Ticagrelor, but not clopidogrel active metabolite, displays antithrombotic properties in the left atrial endocardium.

Science.gov (United States)

Reiner, Martin F; Breitenstein, Alexander; Holy, Erik W; Glanzmann, Martina; Amstalden, Heidi; Stämpfli, Simon F; Bonetti, Nicole R; Falk, Volkmar; Keller, Stephan; Savarese, Gianluigi; Benussi, Stefano; Maisano, Francesco; Lüscher, Thomas F; Beer, Jürg H; Steffel, Jan; Camici, Giovanni G

2017-03-21

Oral anticoagulation is considered standard therapy for stroke prevention in atrial fibrillation (AF). Endocardial activation triggers expression of pro-thrombotic mediators including tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1), and contributes to thrombus formation in the left atrial appendage (LAA) of AF patients. Recently, pleiotropic effects of specific P2Y12 receptor antagonists were demonstrated; however, whether these drugs possess antithrombotic effects on LAA endocardial cells currently remains unknown. LAA were obtained from 14 patients with known AF undergoing elective cardiac surgery including LAA removal at the University Hospital Zurich. LAA endocardial cells were isolated and pre-incubated with ticagrelor (10-7, 10-6, 10-5M) or clopidogrel active metabolite (CAM) (1.5 × 10-8, 1.5 × 10-7, 1.5 × 10-6 M) before stimulation with tumour necrosis factor-alpha (TNF-α) (10 ng/mL). Finally, TF and PAI-1 expression and activity were analysed. Ticagrelor, unlike CAM, concentration dependently decreased TNF-α-induced TF expression and TF activity in LAA endocardial cells. Further, ticagrelor, but not CAM reduced PAI-1 expression and enzyme activity in TNF-α-stimulated LAA endocardial cells. In contrast, TF pathway inhibitor (TFPI) remained unaffected by both dugs. Ticagrelor, but not CAM, reduces expression and activity of TF and PAI-1 in LAA endocardial cells isolated from patients with AF, indicating possible local antithrombotic effects. Such pleiotropic properties of ticagrelor may contribute to a reduction in thromboembolic complications in patients with AF. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Pre-hospital ticagrelor in patients with ST-segment elevation myocardial infarction with long transport time to primary PCI facility.

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Lupi, Alessandro; Schaffer, Alon; Lazzero, Maurizio; Tessitori, Massimo; De Martino, Leonardo; Rognoni, Andrea; Bongo, Angelo S; Porto, Italo

2016-12-01

Pre-hospital ticagrelor, given less than 1h before coronary intervention (PCI), failed to improve coronary reperfusion in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary PCI. It is unknown whether a longer interval from ticagrelor administration to primary PCI might reveal any improvement of coronary reperfusion. We retrospectively compared 143 patients, pre-treated in spoke centers or ambulance with ticagrelor at least 1.5h before PCI (Pre-treatment Group), with 143 propensity score-matched controls treated with ticagrelor in the hub before primary PCI (Control Group) extracted from RENOVAMI, a large observational Italian registry of more than 1400 STEMI patients enrolled from Jan. 2012 to Oct. 2015 (ClinicalTrials.gov id: NCT01347580). The median time from ticagrelor administration and PCI was 2.08h (95% CI 1.66-2.84) in the Pre-treatment Group and 0.56h (95% CI 0.33-0.76) in the Control Group. TIMI flow grade before primary PCI in the infarct related artery was the primary endpoint. The primary endpoint, baseline TIMI flow grade, was significantly higher in Pre-treatment Group (0.88±1.14 vs 0.53±0.86, P=0.02). However in-hospital mortality, in-hospital stent thrombosis, bleeding rates and other clinical and angiographic outcomes were similar in the two groups. In a real world STEMI network, pre-treatment with ticagrelor in spoke hospitals or in ambulance loading at least 1.5h before primary PCI is safe and might improve pre-PCI coronary reperfusion, in comparison with ticagrelor administration immediately before PCI. Copyright © 2016 Elsevier Inc. All rights reserved.

Pharmacodynamic Comparison of Prasugrel Versus Ticagrelor in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease: The OPTIMUS (Optimizing Antiplatelet Therapy in Diabetes Mellitus)-4 Study.

Science.gov (United States)

Franchi, Francesco; Rollini, Fabiana; Aggarwal, Niti; Hu, Jenny; Kureti, Megha; Durairaj, Ashwin; Duarte, Valeria E; Cho, Jung Rae; Been, Latonya; Zenni, Martin M; Bass, Theodore A; Angiolillo, Dominick J

2016-09-13

Patients with diabetes mellitus (DM) are at increased risk of atherothrombotic events, underscoring the importance of effective platelet inhibiting therapies. Prasugrel and ticagrelor reduce thrombotic complications to a greater extent than clopidogrel. Subgroup analyses of pivotal clinical trials testing prasugrel and ticagrelor versus clopidogrel showed DM patients to have benefits that were consistent with the overall trial populations, although the magnitude of the ischemic risk reduction appeared to be enhanced with prasugrel. Whether these findings may be attributed to differences in the pharmacodynamic profiles of these drugs in DM patients remains poorly explored and represented the aim of this study. In this prospective, randomized, double-blind, double-dummy, crossover pharmacodynamic study, aspirin-treated DM patients (n=50) with coronary artery disease were randomly assigned to receive prasugrel (60 mg loading dose [LD]/10 mg maintenance dose once daily) or ticagrelor (180 mg LD/90 mg maintenance dose twice daily) for 1 week. Pharmacodynamic assessments were conducted using 4 different assays, including VerifyNow P2Y12, vasodilator-stimulated phosphoprotein, light transmittance aggregometry, and Multiplate, which allowed us to explore ADP- and non-ADP-induced (arachidonic acid-, collagen-, thrombin receptor-activating, peptide-induced) platelet signaling pathways. The acute (baseline, 30 minutes, and 2 hours post-LD) and maintenance (1 week) effects of therapy were assessed. The primary end point of the study was the comparison of P2Y12 reaction units determined by VerifyNow P2Y12 at 1 week between prasugrel and ticagrelor. ADP- and non-ADP-induced measures of platelet reactivity reduced significantly with both prasugrel and ticagrelor LD and maintenance dose. P2Y12 reaction units defined by VerifyNow were similar between prasugrel and ticagrelor at 30 minutes and 2 hours post-LD. At 1 week, P2Y12 reaction units were significantly lower with ticagrelor

Comparison of bioavailability and antiplatelet action of ticagrelor in patients with ST-elevation myocardial infarction and non-ST-elevation myocardial infarction: A prospective, observational, single-centre study.

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Piotr Adamski

Full Text Available Data from available studies suggest that the presence of ST-elevation myocardial infarction (STEMI may be associated with delayed and attenuated ticagrelor bioavailability and effect compared with non-ST-elevation myocardial infarction (NSTEMI.In a single-center, prospective, observational trial 73 patients with myocardial infarction (STEMI n = 49, NSTEMI n = 24 underwent a pharmacokinetic and pharmacodynamic assessment after a 180 mg ticagrelor loading dose (LD. Ticagrelor and its active metabolite (AR-C124910XX plasma concentrations were determined with liquid chromatography tandem mass spectrometry, and their antiplatelet effect was measured with the VASP assay and multiple electrode aggregometry.During the first six hours after ticagrelor LD, STEMI patients had 38% and 34% lower plasma concentration of ticagrelor and AR-C124910XX, respectively, than NSTEMI (ticagrelor AUC(0-6: 2491 [344-5587] vs. 3991 [1406-9284] ng*h/mL; p = 0.038; AR-C124910XX AUC(0-6: 473 [0-924] vs. 712 [346-1616] ng*h/mL; p = 0.027. STEMI patients also required more time to achieve maximal concentration of ticagrelor (tmax: 4.0 [3.0-12.0] vs. 2.5 [2.0-6.0] h; p = 0.012. Impaired bioavailability of ticagrelor and AR-C124910XX seen in STEMI subjects was associated with diminished platelet inhibition in this group, which was most pronounced during the initial hours of treatment.Plasma concentrations of ticagrelor and AR-C124910XX during the first hours after ticagrelor LD were one third lower in STEMI than in NSTEMI patients. This reduced and delayed ticagrelor bioavailability was associated with weaker antiplatelet effect in STEMI.ClinicalTrials.gov identifier: NCT02602444 (November 09, 2015.

Effect of Pre-Hospital Ticagrelor During the First 24 h After Primary Percutaneous Coronary Intervention in Patients With ST-Segment Elevation Myocardial Infarction

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Montalescot, Gilles; van 't Hof, Arnoud W; Bolognese, Leonardo

2016-01-01

OBJECTIVES: The aim of this landmark exploratory analysis, ATLANTIC-H(24), was to evaluate the effects of pre-hospital ticagrelor during the first 24 h after primary percutaneous coronary intervention (PCI) in the ATLANTIC (Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST...... hypothesized that the effect of pre-hospital ticagrelor may not have manifested until after PCI due to the rapid transfer time (31 min). METHODS: The ATLANTIC-H(24) analysis included 1,629 patients who underwent PCI, evaluating platelet reactivity, Thrombolysis In Myocardial Infarction flow grade 3, ≥ 70% ST...... except death (1.1% vs. 0.2%; p = 0.048) favored pre-hospital ticagrelor, with no differences in bleeding events. CONCLUSIONS: The effects of pre-hospital ticagrelor became apparent after PCI, with numerical differences in platelet reactivity and immediate post-PCI reperfusion, associated with reductions...

