non-clinical study requirements for microdosing have been harmonized among the European Union (EU), United States (US), and Japan. Being conducted according to these regulations, microdosing seems to be ethically well justified in terms of respect for persons, beneficence, justice, human dignity, and animal welfare. Three big projects have been demonstrating the predictability of therapeutic dose pharmacokinetics from microdosing. The article offers suggestions as how microdosing can become a more useful and socially accepted strategy. Copyright © 2011 Elsevier B.V. All rights reserved.

Raising European Citizens: Constructing European Identities in French and English Textbooks

Directory of Open Access Journals (Sweden)

Inari Sakki

2016-06-01

Full Text Available Schools play a pivotal role in the formation of identities and in the political socialization of youth. This study explores the social representations of European integration in French and English school textbooks and shows how the social representations are discursively used to construct national and European identities. By analysing the history and civics textbooks of major educational publishers, this study aims to demonstrate how European integration is understood, made familiar and concretized in the school textbooks of the two influential but different European countries. The findings suggest some shared and some diverse patterns in the way the two European countries portray and construct the political project of European integration. These representations, constructed around French Europe in French textbooks and ambivalent Europe in English textbooks, share the images of a strong European economy and a French-led political Europe. However, they position themselves differently with respect to the United States, motivation for the European unification process and the significance of common values and heritage. In both countries textbooks draw upon memories that are important for group identity. While the French textbooks make European integration meaningful in reference to a shared post-war collective memory and to a cultural memory based on a more ancient idea of Europe, shared values and heritage, the English textbooks anchor it more strongly to domestic policy.

Multicenter Collaborative Trial Evaluation of a Method for Detection of Human Adenoviruses in Berry Fruit

NARCIS (Netherlands)

Agostino, D' C.; Cook, N.; Bartolo, Di I.; Ruggeri, F.M.; Berto, A.; Martelli, F.; Banks, M.; Vasickova, P.; Kralik, P.; Pavlik, I.; Kokkinos, P.; Vantarakis, A.; Söderberg, K.; Maunula, L.; Verhaelen, K.; Rutjes, S.; Roda Husman, De A.M.; Hakze-van der Honing, van der R.W.; Poel, van der W.H.M.; Kaupke, A.; Kozyra, I.; Rzezutka, A.; Prodanov, J.; Lazic, S.; Petrovic, T.; Carratala, A.; Gironés, R.; Diez-Valcarce, M.; Hernandez, M.; Rodriguez-Lazaro, D.

2012-01-01

The qualitative performance characteristics of a qPCR-based method to detect human adenoviruses in raspberries were determined through a collaborative trial involving 11 European laboratories. The method incorporated a sample process control (murine norovirus) and an internal amplification control.

Design of tumor biomarker-monitoring trials: a proposal by the European Group on Tumor Markers

NARCIS (Netherlands)

Sölétormos, György; Duffy, Michael J.; Hayes, Daniel F.; Sturgeon, Catharine M.; Barak, Vivian; Bossuyt, Patrick M.; Diamandis, Eleftherios P.; Gion, Massimo; Hyltoft-Petersen, Per; Lamerz, Rolf M.; Nielsen, Dorte L.; Sibley, Paul; Tholander, Bengt; Tuxen, Malgorzata K.; Bonfrer, Johannes M. G.

2013-01-01

A major application of tumor biomarkers is in serial monitoring of cancer patients, but there are no published guidelines on how to evaluate biomarkers for this purpose. The European Group on Tumor Markers has convened a multidisciplinary panel of scientists to develop guidance on the design of such

Globalization and Europeanization. A Projection on a European Model of Public Administration

Directory of Open Access Journals (Sweden)

Ani Matei

2008-04-01

Full Text Available The specialized studies and literature present moreover and insistently the connection between globalization and Europeanization, more precisely between globalization and a European model of integration, whose features aim to set up a global-type European society. The development of the European model of integration starts with economic elements, it reveals nowadays the Economic and Monetary Union and in perspective it will be structured within a sui generis system of transnational governance. The values of the European model of integration become fundamental values of a social process, with powerful economic and political determinations, aiming the multi-causal interference between individual, community and European construction. This process, remarked increasingly in the specialized literature, being assigned with the name of Europeanization, has got original, functional features in the spectrum of significations of the globalization paradigm. As essential global-type formula, within Europeanization, we shall find models with economic, political or social finality, integrating also a model of administration among the latter ones. When we say administration, we refer to its up dated and adequate contents to the new European developments. This assertion derives from a less economic modality to conceptualize the relationship between globalization and Europeanization, presenting Europeanization more as a political adaptation to globalization and even a political expression of globalization. In this context, the development of a system for European governance on several levels (local, regional, national, intergovernmental and supranational suggests its evolution towards globalization. In fact, the literature specific for Europeanization asserts the fact that the European model has also features with integrative nature related to the supranational and trans-governmental dimensions, as well as features with normative nature in view of harmonization

Enhancement of Fenton and photo-Fenton processes at initial circumneutral pH for the degradation of the β-blocker metoprolol.

Science.gov (United States)

Romero, V; Acevedo, S; Marco, P; Giménez, J; Esplugas, S

2016-01-01

The need for acidification in the Fenton and photo-Fenton process is often outlined as one of its major drawbacks, thus in this work the acidification of the Metoprolol (MET) is avoided by the addition of resorcinol (RES), which is used to simulate model organic matter. The experiments were carried out at natural pH (6.2) with different Fe(2+) (1, 2.5, 5, and 10 mg/L) and H2O2 (25, 50, 125 and 150 mg/L) concentrations. The performance of MET and RES degradation was assessed along the reaction time. Working with the highest concentrations (5 and 10 mg/L of ferrous iron and 125 and 150 mg/L of H2O2) more than 90% of MET and RES removals were reached within 50 and 20 min of treatment, respectively, by Fenton process. However a low mineralization was achieved in both cases, likely, due to by-products accumulation. Regarding to photo-Fenton process, within 3 min with the highest iron and hydrogen peroxide concentrations, a complete MET degradation was obtained and 95% of RES conversion was achieved. Parameters such Total Organic Carbon, Chemical Oxygen Demand, and AOS were measured. Intermediates were identified and MET degradation path was proposed in the presence of resorcinol. Finally, a comparison between Fenton and photo-Fenton processes at acid pH and at initial circumneutral pH was discussed. The positive effect of RES on Fenton and photo-Fenton systems has been confirmed, allowing the work at circumneutral pH. Copyright © 2015 Elsevier Ltd. All rights reserved.

European Union

International Nuclear Information System (INIS)

Schaller, K.

1995-01-01

Different instruments used by European Commission of the European Union for financial support radioactive waste management activities in the Russian Federation are outlined. Three particular programmes in the area are described

European Union response to Fukushima. European stress tests and peer review

Energy Technology Data Exchange (ETDEWEB)

Jamet, Philippe [Autorite de Surete Nucleaire (ASN), Paris (France)

2012-07-01

Following the severe accidents which started in the Fukushima Dai-ichi NPP on 11 March 2011, the European Council requested that a comprehensive safety and risk assessment, in light of preliminary lessons learned, be performed on all EU nuclear plants. Therefore, stress tests and peer review assessing natural initiating events, the loss of safety systems and severe accident management have been performed in the 15 European Union countries with nuclear power plants as well as Switzerland and Ukraine. The final peer review report of the European Nuclear Safety Regulators Group (ENSREG) highlights four main areas for improvement to be explored across Europe: 1. Development by the Western European Nuclear Regulators' Association (WENRA), with the contribution of the best available EU expertise, of a European guidance on assessment of natural hazards and margins; 2. Importance of Periodic Safety Review to be underlined by ENSREG; 3. Expeditious implementation of the recognised measures to protect containment integrity; 4. Prevention of accidents resulting from natural hazards and limitation of their consequences. The peer review of the European stress tests was completed in April 2012. In their conclusive statement issued 26 April 2012, the national European regulators and the European Commission as European Nuclear Safety Regulators Group (ENSREG) required that follow-up would occur by way of an ENSREG action plan. Country specific action plans will be developed and peer review workshop will be organised to share lessons learned on the implementation of post-Fukushima safety improvements.

European Union response to Fukushima. European stress tests and peer review

International Nuclear Information System (INIS)

Jamet, Philippe

2012-01-01

Following the severe accidents which started in the Fukushima Dai-ichi NPP on 11 March 2011, the European Council requested that a comprehensive safety and risk assessment, in light of preliminary lessons learned, be performed on all EU nuclear plants. Therefore, stress tests and peer review assessing natural initiating events, the loss of safety systems and severe accident management have been performed in the 15 European Union countries with nuclear power plants as well as Switzerland and Ukraine. The final peer review report of the European Nuclear Safety Regulators Group (ENSREG) highlights four main areas for improvement to be explored across Europe: 1. Development by the Western European Nuclear Regulators' Association (WENRA), with the contribution of the best available EU expertise, of a European guidance on assessment of natural hazards and margins; 2. Importance of Periodic Safety Review to be underlined by ENSREG; 3. Expeditious implementation of the recognised measures to protect containment integrity; 4. Prevention of accidents resulting from natural hazards and limitation of their consequences. The peer review of the European stress tests was completed in April 2012. In their conclusive statement issued 26 April 2012, the national European regulators and the European Commission as European Nuclear Safety Regulators Group (ENSREG) required that follow-up would occur by way of an ENSREG action plan. Country specific action plans will be developed and peer review workshop will be organised to share lessons learned on the implementation of post-Fukushima safety improvements.

European visit

CERN Multimedia

2006-01-01

The European Commissioner for Science and Research, Janez Potočnik, (on the right) visited the CMS assembly hall accompanied by Jim Virdee, Deputy Spokesman of CMS (on the left), and Robert Aymar, Director-General of CERN. The European Commissioner for Science and Research, Janez Potočnik, visited CERN on Tuesday 31 January. He was welcomed by the Director-General, Robert Aymar, who described the missions and current activities of CERN to him, in particular the realisation of the LHC with its three components: accelerator, detectors, storage and processing of data. The European Commissioner then visited the CMS assembly hall, then the hall for testing the LHC magnets and the ATLAS cavern. During this first visit since his appointment at the end of 2004, Janez Potočnik appeared very interested by the operation of CERN, an example of successful scientific co-operation on a European scale. The many projects (30 on average) that CERN and the European Commission carry out jointly for the benefit of res...

Europeanization by it is tools: the case of European transnational projects

NARCIS (Netherlands)

Sanchez Salgado, R.

2010-01-01

In the understanding of Europeanization, specific tools of governance matter. Europeanization through flexible tools of governance enables strategic uses by domestic actors, and does not necessaritly preclude policy transfer or transformation. As long as they favour participation, European

Europeanization and social movement mobilization during the European sovereign debt crisis

DEFF Research Database (Denmark)

Bourne, Angela; Chatzopoulou, Sevasti

2015-01-01

The article addresses Europeanization of social movements in the context of the European Sovereign Debt Crisis. Europeanization occurs when movements collaborate, or make horizontal communicative linkages with movements in other countries, contest authorities beyond the state, frame issues...

The Recognition and Enforcement of Foreign Judgements in Civil Cases in the Context of Practice of European Court of Human Rights

Directory of Open Access Journals (Sweden)

Тетяна Андріївна Цувіна

2017-09-01

Full Text Available The article addresses recognition and enforcement of foreign judgements in civil cases in the context of the practice of European Court of Human Rights. The conclusion is made, that European Court of Human Rights analyzes institute of recognition and enforcement of foreign judgements through such procedural rights as right to a fair trial (art. 6 ECHR and right to an effective remedy (art. 13 ECHR as long as such substantive conventional rights as right to protection pf property (art. 1 of the First Protocol to ECHR and right to respect for private and family life (art. 8 ECHR. It is considered that the main article through which this institute should be analyzed is art. 6 ECHR containing procedural guaranties of fair trial. According to the art. 13 ECHR the effective remedies of protection of the right to a fair trial in reasonable time should be provided at national level. Moreover reforms of this sphere of judicial practice should be done in accordance with art. 8 ECHR and art. 1 of the First Protocol to ECHR which provide specific substantive rights. All of the above mentioned aspects are analyzed in detail.

Clinical trials of new drugs for the treatment of rheumatoid arthritis: focus on early disease

NARCIS (Netherlands)

Smolen, Josef S.; Collaud Basset, Sabine; Boers, Maarten; Breedveld, Ferdinand; Edwards, Christopher J.; Kvien, Tore K.; Miossec, Pierre; Sokka-Isler, Tuulikki; van Vollenhoven, Ronald F.; Abadie, Eric C.; Bruyère, Olivier; Cooper, Cyrus; Mäkinen, Heidi; Thomas, Thierry; Tugwell, Peter; Reginster, Jean-Yves

2016-01-01

The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases convened a task force of experts in rheumatoid arthritis (RA) and clinical trial methodology to comment on the new draft 'Guideline on clinical investigation of medicinal products for

Sharing and reuse of individual participant data from clinical trials: principles and recommendations.

Science.gov (United States)

Ohmann, Christian; Banzi, Rita; Canham, Steve; Battaglia, Serena; Matei, Mihaela; Ariyo, Christopher; Becnel, Lauren; Bierer, Barbara; Bowers, Sarion; Clivio, Luca; Dias, Monica; Druml, Christiane; Faure, Hélène; Fenner, Martin; Galvez, Jose; Ghersi, Davina; Gluud, Christian; Groves, Trish; Houston, Paul; Karam, Ghassan; Kalra, Dipak; Knowles, Rachel L; Krleža-Jerić, Karmela; Kubiak, Christine; Kuchinke, Wolfgang; Kush, Rebecca; Lukkarinen, Ari; Marques, Pedro Silverio; Newbigging, Andrew; O'Callaghan, Jennifer; Ravaud, Philippe; Schlünder, Irene; Shanahan, Daniel; Sitter, Helmut; Spalding, Dylan; Tudur-Smith, Catrin; van Reusel, Peter; van Veen, Evert-Ben; Visser, Gerben Rienk; Wilson, Julia; Demotes-Mainard, Jacques

2017-12-14

We examined major issues associated with sharing of individual clinical trial data and developed a consensus document on providing access to individual participant data from clinical trials, using a broad interdisciplinary approach. This was a consensus-building process among the members of a multistakeholder task force, involving a wide range of experts (researchers, patient representatives, methodologists, information technology experts, and representatives from funders, infrastructures and standards development organisations). An independent facilitator supported the process using the nominal group technique. The consensus was reached in a series of three workshops held over 1 year, supported by exchange of documents and teleconferences within focused subgroups when needed. This work was set within the Horizon 2020-funded project CORBEL (Coordinated Research Infrastructures Building Enduring Life-science Services) and coordinated by the European Clinical Research Infrastructure Network. Thus, the focus was on non-commercial trials and the perspective mainly European. We developed principles and practical recommendations on how to share data from clinical trials. The task force reached consensus on 10 principles and 50 recommendations, representing the fundamental requirements of any framework used for the sharing of clinical trials data. The document covers the following main areas: making data sharing a reality (eg, cultural change, academic incentives, funding), consent for data sharing, protection of trial participants (eg, de-identification), data standards, rights, types and management of access (eg, data request and access models), data management and repositories, discoverability, and metadata. The adoption of the recommendations in this document would help to promote and support data sharing and reuse among researchers, adequately inform trial participants and protect their rights, and provide effective and efficient systems for preparing, storing and

Benefits and harms in clinical trials of duloxetine for treatment of major depressive disorder

DEFF Research Database (Denmark)

Maund, Emma; Tendal, Britta; Hróbjartsson, Asbjørn

2014-01-01

, with respect to benefits and major harms. DESIGN: Data on primary efficacy analysis and major harms extracted from each data source and compared. SETTING: Nine randomised placebo controlled trials of duloxetine (total 2878 patients) submitted to the European Medicines Agency (EMA) for marketing approval.......gov and the manufacturer's online clinical trial registry were searched for trial results. RESULTS: Clinical study reports fully described the primary efficacy analysis and major harms (deaths (including suicides), suicide attempts, serious adverse events, and discontinuations because of adverse events). There were minor......, respectively. We also found publication bias in relation to beneficial effects. CONCLUSION: Clinical study reports contained extensive data on major harms that were unavailable in journal articles and in trial registry reports. There were inconsistencies between protocols and clinical study reports and within...

News of the Annual Congress of the European Society of Cardiology in Rome: the Obvious and Proven - it's not the Same Thing

Directory of Open Access Journals (Sweden)

S. Yu. Martsevich

2016-01-01

Full Text Available News of the European Society of Cardiology Congress (Rome, 2016 is reviewed. The results of recent randomized controlled trials, observational studies (registers data, common problems in the presentation and interpretation of the reviewed data are discussed.

beta-Blockade used in precision sports: effect on pistol shooting performance.

Science.gov (United States)

Kruse, P; Ladefoged, J; Nielsen, U; Paulev, P E; Sørensen, J P

1986-08-01

In a double-blind cross-over study of 33 marksmen (standard pistol, 25 m) the adrenergic beta 1-receptor blocker, metoprolol, was compared to placebo. Metoprolol obviously improved the pistol shooting performance compared with placebo. Shooting improved by 13.4% of possible improvement (i.e., 600 points minus actual points obtained) as an average (SE = 4%, 2P less than 0.002). The most skilled athletes demonstrated the clearest metoprolol improvement. We found no correlation between the shooting improvement and changes in the cardiovascular variables (i.e., changes of heart rate and systolic blood pressure) and no correlation to the estimated maximum O2 uptake. The shooting improvement is an effect of metoprolol on hand tremor. Emotional increase of heart rate and systolic blood pressure seem to be a beta 1-receptor phenomenon.

Increasing European Support for Neglected Infectious Disease Research

Directory of Open Access Journals (Sweden)

Ole F. Olesen

Full Text Available Neglected infectious diseases (NIDs are a persistent cause of death and disability in low-income countries. Currently available drugs and vaccines are often ineffective, costly or associated with severe side-effects. Although the scale of research on NIDs does not reflect their disease burden, there are encouraging signs that NIDs have begun to attract more political and public attention, which have translated into greater awareness and increased investments in NID research by both public and private donors. Using publicly available data, we analysed funding for NID research in the European Union's (EU's 7th Framework Programme for Research and Technological Development (FP7, which ran from 2007 to 2013. During FP7, the EU provided €169 million for 65 NID research projects, and thereby placed itself among the top global funders of NID research. Average annual FP7 investment in NID research exceeded €24 million, triple that committed by the EU before the launch of FP7. FP7 NID projects involved research teams from 331 different institutions in 72 countries on six continents, underlining the increasingly global nature of European research activities. NID research has remained a priority in the current EU Framework Programme for research and innovation, Horizon 2020, launched in 2014. This has most notably been reflected in the second programme of the European & Developing Countries Clinical Trials Partnership (EDCTP, which provides unprecedented opportunities to advance the clinical development of new medical interventions against NIDs. Europe is thus better positioned than ever before to play a major role in the global fight against NIDs.

European mobility cultures

DEFF Research Database (Denmark)

Haustein, Sonja; Nielsen, Thomas A. Sick

2016-01-01

More targeted European policies promoting green travel patterns require better knowledge on differing mobility cultures across European regions. As a basis for this, we clustered the EU population into eight mobility styles based on Eurobarometer data. The mobility styles - including, for example...... positions on the path towards sustainable mobility and therefore different requirements towards European platforms and support measures, e.g. for 'Sustainable Urban Mobility Plans'. The country clusters can provide a starting point for future communication and targeting of European efforts in sustainable...

Medium intensity oral anticoagulants versus aspirin after cerebral ischaemia of arterial origin (ESPRIT) : a randomised controlled trial

NARCIS (Netherlands)

Halkes, P H A; van Gijn, J; Kappelle, L J; Algra, A; Koudstaal, P J

BACKGROUND: Oral anticoagulants are better than aspirin for secondary prevention after myocardial infarction and after cerebral ischaemia in combination with non-rheumatic atrial fibrillation. The European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) aimed to determine

Medium intensity oral anticoagulants versus aspirin after cerebral ischaemia of arterial origin (ESPRIT): a randomised controlled trial

NARCIS (Netherlands)

Halkes, P. H. A.; van Gijn, J.; Kappelle, L. J.; Koudstaal, P. J.; Algra, A.; Banga, J. D.; Boiten, J.; van der Bom, J. G.; Boon, A. E.; Dippel, D. W. J.; Donders, R. C. J. M.; Eefting, F. D.; Franke, C. L.; Frenken, C. W. G. M.; Frijns, C. J. M.; van Gemert, H. M. A.; de Jaegere, P. P. Th; Kamp, O.; Kwa, V. I. H.; de Leeuw, F.-E.; Linn, F. H. H.; van der Meer, W. K.; Mosterd, A.; Pop, G. A. M.; Raaymakers, T. W. M.; van Schooneveld, M. J.; Stam, J.; Verheugt, F. W. A.; van der Worp, H. B.; Zijlstra, F.; Boekweit, M. P.; van Buuren, M.; Greebe, P.; Mooibroek, G. E.; Slabbers, D. C. V.; Beijer, I. S.; van den Bergh, W. M.; Biessels, G. J.; de Schryver, E. L. L. M.; van Dijk, G. W.; Dorhout-Mees, S. M.; Ferrier, C. H.; Gorter, J. W.; Hofmeijer, J.; Hop, J. W.; Klijn, C. J. M.; Manschot, S. M.; Vermeulen, M.; Foncke, E.; Lucas, C.

2007-01-01

BACKGROUND: Oral anticoagulants are better than aspirin for secondary prevention after myocardial infarction and after cerebral ischaemia in combination with non-rheumatic atrial fibrillation. The European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) aimed to determine

The evolution of the ecological policy and the environmental law of the European community

International Nuclear Information System (INIS)

Dietinger, A.

1998-08-01

This thesis is structured chronologically starting with the origins of a European environment policy. These origins can be found in the foundation treaty of the European Community but are not explicitly codified. The thesis shows that the emphasis on economics in the European Community turned from acceptance of an environment policy as a marginal phenomenon to valuation of environmental policies as a principle of its own. The focus is on the contents of the EC Trial. The normative structure on which the environmental policy is built on aims of making clear that not only political declarations without any codification are made, but that the environment is a field of community activity to be taken seriously. Special attention is given the aim of economic growth and its incompatibles environmental policies. Convergence can only be reached if EC Member States use their potential of cooperation and are ready to make their contribution. A special chapter deals with the competence of member states concerning environmental policies. As contracting partners to GATT, member states of the European Union represent a very large portion of world trade, we have to make sure environmental policy is given the right place it deserves in free world trade. A summary and final reflections are included in the last part of the thesis. (author)

A European legal method? On European private law and scientific method

NARCIS (Netherlands)

Hesselink, M.

2009-01-01

This article examines the relationship between European private law and scientific method. It argues that a European legal method is a good idea. Not primarily because it will make European private law scholarship look more scientific, but because a debate on the method of a normative science

European legislation impedes critical care research and fails to protect patients' rights

DEFF Research Database (Denmark)

Berg, Ronan M G; Møller, Kirsten; Rossel, Peter Johannes Hancke

2011-01-01

in which a waiver of consent is deemed necessary, the Ethical Review Board should ensure that non-therapeutic risks are minimal, that the research is specifically designed to benefit critically ill patients, and that it cannot be conducted under circumstances where an informed consent can be obtained....... If the European Directive is changed accordingly, this permits clinical trials in critical care settings, while adequate protection from risky non-therapeutic procedures is ensured and exploitation of the patient as an easily accessible research subject is prevented....

Selective Europeanization

DEFF Research Database (Denmark)

Hoch Jovanovic, Tamara; Lynggaard, Kennet

2014-01-01

and rules. The article examines the reasons for both resistance and selectiveness to Europeanization of the Danish minority policy through a “path dependency” perspective accentuating decision makers’ reluctance to deviate from existing institutional commitments, even in subsequently significantly altered...... political contexts at the European level. We further show how the “translation” of international norms to a domestic context has worked to reinforce the original institutional setup, dating back to the mid-1950s. The translation of European-level minority policy developed in the 1990s and 2000s works most...

Mixed-meal tolerance test versus glucagon stimulation test for the assessment of beta-cell function in therapeutic trials in type 1 diabetes

DEFF Research Database (Denmark)

Greenbaum, Carla J; Mandrup-Poulsen, Thomas; McGee, Paula Friedenberg

2008-01-01

OBJECTIVE: Beta-cell function in type 1 diabetes clinical trials is commonly measured by C-peptide response to a secretagogue in either a mixed-meal tolerance test (MMTT) or a glucagon stimulation test (GST). The Type 1 Diabetes TrialNet Research Group and the European C-peptide Trial (ECPT) Study...... Group conducted parallel randomized studies to compare the sensitivity, reproducibility, and tolerability of these procedures. RESEARCH DESIGN AND METHODS: In randomized sequences, 148 TrialNet subjects completed 549 tests with up to 2 MMTT and 2 GST tests on separate days, and 118 ECPT subjects...

Deliberate introduction of the European rabbit, Oryctolagus cuniculus, into Australia.

Science.gov (United States)

Fenner, F

2010-04-01

The European rabbit was brought to Australia as a companion animal by early settlers. It sometimes escaped, but failed to survive in the Australian bush. In 1879 wild rabbits were deliberately sent to Victoria to provide game for wealthy settlers to shoot. They soon spread all over Australia, except in the tropics, and became Australia's major animal pest. After careful testing in Australian wildlife and in humans, control by myxoma virus was introduced at various sites between 1937 and 1950, spreading all over the Murray-Darling Basin in 1950. Within one year mutations in the virus had led to slightly less virulence, and these continued for the next 50 years. In the early 21st Century testing viruses obtained from wild rabbits showed that the majority of these viruses were more virulent than the virus used to initiate the epidemic. In 1995 another virus specific for European rabbits, rabbit haemorrhagic disease virus, escaped from areas in which field trials were being carried out and spread around Australia. It was more successful than myxomatosis for rabbit control in arid regions.

Factors Contributing to Exacerbating Vulnerabilities in Global Clinical Trials

Science.gov (United States)

da Silva, Ricardo E.; Amato, Angélica A.; Guilhem, Dirce B.; de Carvalho, Marta R.; Lima, Elisangela da C.; Novaes, Maria Rita C. G.

2018-01-01

Background: Although policies and guidelines make use of the concept of vulnerability, few define it. The European Union's directive for clinical trials does not include explanations for or the reasoning behind the designation of certain groups as vulnerable. Emerging economies from lower middle-income countries have, in recent years, had the largest average annual growth rate, as well as increase, in number of clinical trials registered in the US government's database. Nevertheless, careful supervision of research activities has to be ensured. Objective: To describe and analyze the features of the clinical trials involving vulnerable populations in various countries classified by development status and geographic region. Methods: Retrospective study that involved analysis of data obtained from the International Clinical Trials Registry Platform (ICTRP) database between 01/2014 and 12/2014 from countries with (i) highest trial densities during 2005 to 2012, (ii) highest average growth rate in clinical trials, and (iii) greatest trial capabilities. Results: Statistical analysis of this study showed that patients incapable of giving consent personally are 11.4 times more likely to be vulnerable patients than patients who are capable, and that patients in upper-middle-income countries are 1.7 times more likely to be vulnerable patients than patients from high-income countries when participating in global clinical trials. Malaysia (21%), Egypt (20%), Turkey (19%), Israel (18%), and Brazil (17%) had the highest percentages of vulnerable populations involving children. Conclusions: Although the inability to provide consent personally was a factor associated with vulnerability, arbitrary criteria may have been considered when classifying the populations of clinical trials as vulnerable. The EU Clinical Trials Register should provide guidance regarding exactly what aspects or factors should be taken into account to frame given populations as vulnerable, because

Economic evaluation of the randomized European Achalasia trial comparing pneumodilation with Laparoscopic Heller myotomy

NARCIS (Netherlands)

Moonen, A.; Busch, O.; Costantini, M.; Finotti, E.; Tack, J.; Salvador, R.; Boeckxstaens, G.; Zaninotto, G.

2017-01-01

BackgroundA recent multicenter randomized trial in achalasia patients has shown that pneumatic dilation resulted in equivalent relief of symptoms compared to laparoscopic Heller myotomy. Additionally, the cost of each treatment should be also taken in consideration. Therefore, the aim of the present

Lung volume reduction coil treatment for patients with severe emphysema : a European multicentre trial

NARCIS (Netherlands)

Deslee, Gaetan; Klooster, Karin; Hetzel, Martin; Stanzel, Franz; Kessler, Romain; Marquette, Charles-Hugo; Witt, Christian; Blaas, Stefan; Gesierich, Wolfgang; Herth, Felix J. F.; Hetzel, Juergen; van Rikxoort, Eva M.; Slebos, Dirk-Jan

2014-01-01

Background The lung volume reduction (LVR) coil is a minimally invasive bronchoscopic nitinol device designed to reduce hyperinflation and improve elastic recoil in severe emphysema. We investigated the feasibility, safety and efficacy of LVR coil treatment in a prospective multicentre cohort trial

European Registry of Carotid Artery Stenting: results from a prospective registry of eight high volume EUROPEAN institutions.

Science.gov (United States)

Stabile, Eugenio; Garg, Pallav; Cremonesi, Alberto; Bosiers, Marc; Reimers, Bernhard; Setacci, Carlo; Cao, Piergiorgio; Schmidt, Andrej; Sievert, Horst; Peeters, Patrick; Nikas, Dimitry; Werner, Martin; de Donato, Gianmarco; Parlani, Giambattista; Castriota, Fausto; Hornung, Marius; Mauri, Laura; Rubino, Paolo

2012-08-01

Carotid endarterectomy (CEA) is the standard revascularization therapy to prevent stroke in patients with carotid artery disease. Carotid artery stenting (CAS) could be considered a potential alternative in patients at high surgical risk. Recent clinical trials have challenged this concept due a relatively high incidence of post-CAS adverse events, which occurred in low volume centers. The aim of this study was to evaluate the outcomes associated with neuroprotected CAS in selected high volume centers. From January 2007 to December 2007, 1,611 patients underwent neuroprotected CAS in eight European Centers. For each patients, clinical, procedural, and one month follow-up data from all patients have been collected. An independent clinical events committee adjudicated the events. Overall in hospital death was 0.06% (one patient), whereas in-hospital stroke was 0.49% (eight patients). Between hospital discharge and 30 days three additional patients died (0.18%) and 10 patients experienced a stroke (0.67%). Overall 30 days mortality was 0.24% (four patients) and stroke incidence 1.12% (18 patients). The 30 day stroke/death rate was 1.36%. CAS is a reasonable alternative to CEA to treat carotid artery atherosclerosis in well-experienced high volume centers. These data suggest that future prospective trials comparing CAS and CEA outcomes should include only centers highly experienced in both treatment modalities. Copyright © 2012 Wiley Periodicals, Inc.

International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia: Guidelines for the management of hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) of the European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Asociación Latinoamericana del Tórax (ALAT).

Science.gov (United States)

Torres, Antoni; Niederman, Michael S; Chastre, Jean; Ewig, Santiago; Fernandez-Vandellos, Patricia; Hanberger, Hakan; Kollef, Marin; Li Bassi, Gianluigi; Luna, Carlos M; Martin-Loeches, Ignacio; Paiva, J Artur; Read, Robert C; Rigau, David; Timsit, Jean François; Welte, Tobias; Wunderink, Richard

2017-09-01

The most recent European guidelines and task force reports on hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) were published almost 10 years ago. Since then, further randomised clinical trials of HAP and VAP have been conducted and new information has become available. Studies of epidemiology, diagnosis, empiric treatment, response to treatment, new antibiotics or new forms of antibiotic administration and disease prevention have changed old paradigms. In addition, important differences between approaches in Europe and the USA have become apparent.The European Respiratory Society launched a project to develop new international guidelines for HAP and VAP. Other European societies, including the European Society of Intensive Care Medicine and the European Society of Clinical Microbiology and Infectious Diseases, were invited to participate and appointed their representatives. The Latin American Thoracic Association was also invited.A total of 15 experts and two methodologists made up the panel. Three experts from the USA were also invited (Michael S. Niederman, Marin Kollef and Richard Wunderink).Applying the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology, the panel selected seven PICO (population-intervention-comparison-outcome) questions that generated a series of recommendations for HAP/VAP diagnosis, treatment and prevention. Copyright ©ERS 2017.

Nebivolol Attenuates Neutrophil Lymphocyte Ratio: A Marker of Subclinical Inflammation in Hypertensive Patients

Directory of Open Access Journals (Sweden)

Mazhar Hussain

2017-01-01

Full Text Available Background. High value of neutrophil lymphocyte ratio (NLR is a strong independent predictor and biomarker of ongoing vascular inflammation in various cardiovascular disorders. Objective. The main focus of the study is to investigate the effect of nebivolol on NLR in mild to moderate hypertensive patients in comparison with metoprolol. In addition, BMI, blood pressure, TLC count, blood sugar, and lipid profile were also assayed before and after treatment. Materials and Methods. In this 12-week prospective double-blinded randomized study, 120 patients with mild to moderate hypertension were randomly divided into two groups to prescribed daily dose of tab nebivolol 5–10 mg and metoprolol 50–100 mg, respectively, for 12 weeks. The data were analyzed using SPSS 16 software. Results. A total of 100 patients completed the study. Both drugs lowered blood pressure significantly, nebivolol 20.5/10.5 and metoprolol 22.5/11.2 (p<0.001 from baseline. Regarding inflammation, nebivolol reduced total leukocyte count (p=0.005 and neutrophil count (p=0.003 and increased lymphocyte count (p=0.004 as compared to metoprolol. Similarly, nebivolol but not metoprolol significantly reduced NLR ratio (p=0.07. Nebivolol improved lipid profile and blood sugar compared to metoprolol, but values were nonsignificant. Conclusion. Nebivolol has a strong impact on reducing NLR, a marker of subclinical inflammation in hypertensive patients. Moreover NLR can be used as a disease and drug monitoring tool in these patients.

Are we Europeans?: Correlates and the relation between national and European identity

Directory of Open Access Journals (Sweden)

Mihić Vladimir

2009-01-01

Full Text Available Researches of the correlates of the national identity are plentiful both in Serbian and foreign literature. However, in the past decade or so, a new social identity starts to make its way into the researches of the social psychologists-European identity or the sense of belonging to the Europe and the Europeans. This paper deals with the relation between national and European identity, as well as with the correlates of both of these, or one of them. The sample consisted of 451 subjects, all residents of major cities in the Vojvodina region (northern Serbia, divided into several categories-ethnicity (Serbs and Hungarians, educational level (primary and secondary school or University degree, gender and age. Several scales have been used: Cinnirela's national and European identity scale, Collective self-esteem scale, scale measuring attitudes towards the European integration-STEIN and Social dominance orientation scale-SDO. The questionnaire with the demographic characteristics has also been the part of the instrument. The research has been conducted in 2005 and 2006 in the all of the major Vojvodinian cities. Results show the relation between national and European identity is foggy, but general conclusion is that we can observe them as independent identities. The correlates of the national identity were ethnicity, high social dominance orientation, high collective self-esteem and negative attitude towards the European integrations. Correlates of the European identity were fewer: ethnicity, positive attitude towards the European integration and low social dominance orientation.

Crizotinib in patients with advanced, inoperable inflammatory myofibroblastic tumours with and without anaplastic lymphoma kinase gene alterations (European Organisation for Research and Treatment of Cancer 90101 CREATE): a multicentre, single-drug, prospective, non-randomised phase 2 trial.

Science.gov (United States)

Schöffski, Patrick; Sufliarsky, Jozef; Gelderblom, Hans; Blay, Jean-Yves; Strauss, Sandra J; Stacchiotti, Silvia; Rutkowski, Piotr; Lindner, Lars H; Leahy, Michael G; Italiano, Antoine; Isambert, Nicolas; Debiec-Rychter, Maria; Sciot, Raf; Van Cann, Thomas; Marréaud, Sandrine; Nzokirantevye, Axelle; Collette, Sandra; Wozniak, Agnieszka

2018-06-01

An inflammatory myofibroblastic tumour (IMFT) is a rare mesenchymal neoplasm characterised by anaplastic lymphoma kinase (ALK) gene rearrangements. We assessed the activity and safety of crizotinib, a tyrosine kinase inhibitor, targeting ALK in patients with advanced IMFT either with or without ALK alterations. We did a multicentre, biomarker-driven, single-drug, non-randomised, open-label, two-stage phase 2 trial (European Organisation for Research and Treatment of Cancer 90101 CREATE) at 13 study sites (five university hospitals and eight specialty clinics) in eight European countries (Belgium, France, Germany, Italy, Netherlands, Poland, Slovakia, and the UK). Eligible participants were patients aged at least 15 years with a local diagnosis of advanced or metastatic IMFT deemed incurable with surgery, radiotherapy, or systemic therapy; measurable disease; an Eastern Cooperative Oncology Group performance status of 0-2; and adequate haematological, renal, and liver function. Central reference pathology was done for confirmation of the diagnosis, and ALK positivity or negativity was assessed centrally using immunohistochemistry and fluorescence in-situ hybridisation based on archival tumour tissue and defined as ALK immunopositivity or rearrangements in at least 15% of tumour cells. Eligible ALK-positive and ALK-negative patients received oral crizotinib 250 mg twice per day administered on a continuous daily dosing schedule (the duration of each treatment cycle was 21 days) until documented disease progression, unacceptable toxicity, or patient refusal. If at least two of the first 12 eligible and assessable ALK-positive patients achieved a confirmed complete or partial response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, a maximum of 35 patients were to be enrolled. If at least six ALK-positive patients achieved a confirmed response, the trial would be deemed successful. The primary endpoint was the proportion of patients who achieved

Selectivity of beta-adrenergic stimulating and blocking agents.

Science.gov (United States)

Löfdahl, C G; Svedmyr, N

1984-01-01

Studies have been performed to answer two questions: whether there are subgroups of beta 2-receptors separating effects in bronchial and skeletal muscle and whether beta 1-receptors in asthmatic airways mediate bronchoconstriction. Asthmatic patients have been studied in randomised cross-over trials. Effects on FEV1, heart rate and skeletal muscle tremor have been monitored. In some experimental studies, two new compounds, D2343 and QH-25, have shown a selectivity for beta 2-receptors in bronchial muscle compared to skeletal muscle. Studies in asthmatics did not confirm this. Thus, the beta 2-receptors in the two organs appear to be identical. The clinical effect of beta 1-receptors in the the airways was studied by giving selective beta 1-receptor blocking agents. It was shown that pafenolol , a beta-blocker more beta 1-selective than metoprolol, had less effect on FEV1 than metoprolol given in equipotent beta 1-blocking doses. Beta 1-receptor stimulation with a new selective beta 1-stimulating agent, prenalterol, did not give bronchodilation in doses which gave a significant increase of heart rate. Thus, beta 1-receptors do not contribute to bronchodilation in asthmatic patients.

Vision related quality of life in patients with type 2 diabetes in the EUROCONDOR trial

DEFF Research Database (Denmark)

Trento, Marina; Durando, Olga; Lavecchia, Sonia

2017-01-01

To evaluate vision related quality of life in the patients enrolled in The European Consortium for the Early Treatment of Diabetic Retinopathy, a clinical trial on prevention of diabetic retinopathy. Four-hundred-forty-nine patients, 153 women, with type 2 Diabetes and no or mild diabetic retinop...... acuity. The National Eye Institute Visual Functioning Questionnaire could detect subtle changes in patients' perception of visual function, despite absent/minimal diabetic retinopathy.......To evaluate vision related quality of life in the patients enrolled in The European Consortium for the Early Treatment of Diabetic Retinopathy, a clinical trial on prevention of diabetic retinopathy. Four-hundred-forty-nine patients, 153 women, with type 2 Diabetes and no or mild diabetic....... Diabetic retinopathy was absent in 193 (43.0 %) and mild in 256 (57.0 %). Patients without diabetic retinopathy were older, had shorter diabetes duration and used less insulin and glucose-lowering agents but did not differ by gender, best corrected visual acuity or any subscale, except vision specific...

Differential Globalization of Industry- and Non-Industry-Sponsored Clinical Trials.