Effect of loading-dose ticagrelor on coronary blood flow, left ventricular remodeling and myocardial enzyme spectrum in patients with acute myocardial infarction after interventional therapy

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Xiao-Rui Xie

2016-12-01

Full Text Available Objective: To study the effect of loading-dose ticagrelor on coronary blood flow, left ventricular remodeling and myocardial enzyme spectrum in patients with acute myocardial infarction after interventional therapy. Methods: A total of 86 patients with acute myocardial infarction who received emergency PCI in our hospital between May 2013 and May 2016 were selected and randomly divided into two groups, ticagrelor group received perioperative ticagrelor therapy and clopidogrel group received perioperative clopidogrel therapy. After PCI, coronary blood flow reperfusion was evaluated, serum myocardial remodeling indexes and myocardial enzymes were determined, and cardiac color Doppler ultrasonography was conducted to determine the cardiac function indexes. Results: TIMI grading and TMPG grading of ticagrelor group after PCI were significantly higher than those of clopidogrel group; serum MMP9, BNP, CITP, PICP, PIIINP, CK, CK-MB, cTnI and cTnT content of ticagrelor group 24h after operation were significantly lower than those of clopidogrel group; LVEDD, LVSED and LVMI of ticagrelor group 2 weeks after operation were significantly lower than those of clopidogrel group while LVEF was significantly higher than that of clopidogrel group. Conclusion: Peri-PCI loading-dose ticagrelor can improve coronary blood perfusion and reduce ventricular remodeling and myocardial injury in patients with acute myocardial infarction.

Long-term cost-effectiveness of ticagrelor versus clopidogrel in acute coronary syndrome in Spain

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E. Molina-Cuadrado

2014-07-01

Full Text Available Objective: To assess the cost-effectiveness relationship of Ticagrelor versus Clopidogrel for the management of acute coronary syndrome in Spain. Methods: The data from the PLATO study were used for the calculation of the events rate and health-related quality of life for Ticagrelor and Clopidogrel for the first 12 months, whereas the costs were obtained from Spanish sources. Quality of lifeadjusted survival and costs were estimated according to the fact that the patients did not suffer any thrombotic event (myocardial infarction or ictus or this one was not fatal. The lifetime cots, life years gained, and the quality of life-adjusted survival were estimated for both treatment arms. Incremental costeffectiveness ratios were assessed through the perspective of the Spanish healthcare system for 2013, by using a macro-costs strategy based on published literature and the survival tables for the Spanish population. Results: Treatment with Ticagrelor was associated to an incremental cost of 1,228 per year, an increase in 0.1652 life years gained, and 0.1365 years adjusted by quality of life, as compared to Clopidogrel. The cost for one quality of life-adjusted life year was 8,997 and the cost per one gained life year of 7,435 . The sensitivity analysis showed consistent results. Conclusions: Treatment of acute coronary syndrome for 12 months with Ticagrelor was associated with a cost per 1 life year of quality of life-adjusted cost below the cost-effectiveness limits generally accepted in Spain.

Contemporary use of ticagrelor in patients with acute coronary syndrome: insights from Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART).

Science.gov (United States)

Sahlén, Anders; Varenhorst, Christoph; Lagerqvist, Bo; Renlund, Henrik; Wallentin, Lars; James, Stefan K; Jernberg, Tomas

2016-01-01

The platelet inhibitor ticagrelor is strongly recommended during 12 months post-acute coronary syndrome (ACS) in European guidelines. We analysed clinical characteristics of patients given ticagrelor for ACS in the real world. We studied the use of ticagrelor in patients admitted for ACS in Sweden between 1 January 2012 and 31 December 2013 who were enrolled in the Swedish Web system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART). Clinical characteristics were investigated for patients prescribed ticagrelor at discharge as well as for patients undergoing percutaneous coronary intervention who were prescribed ticagrelor. Independent factors associated with selecting ticagrelor were analysed in logistic regression. We found that 44.0% (n = 12 601) out of a total of 28 639 patients had been prescribed ticagrelor at discharge. After adjusting for age and sex, prior cardiovascular disease was less common in patients discharged on ticagrelor (myocardial infarction, ischaemic stroke, and peripheral vascular disease; P for all <0.001). The risk of death as predicted by GRACE score and the risk of major bleeding as predicted by CRUSADE score were both lower in ticagrelor-treated patients vs. others (median 99 vs. 126 and median 23 vs. 25, respectively; P for both < 0.001). The intended treatment duration at discharge was 12 months in 82.5% of patients and <12 months in 9.3%. Ticagrelor is preferentially being used in patients at lower risk. A minority of patients are recommended ticagrelor during <12 months. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Dual antiplatelet therapy with prasugrel or ticagrelor versus clopidogrel in interventional cardiology

DEFF Research Database (Denmark)

Clemmensen, Peter; Dridi, Nadia Paarup; Holmvang, Lene

2013-01-01

For several years, clopidogrel plus aspirin has been the dual antiplatelet therapy (DAPT) of choice for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) with stent implantation. More recently, prasugrel and ticagrelor have demonstrated greater effica...

Ticagrelor-Induced Angioedema: A Rare and Unexpected Phenomenon

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Rajeev Seecheran

2017-01-01

Full Text Available Angioedema can cause potentially life-threatening airway obstruction. This case report describes an exceedingly rare episode of ticagrelor-induced hypersensitivity reaction, manifesting as angioedema with periorbital and likely respiratory involvement. The heart team should be vigilant for this precarious condition which may require emergent airway management. Desensitization protocols and alternative regimens (e.g., clopidogrel, prasugrel, and addition of an adjunctive anticoagulant should be considered when there is an absolute indication for antiplatelet therapy.

Laquinimod Safety Profile

DEFF Research Database (Denmark)

Sørensen, Per Soelberg; Comi, Giancarlo; Vollmer, Timothy L

2017-01-01

the safety profile of laquinimod versus placebo. Adverse events (AEs), laboratory value changes, and potential risks identified in preclinical studies were evaluated in participants in ALLEGRO and BRAVO treated with at least one dose of laquinimod or matching placebo (1:1 random assignment). RESULTS...... laquinimod studies demonstrate a safety profile comprising benign or manageable AEs and asymptomatic laboratory findings with a clear temporal pattern. Potential risks noted in preclinical studies were not observed....

Spontaneous subdural hematoma and antiplatelet therapy: Does efficacy of Ticagrelor come with added risk?

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Pattanagere Manjunatha Suryanarayana Sharma

2015-12-01

Full Text Available Antiplatelet therapy has established clinical benefit on cardiovascular outcome and has reduced the rates of re-infarction/in stent thrombosis following percutaneous coronary intervention in acute coronary syndromes. Major bleeding episodes can occur with antiplatelet therapy and intracranial hemorrhage (ICH is one of the most feared complications resulting in significant morbidity and mortality. Identification of high risk groups and judicious use of antiplatelet therapy reduces the bleeding risk. Ticagrelor is a newer P2Y12 receptor antagonist with established clinical benefit. However, risks of having an ICH with these newer molecules cannot be ignored. Here, we report a case of spontaneous acute subdural hematoma developing in a patient on antiplatelet therapy with aspirin and ticagrelor. Early recognition, discontinuation of the medication and appropriate management resulted in resolution of hematoma and good clinical outcome. Authors have reviewed the antithrombotic drugs and their tendencies in causing intracranial bleeds from a neurophysicians perspective.

A Profile for Safety Critical Java

DEFF Research Database (Denmark)

Schoeberl, Martin; Søndergaard, Hans; Thomsen, Bent

2007-01-01

We propose a new, minimal specification for real-time Java for safety critical applications. The intention is to provide a profile that supports programming of applications that can be validated against safety critical standards such as DO-178B [15]. The proposed profile is in line with the Java...... specification request JSR-302: Safety Critical Java Technology, which is still under discussion. In contrast to the current direction of the expert group for the JSR-302 we do not subset the rather complex Real-Time Specification for Java (RTSJ). Nevertheless, our profile can be implemented on top of an RTSJ...

The effect of TIcagrelor administered through a nasogastric tube to COMAtose patients undergoing acute percutaneous coronary intervention

DEFF Research Database (Denmark)

Ratcovich, Hanna; Sadjadieh, Golnaz; Andersson, Hedvig B

2017-01-01

resuscitated after an out of hospital cardiac arrest (OHCA) and undergoing primary percutaneous coronary intervention (pPCI). METHODS AND RESULTS: Blood samples were drawn at baseline and at two, four, six, eight, 12, and 24 hours and then daily for up to five days after administration of a 180 mg ticagrelor...... loading dose (LD), followed by 90 mg twice daily in 44 patients. The primary endpoint was the occurrence of high platelet reactivity (HPR) 12 hours after the LD. Assessment by VerifyNow (VFN) showed 96 (15.25-140.5) platelet reactivity units (PRU), and five (12%) patients exhibited HPR. Multiplate...... analysis showed 19 (12-29) units (U) at twelve hours, and three patients (7%) had HPR. Ticagrelor and its main metabolite AR-C124910XX concentrations were 85.2 (37.2-178.5) and 18.3 (6.4-52.4) ng/mL. Median times to sufficient platelet inhibition below the HPR limit were 3 (2-6) hours (VFN) and 4 (2...