Science.gov (United States)

Atal, Ignacio; Trinquart, Ludovic; Porcher, Raphaël; Ravaud, Philippe

2015-01-01

Mapping the international landscape of clinical trials may inform global health research governance, but no large-scale data are available. Industry or non-industry sponsorship may have a major influence in this mapping. We aimed to map the global landscape of industry- and non-industry-sponsored clinical trials and its evolution over time. We analyzed clinical trials initiated between 2006 and 2013 and registered in the WHO International Clinical Trials Registry Platform (ICTRP). We mapped single-country and international trials by World Bank's income groups and by sponsorship (industry- vs. non- industry), including its evolution over time from 2006 to 2012. We identified clusters of countries that collaborated significantly more than expected in industry- and non-industry-sponsored international trials. 119,679 clinical trials conducted in 177 countries were analysed. The median number of trials per million inhabitants in high-income countries was 100 times that in low-income countries (116.0 vs. 1.1). Industry sponsors were involved in three times more trials per million inhabitants than non-industry sponsors in high-income countries (75.0 vs. 24.5) and in ten times fewer trials in low- income countries (0.08 vs. 1.08). Among industry- and non-industry-sponsored trials, 30.3% and 3.2% were international, respectively. In the industry-sponsored network of collaboration, Eastern European and South American countries collaborated more than expected; in the non-industry-sponsored network, collaboration among Scandinavian countries was overrepresented. Industry-sponsored international trials became more inter-continental with time between 2006 and 2012 (from 54.8% to 67.3%) as compared with non-industry-sponsored trials (from 42.4% to 37.2%). Based on trials registered in the WHO ICTRP we documented a substantial gap between the globalization of industry- and non-industry-sponsored clinical research. Only 3% of academic trials but 30% of industry trials are

Differential Globalization of Industry- and Non-Industry–Sponsored Clinical Trials

Science.gov (United States)

Atal, Ignacio; Trinquart, Ludovic; Porcher, Raphaël; Ravaud, Philippe

2015-01-01

Background Mapping the international landscape of clinical trials may inform global health research governance, but no large-scale data are available. Industry or non-industry sponsorship may have a major influence in this mapping. We aimed to map the global landscape of industry- and non-industry–sponsored clinical trials and its evolution over time. Methods We analyzed clinical trials initiated between 2006 and 2013 and registered in the WHO International Clinical Trials Registry Platform (ICTRP). We mapped single-country and international trials by World Bank's income groups and by sponsorship (industry- vs. non- industry), including its evolution over time from 2006 to 2012. We identified clusters of countries that collaborated significantly more than expected in industry- and non-industry–sponsored international trials. Results 119,679 clinical trials conducted in 177 countries were analysed. The median number of trials per million inhabitants in high-income countries was 100 times that in low-income countries (116.0 vs. 1.1). Industry sponsors were involved in three times more trials per million inhabitants than non-industry sponsors in high-income countries (75.0 vs. 24.5) and in ten times fewer trials in low- income countries (0.08 vs. 1.08). Among industry- and non-industry–sponsored trials, 30.3% and 3.2% were international, respectively. In the industry-sponsored network of collaboration, Eastern European and South American countries collaborated more than expected; in the non-industry–sponsored network, collaboration among Scandinavian countries was overrepresented. Industry-sponsored international trials became more inter-continental with time between 2006 and 2012 (from 54.8% to 67.3%) as compared with non-industry–sponsored trials (from 42.4% to 37.2%). Conclusions Based on trials registered in the WHO ICTRP we documented a substantial gap between the globalization of industry- and non-industry–sponsored clinical research. Only 3% of

Effect of beta blockers (metoprolol or propranolol) on effect of simvastatin in lowering C-reactive protein in acute myocardial infarction.

Science.gov (United States)

Quinaglia e Silva, Jose C; Munhoz, Daniel B; Morato, Tiago N; Gurgel, Augusto; Macedo, Antonio C T; Sever, Peter; Sposito, Andrei C

2009-02-15

Recent data indicated that statin therapy may fail to reduce the incidence of coronary events in patients concomitantly using beta blockers. The aim of the present study was to examine whether the concomitant use of beta blockers would modify the anti-inflammatory action of statins. Changes in C-reactive protein (CRP) between days 1 and 5 after myocardial infarction were evaluated in 189 patients treated with simvastatin alone (S), beta blockers alone (B; propranolol or metoprolol), S + B, or neither of these 2 medications (N) in a prospective observational cohort. At baseline, median CRP was lower in the S group (0.40 mg/dl, interquartile range 0.1 to 0.6) than the other groups (B: 0.6 mg/dl, interquartile range 0.4 to 1.6; S + B: 0.5 mg/dl, interquartile range 0.3 to 1.2; and N: 0.6 mg/dl, interquartile range 0.2 to 1.5). By day 5, median CRP was 1.3 mg/dl (interquartile range 0.7 to 2.6), 4.3 (interquartile range 1.6 to 8.8), 4.6 (interquartile range 2.8 to 9.5), and 4.4 (interquartile range 1.9 to 9.9) for the S, B, S + B, and N groups, respectively. After adjusting for log(e) baseline CRP, the difference in log(e) CRP between days 1 and 5 was significantly lower in the S group compared with the B (-0.74 +/- 0.23 [SE], p = 0.001) or S + B group (-0.99 +/- 0.20 [SE], p <0.0001). The significance remained after adjustment for age, gender, and baseline CRP. There was no significant difference in change in CRP between the SB and B groups. In conclusion, the present study confirmed the anti-inflammatory action of statins and showed that concomitant use of beta blockers may significantly attenuate this effect.

Trans-European transport networks and urban systems in European Union

OpenAIRE

Maksin-Mićić Marija

2003-01-01

The trans-European transport network has different effects at interregional macro-regional and mezzo-regional level, and its effectiveness rises at the lower regional levels. Possible approaches to the trans-European transport network impact and effect survey and policy options have been pointed out. In that respect the brief review of survies, strategic framework and policies in European Union has been given. The importance of increased accessibility and mobility for regional expansion and f...

The Europeanization of Welfare - The Domestic Impact of Intra-European Social Security

DEFF Research Database (Denmark)

Martinsen, Dorte Sindbjerg

2005-01-01

Studies of Europeanization have demonstrated that the impact of European integration differs between Member States and across policies. Although Europeanization research has been expanded and clarified in recent years, we still know relatively little about the factors mediating the national...... responses to integration. It is argued that these intervening variables are decisive for how common European demands are mediated nationally and are likely to explain impact variations referring to the same cause....

Predicted effect size of lisdexamfetamine treatment of attention deficit/hyperactivity disorder (ADHD) in European adults: Estimates based on indirect analysis using a systematic review and meta-regression analysis.

Science.gov (United States)

Fridman, M; Hodgkins, P S; Kahle, J S; Erder, M H

2015-06-01

There are few approved therapies for adults with attention-deficit/hyperactivity disorder (ADHD) in Europe. Lisdexamfetamine (LDX) is an effective treatment for ADHD; however, no clinical trials examining the efficacy of LDX specifically in European adults have been conducted. Therefore, to estimate the efficacy of LDX in European adults we performed a meta-regression of existing clinical data. A systematic review identified US- and Europe-based randomized efficacy trials of LDX, atomoxetine (ATX), or osmotic-release oral system methylphenidate (OROS-MPH) in children/adolescents and adults. A meta-regression model was then fitted to the published/calculated effect sizes (Cohen's d) using medication, geographical location, and age group as predictors. The LDX effect size in European adults was extrapolated from the fitted model. Sensitivity analyses performed included using adult-only studies and adding studies with placebo designs other than a standard pill-placebo design. Twenty-two of 2832 identified articles met inclusion criteria. The model-estimated effect size of LDX for European adults was 1.070 (95% confidence interval: 0.738, 1.401), larger than the 0.8 threshold for large effect sizes. The overall model fit was adequate (80%) and stable in the sensitivity analyses. This model predicts that LDX may have a large treatment effect size in European adults with ADHD. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

The european hematology association roadmap for european hematology research : A consensus document

NARCIS (Netherlands)

A. Engert (Andreas); C.L. Balduini (Carlo); A. Brand (Anneke); B. Coiffier (Bertrand); C. Cordonnier (Charlotte); H. Döhner (Hartmut); De Wit, T.D. (Thom Duyvené); Eichinger, S. (Sabine); W.E. Fibbe (Willem); Green, T. (Tony); De Haas, F. (Fleur); A. Iolascon (Achille); T. Jaffredo (Thierry); F. Rodeghiero (Francesco); G. Salles (Gilles); J.J. Schuringa (Jan Jacob)

2016-01-01

textabstractThe European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European

The European Hematology Association Roadmap for European Hematology Research : A consensus document

NARCIS (Netherlands)

Engert, Andreas; Balduini, Carlo; Brand, Anneke; Coiffier, Bertrand; Cordonnier, Catherine; Döhner, Hartmut; de Wit, Thom Duyvené; Eichinger, Sabine; Fibbe, Willem; Green, Tony; de Haas, Fleur; Iolascon, Achille; Jaffredo, Thierry; Rodeghiero, Francesco; Salles, Gilles; Schuringa, Jan Jacob

The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology

The European standard series in 9 European countries, 2002/2003 - First results of the European Surveillance System on Contact Allergies

NARCIS (Netherlands)

Uter, W; Hegewald, J; Aberer, W; Ayala, F; Bircher, AJ; Brasch, J; Coenraads, PJ; Schuttelaar, Marielouise; Elsner, P; Fartasch, M; Mahler, V.; Fortina, AB; Frosch, PJ; Fuchs, T; Johansen, JD; Menne, T; Jolanki, R; Krecisz, B; Kiec-Swierczynska, M; Larese, F; Orton, D; Peserico, A; Rantanen, T; Schnuch, A

Since January 2001, the European Surveillance System on Contact Allergies (ESSCA), supported by European Union funding (contract QLK4-CT-2001-00343), has started to collect patch-test data. This comprises a standardized clinical history and the patch-test results using the European standard series,

Importance of weight loss maintenance and risk prediction in the prevention of type 2 Diabetes: analysis of European Diabetes Prevention Study RCT

NARCIS (Netherlands)

Penn, L.; White, M.; Lindström, J.; Boer, den A.Th.; Blaak, E.E.; Eriksson, J.G.; Feskens, E.J.M.; Ilanne-Parikka, P.; Keinanen-Kiukaanniemi, S.M.; Walker, M.; Mathers, J.C.; Uusitupa, M.; Tuomilehto, J.

2013-01-01

Background Prevalence of type 2 diabetes (T2D) is increasing worldwide. T2D prevention by lifestyle intervention is effective. Pragmatic scalable interventions are needed, with evidence to efficiently target and monitor such interventions. We report pooled analyses of data from three European trial

The influence of mitigation evidence, ethnicity, and SES on death penalty decisions by European American and Latino venire persons.

Science.gov (United States)

Espinoza, Russ K E; Willis-Esqueda, Cynthia

2015-04-01

The purpose of the research was to determine whether European American and Latino mock jurors would demonstrate bias in death penalty decision making when mitigation evidence and defendant ethnicity and socioeconomic status (SES) were varied. A total of 561 actual venire persons acted as mock jurors and read a trial transcript that varied a defendant's case information (mitigating circumstances: strong/weak, defendant ethnicity: European American/Latino, and defendant SES: low/high). European American jurors recommended the death penalty significantly more often for the low SES Latino defendant when strength of mitigation evidence was weak. In addition, they also assigned this defendant higher culpability ratings and lower ratings on positive personality trait measures compared with all other conditions. Strong mitigation evidence contributed to lower guilt ratings by European American jurors for the high SES European American defendant. Latino jurors did not differ in their death penalty sentencing across defendant mitigation, ethnicity, or SES conditions. Discussion of in-group favoritism and out-group derogation, as well as suggestions for procedures to diminish juror bias in death penalty cases, is provided. (c) 2015 APA, all rights reserved).

Flowering time control in European winter wheat

Directory of Open Access Journals (Sweden)

Simon Martin Langer

2014-10-01

Full Text Available Flowering time is an important trait in wheat breeding as it affects adaptation and yield potential. The aim of this study was to investigate the genetic architecture of flowering time in European winter bread wheat cultivars. To this end a population of 410 winter wheat varieties was evaluated in multi-location field trials and genotyped by a genotyping-by-sequencing approach and candidate gene markers. Our analyses revealed that the photoperiod regulator Ppd-D1 is the major factor affecting flowering time in this germplasm set, explaining 58% of the genotypic variance. Copy number variation at the Ppd-B1 locus was present but explains only 3.2% and thus a comparably small proportion of genotypic variance. By contrast, the plant height loci Rht-B1 and Rht-D1 had no effect on flowering time. The genome-wide scan identified six QTL which each explain only a small proportion of genotypic variance and in addition we identified a number of epistatic QTL, also with small effects. Taken together, our results show that flowering time in European winter bread wheat cultivars is mainly controlled by Ppd-D1 while the fine tuning to local climatic conditions is achieved through Ppd-B1 copy number variation and a larger number of QTL with small effects.

A Comparative Effectiveness Meta-Analysis of Drugs for the Prophylaxis of Migraine Headache.

Directory of Open Access Journals (Sweden)

Jeffrey L Jackson

Full Text Available To compare the effectiveness and side effects of migraine prophylactic medications.We performed a network meta-analysis. Data were extracted independently in duplicate and quality was assessed using both the JADAD and Cochrane Risk of Bias instruments. Data were pooled and network meta-analysis performed using random effects models.PUBMED, EMBASE, Cochrane Trial Registry, bibliography of retrieved articles through 18 May 2014.We included randomized controlled trials of adults with migraine headaches of at least 4 weeks in duration.Placebo controlled trials included alpha blockers (n = 9, angiotensin converting enzyme inhibitors (n = 3, angiotensin receptor blockers (n = 3, anticonvulsants (n = 32, beta-blockers (n = 39, calcium channel blockers (n = 12, flunarizine (n = 7, serotonin reuptake inhibitors (n = 6, serotonin norepinephrine reuptake inhibitors (n = 1 serotonin agonists (n = 9 and tricyclic antidepressants (n = 11. In addition there were 53 trials comparing different drugs. Drugs with at least 3 trials that were more effective than placebo for episodic migraines included amitriptyline (SMD: -1.2, 95% CI: -1.7 to -0.82, -flunarizine (-1.1 headaches/month (ha/month, 95% CI: -1.6 to -0.67, fluoxetine (SMD: -0.57, 95% CI: -0.97 to -0.17, metoprolol (-0.94 ha/month, 95% CI: -1.4 to -0.46, pizotifen (-0.43 ha/month, 95% CI: -0.6 to -0.21, propranolol (-1.3 ha/month, 95% CI: -2.0 to -0.62, topiramate (-1.1 ha/month, 95% CI: -1.9 to -0.73 and valproate (-1.5 ha/month, 95% CI: -2.1 to -0.8. Several effective drugs with less than 3 trials included: 3 ace inhibitors (enalapril, lisinopril, captopril, two angiotensin receptor blockers (candesartan, telmisartan, two anticonvulsants (lamotrigine, levetiracetam, and several beta-blockers (atenolol, bisoprolol, timolol. Network meta-analysis found amitriptyline to be better than several other medications including candesartan, fluoxetine, propranolol, topiramate and valproate and no different than

A Comparative Effectiveness Meta-Analysis of Drugs for the Prophylaxis of Migraine Headache

Science.gov (United States)

2015-01-01

Objective To compare the effectiveness and side effects of migraine prophylactic medications. Design We performed a network meta-analysis. Data were extracted independently in duplicate and quality was assessed using both the JADAD and Cochrane Risk of Bias instruments. Data were pooled and network meta-analysis performed using random effects models. Data Sources PUBMED, EMBASE, Cochrane Trial Registry, bibliography of retrieved articles through 18 May 2014. Eligibility Criteria for Selecting Studies We included randomized controlled trials of adults with migraine headaches of at least 4 weeks in duration. Results Placebo controlled trials included alpha blockers (n = 9), angiotensin converting enzyme inhibitors (n = 3), angiotensin receptor blockers (n = 3), anticonvulsants (n = 32), beta-blockers (n = 39), calcium channel blockers (n = 12), flunarizine (n = 7), serotonin reuptake inhibitors (n = 6), serotonin norepinephrine reuptake inhibitors (n = 1) serotonin agonists (n = 9) and tricyclic antidepressants (n = 11). In addition there were 53 trials comparing different drugs. Drugs with at least 3 trials that were more effective than placebo for episodic migraines included amitriptyline (SMD: -1.2, 95% CI: -1.7 to -0.82), -flunarizine (-1.1 headaches/month (ha/month), 95% CI: -1.6 to -0.67), fluoxetine (SMD: -0.57, 95% CI: -0.97 to -0.17), metoprolol (-0.94 ha/month, 95% CI: -1.4 to -0.46), pizotifen (-0.43 ha/month, 95% CI: -0.6 to -0.21), propranolol (-1.3 ha/month, 95% CI: -2.0 to -0.62), topiramate (-1.1 ha/month, 95% CI: -1.9 to -0.73) and valproate (-1.5 ha/month, 95% CI: -2.1 to -0.8). Several effective drugs with less than 3 trials included: 3 ace inhibitors (enalapril, lisinopril, captopril), two angiotensin receptor blockers (candesartan, telmisartan), two anticonvulsants (lamotrigine, levetiracetam), and several beta-blockers (atenolol, bisoprolol, timolol). Network meta-analysis found amitriptyline to be better than several other medications including

European Whiteness?

DEFF Research Database (Denmark)

Blaagaard, Bolette

2008-01-01

Born out of the United States’ (U.S.) history of slavery and segregation and intertwined with gender studies and feminism, the field of critical whiteness studies does not fit easily into a European setting and the particular historical context that entails. In order for a field of European...

Report of the European Society of Cardiology Cardiovascular Round Table regulatory workshop update of the evaluation of new agents for the treatment of acute coronary syndrome

DEFF Research Database (Denmark)

Bueno, Héctor; de Graeff, Pieter; Richard-Lordereau, Isabelle

2016-01-01

syndrome (ACS) to achieve consistency with current knowledge in the field. This manuscript summarizes the key output from a collaborative workshop, organized by the Cardiovascular Round Table and the European Affairs Committee of the European Society of Cardiology, involving clinicians, academic...... researchers, trialists, European and US regulators, and pharmaceutical industry researchers. Specific questions in four key areas were selected as priorities for changes in regulatory guidance: patient selection, endpoints, methodologic issues and issues related to the research for novel agents. Patients......Regulatory authorities interpret the results of randomized controlled trials according to published principles. The European Medicines Agency (EMA) is planning a revision of the 2000 and 2003 guidance documents on clinical investigation of new medicinal products for the treatment of acute coronary...

[European Union regulatory and quality requirements for botanical drugs and their implications for Chinese herbal medicinal products development].

Science.gov (United States)

Zhu, You-Ping

2017-06-01

This paper introduces regulatory pathways and characteristic quality requirements for marketing authorization of herbal medicinal products in the European Union（EU）, and the legal status and applications of "European Union list of herbal substances, preparations and combinations" and "European Union herbal monographs". Also introduced are Chinese herbs that have been granted the EU list entry, those with EU herbal monographs, and registered EU traditional herbal medicinal products with Chinese herbs as active ingredients. Special attention is paid to the technical details of three authorized EU herbal medicinal products (Veregen, Sativex and Episalvan) in comparison with Andrographis paniculata extract HMPL-004 that failed the phase Ⅲ clinical trial for ulcerative colitis. The paper further emphasizes the importance of enriching active fractions of herbal extracts and taking regulatory and quality considerations into account in early stage of botanical drug development. Copyright© by the Chinese Pharmaceutical Association.

Political dimension of European constitutionalism

Directory of Open Access Journals (Sweden)

Kaplánová Patricia

2015-04-01

Full Text Available Author in the article tries to analyse different elements of document called European Constitution. Analysis is supported with theoretical framework of federalism, presented by Brezovšek. Authors is playing with idea of (confederal and international organization elements of European Constitution and their mix. They are also trying to set some connections between so called common European identity as necessary condition to give legitimacy to the European Constitution. This became important question after „votes of non-confidence“ to the European Constitution in France, despite it should be addressed already before. However, European Constitution is important document on the path of European integration and lack of support to it will slow down this process of widening and deepening European ties.

Can the European Central Bank Create a European identity?

DEFF Research Database (Denmark)

Ravn Sørensen, Anders

2014-01-01

In what ways do central banks construct community, and how may the European Central Bank (ECB) contribute to a supranational European identity? In this paper I seek to answer these two questions by developing a conceptual framework for the ways that central banks construct national identities and...

European citizenship and the constitutionalisation of the European Union

NARCIS (Netherlands)

van Eijken, Hanneke|info:eu-repo/dai/nl/314133992

2014-01-01

The concept of citizenship in relatively new legal order of the European Union has its own meaning and dynamics compared to national citizenship. One of the important questions regarding this transnational form of citizenship is how to place this European citizenship in a constitutional context in

The european passive plant (EPP) design: compliance with the european utilities requirements (EUR)

International Nuclear Information System (INIS)

Noviello, L.; Oyarzabal, M.

1996-01-01

Back 1986, most of the European firms have participated to the American program called the Advanced Light Water Reactors (ALWR) including the development of the Utilities Requirements as well as four projects as for instance AP600. Later, in the year 1990, seven European firms have begun to develop the European Utilities Requirements. This development is justified by the fact that the lessons learned by the nuclear power plants designs programs of the years 1980 can be incorporated and the European specific conditions can be taken into consideration. Thus, in 1994, eight European firms - Westinghouse and their industrial partners - have decided to launch a multiphase program in order to check the AP600 compliance with the European Utilities Requirements (EUR) and to develop the required alterations. Today, the phase I of the EPP (European Passive Plant) program has been completed. In this phase, the main important objectives have been reached. (O.M.)

Executive summary of the joint position paper on renal denervation of the Cardiovascular and Interventional Radiological Society of Europe and the European Society of Hypertension.

Science.gov (United States)

Moss, Jonathan G; Belli, Anna-Maria; Coca, Antonio; Lee, Michael; Mancia, Giuseppe; Peregrin, Jan H; Redon, Josep; Reekers, Jim A; Tsioufis, Costas; Vorwerk, Dierk; Schmieder, Roland E

2016-12-01

Renal denervation (RDN) was reported as a novel exciting treatment for resistant hypertension in 2009. An initial randomized trial supported its efficacy and the technique gained rapid acceptance across the globe. However, a subsequent large blinded, sham arm randomized trial conducted in the USA (to gain Food and Drug Administration approval) failed to achieve its primary efficacy end point in reducing office blood pressure at 6 months. Published in 2014 this trial received both widespread praise and criticism. RDN has effectively stopped out with clinical trials pending further evidence. This joint consensus document representing the European Society of Hypertension and the Cardiovascular and Radiological Society of Europe attempts to distill the current evidence and provide future direction and guidance.

European Institutions?

NARCIS (Netherlands)

Meacham, Darian

2016-01-01

The aim of this article is to sketch a phenomenological theory of political institutions and to apply it to some objections and questions raised by Pierre Manent about the project of the European Union and more specifically the question of “European Construction”, i.e. what is the aim of the

European Identity and European Citizenship: the Case of Missing Polis?

Czech Academy of Sciences Publication Activity Database

Šejvl, Michal

2008-01-01

Roč. 2, č. 2 (2008), s. 49-56 ISSN 1789-1035 Institutional research plan: CEZ:AV0Z70680506 Keywords : the European integration * law of citizenship * European identity Subject RIV: AG - Legal Sciences

Multi-center study on the characteristics and treatment strategies of patients with Graves' orbitopathy: the first European Group on Graves' Orbitopathy experience

NARCIS (Netherlands)

Prummel, Mark F.; Bakker, Annemieke; Wiersinga, Wilmar M.; Baldeschi, Lelio; Mourits, Maarten P.; Kendall-Taylor, Pat; Perros, Petros; Neoh, Chris; Dickinson, A. Jane; Lazarus, John H.; Lane, Carol M.; Heufelder, Armin E.; Kahaly, George J.; Pitz, Suzanne; Orgiazzi, Jacques; Hullo, Alain; Pinchera, Aldo; Marcocci, Claudio; Sartini, Maria S.; Rocchi, Roberto; Nardi, Marco; Krassas, Gerry E.; Halkias, A.

2003-01-01

To improve management of patients with Graves' orbitopathy, a multi-center collaborative approach is necessary in order to have large enough sample sizes for meaningful randomized clinical trials. This is hampered by a lack of consensus on how to investigate the eye condition. The European Group on

Reassessing guidelines for heart failure

Directory of Open Access Journals (Sweden)

Helmut Drexler

2004-03-01

Full Text Available Significant progress has been made in the last few years in the management of heart failure. In particular several trials have given significant results. It has become apparent that heart failure may be prevented in some patients by treatment of risk factors such as coronary artery disease. Experience with angiotensin-converting enzyme (ACE inhibitors has shown that the survival and symptomatic benefits do last in the long term, and confirm that they are the first-line treatment in heart failure. The results of a number of trials using the angiotensin receptor blockers (ARBs candesartan, valsartan and losartan are presented and discussed. There is also some experience now in the use of candesartan for patients with heart failure and preserved left ventricular systolic function. The COMET trial compared the β-blockers carvedilol and metoprolol tartrate, and suggests that there may be differences in clinical effect between β-blockers. The selective aldosterone receptor blocker eplerenone was evaluated in the EPHESUS trial in post-MI patients with signs of heart failure. Based on these clinical trials, heart failure guidelines are now being updated.

The European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP)--a sentinel approach in the European Union (EU)/European Economic Area (EEA).

Science.gov (United States)

Spiteri, Gianfranco; Cole, Michelle; Unemo, Magnus; Hoffmann, Steen; Ison, Catherine; van de Laar, Marita

2013-12-01

Antimicrobial resistance in Neisseria gonorrhoeae is monitored in the European Union/European Economic Area through the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) coordinated by the European Centre for Disease Prevention and Control. Euro-GASP includes a sentinel surveillance programme which aims to detect in a timely manner changes in resistance patterns and inform treatment guidelines. The programme aims to test a representative number of isolates from each European Union/European Economic Area member state per year for a range of therapeutically relevant antimicrobials through a biannual hybrid centralised/decentralised system. Testing is supported by an External Quality Assurance programme and a laboratory training programme. Participation in the programme has increased to 21 countries in 2012. Euro-GASP has been able to detect the rapid spread of isolates with decreased susceptibility to cefixime across Europe in 2010 and 2011. Results from the programme have informed changes in European treatment guidelines for gonorrhoea and led to the development of the 'Response plan to control and manage the threat of multidrug resistant gonorrhoea in Europe'. Future challenges for Euro-GASP include supporting countries to participate in Euro-GASP through decentralised testing, improving timeliness and epidemiological data quality, and increasing participation from Eastern Europe.

A pilot test of the new Swiss regulatory procedure for categorizing clinical trials by risk: A randomized controlled trial.

Science.gov (United States)

Cevallos, Myriam; Züllig, Stephanie; Christen, Andri; Meier, Brigitte E; Goetz, Martin; Coslovsky, Michael; Trelle, Sven

2015-12-01

Several countries are working to adapt clinical trial regulations to align the approval process to the level of risk for trial participants. The optimal framework to categorize clinical trials according to risk remains unclear, however. Switzerland is the first European country to adopt a risk-based categorization procedure in January 2014. We assessed how accurately and consistently clinical trials are categorized using two different approaches: an approach using criteria set forth in the new law (concept) or an intuitive approach (ad hoc). This was a randomized controlled trial with a method-comparison study nested in each arm. We used clinical trial protocols from eight Swiss ethics committees approved between 2010 and 2011. Protocols were randomly assigned to be categorized in one of three risk categories using the concept or the ad hoc approach. Each protocol was independently categorized by the trial's sponsor, a group of experts and the approving ethics committee. The primary outcome was the difference in categorization agreement between the expert group and sponsors across arms. Linear weighted kappa was used to quantify agreements, with the difference between kappas being the primary effect measure. We included 142 of 231 protocols in the final analysis (concept=78; ad hoc=64). Raw agreement between the expert group and sponsors was 0.74 in the concept and 0.78 in the ad hoc arm. Chance-corrected agreement was higher in the ad hoc (kappa: 0.34 (95% confidence interval=0.10-0.58)) than in the concept arm (0.27 (0.06-0.50)), but the difference was not significant (p=0.67). The main limitation was the large number of protocols excluded from the analysis mostly because they did not fit with the clinical trial definition of the new law. A structured risk categorization approach was not better than an ad hoc approach. Laws introducing risk-based approaches should provide guidelines, examples and templates to ensure correct application. © The Author(s) 2015.

A European Research Area

International Nuclear Information System (INIS)

Caro, R.

2001-01-01

This article is a summary of the presentation of the European Commissioner, Philippe Busquen, to the European Parliament (beginning of year 2000) with the proposal and method for a revival of the Research and Development in this wider sense in the European Union. The starting point of his thesis is that Europe performs less, and more disorderly, activities in this field that her main competitors. USA and Japan. His basic proposal is a larger coordination among the european research projects, with a previous phase of informatics intoxicator among the european research centres and the cross-linked participation, real of virtual in the experiments and projects. (Author)

Ki-67 as a prognostic marker in mantle cell lymphoma-consensus guidelines of the pathology panel of the European MCL Network

DEFF Research Database (Denmark)

Klapper, W.; Hoster, E.; Determann, O.

2009-01-01

powerful prognostic biomarker. The pathology panel of the European MCL Network evaluated methods to assess the Ki-67 index including stringent counting, digital image analysis, and estimation by eyeballing. Counting of 2 x 500 lymphoma cells is the gold standard to assess the Ki-67 index since this value...... has been shown to predict survival in prospective randomized trials of the European MCL Network. Estimation by eyeballing and digital image analysis showed a poor concordance with the gold standard (concordance correlation coefficients [CCC] between 0.29 and 0.61 for eyeballing and CCC of 0.24 and 0...

The European Location Framework - from National to European

Science.gov (United States)

Pauknerova, E.; Sidlichovsky, P.; Urbanas, S.; Med, M.

2016-06-01

The European Location Framework (ELF) means a technical infrastructure which will deliver authoritative, interoperable geospatial reference data from all over Europe for analysing and understanding information connected to places and features. The ELF has been developed and set up through the ELF Project, which has been realized by a consortium of partners (public, private and academic organisations) since March 2013. Their number increased from thirty to forty in the year 2016, together with a project extension from 36 to 44 months. The project is co-funded by the European Commission's Competitiveness and Innovation Framework Programme (CIP) and will end in October 2016. In broad terms, the ELF Project will deliver a unique gateway to the authoritative reference geospatial information for Europe (harmonised pan-European maps, geographic and land information) sourced from the National Mapping and Cadastral Authorities (NMCAs) around Europe and including transparent licensing. This will be provided as an online ELF web service that will deliver an up-to-date topographic base map and also as view & download services for access to the ELF datasets. To develop and build up the ELF, NMCAs are accompanied and collaborate with several research & academia institutes, a standardisation body, system integrators, software developers and application providers. The harmonisation is in progress developing and triggering a number of geo-tools like edge-matching, generalisation, transformation and others. ELF will provide also some centralised tools like Geo Locator for searching location based on geographical names, addresses and administrative units, and GeoProduct Finder for discovering the available web-services and licensing them. ELF combines national reference geo-information through the ELF platform. ELF web services will be offered to users and application developers through open source (OSKARI) and proprietary (ArcGIS Online) cloud platforms. Recently, 29 NMCAs plus the

THE MANIFESTATION OF THE EUROPEAN CENTRAL BANK’S LEGAL PERSONALITY AT NATIONAL, EUROPEAN AND INTERNATIONAL LEVEL

Directory of Open Access Journals (Sweden)

MONICA ŞAGUNA

2012-05-01

Full Text Available The European Central Bank is one of the world’ s most important central banks, responsible for the monetary policy covering the 17 member States of the Eurozone. Established by the European Union in 1998, it was given the exclusive right to authorize the issue of banknotes within the European Union. The European Central Bank has legal personality under public international law. As article 282, paragraph 3 of the Treaty on functioning of the European Union and article 9, paragraph 1 of the Statute of the European System of Central Banks and of the European Central Bank states, the European Central Bank and the National Central Banks enjoy their own legal personality. The European Central Bank, given its important role in the economic integration, is the single institution of the European Union which has legal personality. This is a premise for it to fulfill its objectives. In this framework, the purpose of my paper is to analyze the effects of the European Central Bank’s legal personality from a complete perspective: at national, European and international level. Therefore the objectives of my study are: an introspection in the concept of legal personality, the identification of the reason why it was entrusted to a single institution of the European Union and a detailed analyze of the effects of the European Central Bank’ s legal personality.

Low-dose and high-dose acetylsalicylic acid, with and without dipyridamole: a review of clinical trial results

NARCIS (Netherlands)

Tijssen, J. G.

1998-01-01

Publication of the results of the second European Stroke Prevention Study (ESPS-2) provided the incentive for an update of the meta-analyses of aspirin and dipyridamole in the secondary prevention of stroke. After review of published randomized trials of prolonged treatment with aspirin,

Formulation and Evaluation of Gastro-retentive Floating Multi ...

African Journals Online (AJOL)

Purpose: To develop a floating multiparticulate unit system for metoprolol tartarate, using a porous carrier, with an outcome for delayed gastric emptying. Methods: Dried microparticles of metoprolol tartarate were prepared by solvent evaporation using Eudragit® RS-PO, polypropylene foam powder, and dichloromethane as ...

Principles of European Contract Law

DEFF Research Database (Denmark)

Lando, Ole; Beale, Hugh

This text provides a comprehensive guide to the principles of European contract law. They have been drawn up by an independent body of experts from each Member State of the EU, under a project supported by the European Commission and many other organizations. The principles are stated in the form...... of articles, with a detailed commentary explaining the purpose and operation of each article and its relation to the remainder. Each article also has extensive comparative notes surveying the national laws and other international provisions on the topic. "The Principles of European Contract Law Parts I &...... in developing a common European legal culture. The European Parliament has twice called for the creation of a European Civil Code. The principles of European contract law are essential steps in these projects. This text provides a comprehensive guide to the Principles of European contract law. They have been...

European multicenter trial of the prevention of cystoid macular edema after cataract surgery in nondiabetics: ESCRS PREMED study report 1.

Science.gov (United States)

Wielders, Laura H P; Schouten, Jan S A G; Winkens, Bjorn; van den Biggelaar, Frank J H M; Veldhuizen, Claudette A; Findl, Oliver; Murta, Joaquim C N; Goslings, Willem R O; Tassignon, Marie-José; Joosse, Maurits V; Henry, Ype P; Rulo, Alexander H F; Güell, José L; Amon, Michael; Kohnen, Thomas; Nuijts, Rudy M M A

2018-04-01

To compare the efficacy of a topical nonsteroidal antiinflammatory drug, topical corticosteroid, and a combination of both drugs to prevent the occurrence of cystoid macular edema (CME) after cataract surgery in nondiabetic patients. Twelve European study centers. Randomized clinical trial. Nondiabetic patients having uneventful cataract surgery were included in this study. Patients were randomized to receive topical bromfenac 0.09% twice daily for 2 weeks or dexamethasone 0.1% 4 times daily with 1 drop less per day every following week, or a combination of both. The primary outcome was the difference in central subfield mean macular thickness 6 weeks postoperatively. Secondary outcome measures included corrected distance visual acuity as well as the incidence of CME and clinically significant macular edema (CSME) within 6 weeks and 12 weeks postoperatively. This study comprised 914 patients. Six weeks postoperatively, the central subfield mean macular thickness was 288.3 μm, 296.0 μm, and 284.5 μm in the bromfenac group, dexamethasone group, and combination treatment group, respectively (overall P = .006). The incidence of clinically significant macular edema within 12 weeks postoperatively was 3.6%, 5.1%, and 1.5%, respectively (overall P = .043). Patients treated with a combination of topical bromfenac 0.09% and dexamethasone 0.1% had a lower risk for developing CSME after cataract surgery than patients treated with a single drug. Copyright © 2018 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Renal denervation decreases blood pressure and renal tyrosine hydroxylase but does not augment the effect of hypotensive drugs.

Science.gov (United States)

Skrzypecki, Janusz; Gawlak, Maciej; Huc, Tomasz; Szulczyk, Paweł; Ufnal, Marcin

2017-01-01

The effect of renal denervation on the efficacy of antihypertensive drugs has not yet been elucidated. Twenty-week-old spontaneously hypertensive rats were treated with metoprolol, losartan, indapamide, or saline (controls) and assigned to renal denervation or a sham procedure. Acute hemodynamic measurements were performed ten days later. Series showing a significant interaction between renal denervation and the drugs were repeated with chronic telemetry measurements. In the saline series, denervated rats showed a significantly lower mean arterial blood pressure (blood pressure) than the sham-operated rats. In contrast, in the metoprolol series denervated rats showed a significantly higher blood pressure than sham rats. There were no differences in blood pressure between denervated and sham rats in the losartan and indapamide series. In chronic studies, a 4-week treatment with metoprolol caused a decrease in blood pressure. Renal denervation and sham denervation performed 10 days after the onset of metoprolol treatment did not affect blood pressure. Denervated rats showed markedly reduced renal nerve tyrosine hydroxylase levels. In conclusion, renal denervation decreases blood pressure in hypertensive rats. The hypotensive action of metoprolol, indapamide, and losartan is not augmented by renal denervation, suggesting the absence of synergy between renal denervation and the drugs investigated in this study.

Differential Serum Cytokine Levels and Risk of Lung Cancer between African and European Americans

Science.gov (United States)

Pine, Sharon R.; Mechanic, Leah E.; Enewold, Lindsey; Bowman, Elise D.; Ryan, Bríd M.; Cote, Michele L.; Wenzlaff, Angela S.; Loffredo, Christopher A.; Olivo-Marston, Susan; Chaturvedi, Anil; Caporaso, Neil E.; Schwartz, Ann G.; Harris, Curtis C.

2015-01-01

Background African Americans have a higher risk of developing lung cancer than European Americans. Previous studies suggested that certain circulating cytokines were associated with lung cancer. We hypothesized that variations in serum cytokine levels exist between African Americans and European Americans, and increased circulating cytokine levels contribute to lung cancer differently in the two races. Methods Differences in ten serum cytokine levels, interleukin (IL)-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, granulocyte macrophage colony-stimulating factor (GMCSF), interferon (IFN)-γ and tumor necrosis factor (TNF)-α between 170 African-American and 296 European-American controls from the National Cancer Institute-Maryland (NCI-MD) case-control study were assessed. Associations of the serum cytokine levels with lung cancer were analyzed. Statistically significant results were replicated in the prospective Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and the Wayne State University (WSU) Karmanos Cancer Institute case-control study. Results Six cytokines: IL-4, IL-5, IL-8, IL-10, IFNγ, and TNFα, were significantly higher among European-American as compared to African-American controls. Elevated IL-6 and IL-8 levels were associated with lung cancer among both races in all three studies. Elevated IL-1β, IL-10 and TNFα levels were associated with lung cancer only among African Americans. The association between elevated TNFα levels and lung cancer among European Americans was significant after adjustment for additional factors. Conclusions Serum cytokine levels vary by race and might contribute to lung cancer differently between African Americans and European Americans. Impact Future work examining risk prediction models of lung cancer can measure circulating cytokines to accurately characterize risk within racial groups. PMID:26711330

Concordance between four European centres of PET reporting criteria designed for use in multicentre trials in Hodgkin lymphoma

DEFF Research Database (Denmark)

Barrington, Sally F; Qian, Wendi; Somer, Edward J

2010-01-01

To determine if PET reporting criteria for the Response Adapted Treatment in Hodgkin Lymphoma (RATHL) trial could enable satisfactory agreement to be reached between 'core' laboratories operating in different countries.......To determine if PET reporting criteria for the Response Adapted Treatment in Hodgkin Lymphoma (RATHL) trial could enable satisfactory agreement to be reached between 'core' laboratories operating in different countries....

European Vegetation Archive (EVA)

NARCIS (Netherlands)

Chytrý, Milan; Hennekens, S.M.; Jiménez-Alfaro, Borja; Schaminée, J.H.J.; Haveman, Rense; Janssen, J.A.M.

2016-01-01

The European Vegetation Archive (EVA) is a centralized database of European vegetation plots developed by the IAVS Working Group European Vegetation Survey. It has been in development since 2012 and first made available for use in research projects in 2014. It stores copies of national and

The European Medicines Agency's approval of new medicines for type 2 diabetes.

Science.gov (United States)

Blind, Eberhard; Janssen, Heidi; Dunder, Kristina; de Graeff, Pieter A

2018-05-08

Since 2005, more than 40 new medicines for the treatment of type 2 diabetes have been introduced on the market. These consist of 15 new active substances establishing three new classes of non-insulin products, and several new or modified insulin products and combinations. The approval of these products in Europe is regulated via the centralized procedure at the European Medicines Agency. Demonstration of benefit with regard to improved glucose control remains the principal outcome required from confirmatory studies to demonstrate efficacy. For the majority of these new medicines approved since 2005, cardiovascular outcome trials have now been completed, and have invariably supported the cardiovascular safety of these products. In some of these trials additional important benefits have been observed, for instance, a reduction in major adverse cardiovascular events and improvement of renal outcome. The existing regulatory framework and the continuous adaption of regulatory requirements to emerging developments will continue to guide the approval of new products in the future. © 2018 John Wiley & Sons Ltd.

A randomized controlled Phase Ib trial of the malaria vaccine candidate GMZ2 in African children

DEFF Research Database (Denmark)

Bélard, Sabine; Issifou, Saadou; Hounkpatin, Aurore B

2011-01-01

GMZ2 is a fusion protein of Plasmodium falciparum merozoite surface protein 3 (MSP3) and glutamate rich protein (GLURP) that mediates an immune response against the blood stage of the parasite. Two previous phase I clinical trials, one in naïve European adults and one in malaria-exposed Gabonese ...... adults showed that GMZ2 was well tolerated and immunogenic. Here, we present data on safety and immunogenicity of GMZ2 in one to five year old Gabonese children, a target population for future malaria vaccine efficacy trials....