Direct healthcare costs and cost-effectiveness of acute coronary syndrome secondary prevention with ticagrelor compared to clopidogrel: economic evaluation from the public payer's perspective in Poland based on the PLATO trial results.

Science.gov (United States)

Pawęska, Justyna; Macioch, Tomasz; Perkowski, Piotr; Budaj, Andrzej; Niewada, Maciej

2014-01-01

Ticagrelor is the first reversibly binding oral P2Y12 receptor antagonist designed to reduce clinical thrombotic events in patients with acute coronary syndrome (ACS). Compared to clopidogrel, ticagrelor has been proven to significantly reduce the rate of death from vascular causes, myocardial infarction (MI), or stroke without an increase in the rate of overall major bleeding in patients who have an ACS with or without ST-segment elevation (STEMI and NSTEMI) or unstable angina (UA). To evaluate the cost-effectiveness and healthcare costs associated with secondary prevention of ACS using ticagrelor or clopidogrel in patients after STEMI, NSTEMI and UA. An economic model based on results from the PLATO trial was used to evaluate the cost-effectiveness of one-year therapy with ticagrelor or clopidogrel. The structure of the model consisted of two parts, i.e. the decision tree with one-year PLATO results and the Markov model with lifelong estimations, which exceeded PLATO follow-up data. The model was adjusted to Polish settings with country-specific data on death rates in the general population and direct medical costs calculated from the public payer's perspective. Costs were derived from the National Health Fund (NHF) and the Ministry of Health and presented in PLN 2013 values. Annual mean costs of second and subsequent years after stroke or MI were obtained from the literature. Uncertainty of assumed parameters was tested in scenarios and probabilistic sensitivity analyses. The adopted model allowed the estimation of an incremental cost-effectiveness ratio for life years gained (LYG) and an incremental cost-utility ratio for quality adjusted life years (QALY). Total direct medical costs to the public payer at a one year horizon were 2,905 PLN higher with ticagrelor than with clopidogrel. However, mean healthcare costs at a one year horizon (excluding drug costs and concomitant drugs) were 690 PLN higher for patients treated with clopidogrel. In a lifetime horizon

The experimental and theoretical landscape of a new antiplatelet drug ticagrelor: Insight into supramolecular architecture directed by Csbnd H⋯F, π⋯π and Csbnd H⋯π interactions

Science.gov (United States)

Bojarska, Joanna; Remko, Milan; Fruziński, Andrzej; Maniukiewicz, Waldemar

2018-02-01

The crystal and molecular structure landscape of a new drug ticagrelor has been investigated by using experimental and theoretical approach. The structures of this cyclopentyl-triazolo-pyrimidine derivative, (1) and its DMSO solvate (2), were determined by SC-XRD at 100 K. (1) crystallizes in the orthorhombic space group P21212 with four independent molecules, while (2) belongs to the monoclinic system with the space group C2, including two ticagrelor and 0.5 DMSO molecules in the asymmetric unit. Both crystals present diverse interactions, such as: Osbnd H⋯O, Nsbnd H⋯O and Csbnd H⋯X (X = O, N, F, S). H-bonds between Ntriazolopyrimidine and sbnd OH groups of cyclopentane-1,2-diol ring connect ticagrelor molecules into dimers forming three fused rings, encoded as R22(9) and R22(10) graph-set motifs, which are further linked by Chydroxyethoxy-H⋯Fsbnd C3,4difluorophenyl into a supramolecular chain. A comparative insight into the studies of all contacts in the crystal lattices of ticagrelors and other related adenosine derivatives from the CSD was provided using Hirshfeld surface analysis. It highlights a significant difference in terms of various substituents. Notably, F⋯H/H⋯F are more meaningful than O⋯H/H⋯O and N⋯H/H⋯N H-bonds. The π⋯π stacking and Csbnd H⋯π interactions participate in a cooperative way to stabilize the supramolecular architecture. The geometry of both ticagrelor forms was optimized in the gas-phase and solvated state, using the DFT method, at the Becke 3LYP/B97D level. The theoretical results show a good agreement with those obtained from the X-ray study. Moreover, structural elucidation of a new drug was extended by 1D 1H, 13C NMR, 2D 1H, 13C HSQC NMR, FT-IR and TG/DTG techniques.

[Safety profile of dolutegravir].

Science.gov (United States)

Rivero, Antonio; Domingo, Pere

2015-03-01

Integrase inhibitors are the latest drug family to be added to the therapeutic arsenal against human immunodeficiency virus infection. Drugs in this family that do not require pharmacological boosting are characterized by a very good safety profile. The latest integrase inhibitor to be approved for use is dolutegravir. In clinical trials, dolutegravir has shown an excellent tolerability profile, both in antiretroviral-naïve and previously treated patients. Discontinuation rates due to adverse effects were 2% and 3%, respectively. The most frequent adverse effects were nausea, headache, diarrhea and sleep disturbance. A severe hypersensitivity reaction has been reported in only one patient. In patients coinfected with hepatropic viruses, the safety profile is similar to that in patients without coinfection. The lipid profile of dolutegravir is similar to that of raltegravir and superior to those of Atripla® and darunavir/ritonavir. Dolutegravir induces an early, predictable and non-progressive increase in serum creatinine of around 10% of baseline values in treatment-naïve patients and of 14% in treatment-experienced patients. This increase is due to inhibition of tubular creatinine secretion through the OCT2 receptor and does not lead to a real decrease in estimated glomerular filtration rate with algorithms that include serum creatinine. The effect of the combination of dolutegravir plus Kivexa(®) on biomarkers of bone remodeling is lower than that of Atripla(®). Dolutegravir has an excellent tolerability profile with no current evidence of long-term adverse effects. Its use is accompanied by an early and non-progressive increase in serum creatinine due to OCT2 receptor inhibition. In combination with abacavir/lamivudine, dolutegravir has a lower impact than enofovir/emtricitabine/efavirenz on bone remodelling markers. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Functional Safety Specification of Communication Profile PROFIsafe

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Jan Rofar

2006-01-01

Full Text Available Paper maps the trends in area of safety-related communication within PROFIBUS and PROFINET industry networks. There are analyses safety measures and Fail-safe parameters of PROFIsafe profile in version V2 and their localisation in Safety Communication Layer SCL, which guarantees Safety Integrity Level SIL according to standard IEC 61508. The last chapter analyses the reaction in the event of fault during transmission of messages.

Safety and security profiles of industry networks used in safety- critical applications

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Mária FRANEKOVÁ

2008-01-01

Full Text Available The author describes the mechanisms of safety and security profiles of industry and communication networks used within safety – related applications in technological and information levels of process control recommended according to standards IEC 61784-3,4. Nowadays the number of vendors of the safety – related communication technologies who guarantees besides the standard communication, the communication amongst the safety – related equipment according to IEC 61508 is increasing. Also the number of safety – related products is increasing, e. g. safety Fieldbus, safety PLC, safety curtains, safety laser scanners, safety buttons, safety relays and other. According to world survey the safety Fieldbus denoted the highest growth from all manufactured safety products.The main part of this paper is the description of the safety-related Fieldbus communication system, which has to guaranty Safety Integrity Level.

Reducing Microvascular Dysfunction in Revascularized Patients with ST-Elevation Myocardial Infarction by Off-Target Properties of Ticagrelor versus Prasugrel. Rationale and Design of the REDUCE-MVI Study

NARCIS (Netherlands)

G.N. Janssens (Gladys N.); M.A.H. van Leeuwen (Maarten); N.W. van der Hoeven (Nina W.); G.A. de Waard (Guus); R. Nijveldt (Robin); R. Diletti (Roberto); F. Zijlstra (Felix); C. Von Birgelen (Clemens); J. Escaned (Javier); M. Valgimigli (Marco); N. van Royen (Niels)

2016-01-01

textabstractMicrovascular injury is present in a large proportion of patients with ST-elevation myocardial infarction (STEMI) despite successful revascularization. Ticagrelor potentially mitigates this process by exerting additional adenosine-mediated effects. This study aims to determine whether

Laser safety at high profile projects

Science.gov (United States)

Barat, K.

2011-03-01

Laser Safety at high profile laser facilities tends to be more controlled than in the standard laser lab found at a research institution. The reason for this is the potential consequences for such facilities from incidents. This ranges from construction accidents, to equipment damage to personnel injuries. No laser user wants to sustain a laser eye injury. Unfortunately, many laser users, most commonly experienced researchers and inexperienced graduate students, do receive laser eye injuries during their careers. . More unforgiveable is the general acceptance of this scenario, as part of the research & development experience. How do senior researchers, safety personnel and management stop this trend? The answer lies in a cultural change that involves institutional training, user mentoring, hazard awareness by users and administrative controls. None of these would inhibit research activities. As a matter of fact, proper implementation of these controls would increase research productivity. This presentation will review and explain the steps needed to steer an institution, research division, group or individual lab towards a culture that should nearly eliminate laser accidents. As well as how high profile facilities try to avoid laser injuries. Using the definition of high profile facility as one who's funding in the million to billions of dollars or Euros and derives form government funding.