Assessment of Adverse Events in Protocols, Clinical Study Reports, and Published Papers of Trials of Orlistat

DEFF Research Database (Denmark)

Schroll, Jeppe Bennekou; Penninga, Elisabeth I; Gøtzsche, Peter C

2016-01-01

BACKGROUND: Little is known about how adverse events are summarised and reported in trials, as detailed information is usually considered confidential. We have acquired clinical study reports (CSRs) from the European Medicines Agency through the Freedom of Information Act. The CSRs describe......Med and adverse event data were extracted from this source as well. All three sources were compared. Individual adverse events from one trial were summed and compared to the totals in the summary report. None of the protocols or CSRs contained instructions for investigators on how to question participants about...

European Vegetation Archive (EVA): an integrated database of European vegetation plots

DEFF Research Database (Denmark)

Chytrý, M; Hennekens, S M; Jiménez-Alfaro, B

2015-01-01

vegetation- plot databases on a single software platform. Data storage in EVA does not affect on-going independent development of the contributing databases, which remain the property of the data contributors. EVA uses a prototype of the database management software TURBOVEG 3 developed for joint management......The European Vegetation Archive (EVA) is a centralized database of European vegetation plots developed by the IAVS Working Group European Vegetation Survey. It has been in development since 2012 and first made available for use in research projects in 2014. It stores copies of national and regional...... data source for large-scale analyses of European vegetation diversity both for fundamental research and nature conservation applications. Updated information on EVA is available online at http://euroveg.org/eva-database....

Standardized End Point Definitions for Coronary Intervention Trials: The Academic Research Consortium-2 Consensus Document.

Science.gov (United States)

Garcia-Garcia, Hector M; McFadden, Eugène P; Farb, Andrew; Mehran, Roxana; Stone, Gregg W; Spertus, John; Onuma, Yoshinobu; Morel, Marie-Angèle; van Es, Gerrit-Anne; Zuckerman, Bram; Fearon, William F; Taggart, David; Kappetein, Arie-Pieter; Krucoff, Mitchell W; Vranckx, Pascal; Windecker, Stephan; Cutlip, Donald; Serruys, Patrick W

2018-06-14

The Academic Research Consortium (ARC)-2 initiative revisited the clinical and angiographic end point definitions in coronary device trials, proposed in 2007, to make them more suitable for use in clinical trials that include increasingly complex lesion and patient populations and incorporate novel devices such as bioresorbable vascular scaffolds. In addition, recommendations for the incorporation of patient-related outcomes in clinical trials are proposed. Academic Research Consortium-2 is a collaborative effort between academic research organizations in the United States and Europe, device manufacturers, and European, US, and Asian regulatory bodies. Several in-person meetings were held to discuss the changes that have occurred in the device landscape and in clinical trials and regulatory pathways in the last decade. The consensus-based end point definitions in this document are endorsed by the stakeholders of this document and strongly advocated for clinical trial purposes. This Academic Research Consortium-2 document provides further standardization of end point definitions for coronary device trials, incorporating advances in technology and knowledge. Their use will aid interpretation of trial outcomes and comparison among studies, thus facilitating the evaluation of the safety and effectiveness of these devices.

Improving the profile of the European tourist destinations through the European tourism indicators system

Directory of Open Access Journals (Sweden)

Laura CISMARU

2015-06-01

Full Text Available Within the most recent European Policy for Tourism, the competitiveness of the European tourism industry is directly linked to the image of Europe and to its perception, as a collection of sustainable and high-quality tourist destinations. In such context, improving the profile of the European tourist destinations has become a main target. During the last years, the European Commission focused on the sustainable development of tourist destinations. Several projects were developed, the most recent one introducing a practical tool - the European Tourism Indicators System (ETIS for the sustainable development of destinations. The present paper advances the idea that such tool can be successfully used in order to achieve the goal of improving the profile of the European tourist destinations.

Experimental infection of pigs with two East European variants of Type 1 PRRSV

DEFF Research Database (Denmark)

Hjulsager, Charlotte Kristiane; Larsen, Lars Erik; Heegaard, Peter M. H.

Porcine reproductive and respiratory syndrome viruses (PRRSV) have been divided into Type 1 (European) and Type 2 (North American) viruses. PRRSV are very diverse and Type 1 viruses have even been further divided into subtypes. While Type 1 viruses from Western Europe belong to subtype 1, viruses...... the subtype 1 strains. The aim of this project was to study the infection dynamics and clinical and pathological impact of two east European Type 1 strains. In an experimental trial, infection of pigs with the Russian subtype 2 strain “Ili6” and the Belarusian atypical isolate “Bor59” were compared...... to an early “Lelystad-like” Danish subtype 1 isolate “18794”. Groups of seven pigs of unique high sanitary status were infected with one of the three PRRSV isolates, and a fourth group served as sham-inoculated controls. The pigs were monitored for 24 days, and nasal swabs and blood samples were taken at 0, 3...

The European Small Claims Procedure: Striking the Balance between Simplicity and Fairness in European Litigation

NARCIS (Netherlands)

X.E. Kramer (Xandra)

2008-01-01

textabstractThis article deals with the European Small Claims Procedure (ESCP). After the European Order for Payment procedure, this is the second autonomous European procedure that has been established. Attention is paid to the background of harmonization of small claims proceedings in the European

The European Photovoltaic Technology Platform

International Nuclear Information System (INIS)

Nowak, S.; Aulich, H.; Bal, J.L.; Dimmler, B.; Garnier, A.; Jongerden, G.; Luther, J.; Luque, A.; Milner, A.; Nelson, D.; Pataki, I.; Pearsall, N.; Perezagua, E.; Pietruszko, S.; Rehak, J.; Schellekens, E.; Shanker, A.; Silvestrini, G.; Sinke, W.; Willemsen, H.

2006-05-01

The European Photovoltaic Technology Platform is one of the European Technology Platforms, a new instrument proposed by the European Commission. European Technology Platforms (ETPs) are a mechanism to bring together all interested stakeholders to develop a long-term vision to address a specific challenge, create a coherent, dynamic strategy to achieve that vision and steer the implementation of an action plan to deliver agreed programmes of activities and optimise the benefits for all parties. The European Photovoltaic Technology Platform has recently been established to define, support and accompany the implementation of a coherent and comprehensive strategic plan for photovoltaics. The platform will mobilise all stakeholders sharing a long-term European vision for PV, helping to ensure that Europe maintains and improves its industrial position. The platform will realise a European Strategic Research Agenda for PV for the next decade(s). Guided by a Steering Committee of 20 high level decision-makers representing all relevant European PV Stakeholders, the European PV Technology Platform comprises 4 Working Groups dealing with the subjects policy and instruments; market deployment; science, technology and applications as well as developing countries and is supported by a secretariat

Escherichia Coli-Lux Biosensor Used to Monitor the Cytotoxicity and Genotoxicity of Pharmacological Residues in Environment

Directory of Open Access Journals (Sweden)

Eliza Hawrylik

2018-05-01

Full Text Available The aim of the study was to evaluate the usefulness of Escherichia coli K-12 RFM 443 recA::lux for cytotoxicity and genotoxicity monitoring of metoprolol in the environment. Metoprolol is one of the most popular cardiac drug which belongs to the group of β–blockers. The drug was applied at concentrations ranging from 0.01 µg/cm3 to 100 µg/cm3. The conducted studies are preliminary studies aimed at validation of the recA::lux gene construct in the direction of determining its sensitivity to metoprolol. The drug concentrations were selected experimentally to obtain a positive luminescence response. Obtained data indicated the influence of metoprolol on lux gene expression and recA promoter activity based on the use of laboratory samples using PBS buffer. Results indicate a potential possibility of using a bacterial biosensor Escherichia coli K - 12 RFM 443 with recA::lux gene fusion in cytotoxicity and genotoxicity monitoring of the cardiac drugs residue in the environment.

European Security

DEFF Research Database (Denmark)

Møller, Bjørn

Theoretical chapters on "Security", "Organisations" and "Regions," Historical Chapters on "Europe and Its Distinguishing Features" and on "The United Nations," "NATO," "The CSCE/OSCE and the Council of Europe" and "The European Union"......Theoretical chapters on "Security", "Organisations" and "Regions," Historical Chapters on "Europe and Its Distinguishing Features" and on "The United Nations," "NATO," "The CSCE/OSCE and the Council of Europe" and "The European Union"...

European Criminal Law a! er the Lisbon Treaty, or Europeanization of European law, under the co-responsibility of the Member States

Directory of Open Access Journals (Sweden)

Arif Riza

2016-11-01

Full Text Available Same as EU Law, that presents a new area of law and that it is still in progress, the EU Criminal Law is developing. The development of EU criminal law, of course, is dictated by the development of European Law itself, or the EU itself. Depending on it, the EU will be a supranational structure, or will undergo changes and become a Federal State, or another unified form. Taking into consideration the importance of this area of law, which is created for cooperation among states to combat organized crime, and especially terrorism, we can have a Criminal Code European and a European code of Criminal Procedure certainly in the near future, namely, a codification of European criminal field. This paper aims to discuss the development of European criminal law, until the Treaty of Lisbon.

The Europeanization of Politics: Building a Terminology for European Studies

Directory of Open Access Journals (Sweden)

Damir Grubiša

2005-01-01

Full Text Available The article discusses the problem of Europeanisation, one of the key concepts developed within the European Studies in the last ten years or so, since the adoption and entry into force of the Maastricht Treaty. The fi rst part of the article deals with various models of Europeanisation in a context extending beyond the conceptual framework of the European Union, within which the phenomenon of Europeanisation arises. Therefore, the author attempts to develop a typology of broader approaches to the identifi cation of the phenomenon and process of Europeanisation, which includes six conceptions thereof: the fi rst approach is a geographical-political one, where Europeanisation is seen as a change in outer borders of Europe, from the reduction of Europe to the countries of Western Europe and Central Europe, to the extension of the concept of Europe to marginal countries; the second approach links the concept of Europeanisation with the development of political institutions on the European level. The third defi nition identifi es Europeanisation as an export of various forms of political organisation, a process which proceeds from the experience of European colonisation to the diff usion of European values as a role model for other continents; the fourth model of Europeanisation is the identifi cation with the project of European unifi cation, i. e. the process of integration which ends up in a federal, unifi ed Europe; the fi fth subtype is the penetration of national systems of governance by the European model of multilevel governance, which becomes manifest in the adaptation, convergence and harmonisation of the political and legal systems of member nations. The author elaborates on this classic typology by adding the sixth approach, which he calls “retrospective Europeanisation”. It involves Europeanisation as identifi cation with traditional European values that existed before EC and EU, primarily with the preintegration traditional

Elicitation of expert prior opinion: application to the MYPAN trial in childhood polyarteritis nodosa.

Directory of Open Access Journals (Sweden)

Lisa V Hampson

Full Text Available Definitive sample sizes for clinical trials in rare diseases are usually infeasible. Bayesian methodology can be used to maximise what is learnt from clinical trials in these circumstances. We elicited expert prior opinion for a future Bayesian randomised controlled trial for a rare inflammatory paediatric disease, polyarteritis nodosa (MYPAN, Mycophenolate mofetil for polyarteritis nodosa.A Bayesian prior elicitation meeting was convened. Opinion was sought on the probability that a patient in the MYPAN trial treated with cyclophosphamide would achieve disease remission within 6-months, and on the relative efficacies of mycophenolate mofetil and cyclophosphamide. Expert opinion was combined with previously unseen data from a recently completed randomised controlled trial in ANCA associated vasculitis.A pan-European group of fifteen experts participated in the elicitation meeting. Consensus expert prior opinion was that the most likely rates of disease remission within 6 months on cyclophosphamide or mycophenolate mofetil were 74% and 71%, respectively. This prior opinion will now be taken forward and will be modified to formulate a Bayesian posterior opinion once the MYPAN trial data from 40 patients randomised 1:1 to either CYC or MMF become available.We suggest that the methodological template we propose could be applied to trial design for other rare diseases.

On Law and Policy in a European and European Union Patent Court (EEUPC)

DEFF Research Database (Denmark)

Schovsbo, Jens Hemmingsen; Petersen, Clement Salung

On 4 December 2009, the European Council unanimously adopted conclusions on an enhanced patent system in Europe, which inter alia intends to establish a new EU patent as well as a new common patent judiciary - the European and European Union Patent Court (EEUPC). The EEUPC will constitute a new sui...... generis, transnational court system with exclusive jurisdiction in respect of civil litigation related to the infringement and validity of European patents and EU patent. This paper considers this proposal for the establishment of the EEUPC under two basic observations, namely that substantive law...

On Law and Policy in a European and European Union Patent Court (EEUPC)

DEFF Research Database (Denmark)

Petersen, Clement Salung; Schovsbo, Jens Hemmingsen

2010-01-01

On 4 December 2009, the European Council unanimously adopted conclusions on an enhanced patent system in Europe, which inter alia intends to establish a new EU patent as well as a new common patent judiciary – the European and European Union Patent Court (EEUPC). The EEUPC will constitute a new sui...... generis, transnational court system with exclusive jurisdiction in respect of civil litigation related to the infringement and validity of European patents and EU patent. This paper considers this proposal for the establishment of the EEUPC under two basic observations, namely that substantive law...

An important day for European science

CERN Document Server

2009-01-01

Today is an important day for the future of European science. It is the day on which CERN’s relationship with the European Union reaches maturity. Ever since the early 1950s, CERN and the European project have grown together. CERN was a child of the European movement: the first discussions at Denis de Rougemont’s European Cultural Conference in Lausanne in 1949 led directly to the foundation of CERN in 1954. More recently, the European Union has become an Observer at the CERN Council, links between CERN and the EU have strengthened as Europe has pursued the goal of creating a European Research Area, and CERN has benefited from European support for projects as varied as Grid computing and future accelerator R&D, not forgetting, of course, the numerous Marie Curie fellows whose careers have received a boost thanks to European funds. Today, that collaboration goes one step further with the signature of a Memorandum of Understanding between CERN and the European C...

Prevention of Pazopanib-Induced Prolonged Cardiac Repolarization and Proarrhythmic Effects

Directory of Open Access Journals (Sweden)

Tulay Akman

2014-11-01

Full Text Available Background: Pazopanib (PZP may induce prolonged cardiac repolarization and proarrhythmic effects, similarly to other tyrosine kinase inhibitors. Objectives: To demonstrate PZP-induced prolonged cardiac repolarization and proarrhythmic electrophysiological effects and to investigate possible preventive effects of metoprolol and diltiazem on ECG changes (prolonged QT in an experimental rat model. Methods: Twenty-four Sprague-Dawley adult male rats were randomly assigned to 4 groups (n = 6. The first group (normal group received 4 mL of tap water and the other groups received 100 mg/kg of PZP (Votrient® tablet perorally, via orogastric tubes. After 3 hours, the following solutions were intraperitoneally administered to the animals: physiological saline solution (SP, to the normal group and to the second group (control-PZP+SP group; 1 mg/kg metoprolol (Beloc, Ampule, AstraZeneca, to the third group (PZP+metoprolol group; and 1mg/kg diltiazem (Diltiazem, Mustafa Nevzat, to the fourth group (PZP+diltiazem group. One hour after, and under anesthesia, QTc was calculated by recording ECG on lead I. Results: The mean QTc interval values were as follows: normal group, 99.93 ± 3.62 ms; control-PZP+SP group, 131.23 ± 12.21 ms; PZP+metoprolol group, 89.36 ± 3.61 ms; and PZP+diltiazem group, 88.86 ± 4.04 ms. Both PZP+metoprolol and PZP+diltiazem groups had significantly shorter QTc intervals compared to the control-PZP+SP group (p < 0.001. Conclusion: Both metoprolol and diltiazem prevented PZP-induced QT interval prolongation. These drugs may provide a promising prophylactic strategy for the prolonged QTc interval associated with tyrosine kinase inhibitor use.

European nuclear education network

International Nuclear Information System (INIS)

Blomgren, J.; Moons, F.; Safieh, J.

2005-01-01

In most countries within the European Union that rely to a significant extent on nuclear power, neither undergraduate nor PhD education is producing a sufficient number of engineers and doctors to fill the needs of the industry. As a result of an EU-supported project, a new education organisation, European Nuclear Education Network (ENEN), has recently been established, with the aim to establish a European master's degree of nuclear engineering. Recently, a new EU project, Nuclear European Platform of Training and University Organisations (NEPTUNO), has been launched, aiming at the practical implementation of ENEN and harmonisation of training activities. (author)

European Union and oil

International Nuclear Information System (INIS)

Paillard, Christophe Alexandre

2004-01-01

In a context of oil price increase, problems about a Russian oil company (Loukos), and uncertainties in the Middle-East, the possibility of a new oil shock is a threat for Europe, and raises the issue of a true European energy policy which would encompass, not only grid development, environmental issues or market regulation issues, but also strategic issues related to energy supply security. This article proposes an overview of the European policy: first steps for a future European energy and oil policy in the green paper of the European Commission published in November 2000, issues of pollution and safety for hydrocarbon maritime transport. The article then examines the possibility of a third oil shock due to a crisis in the Middle East, and discusses whether European must have strategic stocks to face an outage of oil supplies

Recent clinical trials in idiopathic pulmonary fibrosis and the BUILD-1 study

Directory of Open Access Journals (Sweden)

K. K. Brown

2008-12-01

Full Text Available Idiopathic pulmonary fibrosis (IPF, the most common of the interstitial pneumonias, is a progressive, life-limiting disease for which there are no truly effective therapies. In patients with biopsy-confirmed IPF, median survival is still <3 yrs. Although potent immunosuppressive therapy has underpinned the treatment of IPF in recent years and remains the standard of care, there is little quality evidence to support the efficacy and safety of traditional therapeutic strategies. This has spurred the search for new treatments for IPF and has led to a series of clinical trials of new therapies, seven of which are reviewed herein. They include the Bosentan Use in Interstitial Lung Disease (BUILD-1 trial, the results of which are discussed in detail, the European Idiopathic Pulmonary Fibrosis International Group Exploring N-acetylcysteine 1 Annual (IFIGENIA trial, the interferon gamma (GIPF-001 trial and the INSPIRE trial, as well as trials of anticoagulant therapy, pirfenidone and etanercept. Treatment trials in IPF are hindered by difficulties in achieving a secure diagnosis of IPF and the lack of validated outcome measures that represent either improvement or progression of disease. These and other limitations are discussed in the present article, as well as how some of these problems might be addressed in future trials. Although few of the seven studies met their primary end-points, marginal trends either on primary end-points or statistically significant trends on exploratory end-points were a recurrent theme in most trials. In the BUILD-1 trial, for example, a trend in favour of bosentan was observed on time-to-disease progression or death.

European Home Energy

DEFF Research Database (Denmark)

Tommerup, Henrik M.

2009-01-01

An important aim of the european energy performance of buildings directive is to improve the overall energy efficiency of new homes......An important aim of the european energy performance of buildings directive is to improve the overall energy efficiency of new homes...

Mineral metabolism in European children living with a renal transplant: a European society for paediatric nephrology/european renal association-European dialysis and transplant association registry study

NARCIS (Netherlands)

Bonthuis, Marjolein; Busutti, Marco; van Stralen, Karlijn J.; Jager, Kitty J.; Baiko, Sergey; Bakkaloğlu, Sevcan; Battelino, Nina; Gaydarova, Maria; Gianoglio, Bruno; Parvex, Paloma; Gomes, Clara; Heaf, James G.; Podracka, Ludmila; Kuzmanovska, Dafina; Molchanova, Maria S.; Pankratenko, Tatiana E.; Papachristou, Fotios; Reusz, György; Sanahuja, Maria José; Shroff, Rukshana; Groothoff, Jaap W.; Schaefer, Franz; Verrina, Enrico

2015-01-01

Data on mineral metabolism in pediatric renal transplant recipients largely arise from small single-center studies. In adult patients, abnormal mineral levels are related to a higher risk of graft failure. This study used data from the European Society for Paediatric Nephrology/European Renal

Translation of randomised controlled trial findings into clinical practice: comparison of olanzapine and valproate in the EMBLEM study

DEFF Research Database (Denmark)

Novick, D; Gonzalez-Pinto, A; Haro, J M

2009-01-01

OBJECTIVES: The aim of this study was to compare the outcomes of olanzapine- and valproate-treated patients in an observational study of acute mania with the results of a randomised controlled trial (RCT) assessing the same treatments. METHODS: EMBLEM (European Mania in Bipolar Evaluation of Medi...

Kicking the tyres of a heart failure trial: physician response to the approval of sacubitril/valsartan in the USA.