The P2Y12 Receptor Antagonist Ticagrelor Reduces Lysosomal pH and Autofluorescence in Retinal Pigmented Epithelial Cells From the ABCA4-/- Mouse Model of Retinal Degeneration

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Wennan Lu

2018-04-01

Full Text Available The accumulation of partially degraded lipid waste in lysosomal-related organelles may contribute to pathology in many aging diseases. The presence of these lipofuscin granules is particularly evident in the autofluorescent lysosome-associated organelles of the retinal pigmented epithelial (RPE cells, and may be related to early stages of age-related macular degeneration. While lysosomal enzymes degrade material optimally at acidic pH levels, lysosomal pH is elevated in RPE cells from the ABCA4-/- mouse model of Stargardt’s disease, an early onset retinal degeneration. Lowering lysosomal pH through cAMP-dependent pathways decreases accumulation of autofluorescent material in RPE cells in vitro, but identification of an appropriate receptor is crucial for manipulating this pathway in vivo. As the P2Y12 receptor for ADP is coupled to the inhibitory Gi protein, we asked whether blocking the P2Y12 receptor with ticagrelor could restore lysosomal acidity and reduce autofluorescence in compromised RPE cells from ABCA4-/- mice. Oral delivery of ticagrelor giving rise to clinically relevant exposure lowered lysosomal pH in these RPE cells. Ticagrelor also partially reduced autofluorescence in the RPE cells of ABCA4-/- mice. In vitro studies in ARPE-19 cells using more specific antagonists AR-C69931 and AR-C66096 confirmed the importance of the P2Y12 receptor for lowering lysosomal pH and reducing autofluorescence. These observations identify P2Y12 receptor blockade as a potential target to lower lysosomal pH and clear lysosomal waste in RPE cells.

Pre-hospital ticagrelor in ST-segment elevation myocardial infarction in the French ATLANTIC population

DEFF Research Database (Denmark)

Cayla, Guillaume; Lapostolle, Frederic; Ecollan, Patrick

2017-01-01

BACKGROUND: ATLANTIC was a randomized study comparing pre- and in-hospital treatment with a ticagrelor loading dose (LD) in ongoing ST-segment elevation myocardial infarction (STEMI). We sought to compare patient characteristics and clinical outcomes in France with other countries participating...... in ATLANTIC. METHODS: The population comprised 1862 patients, 660 (35.4%) from France and 1202 from 12 other countries. The main endpoints were reperfusion (≥70% ST-segment elevation resolution) and TIMI flow grade 3 before (co-primary endpoints) and after percutaneous coronary intervention (PCI). Other...... endpoints included a composite ischaemic endpoint (death/myocardial infarction/stroke/urgent revascularization/definite stent thrombosis) and bleeding events at 30days. RESULTS: In France, median times from first LD to angiography and between first and second LDs were 49 and 35min, respectively, and were...

Prediction of Clinically Relevant Safety Signals of Nephrotoxicity through Plasma Metabolite Profiling

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W. B. Mattes

2013-01-01

Full Text Available Addressing safety concerns such as drug-induced kidney injury (DIKI early in the drug pharmaceutical development process ensures both patient safety and efficient clinical development. We describe a unique adjunct to standard safety assessment wherein the metabolite profile of treated animals is compared with the MetaMap Tox metabolomics database in order to predict the potential for a wide variety of adverse events, including DIKI. To examine this approach, a study of five compounds (phenytoin, cyclosporin A, doxorubicin, captopril, and lisinopril was initiated by the Technology Evaluation Consortium under the auspices of the Drug Safety Executive Council (DSEC. The metabolite profiles for rats treated with these compounds matched established reference patterns in the MetaMap Tox metabolomics database indicative of each compound’s well-described clinical toxicities. For example, the DIKI associated with cyclosporine A and doxorubicin was correctly predicted by metabolite profiling, while no evidence for DIKI was found for phenytoin, consistent with its clinical picture. In some cases the clinical toxicity (hepatotoxicity, not generally seen in animal studies, was detected with MetaMap Tox. Thus metabolite profiling coupled with the MetaMap Tox metabolomics database offers a unique and powerful approach for augmenting safety assessment and avoiding clinical adverse events such as DIKI.

Influenza vaccines: Evaluation of the safety profile

Science.gov (United States)

Trombetta, Claudia Maria; Gianchecchi, Elena; Montomoli, Emanuele

2018-01-01

ABSTRACT The safety of vaccines is a critical factor in maintaining public trust in national vaccination programs. Vaccines are recommended for children, adults and elderly subjects and have to meet higher safety standards, since they are administered to healthy subjects, mainly healthy children. Although vaccines are strictly monitored before authorization, the possibility of adverse events and/or rare adverse events cannot be totally eliminated. Two main types of influenza vaccines are currently available: parenteral inactivated influenza vaccines and intranasal live attenuated vaccines. Both display a good safety profile in adults and children. However, they can cause adverse events and/or rare adverse events, some of which are more prevalent in children, while others with a higher prevalence in adults. The aim of this review is to provide an overview of influenza vaccine safety according to target groups, vaccine types and production methods. PMID:29297746

Biological and haematological safety profile of oral amodiaquine ...

African Journals Online (AJOL)

Biological and haematological safety profile of oral amodiaquine and chloroquine in healthy volunteers with or without Plasmodium falciparum infection in northeast Tanzania. JJ Massaga, JP Lusingu, R Makunde, HM Malebo, MM Chile, JA Akida, MM Lemnge, AM Rønn, TG Theander, IC Bygbjerg, AY Kitua ...

Safety and Tolerability Profile of Artemisinin-Based Antimalarial ...

African Journals Online (AJOL)

The WHO in 2001 advocated artemisinin- based antimalarial combination therapy (ACT), which was adopted by Nigeria in 2005. The objective of this study was to characterize the safety and tolerability profile of the ACTs in adult patients with uncomplicated malaria. A descriptive longitudinal study was conducted in the ...

Cardiovascular events in acute coronary syndrome patients with peripheral arterial disease treated with ticagrelor compared to clopidogrel: Data from the PLATO trials

DEFF Research Database (Denmark)

Patel, Manesh R.; Becker, Richard C.; Wojdyla, Daniel M.

Abstract 14299: Cardiovascular Events in Acute Coronary Syndrome Patients With Peripheral Arterial Disease Treated With Ticagrelor Compared to Clopidogrel: Data From the PLATO Trial Manesh R Patel1; Richard C Becker1; Daniel M Wojdyla2; Håkan Emanuelsson3; William Hiatt4; Jay Horrow5; Steen Husted6...... Uppsala, Sweden 10 Cardiology, Uppsala Clinical Rsch center, 75185 Uppsala, Sweden Background: Patients with peripheral artery disease (PAD) and acute coronary syndrome (ACS) are at high risk for clinical events and are often difficult to manage. We evaluated cardiovascular outcomes of ACS patients...

Laser safety at high profile laser facilities

International Nuclear Information System (INIS)

Barat, K.

2010-01-01

Complete text of publication follows. Laser safety has been an active concern of laser users since the invention of the laser. Formal standards were developed in the early 1970's and still continue to be developed and refined. The goal of these standards is to give users guidance on the use of laser and consistent safety guidance and requirements for laser manufacturers. Laser safety in the typical research setting (government laboratory or university) is the greatest challenge to the laser user and laser safety officer. This is due to two factors. First, the very nature of research can put the user at risk; consider active manipulation of laser optics and beam paths, and user work with energized systems. Second, a laser safety culture that seems to accept laser injuries as part of the graduate student educational process. The fact is, laser safety at research settings, laboratories and universities still has long way to go. Major laser facilities have taken a more rigid and serious view of laser safety, its controls and procedures. Part of the rationale for this is that these facilities draw users from all around the world presenting the facility with a work force of users coming from a wide mix of laser safety cultures. Another factor is funding sources do not like bad publicity which can come from laser accidents and a poor safety record. The fact is that injuries, equipment damage and lost staff time slow down progress. Hence high profile/large laser projects need to adapt a higher safety regimen both from an engineering and administrative point of view. This presentation will discuss all these points and present examples. Acknowledgement. This work has been supported by the University of California, Director, Office of Science.

Lyapunov-based distributed control of the safety-factor profile in a tokamak plasma

International Nuclear Information System (INIS)

Bribiesca Argomedo, Federico; Witrant, Emmanuel; Prieur, Christophe; Brémond, Sylvain; Nouailletas, Rémy; Artaud, Jean-François

2013-01-01

A real-time model-based controller is developed for the tracking of the distributed safety-factor profile in a tokamak plasma. Using relevant physical models and simplifying assumptions, theoretical stability and robustness guarantees were obtained using a Lyapunov function. This approach considers the couplings between the poloidal flux diffusion equation, the time-varying temperature profiles and an independent total plasma current control. The actuator chosen for the safety-factor profile tracking is the lower hybrid current drive, although the results presented can be easily extended to any non-inductive current source. The performance and robustness of the proposed control law is evaluated with a physics-oriented simulation code on Tore Supra experimental test cases. (paper)

Protecting the pipeline of science: openness, scientific methods and the lessons from ticagrelor and the PLATO trial.

Science.gov (United States)

Coats, Andrew J Stewart; Nijjer, Sukhjinder S; Francis, Darrel P

2014-10-20

Ticagrelor, a potent antiplatelet, has been shown to be beneficial in patients with acute coronary syndromes in a randomised controlled trial published in a highly ranked peer reviewed journal. Accordingly it has entered guidelines and has been approved for clinical use by authorities. However, there remains a controversy regarding aspects of the PLATO trial, which are not immediately apparent from the peer-reviewed publications. A number of publications have sought to highlight potential discrepancies, using data available in publicly published documents from the US Food and Drug Administration (FDA) leading to disagreement regarding the value of open science and data sharing. We reflect upon potential sources of bias present in even rigorously performed randomised controlled trials, on whether peer review can establish the presence of bias and the need to constantly challenge and question even accepted data. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Safety Profile of Cough and Cold Medication Use in Pediatrics.

Science.gov (United States)

Green, Jody L; Wang, George Sam; Reynolds, Kate M; Banner, William; Bond, G Randall; Kauffman, Ralph E; Palmer, Robert B; Paul, Ian M; Dart, Richard C

2017-06-01

The safety of cough and cold medication (CCM) use in children has been questioned. We describe the safety profile of CCMs in children pediatric (75.5%), and single-ingredient (77.5%) formulations were most commonly involved. AEs occurring in >20% of all cases included tachycardia, somnolence, hallucinations, ataxia, mydriasis, and agitation. Twenty cases (0.6%) resulted in death; most were in children pediatric liquid formulations were the most commonly reported products. These characteristics present an opportunity for targeted prevention efforts. Copyright © 2017 by the American Academy of Pediatrics.

Impact of axial burnup profile on criticality safety of ANPP spent fuel cask

International Nuclear Information System (INIS)

Bznuni, S.

2006-01-01

Criticality safety assessment for WWER-440 NUHOMS cask with spent nuclear fuel from Armenian NPP has been performed. The cask was designed in such way that the neutron multiplication factor k eff must be below 0,95 for all operational modes and accident conditions. Usually for criticality analysis, fresh fuel approach with the highest enrichment is taken as conservative assumption as it was done for ANPP. NRSC ANRA in order to improve future fuel storage efficiency initiated research with taking into account burn up credit in the criticality safety assessment. Axial burn up profile (end effect) has essential impact on criticality safety justification analysis. However this phenomenon was not taken into account in the Safety Analysis Report of NUHOMS spent fuel storage constructed on the site of ANPP. Although ANRA does not yet accept burn up credit approach for ANPP spent fuel storage, assessment of impact of axial burnup profile on criticality of spent fuel assemblies has important value for future activities of ANRA. This paper presents results of criticality calculations of spent fuel assemblies with axial burn up profile. Horizontal burn up profile isn't taken account since influence of the horizontal variation of the burn up is much less than the axial variation. The actinides and actinides + fission products approach are discussed. The calculations were carried out with STARBUCS module of SCALE 5.0 code package developed at Oak Ridge National laboratory. SCALE5.0 sequence CSAS26 (KENO-VI) was used for evaluation the k eff for 3-D problems. Obtained results showed that criticality of ANPP spent fuel cask is very sensitive to the end effect

Assessment of oral safety profile of aqueous extract blend of three ...

African Journals Online (AJOL)

... did not reveal any pathological changes attributable to treatment with the spice blend extract. Conclusions: These findings indicate that oral consumption of a spice blend of garlic, ginger and cayenne pepper in humans may be safe. Keywords: Spice blend, Toxicity, Histology, Marker enzymes, Medicinal, Safety profile ...

Method of calculating the safety factor profile on the HT-7 tokamak

International Nuclear Information System (INIS)

Zhang Xianmei; Lu Yuancheng; Wan Baonian

2001-01-01

A method of calculating the safety factor profile on the HT-7 tokamak has been described. It is derived from Maxwell's equations, among which the authors mainly use two of them: one is the magnetic field diffusion equation, and the other is Ampere's Law. This method can be also used to evaluate the safety factor on other devices with a circular cross sections. It is helpful to the study of the plasma MHD behavior on the HT-7 tokamak

Safety factor profile dependence of turbulent structure formation in relevant to internal transport barrier relaxation

International Nuclear Information System (INIS)

Tokunaga, S.; Yagi, M.; Itoh, S.-I.; Itoh, K.

2009-01-01

Full text: It is widely understood that the improved confinement mode with transport barrier is necessary to achieve the self-ignition condition in ITER. The negative magnetic shear, mean ExB flow shear, and zonal flow are considered to play important roles for ITB formation. In our previous study, it is found that the non-linear interaction between the meso-scale modes produces non-local energy transfer to the off-resonant mode in the vicinity of q min surface and brings global relaxation of the temperature profile involving ITB collapse. Experimental studies indicate that a relationship exists between the ITB formation and safety factor q-profile, with a reversed magnetic shear (RS) configuration. Transitional ITB events occur on the low-order rational resonant surface. The ITB shape and location depend on the q-profile and q min position. These observations indicate that the q-profile might play an essential role in determining the turbulent structure. In this study, the effect of safety factor profile on the ion temperature gradient driven drift wave (ITG) turbulence is investigated using a global non-linear simulation code based on the gyro-fluid model. A heat source and toroidal momentum source are introduced. Dependence of safety factor profiles on ITB formation and its stability is examined to clarify the influence of the radial distribution of the rational surfaces and the q min value. It is found that the nonlinearly excited meso-scale mode in the vicinity of q min depends on the value of q min . A detailed analysis of the structure selection rule is in progress. (author)

Demonstration of Risk Profiling for promoting safety in SME´s

DEFF Research Database (Denmark)

Jørgensen, Kirsten; Duijm, Nijs Jan; Troen, Hanne

2011-01-01

Purpose – The purpose of this paper is to identify and assess the risks and potential risks that may lead to accidents. It aims to look at how to improve risk assessment within SMEs for the benefit of all staff. Design/methodology/approach – The research included results from a Dutch project which...... identifies accident risks and safety barriers that are presented in a huge database and risk calculator. The method was first to develop a simple way of accessing this enormous amount of data, second, to develop a tool to observe risks and safety barriers in SMEs and to investigate the usefulness...... of the developed tools in real life, third, to collect data on risks and safety barriers in SMEs for two occupations by following 20 people for three days each and to create a risk profile for each occupations. Findings – The result is a simple way to go through all types of risks for accidents – a tool for risk...

Safety against formation of through cracks of profiled fibre-reinforced cement sheets for roofing

DEFF Research Database (Denmark)

Hansen, Klavs Feilberg; Stang, Birgitte Friis Dela

2009-01-01

  Loads due to wind, snow or traffic on a roof determine the requirements to the strength and stiffness properties of profiled sheets for roofing. Apart from these loads, locked-in stresses can occur due to differences in temperature and moisture strains in the profiled sheets and the wooden laths...... supporting the sheets. These tensile and compressive stresses are induced in the sheets if they are firmly fastened to the laths with fastening screws. The purpose of this investigation was to analyse the safety of the profiled sheets in transmitting these loads without the formation of through cracks...

The importance of Pharmacovigilance for the drug safety: Focus on cardiovascular profile of incretin-based therapy.

Science.gov (United States)

Sportiello, Liberata; Rafaniello, Concetta; Scavone, Cristina; Vitale, Cristiana; Rossi, Francesco; Capuano, Annalisa

2016-01-01

With the recent introduction of the new European Pharmacovigilance legislation, all new drugs must be carefully monitored after admission on the European market, in order to assess the long safety profile. Currently, special attention is given to several hypoglycemic agents with recent market approval (agonists of glucagon-like peptide-1 [GLP-1] receptor and dipeptidyl peptidase 4 inhibitors [DPP-4i]), which act through the potentiation of incretin hormone signaling. Their inclusion in European additional monitoring is also due to safety problems, which seem to characterize their pharmacological class. In fact, these drugs initially showed a good tolerability profile with mainly gastrointestinal adverse events, low risk of hypoglycemia and minor effects on body weight. But, new concerns such as infections, pancreatitis, pancreatic cancer and above all cardiovascular events (especially risk of heart failure requiring hospitalization) are now arising. In this review, we highlighted aspects of the new Pharmacovigilance European dispositions, and then we investigated the tolerability profile of incretin-based therapies, in particular DPP-4 inhibitors. Notably, we focused our attention on new safety concerns, which are emerging mostly in the post-marketing period, as the cardiovascular risk profile. Evidence in literature and opinions of regulatory agencies (e.g., European Medicines Agency and Food and Drug Administration) about risks of incretin-based therapies are yet controversial, and there are many open questions in particular on cancer and cardiovascular effects. Thus, it is important to continue to monitor closely the use of these drugs in clinical practice to improve the knowledge on their long-term safety and their place in diabetes therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Safety factor profile control in a tokamak

CERN Document Server

Bribiesca Argomedo, Federico; Prieur, Christophe

2014-01-01

Control of the Safety Factor Profile in a Tokamak uses Lyapunov techniques to address a challenging problem for which even the simplest physically relevant models are represented by nonlinear, time-dependent, partial differential equations (PDEs). This is because of the  spatiotemporal dynamics of transport phenomena (magnetic flux, heat, densities, etc.) in the anisotropic plasma medium. Robustness considerations are ubiquitous in the analysis and control design since direct measurements on the magnetic flux are impossible (its estimation relies on virtual sensors) and large uncertainties remain in the coupling between the plasma particles and the radio-frequency waves (distributed inputs). The Brief begins with a presentation of the reference dynamical model and continues by developing a Lyapunov function for the discretized system (in a polytopic linear-parameter-varying formulation). The limitations of this finite-dimensional approach motivate new developments in the infinite-dimensional framework. The t...