Science.gov (United States)

Packer, Milton

2016-10-01

Angiotensin receptor-neprilysin inhibition has been shown to be superior to target doses of an ACE inhibitor in reducing the risk of cardiovascular death and clinical disease progression in patients with chronic heart failure and a reduced EF. Nevertheless, although sacubitril/valsartan has been available in the USA for a year, uptake of the drug by practitioners has been slow, in part because of misconceptions about the pivotal trial that demonstrated its efficacy in heart failure (PARADIGM-HF). This review addresses questions that have been raised in the USA about the design of the trial as well as the patients who were studied, the replicability and applicability of the results, and the safety of neprilysin inhibition. The totality of evidence indicates that the PARADIGM-HF trial used an appropriate comparator; enrolled patients typical of those seen in the community with mild to moderate symptoms; yielded highly persuasive and replicable results; and demonstrated benefits that are applicable to patients taking subtarget doses of ACE inhibitors and ARBs. Regulatory review in the USA concluded that the established advantages of sacubitril/valsartan on cardiovascular death and disease progression outweighed hypothetical uncertainties about the long-term effects of neprilysin inhibition in patients who might not have survived without the drug. Accordingly, both the new US and European Society of Cardiology heart failure guidelines recommend sacubitril/valsartan as the preferred approach to inhibiting the renin-angiotensin system in patients with chronic heart failure who are currently receiving an ACE inhibitor or ARB. © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.

European media law

NARCIS (Netherlands)

Castendyk, O.; Dommering, E.; Scheuer, A.

2008-01-01

European Union legislation concerning electronic communications media is firmly established as an essential part of the law in the field in Europe. From relevant provisions of the European Convention of Human Rights and the EC Treaty to numerous directives, the most recent being the Audiovisual

European works councils

DEFF Research Database (Denmark)

Knudsen, Herman Lyhne

2004-01-01

The theme addressed by this artcle is the opportunities for European Works Councils of gaining influence on corporate decisions in multinational companies.......The theme addressed by this artcle is the opportunities for European Works Councils of gaining influence on corporate decisions in multinational companies....

European [Security] Union

DEFF Research Database (Denmark)

Manners, Ian James

2013-01-01

The past 20 years, since the 1992 Treaty on European Union, have seen the gradual creation of both an “Area of Freedom, Security and Justice” and a “Common Foreign and Security Policy”. More recent is the development of a “European Neighbourhood Policy” over the past 10 years. All three...... of these policies involved the navigation and negotiation of security, borders and governance in and by the European Union (EU). This article analyses these practices of bordering and governance through a five-fold security framework. The article argues that a richer understanding of EU security discourses can...

Cognitive Behavioral Therapy for 4- to 7-Year-Old Children with Anxiety Disorders: A Randomized Clinical Trial

Science.gov (United States)

Hirshfeld-Becker, Dina R.; Masek, Bruce; Henin, Aude; Blakely, Lauren Raezer; Pollock-Wurman, Rachel A.; McQuade, Julia; DePetrillo, Lillian; Briesch, Jacquelyn; Ollendick, Thomas H.; Rosenbaum, Jerrold F.; Biederman, Joseph

2010-01-01

Objective: To examine the efficacy of a developmentally appropriate parent-child cognitive behavioral therapy (CBT) protocol for anxiety disorders in children ages 4-7 years. Method: Design: Randomized wait-list controlled trial. Conduct: Sixty-four children (53% female, mean age 5.4 years, 80% European American) with anxiety disorders were…

Trans-European transport networks and urban systems in European Union

Directory of Open Access Journals (Sweden)

Maksin-Mićić Marija

2003-01-01

Full Text Available The trans-European transport network has different effects at interregional macro-regional and mezzo-regional level, and its effectiveness rises at the lower regional levels. Possible approaches to the trans-European transport network impact and effect survey and policy options have been pointed out. In that respect the brief review of survies, strategic framework and policies in European Union has been given. The importance of increased accessibility and mobility for regional expansion and for more balanced and polycentric system of city networks has been underlined. The question is how the new major transport infrastructure affects the development of functional complementarity between cities and regions. The new trans-European or major transport infrastructure does not per se create regional and urban system network development, although it can affect the conditions for the processes that create growth and development. The effects can be increased by co-ordination of measures of regional and urban policy, land use, transport and other policies. The necessary measure is the introduction of spatial impact assessment as sectorial policy instrument for the large transport infrastructure projects.

National choices in a European perspective. Proceedings of the European Forum 2003

International Nuclear Information System (INIS)

Sido, Bruno; Lamoureux, Francois; ); Herzog, Philippe; ); Barre, Bertrand; Bataille, Christian; Colombani, Pascal; Gonzalez Gomez, Jose Luis; Lescoeur, DBruno; Perez, Serge; Weh, Rudolf; Westerlind, Magnus; Houssin, Didier; Nagashima, Hideo; Pavlopoulos, Panagiotis; Linkohr, Rolf; ); Allemeersch, Antoine; Beveridge, George; Bonnemains, Jacky; Fritschi, Markus; Piguet, Jack-Pierre; Rigny, Paul; Streydio, Jean-Marie; Tallec, Michele; Vasa, Ivo; Pancher, Bertrand

2003-01-01

In 2003, the 'Entretiens europeens' engaged a dialogue between stakeholders of various socio-professional backgrounds from several countries and with the European Commission, in order to compare the selected options of management of radioactive waste and materials and to emphasize the best experiments, which could inspire an innovating European policy in the world. This document is the proceedings of this first European Forum on this topic. Content: 1 - Introduction by Bruno Sido, senator and chairman of the County Council of Haute-Marne; 2 - talk by Francois Lamoureux, General Director of DG TREN, European Commission. 3 - Debate with the audience. 4 - First round table chaired by Philippe Herzog, Member of the European Parliament and President of Confrontations Europe: Is a European directive feasible? Within what time frame? What flexibility is required? What democratic process is needed? With the contributions from: Bertrand Barre, Manager in charge of Scientific Communications (AREVA), Christian Bataille, Member of the French Parliament, author of the 'Bataille Law', Pascal Colombani, Administrator, British Energy (nuclear power producer in UK), Jose Luis Gonzalez Gomez, ENRESA (Spain), Bruno Lescoeur, Director of the Energy sector, EDF, Serge Perez, Trade Unionist, Member of the National Bureau, FNME CGT (France), Rudolf Weh, Head of Department Spent Fuel and Waste Management Services/Interim Storage, GNS Gesellschaft fuer Nuklear-Service mbH (Germany), Magnus Westerlind, Manager Nuclear Security, SKI (Sweden). 5 - Hearing Didier Houssin, Director, Raw Materials and Hydrocarbons, DGEMP. 6 - Interventions of Hideo Nagashima, Executive Director, NUMO (Japan) and of Panagiotis Pavlopoulos, Research Director CERN, Geneva. 7 - Second round table chaired by Rolf Linkohr, Member of the European Parliament and chairman of European Energy Foundation: 'The scientific and social importance of the various options for the management of nuclear waste' With the contributions

EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group (EUSTAR)

NARCIS (Netherlands)

Kowal-Bielecka, O.; Landewé, R.; Avouac, J.; Chwiesko, S.; Miniati, I.; Czirjak, L.; Clements, P.; Denton, C.; Farge, D.; Fligelstone, K.; Földvari, I.; Furst, D. E.; Müller-Ladner, U.; Seibold, J.; Silver, R. M.; Takehara, K.; Toth, B. Garay; Tyndall, A.; Valentini, G.; van den Hoogen, F.; Wigley, F.; Zulian, F.; Matucci-Cerinic, Marco

2009-01-01

The optimal treatment of systemic sclerosis (SSc) is a challenge because the pathogenesis of SSc is unclear and it is an uncommon and clinically heterogeneous disease affecting multiple organ systems. The aim of the European League Against Rheumatism (EULAR) Scleroderma Trials and Research group

Eurados trial performance test for personal dosemeters for external beta radiation

DEFF Research Database (Denmark)

Christensen, P.; Bordy, J.M.; Ambrosi, P.

2001-01-01

On the initiative of the European Dosimetry Group (EURADOS) action group 'Harmonisation and Dosimetric Quality Assurance in Individual Monitoring for External Radiation' a trial performance test for whole-body and extremity personal dosemeters broadly representative of those in use in the EU...... the results obtained from the exercise. In particular, based on the replies to a questionnaire issued to each participant, the results are analysed in relation to important design characteristics of the dosemeters taking part in the test....

Demand Side Management for the European Supergrid: Occupancy variances of European single-person households

International Nuclear Information System (INIS)

Torriti, Jacopo

2012-01-01

The prospect of a European Supergrid calls for research on aggregate electricity peak demand and Europe-wide Demand Side Management. No attempt has been made as yet to represent a time-related demand curve of residential electricity consumption at the European level. This article assesses how active occupancy levels of single-person households vary in single-person household in 15 European countries. It makes use of occupancy time-series data from the Harmonised European Time Use Survey database to build European occupancy curves; identify peak occupancy periods; construct time-related electricity demand curves for TV and video watching activities and assess occupancy variances of single-person households. - Highlights: ► Morning peak occupancies of European single households tale place between 7h30 and 7h40. ► Evening peaks take place between 20h10 and 20h20. ► TV and video activities during evening peaks make up about 3.1 GWh of European peak electricity load. ► Baseline and peak occupancy variances vary across countries. ► Baseline and peak occupancy variances can be used as input for Demand Side Management choices.

Rapid and Sensitive LC-MS/MS Method for the Determination of Metoprolol in Beagle Dog Plasma with a Simple Protein Precipitation Treatment and Its Pharmacokinetic Applications

Directory of Open Access Journals (Sweden)

Aihua Hong

2012-03-01

Full Text Available : A rapid LC-MS/MS method with good accuracy and sensitivity was developed and validated for the pharmacokinetics study of metoprolol (MP in beagle dogs. The plasma samples were simply precipitated by methanol and then analyzed by LC-MS/MS. An Ultimate XB-C18 column (150 × 2.1 mm ID, 5 μm was used for separation, with methanol-water containing 0.2% formic acid (65:35, v/v as the mobile phase at a flow rate of 0.2 mL/min. Monitoring ions of MP and internal standard (hydroxypioglitazone were m/z 268.1/115.6 and m/z 373.1/150.2, respectively. The linear range was 3.03–416.35 ng/mL with an average correlation coefficient of 0.9996, and the limit of quantification was 3.03 ng/mL. The intra- and inter-day precision was less than 15%. At low, middle and high concentrations, the recovery, the matrix effect and the accuracy was in the range of 76.06%–95.25%, 93.67%–104.19% and 95.20%–99.96% respectively. The method was applied for the pharmacokinetics study of MP tartrate tablets (50 mg. The AUC0-t, Tmax and Cmax were respectively 919.88 ± 195.67 μg/L·h, 0.96 ± 0.33 h, 349.12 ± 78.04 ng/mL.

European Metals Conference

CERN Document Server

Vereecken, Jean

1991-01-01

This volume contains the papers that will be presented at 'EMC '91 '-the European Metals Conference-to be held in Brussels, Belgium, from 15 to 20 September 1991, and organized by Benelux Metallurgie, GDMB (Gesellschaft Deutscher Metallhutten­ und Bergleute) and IMM (the Institution of Mining and Metallurgy). 'EMC '91' is the first of an intended major series organized at the European level with the aim of bringing together all those who are involved with the extraction and processing of non-ferrous metals-European metallurgists and their international colleagues-to provide them with the opportunity to exchange views on the state and evolution of their industry. The programme covers all the different aspects of the metallurgy of non-ferrous metals from mining to fabricated products. Particular attention is being paid to the European non -ferrous industry with respect to changes in demand, the technology used, pressures on the environment and the competitive position of manufacturers. The contributions of the...

Early clinical outcomes as a function of use of newer oral P2Yinhibitors versus clopidogrel in the EUROMAX trial

DEFF Research Database (Denmark)

Huber, Kurt; Ducrocq, Gregory; Hamm, Christian W

2017-01-01

Objective: To ascertain whether different oral P2Y12inhibitors might affect rates of acute stent thrombosis and 30-day outcomes after primary percutaneous coronary intervention (pPCI). Methods: The European Ambulance Acute Coronary Syndrome Angiography (EUROMAX) randomised trial compared prehospi...

Effect of Short-Term Fasting on Systemic Cytochrome P450-Mediated Drug Metabolism in Healthy Subjects: A Randomized, Controlled, Crossover Study Using a Cocktail Approach.

Science.gov (United States)

Lammers, Laureen A; Achterbergh, Roos; van Schaik, Ron H N; Romijn, Johannes A; Mathôt, Ron A A

2017-10-01

Short-term fasting can alter drug exposure but it is unknown whether this is an effect of altered oral bioavailability and/or systemic clearance. Therefore, the aim of our study was to assess the effect of short-term fasting on oral bioavailability and systemic clearance of different drugs. In a randomized, controlled, crossover trial, 12 healthy subjects received a single administration of a cytochrome P450 (CYP) probe cocktail, consisting of caffeine (CYP1A2), metoprolol (CYP2D6), midazolam (CYP3A4), omeprazole (CYP2C19) and warfarin (CYP2C9), on four occasions: an oral (1) and intravenous (2) administration after an overnight fast (control) and an oral (3) and intravenous (4) administration after 36 h of fasting. Pharmacokinetic parameters of the probe drugs were analyzed using the nonlinear mixed-effects modeling software NONMEM. Short-term fasting increased systemic caffeine clearance by 17% (p = 0.04) and metoprolol clearance by 13% (p < 0.01), whereas S-warfarin clearance decreased by 19% (p < 0.01). Fasting did not affect bioavailability. The study demonstrates that short-term fasting alters CYP-mediated drug metabolism in a non-uniform pattern without affecting oral bioavailability.

European Analytical Column

DEFF Research Database (Denmark)

Karlberg, B.; Grasserbauer, M.; Andersen, Jens Enevold Thaulov

2009-01-01

for European analytical chemistry. During the period 2002–07, Professor Grasserbauer was Director of the Institute for Environment and Sustainability, Joint Research Centre of the European Commission (EC), Ispra, Italy. There is no doubt that many challenges exist at the present time for all of us representing...

Daily supplementation with 15 μg vitamin D2 compared with vitamin D3 to increase wintertime 25-hydroxyvitamin D status in healthy South Asian and white European women: a 12-wk randomized, placebo-controlled food-fortification trial.

Science.gov (United States)

Tripkovic, Laura; Wilson, Louise R; Hart, Kathryn; Johnsen, Sig; de Lusignan, Simon; Smith, Colin P; Bucca, Giselda; Penson, Simon; Chope, Gemma; Elliott, Ruan; Hyppönen, Elina; Berry, Jacqueline L; Lanham-New, Susan A

2017-08-01

Background: There are conflicting views in the literature as to whether vitamin D 2 and vitamin D 3 are equally effective in increasing and maintaining serum concentrations of 25-hydroxyvitamin D [25(OH)D], particularly at lower doses of vitamin D. Objective: We aimed to investigate whether vitamin D 2 or vitamin D 3 fortified in juice or food, at a relatively low dose of 15 μg/d, was effective in increasing serum total 25(OH)D and to compare their respective efficacy in South Asian and white European women over the winter months within the setting of a large randomized controlled trial. Design: A randomized, double-blind, placebo-controlled food-fortification trial was conducted in healthy South Asian and white European women aged 20-64 y ( n = 335; Surrey, United Kingdom) who consumed placebo, juice supplemented with 15 μg vitamin D 2 , biscuit supplemented with 15 μg vitamin D 2 , juice supplemented with 15 μg vitamin D 3 , or biscuit supplemented with 15 μg vitamin D 3 daily for 12 wk. Serum 25(OH)D was measured by liquid chromatography-tandem mass spectrometry at baseline and at weeks 6 and 12 of the study. Results: Postintervention in the 2 ethnic groups combined, both the vitamin D 3 biscuit and the vitamin D 3 juice groups showed a significantly greater absolute incremental change (Δ) in total 25(OH)D when compared with the vitamin D 2 biscuit group [Δ (95% CI): 15.3 nmol/L (7.4, 23.3 nmol/L) ( P < 0.0003) and 16.0 nmol/L (8.0, 23.9 nmol/L) ( P < 0.0001)], the vitamin D 2 juice group [Δ (95% CI): 16.3 nmol/L (8.4, 24.2 nmol/L) ( P < 0.0001) and 16.9 nmol/L (9.0, 24.8 nmol/L) ( P < 0.0001)], and the placebo group [Δ (95% CI): 42.3 nmol/L (34.4, 50.2 nmol/L) ( P < 0.0001) and 42.9 nmol/L (35.0, 50.8 nmol/L) ( P < 0.0002)]. Conclusions: With the use of a daily dose of vitamin D relevant to public health recommendations (15 μg) and in vehicles relevant to food-fortification strategies, vitamin D 3 was more effective than vitamin D 2 in increasing

The contributions of the European Medicines Agency and its pediatric committee to the fight against childhood leukemia

Directory of Open Access Journals (Sweden)

Rose K

2015-11-01

Full Text Available Klaus Rose,1,* Philip D Walson,2,* 1klausrose Consulting, Pediatric Drug Development and More, Riehen, Switzerland; 2Department of Clinical Pharmacology, University Medical School, Goettingen, Germany *These authors contributed equally to this work Background: Although the diagnosis of childhood leukemia is no longer a death sentence, too many patients still die, more with acute myeloid leukemia than with acute lymphoblastic leukemia. The European Union pediatric legislation was introduced to improve pharmaceutical treatment of children, but some question whether the European Medicines Agency (EMA approach is helping children with leukemia. Some have even suggested that the decisions of EMA pediatric committee (PDCO are counterproductive. This study was designed to investigate the impact of PDCO-issued pediatric investigation plans (PIPs for leukemia drugs.Methods: All PIPs listed under “oncology” were downloaded from the EMA website. Non-leukemia decisions including misclassifications, waivers (no PIP, and solid tumors were discarded. The leukemia decisions were analyzed, compared to pediatric leukemia trials in the database http://www.clinicaltrials.gov, and discussed in the light of current literature.Results: The PDCO leukemia decisions demand clinical trials in pediatric leukemia for all new adult drugs without prioritization. However, because leukemia in children is different and much rarer than in adults, these decisions have resulted in proposed studies that are scientifically and ethically questionable. They are also unnecessary, since once promising new compounds are approved for adults, more appropriate, prioritized pediatric leukemia trials are initiated worldwide without PDCO involvement.Conclusion: EMA/PDCO leukemia PIPs do little to advance the treatment of childhood leukemia. The unintended negative effects of the flawed EMA/PDCO's standardized requesting of non-prioritized testing of every new adult leukemia drug in

European Union Energy Research

International Nuclear Information System (INIS)

Valdalbero, D.R.; Schmitz, B.; Raldow, W.; Poireau, M.

2007-01-01

This article presents an extensive state of the art of the energy research conducted at European Union level between 1984 and 2006, i.e. from the first to the sixth European Community Framework Programmes (FP1-FP6) for Research, Technological Development and Demonstration (RTD and D). The FP is the main legal tool and financial instrument of EU RTD and D policy. It sets the objectives, priorities and budgets for a period of several years. It has been complemented over time with a number of policy oriented initiatives and notably with the launch of the European Research Area. FP7 will cover the period 2007-2013 and will have a total budget of more than euros 50 billion. Energy has been a main research area in Europe since the founding Treaties (European Coal and Steel Community, European Atomic Energy Community-Euratom and European Economic Community), and energy RTD and D has always been a substantial part of common EU research. Nevertheless, when inflation and successive European enlargements are taken into account, over time the RTD and D effort in the field of energy has decreased significantly in relative terms. In nominal terms it has remained relatively stable at about euros 500 million per year. For the next years (FP7), it is expected that energy will still represent about 10 % of total EU research effort but with an annual budget of more than euros 800 million per year. This article presents a detailed review of the thematic areas and budget in both European nuclear energy research (fusion and fission) and non-nuclear energy research (energy efficiency/rational use of energy, fossil fuels, CO 2 capture and storage, fuel cells and hydrogen, renewable energy sources, strategic energy research/socio-economy). (authors)

The EULAR Scleroderma Trials and Research Group (EUSTAR): an international framework for accelerating scleroderma research.

Science.gov (United States)

Tyndall, Alan; Ladner, Ulf M; Matucci-Cerinic, Marco

2008-11-01

Systemic sclerosis has a complex pathogenesis and a multifaceted clinical spectrum without a specific treatment. Under the auspices of the European League Against Rheumatism, the European League Against Rheumatism Scleroderma Trials And Research group (EUSTAR) has been founded in Europe to foster the study of systemic sclerosis with the aim of achieving equality of assessment and care of systemic sclerosis patients throughout the world according to evidence-based principles. EUSTAR created the minimal essential data set, a simple two-page form with basic demographics and mostly yes/no answers to clinical and laboratory parameters, to track patients throughout Europe. Currently, over 7000 patients are registered from 150 centres in four continents, and several articles have been published with the data generated by the minimal essential data set. A commitment of EUSTAR is also to teaching and educating, and for this reason there are two teaching courses and a third is planned for early in 2009. These courses have built international networks among young investigators improving the quality of multicentre clinical trials. EUSTAR has organized several rounds of 'teach the teachers' to further standardize the skin scoring. EUSTAR activities have extended beyond European borders, and EUSTAR now includes experts from several nations. The growth of data and biomaterial might ensure many further fruitful multicentre studies, but the financial sustainability of EUSTAR remains an issue that may jeopardize the existence of this group as well as that of other organizations in the world.