Modifying locally the safety profile to improve the confinement of magnetic field lines in tokamak plasmas

International Nuclear Information System (INIS)

Constantinescu, D.; Firpo, M.-C.

2012-01-01

Using Hamiltonian models for the magnetic field lines, we propose a methodology to improve their confinement through the creation of transport barriers. A local modification of the safety profile creating a low-shear zone is shown to be sufficient to locally enhance drastically the regularity of the magnetic field lines without requesting a reversed shear. The optimal benefits of low-shear are obtained when the value q 0 of the safety profile in the low-shear zone is sufficiently far from the main resonance values m/n with low m and n, in the case of large enough values of those (m, n) mode amplitudes. A practical implementation in tokamak plasmas should involve electron cyclotron current drive to locally modify the magnetic shear. (paper)

Systematic review: cardiovascular safety profile of 5-HT(4) agonists developed for gastrointestinal disorders.

Science.gov (United States)

Tack, J; Camilleri, M; Chang, L; Chey, W D; Galligan, J J; Lacy, B E; Müller-Lissner, S; Quigley, E M M; Schuurkes, J; De Maeyer, J H; Stanghellini, V

2012-04-01

The nonselective 5-HT(4) receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT(4) agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006-2008 and DDW 2008-2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data. Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5-HT(4) agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5-HT(4) agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5-HT(1) receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5-HT(4) agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT(4) agonists with no hERG or 5-HT(1) affinity (renzapride, clebopride, mosapride). 5-HT(4) agonists for GI disorders differ in chemical structure and selectivity for 5-HT(4) receptors. Selectivity for 5-HT(4) over non-5-HT(4) receptors may influence the agent's safety and overall risk-benefit profile. Based on available evidence, highly selective 5-HT(4) agonists may offer improved safety to treat patients with impaired GI motility. © 2012 Blackwell Publishing Ltd.

Systematic review: cardiovascular safety profile of 5-HT4 agonists developed for gastrointestinal disorders

Science.gov (United States)

Tack, J; Camilleri, M; Chang, L; Chey, W D; Galligan, J J; Lacy, B E; Müller-Lissner, S; Quigley, E M M; Schuurkes, J; Maeyer, J H; Stanghellini, V

2012-01-01

Summary Background The nonselective 5-HT4 receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). Aim To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT4 agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. Methods Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) and ATI-7505 (naronapride) were identified through a systematic search of the Cochrane Library, Medline, Embase and Toxfile. Abstracts from UEGW 2006–2008 and DDW 2008–2010 were searched for these drug names, and pharmaceutical companies approached to provide unpublished data. Results Retrieved articles on pharmacokinetics, human pharmacodynamics and clinical data with these 5-HT4 agonists, are reviewed and summarised nonsystematically. Articles relating to cardiac safety and tolerability of these agents, including any relevant case reports, are reported systematically. Two nonselective 5-HT4 agonists had reports of cardiovascular AEs: cisapride (QT prolongation) and tegaserod (ischaemia). Interactions with, respectively, the hERG cardiac potassium channel and 5-HT1 receptor subtypes have been suggested to account for these effects. No cardiovascular safety concerns were reported for the newer, selective 5-HT4 agonists prucalopride, velusetrag, naronapride, or for nonselective 5-HT4 agonists with no hERG or 5-HT1 affinity (renzapride, clebopride, mosapride). Conclusions 5-HT4 agonists for GI disorders differ in chemical structure and selectivity for 5-HT4 receptors. Selectivity for 5-HT4 over non-5-HT4 receptors may influence the agent's safety and overall risk–benefit profile. Based on available evidence, highly selective 5-HT4 agonists may offer improved safety to treat patients with impaired GI motility. PMID:22356640

Relative safety profiles of high dose statin regimens

Directory of Open Access Journals (Sweden)

Carlos Escobar

2008-06-01

Full Text Available Carlos Escobar, Rocio Echarri, Vivencio BarriosDepartment of Cardiology, Hospital Ramón y Cajal, Madrid, SpainAbstract: Recent clinical trials recommend achieving a low-density lipoprotein cholesterol level of <100 mg/dl in high-risk and <70 mg/dl in very high risk patients. To attain these goals, however, many patients will need statins at high doses. The most frequent side effects related to the use of statins, myopathy, rhabdomyolysis, and increased levels of transaminases, are unusual. Although low and moderate doses show a favourable profile, there is concern about the tolerability of higher doses. During recent years, numerous trials to analyze the efficacy and tolerability of high doses of statins have been published. This paper updates the published data on the safety of statins at high doses.Keywords: statins, high doses, tolerability, liver, muscle

New geometric design consistency model based on operating speed profiles for road safety evaluation.

Science.gov (United States)

Camacho-Torregrosa, Francisco J; Pérez-Zuriaga, Ana M; Campoy-Ungría, J Manuel; García-García, Alfredo

2013-12-01

To assist in the on-going effort to reduce road fatalities as much as possible, this paper presents a new methodology to evaluate road safety in both the design and redesign stages of two-lane rural highways. This methodology is based on the analysis of road geometric design consistency, a value which will be a surrogate measure of the safety level of the two-lane rural road segment. The consistency model presented in this paper is based on the consideration of continuous operating speed profiles. The models used for their construction were obtained by using an innovative GPS-data collection method that is based on continuous operating speed profiles recorded from individual drivers. This new methodology allowed the researchers to observe the actual behavior of drivers and to develop more accurate operating speed models than was previously possible with spot-speed data collection, thereby enabling a more accurate approximation to the real phenomenon and thus a better consistency measurement. Operating speed profiles were built for 33 Spanish two-lane rural road segments, and several consistency measurements based on the global and local operating speed were checked. The final consistency model takes into account not only the global dispersion of the operating speed, but also some indexes that consider both local speed decelerations and speeds over posted speeds as well. For the development of the consistency model, the crash frequency for each study site was considered, which allowed estimating the number of crashes on a road segment by means of the calculation of its geometric design consistency. Consequently, the presented consistency evaluation method is a promising innovative tool that can be used as a surrogate measure to estimate the safety of a road segment. Copyright © 2012 Elsevier Ltd. All rights reserved.

Safety and Efficacy Profile of Commercial Veterinary Vaccines against Rift Valley Fever: A Review Study

Directory of Open Access Journals (Sweden)

Moataz Alhaj

2016-01-01

Full Text Available Rift Valley Fever (RVF is an infectious illness with serious clinical manifestations and health consequences in humans as well as a wide range of domestic ruminants. This review provides significant information about the prevention options of RVF along with the safety-efficacy profile of commercial vaccines and some of RVF vaccination strategies. Information presented in this paper was obtained through a systematic investigation of published data about RVF vaccines. Like other viral diseases, the prevention of RVF relies heavily on immunization of susceptible herds with safe and cost-effective vaccine that is able to confer long-term protective immunity. Several strains of RVF vaccines have been developed and are available in commercial production including Formalin-Inactivated vaccine, live attenuated Smithburn vaccine, and the most recent Clone13. Although Formalin-Inactivated vaccine and live attenuated Smithburn vaccine are immunogenic and widely used in prevention programs, they proved to be accompanied by significant concerns. Despite Clone13 vaccine being suggested as safe in pregnant ewes and as highly immunogenic along with its potential for differentiating infected from vaccinated animals (DIVA, a recent study raised concerns about the safety of the vaccine during the first trimester of gestation. Accordingly, RVF vaccines that are currently available in the market to a significant extent do not fulfill the requirements of safety, potency, and DIVA. These adverse effects stressed the need for developing new vaccines with an excellent safety profile to bridge the gap in safety and immunity. Bringing RVF vaccine candidates to local markets besides the absence of validated serological test for DIVA remain the major challenges of RVF control.

Safety profile and long-term engraftment of human CD31+ blood progenitors in bone tissue engineering.

Science.gov (United States)

Zigdon-Giladi, Hadar; Elimelech, Rina; Michaeli-Geller, Gal; Rudich, Utai; Machtei, Eli E

2017-07-01

Endothelial progenitor cells (EPCs) participate in angiogenesis and induce favorable micro-environments for tissue regeneration. The efficacy of EPCs in regenerative medicine is extensively studied; however, their safety profile remains unknown. Therefore, our aims were to evaluate the safety profile of human peripheral blood-derived EPCs (hEPCs) and to assess the long-term efficacy of hEPCs in bone tissue engineering. hEPCs were isolated from peripheral blood, cultured and characterized. β tricalcium phosphate scaffold (βTCP, control) or 10 6 hEPCs loaded onto βTCP were transplanted in a nude rat calvaria model. New bone formation and blood vessel density were analyzed using histomorphometry and micro-computed tomography (CT). Safety of hEPCs using karyotype analysis, tumorigenecity and biodistribution to target organs was evaluated. On the cellular level, hEPCs retained their karyotype during cell expansion (seven passages). Five months following local hEPC transplantation, on the tissue and organ level, no inflammatory reaction or dysplastic change was evident at the transplanted site or in distant organs. Direct engraftment was evident as CD31 human antigens were detected lining vessel walls in the transplanted site. In distant organs human antigens were absent, negating biodistribution. Bone area fraction and bone height were doubled by hEPC transplantation without affecting mineral density and bone architecture. Additionally, local transplantation of hEPCs increased blood vessel density by nine-fold. Local transplantation of hEPCs showed a positive safety profile. Furthermore, enhanced angiogenesis and osteogenesis without mineral density change was found. These results bring us one step closer to first-in-human trials using hEPCs for bone regeneration. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Recent RF Experiments and Application of RF Waves to Real-Time Control of Safety Factor Profile in JT-60U

International Nuclear Information System (INIS)

Suzuki, T.; Isayama, A.; Ide, S.; Fujita, T.; Oikawa, T.; Sakata, S.; Sueoka, M.; Hosoyama, H.; Seki, M.

2005-01-01

Two topics of applications of RF waves to current profile control in JT-60U are presented; application of lower-hybrid (LH) waves to safety factor profile control and electron cyclotron (EC) waves to neo-classical tearing mode (NTM) control. A real-time control system of safety factor (q) profile was developed. This system, for the first time, enables 1) real time evaluation of q profile using local magnetic pitch angle measurement by motional Stark effect (MSE) diagnostic and 2) control of current drive (CD) location (ρCD) by controlling the parallel refractive index N parallel of LH waves through control of phase difference (Δφ) of LH waves between multi-junction launcher modules. The method for real-time q profile evaluation was newly developed, without time-consuming reconstruction of equilibrium, so that the method requires less computational time. Safety factor profile by the real-time calculation agrees well with that by equilibrium reconstruction with MSE. The control system controls ρCD through Δφ in such a way to decrease the largest residual between the real-time evaluated q profile q(r) and its reference profile qref(r). The real-time control system was applied to a positive shear plasma (q(0)∼1). The reference q profile was set to monotonic positive shear profile having qref(0)=1.3. The real-time q profile approached to the qref(r) during application of real-time control, and was sustained for 3s, which was limited by the duration of the injected LH power. Temporal evolution of current profile was consistent with relaxation of inductive electric field induced by theoretical LH driven current. An m/n=3/2 NTM that appeared at βN∼3 was completely stabilized by ECCD applied to a fully-developed NTM. Precise ECCD at NTM island was essential for the stabilization. ECCD that was applied to resonant rational surface (q=3/2) before an NTM onset suppressed appearance of NTM. In order to keep NTM intensity below a level, ECCD before the mode onset was

Toxicity and Safety Profiles of Methanolic Extract of Pistacia integerrima J. L. Stewart ex Brandis (PI for Wistar Rats

Directory of Open Access Journals (Sweden)

Gotmi Sharwan

2016-09-01

Full Text Available Objectives: The goals of this research were to evaluate acute (single-dose and sub-acute (repeated-dose toxicity profiles of methanolic extract of Pistacia integerrima J. L. Stewart ex Brandis (PI for Wistar rats and to assess the safety profile of PI by observing physiological changes, mortality, changes in body weight

Safety profile of the 9-valent HPV vaccine

DEFF Research Database (Denmark)

Moreira, Edson D; Block, Stan L; Ferris, Daron G

2016-01-01

OBJECTIVES: The overall safety profile of the 9-valent human papillomavirus (9vHPV) vaccine was evaluated across 7 Phase III studies, conducted in males and females (nonpregnant at entry), 9 to 26 years of age. METHODS: Vaccination was administered as a 3-dose regimen at day 1, and months 2 and 6....... More than 15 000 subjects received ≥1 dose of 9vHPV vaccine. In 2 of the studies, >7000 control subjects received ≥1 dose of quadrivalent HPV (qHPV) vaccine. Serious and nonserious adverse events (AEs) and new medical conditions were recorded throughout the study. Subjects testing positive...... for pregnancy at day 1 were not vaccinated; those who became pregnant after day 1 were discontinued from further vaccination until resolution of the pregnancy. Pregnancies detected after study start (n = 2950) were followed to outcome. RESULTS: The most common AEs (≥5%) experienced by 9vHPV vaccine recipients...

Input-profile-based software failure probability quantification for safety signal generation systems

International Nuclear Information System (INIS)

Kang, Hyun Gook; Lim, Ho Gon; Lee, Ho Jung; Kim, Man Cheol; Jang, Seung Cheol

2009-01-01

The approaches for software failure probability estimation are mainly based on the results of testing. Test cases represent the inputs, which are encountered in an actual use. The test inputs for the safety-critical application such as a reactor protection system (RPS) of a nuclear power plant are the inputs which cause the activation of protective action such as a reactor trip. A digital system treats inputs from instrumentation sensors as discrete digital values by using an analog-to-digital converter. Input profile must be determined in consideration of these characteristics for effective software failure probability quantification. Another important characteristic of software testing is that we do not have to repeat the test for the same input value since the software response is deterministic for each specific digital input. With these considerations, we propose an effective software testing method for quantifying the failure probability. As an example application, the input profile of the digital RPS is developed based on the typical plant data. The proposed method in this study is expected to provide a simple but realistic mean to quantify the software failure probability based on input profile and system dynamics.

Systematic review: cardiovascular safety profile of 5-HT4 agonists developed for gastrointestinal disorders

OpenAIRE

Tack, J; Camilleri, M; Chang, L; Chey, W D; Galligan, J J; Lacy, B E; Müller-Lissner, S; Quigley, E M M; Schuurkes, J; Maeyer, J H; Stanghellini, V

2012-01-01

Summary Background The nonselective 5-HT4 receptor agonists, cisapride and tegaserod have been associated with cardiovascular adverse events (AEs). Aim To perform a systematic review of the safety profile, particularly cardiovascular, of 5-HT4 agonists developed for gastrointestinal disorders, and a nonsystematic summary of their pharmacology and clinical efficacy. Methods Articles reporting data on cisapride, clebopride, prucalopride, mosapride, renzapride, tegaserod, TD-5108 (velusetrag) an...

Cost-effectiveness of antiplatelet drugs after percutaneous coronary intervention.

Science.gov (United States)

Wisløff, Torbjørn; Atar, Dan

2016-01-01

Clopidogrel has, for long time, been accepted as the standard treatment for patients who have undergone a percutaneous coronary intervention (PCI). The introduction of prasugrel-and more recently, ticagrelor-has introduced a decision-making problem for clinicians and governments worldwide: to use the cheaper clopidogrel or the more effective, and also more expensive prasugrel or ticagrelor. We aim to give helpful contributions to this debate by analysing the cost-effectiveness of clopidogrel, prasugrel, and ticagrelor compared with each other. We modified a previously developed Markov model of cardiac disease progression. In the model, we followed up cohorts of patients who have recently had a PCI until 100 years or death. Possible events are revascularization, bleeding, acute myocardial infarction, and death. Our analysis shows that ticagrelor is cost-effective in 77% of simulations at an incremental cost-effectiveness ratio of €7700 compared with clopidogrel. Ticagrelor was also cost-effective against prasugrel at a cost-effectiveness ratio of €7800. Given a Norwegian cost-effectiveness threshold of €70 000, both comparisons appear to be clearly cost-effective in favour of ticagrelor. Ticagrelor is cost-effective compared with both clopidogrel and prasugrel for patients who have undergone a PCI.

[Safety profile of zolpidem: two studies of 3805 patients by Swiss practitioners].

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Ganzoni, E; Gugger, M

1999-06-24

Evaluation and treatment of insomnia are frequent procedures in the physician's everyday practice, since many patients seek medical treatment for this condition. Knowledge of pharmacological therapeutical alternatives is therefore decisive, in order to identify the most efficaceous and safe therapy for the patient among the available hypnotics. The short-acting hypnotic zolpidem has been investigated in Switzerland in two multicenter safety studies in ambulatory practice. In the first study 8.9% (n = 125 of 1,972 treated patients), and in the second 7.2% of the patients (n = 175 of 1,833 treated patients) reported an adverse event. The most frequent events were related to the central nervous system (CNS) (somnolence, headache, confusion, vertigo); gastrointestinal and cutaneous symptoms were the most frequent non CNS-dependent effects. New, unknown or serious adverse events were not found and no specific risk factor or population at risk was identified. The safety profile of zolpidem is consistent with its known pharmacological properties, the results of previous clinical trials and the international experience obtained in large patients groups.

Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches.