ELSY. European LFR activities

International Nuclear Information System (INIS)

Alemberti, Alessandro; Carlsson, Johan; Malambu, Edouard; Orden, Alfredo; Cinotti, Luciano; Struwe, Dankward; Agostini, Pietro; Monti, Stefano

2011-01-01

The European Lead Fast Reactor has been developed in the frame of the European lead system (ELSY) project funded by the Sixth Framework Programme of EURATOM. The project, coordinated by Ansaldo Nucleare, involved a wide consortium of European organizations. The ELSY reference design is a 600 MWe pool-type reactor cooled by pure lead. The project demonstrates the possibility of designing a competitive and safe fast critical reactor using simple engineered technical features, whilst fully complying with the Generation IV goals. The paper focuses on the main aspects of the proposed design for the European lead fast reactor highlighting the innovation of this reactor concept and overall objectives. Special attention has been dedicated to safety starting from the first step of the design development taking into account other important aspects, such as the investment protection, the compactness of the primary system as well as sustainability. The main safety features of the proposed innovative decay heat removal (DHR) systems are presented. From the beginning of 2010, and for a duration of three years, the European Commission (EC) is financing the new project Lead European Advanced Demonstration Reactor (LEADER) as part of the 7th Framework Program. This paper highlights the main objectives of the LEADER project. (author)

Parameters of measuring of european political consciousness

Directory of Open Access Journals (Sweden)

M. M. Pikula

2015-09-01

Full Text Available In the article the author analyzes the parameters of European political consciousness, i.e. European research field of political consciousness in qualitative and quantitative terms, which may be based on different indicators. The issue of emergence and development of European political consciousness becomes topical because firstly, its formation as the subjective dimension of European integration policy is not a spontaneous process and, secondly, European integration is carried out not only from the top but from the bottom, requiring deliberate interference of the public with the process; the public possesses the formed European political consciousness. Since the latter is a specific mental construct, the author offers to apply the triad «criteria ­ parameters – indicators». The characteristic that makes it possible to evaluate certain processes or phenomena in the system of Europeanness / Europeanism and specifies the quality system of views and opinions, which are realized in European behavior, is considered to be the criterion of European political consciousness. The European political consciousness parameters are seen to include the relevant historical memory, trends of public opinion and awareness regarding the European Union and position of its members in the European integration process, including the assessment of the existence and development of the EU; knowledge and views on the main EU institutions, assessing the importance of the main institutions of the EU and trust in them; a positive vision for the future of the European Union etc. The author considers the performance and objective characteristics and dimensions, including positive correlation of national and European levels of identity (European identity and European behavior to be the indicatiors of European political awareness. On the basis of these indicators the control of the condition and trends of European political consciousness development will be carried out.

A New Ethical Challenge for Institutional Review Boards (IRBs/Ethics Committees (ECs in the Assessment of Pediatric Clinical Trials

Directory of Open Access Journals (Sweden)

Klaus Rose

2015-05-01

Full Text Available Both the US and EU have introduced pediatric pharmaceutical legislation to facilitate clinical trials in children and development of better medicines for children. The first concerns were published in 2014 that the European Medicines Agency (EMA’s Pediatric Committee (PDCO may be over-enthusiastic and has compelled questionable pediatric clinical trials from pharmaceutical companies. Numerous clinical trials are mandated in rare conditions for which not enough patients exist for even one trial. Furthermore, where these trials are mandated in adolescent patients, the legal age limit of the 18th birthday is confused with a medical age limit and can result in separate clinical trials in adolescent patients that neither make medical nor scientific sense nor will ever recruit enough patients for a meaningful outcome. To confirm our concerns we searched the registry clinicaltrials.gov and found examples for PDCO-triggered unethical trials. We conclude that such trials should not be accepted by institutional review boards (IRBs/ethics committees (ECs and that clinical trials resulting from negotiations with EMA’s PDCO need extra careful scrutiny by IRBs/ECs in order to prevent unethical studies and damage to pediatric research and unnecessary risks to pediatric patients.

Environment in the European Union 1995

DEFF Research Database (Denmark)

The update to the 1992 report on the state of the environment in the European Union requested by the European Commission......The update to the 1992 report on the state of the environment in the European Union requested by the European Commission...

NILVAD protocol: a European multicentre double-blind placebo-controlled trial of nilvadipine in mild-to-moderate Alzheimer's disease.

Science.gov (United States)

Lawlor, Brian; Kennelly, Sean; O'Dwyer, Sarah; Cregg, Fiona; Walsh, Cathal; Coen, Robert; Kenny, Rose Anne; Howard, Robert; Murphy, Caroline; Adams, Jessica; Daly, Leslie; Segurado, Ricardo; Gaynor, Siobhan; Crawford, Fiona; Mullan, Michael; Lucca, Ugo; Banzi, Rita; Pasquier, Florence; Breuilh, Laetitia; Riepe, Matthias; Kalman, Janos; Wallin, Anders; Borjesson, Anne; Molloy, William; Tsolaki, Magda; Olde Rikkert, Marcel

2014-10-09

This study is a European multicentre, randomised, double-blind, placebo-controlled trial investigating the efficacy and safety of nilvadipine as a disease course modifying treatment for mild-to-moderate Alzheimer's disease (AD) in a phase III study that will run for a period of 82 weeks with a treatment period of 78 weeks. Adult patients, males and females over 50 years with mild-to-moderate AD as defined by the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's disease and Related Disorders Association (NINCDS-ADRDA) criteria, will be included in the study. It aims to recruit a total of 500 patients with AD; 250 in the nilvadipine group and 250 in the placebo group. Participants will be randomised to receive nilvadipine, an 8 mg overencapsulated, sustained release capsule, or a matching overencapsulated placebo (sugar pill) for a period of 78 weeks of treatment. The primary efficacy outcome measure in this study is the change in cognitive function as assessed by the Alzheimer's disease Assessment Scale (ADAS-Cog 12) from baseline to the end of treatment duration (78 weeks). There are two key secondary outcome measures, the Clinical Dementia Rating Scale Sum of Boxes (CDR-sb) and the Disability Assessment for Dementia (DAD). If a statistically significant effect is seen in the primary outcome, CDR-sb will be considered to be a coprimary end point and only the DAD will contribute to the secondary outcome analysis. The study and all subsequent amendments have received ethical approval within each participating country according to national regulations. Each participant will provide written consent to participate in the study. All participants will remain anonymised throughout and the results of the study will be published in an international peer-reviewed journal. EUDRACT Reference Number: 2012-002764-27. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence

European standards for composite construction

NARCIS (Netherlands)

Stark, J.W.B.

2000-01-01

The European Standards Organisation (CEN) has planned to develop a complete set of harmonized European building standards. This set includes standards for composite steel and concrete buildings and bridges. The Eurocodes, being the design standards, form part of this total system of European

European oil product supply modelling

International Nuclear Information System (INIS)

Saint-Antonin, V.

1998-01-01

Over the last few years, trends in European oil product consumption (in terms of level as structure and quality) has important implications of the refining industry. In this context, the purpose of this thesis consists in building a mathematical programming model applied to the European refineries in order to determine oil product supply prices, European refining industry investments and oil product exchanges of the European Union. The first part presents the reason for our choice for a long-term aggregate multi-refineries linear programming model, based on European refineries characteristics and the objectives of our model. Its dual properties are studied in detail and we focus particularly on the European exchange modelling. In the second part, an analysis of the European refining trends leads us to identify parameters and variables of the model that are essential to the aggregate representation of the European oil product supply. The third part is devoted to the use of this model, regarding two scenarios of increasingly stringent specifications for gasoline and diesel oil. Our interest for these products is due to their important share of the European oil product consumption and the not insignificant responsibility of the transport sector for atmospheric pollution. Finally, in order to have the use of an overall picture of the European refining industry, we build a regression model summarizing, though a few equations, the main relations between the major endogenous and exogenous variables o the LP model. Based on pseudo-data, this kind of model provides a simple and robust representation of the oil product supply. But a more specialized analysis of the refining industry operations, turning on a technical assessment of processing units, is reliant on the use of an optimization model such as the model we have built. (author)

The constitutional momentum of European contract law (II): The DCFR and the European constitutional order

OpenAIRE

Mak, C.

2009-01-01

This paper analyses the potential impact of the recently published Draft Common Frame of Reference for European contract law (DCFR) on the European constitutional process. Looking at the combination of characteristics of codification and aspects of constitutionalism reflected in the DCFR, it is submitted that the further harmonisation of European contract law may contribute to the definition of the European constitutional order both on the institutional level (regarding the forms in which Eur...

Guidelines for time-to-event end point definitions in breast cancer trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)†.

Science.gov (United States)

Gourgou-Bourgade, S; Cameron, D; Poortmans, P; Asselain, B; Azria, D; Cardoso, F; A'Hern, R; Bliss, J; Bogaerts, J; Bonnefoi, H; Brain, E; Cardoso, M J; Chibaudel, B; Coleman, R; Cufer, T; Dal Lago, L; Dalenc, F; De Azambuja, E; Debled, M; Delaloge, S; Filleron, T; Gligorov, J; Gutowski, M; Jacot, W; Kirkove, C; MacGrogan, G; Michiels, S; Negreiros, I; Offersen, B V; Penault Llorca, F; Pruneri, G; Roche, H; Russell, N S; Schmitt, F; Servent, V; Thürlimann, B; Untch, M; van der Hage, J A; van Tienhoven, G; Wildiers, H; Yarnold, J; Bonnetain, F; Mathoulin-Pélissier, S; Bellera, C; Dabakuyo-Yonli, T S

2015-05-01

Using surrogate end points for overall survival, such as disease-free survival, is increasingly common in randomized controlled trials. However, the definitions of several of these time-to-event (TTE) end points are imprecisely which limits interpretation and cross-trial comparisons. The estimation of treatment effects may be directly affected by the definitions of end points. The DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for randomized cancer clinical trials (RCTs) in breast cancer. A literature review was carried out to identify TTE end points (primary or secondary) reported in publications of randomized trials or guidelines. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points based on a validated consensus method that formalize the degree of agreement among experts. Recommended guidelines for the definitions of TTE end points commonly used in RCTs for breast cancer are provided for non-metastatic and metastatic settings. The use of standardized definitions should facilitate comparisons of trial results and improve the quality of trial design and reporting. These guidelines could be of particular interest to those involved in the design, conducting, reporting, or assessment of RCT. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Cabozantinib Versus Everolimus in Patients with Advanced Renal Cell Carcinoma: Results of a Randomised Phase III Trial (METEOR

Directory of Open Access Journals (Sweden)

Toni Choueiri

2015-11-01

Full Text Available The METEOR trial of cabozantinib versus everolimus in advanced renal cell carcinoma (RCC was reported by Prof Choueiri at the European Cancer Congress 2015. This presentation follows the publication in the New England Journal of Medicine of the METEOR trial back-to-back with the CheckMate 025 trial of nivolumab versus everolimus in the same patient setting. Excitingly, these trials demonstrated, for the first time, significant benefits over the standard of care for heavily pre-treated patients with advanced RCC. Cabozantinib, an oral multi-targeted tyrosine kinase inhibitor (TKI aims to address the challenge of resistance to targeted therapy with TKIs. While the METEOR trial has not yet reached its final analysis of overall survival (OS, the clear progression-free survival (PFS benefit, acceptable safety profile, and similar tolerability to other TKIs shown by cabozantinib indicate that this represents a promising new treatment option for second-line or subsequent therapy for patients with advanced RCC.

nab-Paclitaxel plus gemcitabine for metastatic pancreatic cancer: a subgroup analysis of the Western European cohort of the MPACT trial

Directory of Open Access Journals (Sweden)

Tabernero J

2017-02-01

Full Text Available Josep Tabernero,1 Volker Kunzmann,2 Werner Scheithauer,3 Michele Reni,4 Jack Shiansong Li,5 Stefano Ferrara,6 Kamel Djazouli7 1Medical Oncology Department, Vall d’Hebron University Hospital, Barcelona, Spain; 2Medizinische Klinik und Poliklinik II, University of Würzburg, Würzburg, Germany; 3Medizinische Universität Wien, Wien, Austria; 4San Raffaele Scientific Institute, Milan, Italy; 5Celgene Corporation, Summit, NJ, USA; 6Celgene Corporation, Boudry, Switzerland; 7Celgene Corporation, Paris, France Purpose: The global Phase III MPACT trial demonstrated superior efficacy of nab-paclitaxel plus gemcitabine over gemcitabine alone as first-line treatment for metastatic pancreatic cancer. Region was a randomization stratification factor in the MPACT trial. This subgroup analysis of MPACT examined efficacy and safety of patients treated in Western Europe.Patients and methods: Patients received nab-paclitaxel plus gemcitabine or gemcitabine alone as first-line treatment for metastatic pancreatic cancer as previously described. A total of 76 patients were included in this analysis (n=38 for each arm.Results: Differences between the overall Western European cohort and the intention-to-treat population included lower percentages of male patients (46% and 58%, respectively and patients with biliary stents (8% and 17%, and higher percentages of patients with Karnofsky performance status of 90–100 (78% and 60% and primary tumors in the body of the pancreas (48% and 31%. The median overall survival was 10.7 months with nab-paclitaxel plus gemcitabine vs 6.9 months with gemcitabine alone (hazard ratio [HR]: 0.82 [95% confidence interval (CI: 0.48–1.40]; P=0.471. Median progression-free survival was 5.3 vs 3.7 months, respectively (HR: 0.70 [95% CI: 0.37–1.33]; P=0.277. The independently assessed overall response rate was 18% vs 5% (response rate ratio, 3.50 [95% CI: 0.78–15.78]; P=0.076. The most common grade ≥3 adverse events with nab

Pan European Phenological database (PEP725): a single point of access for European data

Science.gov (United States)

Templ, Barbara; Koch, Elisabeth; Bolmgren, Kjell; Ungersböck, Markus; Paul, Anita; Scheifinger, Helfried; Rutishauser, This; Busto, Montserrat; Chmielewski, Frank-M.; Hájková, Lenka; Hodzić, Sabina; Kaspar, Frank; Pietragalla, Barbara; Romero-Fresneda, Ramiro; Tolvanen, Anne; Vučetič, Višnja; Zimmermann, Kirsten; Zust, Ana

2018-02-01

The Pan European Phenology (PEP) project is a European infrastructure to promote and facilitate phenological research, education, and environmental monitoring. The main objective is to maintain and develop a Pan European Phenological database (PEP725) with an open, unrestricted data access for science and education. PEP725 is the successor of the database developed through the COST action 725 "Establishing a European phenological data platform for climatological applications" working as a single access point for European-wide plant phenological data. So far, 32 European meteorological services and project partners from across Europe have joined and supplied data collected by volunteers from 1868 to the present for the PEP725 database. Most of the partners actively provide data on a regular basis. The database presently holds almost 12 million records, about 46 growing stages and 265 plant species (including cultivars), and can be accessed via http://www.pep725.eu/. Users of the PEP725 database have studied a diversity of topics ranging from climate change impact, plant physiological question, phenological modeling, and remote sensing of vegetation to ecosystem productivity.

Pan European Phenological database (PEP725): a single point of access for European data

Science.gov (United States)

Templ, Barbara; Koch, Elisabeth; Bolmgren, Kjell; Ungersböck, Markus; Paul, Anita; Scheifinger, Helfried; Rutishauser, This; Busto, Montserrat; Chmielewski, Frank-M.; Hájková, Lenka; Hodzić, Sabina; Kaspar, Frank; Pietragalla, Barbara; Romero-Fresneda, Ramiro; Tolvanen, Anne; Vučetič, Višnja; Zimmermann, Kirsten; Zust, Ana

2018-06-01

The Pan European Phenology (PEP) project is a European infrastructure to promote and facilitate phenological research, education, and environmental monitoring. The main objective is to maintain and develop a Pan European Phenological database (PEP725) with an open, unrestricted data access for science and education. PEP725 is the successor of the database developed through the COST action 725 "Establishing a European phenological data platform for climatological applications" working as a single access point for European-wide plant phenological data. So far, 32 European meteorological services and project partners from across Europe have joined and supplied data collected by volunteers from 1868 to the present for the PEP725 database. Most of the partners actively provide data on a regular basis. The database presently holds almost 12 million records, about 46 growing stages and 265 plant species (including cultivars), and can be accessed via http://www.pep725.eu/ . Users of the PEP725 database have studied a diversity of topics ranging from climate change impact, plant physiological question, phenological modeling, and remote sensing of vegetation to ecosystem productivity.

The European Natural Gas Market

NARCIS (Netherlands)

Correlje, A.F.

The European Union started the introduction of competition in the European market for natural gas. Today, mid-2016, the process of restructuring is still going on. In parallel, important changes in geopolitical, environmental and technological determinants can be observed in the European and global

European validation of Real-Time PCR method for detection of Salmonella spp. in pork meat.

Science.gov (United States)

Delibato, Elisabetta; Rodriguez-Lazaro, David; Gianfranceschi, Monica; De Cesare, Alessandra; Comin, Damiano; Gattuso, Antonietta; Hernandez, Marta; Sonnessa, Michele; Pasquali, Frédérique; Sreter-Lancz, Zuzsanna; Saiz-Abajo, María-José; Pérez-De-Juan, Javier; Butrón, Javier; Prukner-Radovcic, Estella; Horvatek Tomic, Danijela; Johannessen, Gro S; Jakočiūnė, Džiuginta; Olsen, John E; Chemaly, Marianne; Le Gall, Francoise; González-García, Patricia; Lettini, Antonia Anna; Lukac, Maja; Quesne, Segolénè; Zampieron, Claudia; De Santis, Paola; Lovari, Sarah; Bertasi, Barbara; Pavoni, Enrico; Proroga, Yolande T R; Capuano, Federico; Manfreda, Gerardo; De Medici, Dario

2014-08-01

The classical microbiological method for detection of Salmonella spp. requires more than five days for final confirmation, and consequently there is a need for an alternative methodology for detection of this pathogen particularly in those food categories with a short shelf-life. This study presents an international (at European level) ISO 16140-based validation study of a non-proprietary Real-Time PCR-based method that can generate final results the day following sample analysis. It is based on an ISO compatible enrichment coupled to an easy and inexpensive DNA extraction and a consolidated Real-Time PCR assay. Thirteen laboratories from seven European Countries participated to this trial, and pork meat was selected as food model. The limit of detection observed was down to 10 CFU per 25 g of sample, showing excellent concordance and accordance values between samples and laboratories (100%). In addition, excellent values were obtained for relative accuracy, specificity and sensitivity (100%) when the results obtained for the Real-Time PCR-based methods were compared to those of the ISO 6579:2002 standard method. The results of this international trial demonstrate that the evaluated Real-Time PCR-based method represents an excellent alternative to the ISO standard. In fact, it shows an equal and solid performance as well as it reduces dramatically the extent of the analytical process, and can be easily implemented routinely by the Competent Authorities and Food Industry laboratories. Copyright © 2014 Elsevier B.V. All rights reserved.

European hadrons

International Nuclear Information System (INIS)

Anon.

1986-01-01

The European Hadron Facility (EHF) is a project for particle and nuclear physics in the 1990s which would consist of a fast cycling high intensity proton synchrotron of about 30 GeV primary energy and providing a varied spectrum of intense high quality secondary beams (polarized protons, pions, muons, kaons, antiprotons, neutrinos). The physics case of this project has been studied over the last two years by a European group of particle and nuclear physicists (EHF Study Group), whilst the conceptual design for the accelerator complex was worked out (and is still being worked on) by an international group of machine experts (EHF Design Study Group). Both aspects have been discussed in recent years in a series of working parties, topical seminars, and workshops held in Freiburg, Trieste, Heidelberg, Karlsruhe, Les Rasses and Villigen. This long series of meetings culminated in the International Conference on a European Hadron Facility held in Mainz from 10-14 March

EUROPEAN MONETARY FUND - BETWEEN ILLUSION AND FUTURE INSTRUMENT FOR EUROPEAN FINANCIAL STABILITY

Directory of Open Access Journals (Sweden)

Firtescu Bogdan

2010-12-01

Full Text Available The finance crises that culminate with the Greece situation shows that majority of European countries are facing balance-of-payments difficulties and it is clear that actual mechanism couldnt face the situation. This paper wants to highlight some of the proposals related to the development mechanisms, such the creation of the European Monetary Fund or the design of the European Mechanism for Financial Stability (EMFS, which could include the EMF, showing also the actual mechanism of financing through International Monetary Fund (IMF.Some pro and counter arguments are furthermore taken into discussion.

European Conference „Meetbike“. Information

Directory of Open Access Journals (Sweden)

Gerd-Axel AHRENS

2008-01-01

Full Text Available The information is devoted European Conference „Meetbike“ 3-4 April2008 in Dresden, Germany. Stronger networking of European bicycle-friendly cities and better cooperation of bike use and public transport has been considered. Results of the European Conference „MeetBike“ are presented.

European brown hare syndrome virus in free-ranging European brown hares from Argentina

DEFF Research Database (Denmark)

Frolich, K.; Kujawski, G.E.J.G.; Rudolph, M.

2003-01-01

From 1998 to 2000, serum samples of 80 shot European brown hares (Lepus europaeus) from Argentina were examined for antibodies against European brown hare syndrome virus (EBHSV) and 80 spleen samples were tested for EBHSV-antigen by enzyme linked immunosorbent assay (ELISA). Nine hares were posit...... in these hares. This is the first report of antibodies to EBHSV, EBHSV-antigen, and electron microscopy findings in free-ranging European brown hares from South America....

Gendering European welfare states and citizenship

DEFF Research Database (Denmark)

Siim, Birte; Borchorst, Anette

2017-01-01

on gender, class, ethnicity or race, and nationality. One issue is what has been the effect of the European emphasis on women’s wage work and gender equality policies for women in different European countries? Another issue concerns how multiple discrimination is tackled and institutionalized in European......The chapter revisits the feminist scholarship on gendering of European welfare states and European citizenship, and reflects on the effects of globalization, Europeanization and migration. It first presents feminist perspectives on the liberal, the conservative and the social democratic welfare...... welfare states. A third issue is to what extent the Nordic welfare states still represent an attractive alternative model of social and gender equality to neo-liberalism. The final part discusses feminist approaches to reframe gender equality and gender justice from the transnational European contexts....

Introductory Guide to European Corporate Law

DEFF Research Database (Denmark)

Fomcenco, Alex

Introductory Guide to European Corporate Law presents in an easily comprehensible and accessible way the main features and principles that govern European corporate law.......Introductory Guide to European Corporate Law presents in an easily comprehensible and accessible way the main features and principles that govern European corporate law....

Prevention of disease progression by cardiac resynchronization therapy in patients with asymptomatic or mildly symptomatic left ventricular dysfunction: insights from the European cohort of the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial

DEFF Research Database (Denmark)

Daubert, Claude; Gold, Michael R; Abraham, William T

2009-01-01

were decreased in this patient population in New York Heart Association functional classes I or II. These observations suggest that CRT prevents the progression of disease in patients with asymptomatic or mildly symptomatic LV dysfunction. (REsynchronization reVErses Remodeling in Systolic Left v......OBJECTIVES: The aim of this study was to determine the long-term effects of cardiac resynchronization therapy (CRT) in the European cohort of patients enrolled in the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial. BACKGROUND: Previous data suggest...... that CRT slows disease progression and improves the outcomes of asymptomatic or mildly symptomatic patients with left ventricular (LV) dysfunction and a wide QRS complex. METHODS: We randomly assigned 262 recipients of CRT pacemakers or defibrillators, with QRS > or =120 ms and LV ejection fraction...

Hydration and chemical ingredients in sport drinks: food safety in the European context.

Science.gov (United States)

Urdampilleta, Aritz; Gómez-Zorita, Saioa; Soriano, José M; Martínez-Sanz, José M; Medina, Sonia; Gil-Izquierdo, Angel

2015-05-01

Before, during and after physical activity, hydration is a limiting factor in athletic performance. Therefore, adequate hydration provides benefits for health and performance of athletes. Besides, hydration is associated to the intake of carbohydrates, protein, sodium, caffeine and other substances by different dietary aids, during the training and/or competition by athletes. These requirements have led to the development of different products by the food industry, to cover the nutritional needs of athletes. Currently in the European context, the legal framework for the development of products, substances and health claims concerning to sport products is incomplete and scarce. Under these conditions, there are many products with different ingredients out of European Food Safety Authority (EFSA) control where claims are wrong due to no robust scientific evidence and it can be dangerous for the health. Further scientific evidence should be constructed by new clinical trials in order to assist to the Experts Commitees at EFSA for obtaining robust scientific opinions concerning to the functional foods and the individual ingredients for sport population. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

European Synchrotron Radiation Facility

International Nuclear Information System (INIS)

Buras, B.

1985-01-01

How a European Synchrotron Radiation Facility has developed into a detailed proposal recently accepted as the basis for construction of the facility at Grenoble is discussed. In November 1977, the General Assembly of the European Science Foundation (ESF) approved the report of the ESF working party on synchrotron radiation entitled Synchrotron Radiation - a Perspective View for Europe. This report contained as one of its principal recommendations that work should commence on a feasibility study for a European synchrotron radiation laboratory having a dedicated hard X-ray storage ring and appropriate advanced instrumentation. In order to prepare a feasibility study the European Science Foundation set up the Ad-hoc Committee on Synchrotron Radiation, which in turn formed two working groups: one for the machine and another for instrumentation. This feasibility study was completed in 1979 with the publication of the Blue Book describing in detail the so called 1979 European Synchrotron Radiation Facility. The heart of the facility was a 5 GeV electron storage ring and it was assumed that mainly the radiation from bending magnets will be used. The facility is described

Cardiac mucosa at the gastro-oesophageal junction: indicator of gastro-oesophageal reflux disease? Data from a prospective central European multicentre study on histological and endoscopic diagnosis of oesophagitis (histoGERD trial).

Science.gov (United States)

Langner, Cord; Schneider, Nora I; Plieschnegger, Wolfgang; Schmack, Bertram; Bordel, Hartmut; Höfler, Bernd; Eherer, Andreas J; Wolf, Eva-Maria; Rehak, Peter; Vieth, Michael

2014-07-01

The origin and significance of cardiac mucosa at the gastro-oesophageal junction are controversial. In the prospective Central European multicentre histoGERD trial, we aimed to assess the prevalence of cardiac mucosa, characterized by the presence of glands composed of mucous cells without parietal cells, and to relate its presence to features related to gastro-oesophageal reflux disease (GORD). One thousand and seventy-one individuals (576 females and 495 males; median age 53 years) were available for analysis. Overall, in biopsy specimens systematically taken from above and below the gastro-oesophageal junction, cardiac mucosa was observed in 713 (66.6%) individuals. Its presence was associated with patients' symptoms and/or complaints (P = 0.0025), histological changes of the squamous epithelium (P gastro-oesophageal junction. Its association with reflux symptoms, histological changes indicating GORD and the endoscopic diagnosis of oesophagitis suggests that injury and repair related to GORD contribute to its development and/or expansion. © 2014 John Wiley & Sons Ltd.

METHODOLOGICAL APPROACHES TO EXPERT EVALUATION OF PRECLINICAL AND CLINICAL TRIALS OF HUMAN IMMUNOGLOBULIN PRODUCTS

Directory of Open Access Journals (Sweden)

V. B. Ivanov

2017-01-01

Full Text Available The article considers the experience of Russian and leading foreign regulatory agencies in organisation and conduction of preclinical and clinical trials of human immunoglobulin products. The authors suggest a classification of human immunoglobulins and provide updated information on authorization of these products in Russia. The article summarizes methodological approaches, basic scientific principles and criteria relating to expert evaluation of preclinical and clinical trials of blood products. The authors further define the expert body’s requirements for data on preclinical and clinical trials of human normal immuniglobulins and human specific immunoglobulins for the prevention and/or treatment of infectious and non-infectious diseases which are submitted as part of applications for marketing authorization or marketing authorization variation. The article suggests programs of preclinical and clinical trials for human normal immunoglobulins and human specific immunoglobulins for the prevention and/or treatment of infectious and non-infectious diseases that are aligned with the Russian legislation and Eurasian Economic Union’s regulations on medicines circulation, and have been elaborated with respect to the guidelines of the European Medicines Agency.

Good for your health? An analysis of the requirements for scientific substantiation in European health claims regulation

Directory of Open Access Journals (Sweden)

Oliver Todt

2016-05-01

Full Text Available Objective. To identify the various types of evidence, as well as their relative importance in European health claims regulation, in order to analyze the consequences for consumer protection of the requirements for scientific substantiation in this regulation. Materials and methods. Qualitative analysis of various documents relevant to the regulatory process, particularly as to the implications of the standards of proof for the functional food market, as well as consumer behavior. Results. European regulation defines a hierarchy of evidence that turns randomized controlled trials into a necessary and sufficient condition for health claim autho- rizations. Conclusions. Consumer protection can be interpreted in different manners. High standards of proof protect consumers from false information about the health outcomes of functional foods, while lower standards lead to more, albeit less accurate information about such outcomes being available to consumers.

European environmental stratifications and typologies

DEFF Research Database (Denmark)

Hazeu, G.W,; Metzger, M.J.; Mücher, C.A.

2011-01-01

their limitations and challenges. As such, they provide a sound basis for describing the factors affecting the robustness of such datasets. The latter is especially relevant, since there is likely to be further interest in European environmental assessment. In addition, advances in data availability and analysis......A range of new spatial datasets classifying the European environment has been constructed over the last few years. These datasets share the common objective of dividing European environmental gradients into convenient units, within which objects and variables of interest have relatively homogeneous...... scale. This paper provides an overview of five recent European stratifications and typologies, constructed for contrasting objectives, and differing in spatial and thematic detail. These datasets are: the Environmental Stratification (EnS), the European Landscape Classification (LANMAP), the Spatial...

European academy of dermatology and venereology European prurigo project: expert consensus on the definition, classification and terminology of chronic prurigo.

Science.gov (United States)

Pereira, M P; Steinke, S; Zeidler, C; Forner, C; Riepe, C; Augustin, M; Bobko, S; Dalgard, F; Elberling, J; Garcovich, S; Gieler, U; Gonçalo, M; Halvorsen, J A; Leslie, T A; Metz, M; Reich, A; Şavk, E; Schneider, G; Serra-Baldrich, E; Ständer, H F; Streit, M; Wallengren, J; Weller, K; Wollenberg, A; Bruland, P; Soto-Rey, I; Storck, M; Dugas, M; Weisshaar, E; Szepietowski, J C; Legat, F J; Ständer, S

2017-08-31

The term prurigo has been used for many decades in dermatology without clear definition, and currently used terminology of prurigo is inconsistent and confusing. Especially, itch-related prurigo remains unexplored regarding the epidemiology, clinical profile, natural course, underlying causes, available treatments and economic burden, although burdensome and difficult to treat. To address these issues, the multicentre European Prurigo Project (EPP) was designed to increase knowledge on chronic prurigo (CPG). In the first step, European experts of the EADV Task Force Pruritus (TFP) aimed to achieve a consensus on the definition, classification and terminology of CPG. Additionally, procedures of the cross-sectional EPP were discussed and agreed upon. Discussions and surveys between members of the TFP served as basis for a consensus conference. Using the Delphi method, consensus was defined as an agreement ≥75% among the present members. Twenty-four members of the TFP participated in the consensus conference. Experts consented that CPG should be used as an umbrella term for the range of clinical manifestations (e.g. papular, nodular, plaque or umbilicated types). CPG is considered a distinct disease defined by the presence of chronic pruritus for ≥6 weeks, history and/or signs of repeated scratching and multiple localized/generalized pruriginous skin lesions (whitish or pink papules, nodules and/or plaques). CPG occurs due to a neuronal sensitization to itch and the development of an itch-scratch cycle. This new definition and terminology of CPG should be implemented in dermatology to harmonize communication in the clinical routine, clinical trials and scientific literature. Acute/subacute forms of prurigo are separated entities, which need to be differentiated from CPG and will be discussed in a next step. In the near future, the cross-sectional EPP will provide relevant clinical data on various aspects of CPG leading to new directions in the scientific

"We have made Europe, now we have to make Europeans." Researching European Identity Among Flemish Youths

Directory of Open Access Journals (Sweden)

Petra Huyst

2008-12-01

Full Text Available After the rejection of the European Constitution in 2005, questions were raised about if and how European citizens feel connected to the European Union (EU. This article examines the image young, Flemish people have of the EU and whether they feel some sense of belonging in the EU. The research draws upon a qualitative study in which Flemish young people were asked how they felt towards the EU and how they perceived it. Using a social-constructionist perspective, the first part of the article concentrates on the concept of European identity and the theoretical divide between a civic and a cultural European political identity, as proposed by Bruter (2004. The second part of the article focuses on the results of a series of focus groups with young people (aged 17 to 19, held in spring 2007. The article argues that no strong European identity is yet present in the hearts and minds of these young people, although contexts and interactions might evoke a limited notion of European identity. This article offers an empirical account of a theoretical debate and presents a critical understanding of the dynamics at play in European identity construction.

The technical report on sodium intake and cardiovascular disease in low- and middle-income countries by the joint working group of the World Heart Federation, the European Society of Hypertension and the European Public Health Association.

Science.gov (United States)

Mancia, Giuseppe; Oparil, Suzanne; Whelton, Paul K; McKee, Martin; Dominiczak, Anna; Luft, Friedrich C; AlHabib, Khalid; Lanas, Fernando; Damasceno, Albertino; Prabhakaran, Dorairaj; La Torre, Giuseppe; Weber, Michael; O'Donnell, Martin; Smith, Sidney C; Narula, Jagat

2017-03-07

Ingestion of sodium is essential to health, but excess sodium intake is a risk factor for hypertension and cardiovascular disease. Defining an optimal range of sodium intake in populations has been challenging and controversial. Clinical trials evaluating the effect of sodium reduction on blood pressure have shown blood pressure lowering effects down to sodium intake of less than 1.5 g/day. Findings from these blood pressure trials form the basis for current guideline recommendations to reduce sodium intake to less than 2.3 g/day. However, these clinical trials employed interventions that are not feasible for population-wide implementation (i.e. feeding studies or intensive behavioural interventions), particularly in low and middle-income countries. Prospective cohort studies have identified the optimal range of sodium intake to reside in the moderate range (3-5 g/day), where the risk of cardiovascular disease and death is lowest. Therefore, there is consistent evidence from clinical trials and observational studies to support reducing sodium intake to less than 5 g/day in populations, but inconsistent evidence for further reductions below a moderate intake range (3-5 g/day). Unfortunately, there are no large randomized controlled trials comparing low sodium intake ( 5 g/day), which should be embedded within an overall healthy dietary pattern. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For Permissions, please email: journals.permissions@oup.com.

New Serbian criminal procedure: New reasons for harmonization with European legal standards

Directory of Open Access Journals (Sweden)

Đurđić Vojislav

2014-01-01

Full Text Available The new criminal procedure, set forth in 2011, represents a compilation of the inquisitive model of preliminary proceedings, on the one hand, and adversarial trial of the Anglo-American type of criminal procedure on the other. Introduction of the public prosecutor's investigation required a subtle legislative approach to the protection of human rights in criminal proceedings, in order to establish equilibrium between efficient and just procedure. Instead of the expected, the erroneous conception based on the ideas that the public prosecutor's investigation should be strictly formal as that of a court, that evidence taken by the non-judicial authorities should have the same bearing as those taken by the courts, and that the court should have no role in conducting investigation, resulted in an overly inferior position of the accuses compared to that of the public prosecutor. Beside the fact that such conception can not pass the ECJ test, the specific legal solutions referring the investigation open the question of harmonization with the European legal standards. The provisions on initiation of this phase of the proceedings, not being legally sanctioned, put in question the right of the accused to access justice, as well as his right to an effective legal remedy, and the introduced investigation against the unknown perpetrator, the right to be present at one's own trial is being jeopardized. Neither do all procedural rules pertaining to the trial support the fair procedure principle: the indirect extortion of evidence from the defense is discordant with the rule that the burden of proof lies on the prosecutor, as one of the main pillars of the assumption of innocence; as well as the broad opportunity to use non-judicial evidence at the hearing without any major legal obstacles, have demolished the principles of directness and contradictoriness. Even some of the minimal right of the defense as well as the guarantees of personal freedom in the course

ESN information bulletin. European science notes information bulletin reports on current European/Middle eastern science

Energy Technology Data Exchange (ETDEWEB)

Orendorf, C.R.

1990-06-01

The European Science Notes Information Bulletin (ESNIB) 90-05 is a compilation of reports on recent developments in European science of specific interest to the U.S. research and development community, and is issued in support of the mission of the Office of Naval Research European Office. Issue Number 90-05, in addition to European area news, notes, and abstracts, contains reports in the fields of Acoustics, Atmospheric Electricity, Computer Science, Electronics, and Physics. The value of the ESNIB to Americans is to call attention to current activity in European science and technology and to identify the institutions and people responsible for these efforts. The ESNIB authors are primarily ONREUR staff members; other reports are prepared by or in cooperation with staff members of the USAF European Office of Aerospace Research and Development or the U.S. Army Research, Development and Standardination Group. Scientists from the U.S. who are traveling in Europe may also be invited to submit reports.

Study protocol of European Fans in Training (EuroFIT: a four-country randomised controlled trial of a lifestyle program for men delivered in elite football clubs

Directory of Open Access Journals (Sweden)

Femke van Nassau

2016-07-01

Full Text Available Abstract Background Lifestyle interventions targeting physical activity, sedentary time and dietary behaviours have the potential to initiate and support behavioural change and result in public health gain. Although men have often been reluctant to engage in such lifestyle programs, many are at high risk of several chronic conditions. We have developed an evidence and theory-based, gender sensitised, health and lifestyle program (European Fans in Training (EuroFIT, which is designed to attract men through the loyalty they feel to the football club they support. This paper describes the study protocol to evaluate the effectiveness and cost-effectiveness of the EuroFIT program in supporting men to improve their level of physical activity and reduce sedentary behaviour over 12 months. Methods The EuroFIT study is a pragmatic, two-arm, randomised controlled trial conducted in 15 football clubs in the Netherlands, Norway, Portugal and the UK (England. One-thousand men, aged 30 to 65 years, with a self-reported Body Mass Index (BMI ≥27 kg/m2 will be recruited and individually randomised. The primary outcomes are objectively-assessed changes in total physical activity (steps per day and total sedentary time (minutes per day at 12 months after baseline assessment. Secondary outcomes are weight, BMI, waist circumference, resting systolic and diastolic blood pressure, cardio-metabolic blood biomarkers, food intake, self-reported physical activity and sedentary time, wellbeing, self-esteem, vitality and quality of life. Cost-effectiveness will be assessed and a process evaluation conducted. The EuroFIT program will be delivered over 12 weekly, 90-minute sessions that combine classroom discussion with graded physical activity in the setting of the football club. Classroom sessions provide participants with a toolbox of behaviour change techniques to initiate and sustain long-term lifestyle changes. The coaches will receive two days of training to

The Europeanization of National Judiciaries

DEFF Research Database (Denmark)

Jaremba, Urszula; Mayoral, Juan A.

2018-01-01

judiciaries is still somewhat scattered and fragmented. The central ambition of this article is to provide a theoretical framework that would contribute to the understanding of Europeanization of judiciaries by: 1) offering a definition and theoretical developments useful for the study Europeanization and its......The article is underpinned by the idea that the national courts/judges are expected to act as decentralized European Union judges. However, the general knowledge concerning the impact of EU law on the functioning of national courts as EU judges and the process of Europeanization of national...

25-Hydroxyvitamin-D3 serum modulation after use of sunbeds compliant with European Union standards: A randomized open observational controlled trial.

Science.gov (United States)

Weber, Benedikt; Bachmann, Chantal C; Braun, Ralph; Abraham, Alison G; Serra, Andreas L; Hofbauer, Günther F L

2017-07-01

Regular use of sunbed exposure has been reported to increase 25-hydroxyvitamin-D3 [25(OH)D] serum levels. However, the influence of sunbeds compliant with the recent European Union standard EN-60335-2-27 on 25(OH)D serum levels is unknown. We investigated the impact of standard sunbed use compliant with the European Union standard on 25(OH)D serum modulation and well-being. In a randomized controlled study, 25(OH)D serum levels were measured at enrollment, after 1 week, and after completion of the 12-week period of sunbed use with twice weekly exposure and compared with the control group without any sunbed exposure. In the sunbed intervention group (N = 31), a 27% increase of mean 25(OH)D levels was noted 1 week after starting sunbed use (P European Union standard induced a transient increase of 25(OH)D levels, whereas no change in well-being was observed. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

The European Hematology Association Roadmap for European Hematology Research: a consensus document.