Science.gov (United States)

Madureira, Ana Raquel; Nunes, Sara; Campos, Débora A; Fernandes, João C; Marques, Cláudia; Zuzarte, Monica; Gullón, Beatriz; Rodríguez-Alcalá, Luís M; Calhau, Conceição; Sarmento, Bruno; Gomes, Ana Maria; Pintado, Maria Manuela; Reis, Flávio

2016-01-01

Rosmarinic acid (RA) possesses several protective bioactivities that have attracted increasing interest by nutraceutical/pharmaceutical industries. Considering the reduced bioavailability after oral use, effective (and safe) delivery systems are crucial to protect RA from gastrointestinal degradation. This study aims to characterize the safety profile of solid lipid nanoparticles produced with Witepsol and Carnauba waxes and loaded with RA, using in vitro and in vivo approaches, focused on genotoxicity and cytotoxicity assays, redox status markers, hematological and biochemical profile, liver and kidney function, gut bacterial microbiota, and fecal fatty acids composition. Free RA and sage extract, empty nanoparticles, or nanoparticles loaded with RA or sage extract (0.15 and 1.5 mg/mL) were evaluated for cell (lymphocytes) viability, necrosis and apoptosis, and antioxidant/prooxidant effects upon DNA. Wistar rats were orally treated for 14 days with vehicle (control) and with Witepsol or Carnauba nanoparticles loaded with RA at 1 and 10 mg/kg body weight/d. Blood, urine, feces, and several tissues were collected for analysis. Free and loaded RA, at 0.15 mg/mL, presented a safe profile, while genotoxic potential was found for the higher dose (1.5 mg/mL), mainly by necrosis. Our data suggest that both types of nanoparticles are safe when loaded with moderate concentrations of RA, without in vitro genotoxicity and cytotoxicity and with an in vivo safety profile in rats orally treated, thus opening new avenues for use in nutraceutical applications.

Safety assessment of genetically modified rice expressing human serum albumin from urine metabonomics and fecal bacterial profile.

Science.gov (United States)

Qi, Xiaozhe; Chen, Siyuan; Sheng, Yao; Guo, Mingzhang; Liu, Yifei; He, Xiaoyun; Huang, Kunlun; Xu, Wentao

2015-02-01

The genetically modified (GM) rice expressing human serum albumin (HSA) is used for non-food purposes; however, its food safety assessment should be conducted due to the probability of accidental mixture with conventional food. In this research, Sprague Dawley rats were fed diets containing 50% (wt/wt) GM rice expressing HSA or non-GM rice for 90 days. Urine metabolites were detected by (1)H NMR to examine the changes of the metabolites in the dynamic process of metabolism. Fecal bacterial profiles were detected by denaturing gradient gel electrophoresis to reflect intestinal health. Additionally, short chain fatty acids and fecal enzymes were investigated. The results showed that compared with rats fed the non-GM rice, some significant differences were observed in rats fed with the GM rice; however, these changes were not significantly different from the control diet group. Additionally, the gut microbiota was associated with blood indexes and urine metabolites. In conclusion, the GM rice diet is as safe as the traditional daily diet. Furthermore, urine metabonomics and fecal bacterial profiles provide a non-invasive food safety assessment rat model for genetically modified crops that are used for non-food/feed purposes. Fecal bacterial profiles have the potential for predicting the change of blood indexes in future. Copyright © 2014 Elsevier Ltd. All rights reserved.

Direct measurements of safety factor profiles with motional Stark effect for KSTAR tokamak discharges with internal transport barriers

Science.gov (United States)

Ko, J.; Chung, J.

2017-06-01

The safety factor profile evolutions have been measured from the plasma discharges with the external current drive mechanism such as the multi-ion-source neutral beam injection for the Korea Superconducting Tokamak Advanced Research (KSTAR) for the first time. This measurement has been possible by the newly installed motional Stark effect (MSE) diagnostic system that utilizes the polarized Balmer-alpha emission from the energetic neutral deuterium atoms induced by the Stark effect under the Lorentz electric field. The 25-channel KSTAR MSE diagnostic is based on the conventional photoelastic modulator approach with the spatial and temporal resolutions less than 2 cm (for the most of the channels except 2 to 3 channels inside the magnetic axis) and about 10 ms, respectively. The strong Faraday rotation imposed on the optical elements in the diagnostic system is calibrated out from a separate and well-designed polarization measurement procedure using an in-vessel reference polarizer during the toroidal-field ramp-up phase before the plasma experiment starts. The combination of the non-inductive current drive during the ramp-up and shape control enables the formation of the internal transport barrier where the pitch angle profiles indicate flat or slightly hollow profiles in the safety factor.

Reporting and understanding the safety and adverse effect profile of mobile apps for psychosocial interventions: An update.

Science.gov (United States)

Naeem, Farooq; Gire, Nadeem; Xiang, Shuo; Yang, Megan; Syed, Yumeen; Shokraneh, Farhad; Adams, Clive; Farooq, Saeed

2016-06-22

Recent years have seen a rapidly increasing trend towards the delivery of health technology through mobile devices. Smartphones and tablet devices are thus becoming increasingly popular for accessing information and a wide range of services, including health care services. Modern mobile apps can be used for a variety of reasons, ranging from education for the patients and assistance to clinicians to delivery of interventions. Mobile phone apps have also been established to benefit patients in a scope of interventions across numerous medical specialties and treatment modalities. Medical apps have their advantages and disadvantages. It is important that clinicians have access to knowledge to make decisions regarding the use of medical apps on the basis of risk-benefit ratio. Mobile apps that deliver psycho social interventions offer unique challenges and opportunities. A number of reviews have highlighted the potential use of such apps. There is a need to describe, report and study their side effects too. The adverse effects associated with these apps can broadly be divided into: (1) those resulting from the security and safety concerns; (2) those arising from the use of a particular psycho social intervention; and (3) those due to the interaction with digital technology. There is a need to refine and reconsider the safety and adverse effects in this area. The safety profile of a mobile PSI app should describe its safety profile in: (1) privacy and security; (2) adverse effects of psychotherapy; and (3) adverse effects unique to the use of apps and the internet. This is, however, a very new area and further research and reporting is required to inform clinical decision making.

Patient safety climate profiles across time: Strength and level of safety climate associated with a quality improvement program in Switzerland—A cross-sectional survey study

Science.gov (United States)

Mascherek, Anna C.

2017-01-01

Safety Climate has been acknowledged as an unspecific factor influencing patient safety. However, studies rarely provide in-depth analysis of climate data. As a helpful approach, the concept of “climate strength” has been proposed. In the present study we tested the hypotheses that even if safety climate remains stable on mean-level across time, differences might be evident in strength or shape. The data of two hospitals participating in a large national quality improvement program were analysed for differences in climate profiles at two measurement occasions. We analysed differences on mean-level, differences in percent problematic response, agreement within groups, and frequency histograms in two large hospitals in Switzerland at two measurement occasions (2013 and 2015) applying the Safety Climate Survey. In total, survey responses of 1193 individuals were included in the analyses. Overall, small but significant differences on mean-level of safety climate emerged for some subgroups. Also, although agreement was strong at both time-points within groups, tendencies of divergence or consensus were present in both hospitals. Depending on subgroup and analyses chosen, differences were more or less pronounced. The present study illustrated that taking several measures into account and describing safety climate from different perspectives is necessary in order to fully understand differences and trends within groups and to develop interventions addressing the needs of different groups more precisely. PMID:28753633

The effects of the non-contingent presentation of safety signals on the elimination of safety behaviors: An experimental comparison between individuals with low and high obsessive-compulsive profiles.

Science.gov (United States)

Angelakis, Ioannis; Austin, Jennifer L

2018-06-01

Safety behaviors, defined as engagement in avoidance within safe environments, are a key symptom of obsessive-compulsive and related disorders. They may interfere with daily functioning and as such their emission should be reduced. The purpose of the current study is to investigate the effects of the non-contingent presentation of safety signals (cues produced by safety behaviors) on reducing safety behaviors in participants self-reporting low and high OCD profiles. In total, 32 participants were asked to play a game to gain points and avoid their loss. After having developed avoidance behavior, evidenced by maintaining all of their earned points, they were exposed to safe environments where no point loss was programmed. In Test 1, safety cues (blue bar) were produced contingent on performing safety behaviors. In Test 2, safety cues were presented continuously without any response requirement. Findings demonstrated that high OCD group displayed higher rates of safety behaviors than low OCD group. However, exposure to the non-contingent presentation of safety signals eliminated their emission in both groups. Future studies need to evaluate the effects of different non-contingent schedules on the suppression of safety behaviors. These findings contribute to the literature by demonstrating that non-contingent introduction of safety signals eliminated safety behaviors completely, even in high OCD participants, who performed safety behavior at higher rates. Such a treatment protocol may ameliorate exposure therapy in which response prevention constitutes a key element and is generally associated with increased drop-out rates. Copyright © 2017 Elsevier Ltd. All rights reserved.

Integration profile and safety of an adenovirus hybrid-vector utilizing hyperactive sleeping beauty transposase for somatic integration.

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Wenli Zhang

Full Text Available We recently developed adenovirus/transposase hybrid-vectors utilizing the previously described hyperactive Sleeping Beauty (SB transposase HSB5 for somatic integration and we could show stabilized transgene expression in mice and a canine model for hemophilia B. However, the safety profile of these hybrid-vectors with respect to vector dose and genotoxicity remains to be investigated. Herein, we evaluated this hybrid-vector system in C57Bl/6 mice with escalating vector dose settings. We found that in all mice which received the hyperactive SB transposase, transgene expression levels were stabilized in a dose-dependent manner and that the highest vector dose was accompanied by fatalities in mice. To analyze potential genotoxic side-effects due to somatic integration into host chromosomes, we performed a genome-wide integration site analysis using linker-mediated PCR (LM-PCR and linear amplification-mediated PCR (LAM-PCR. Analysis of genomic DNA samples obtained from HSB5 treated female and male mice revealed a total of 1327 unique transposition events. Overall the chromosomal distribution pattern was close-to-random and we observed a random integration profile with respect to integration into gene and non-gene areas. Notably, when using the LM-PCR protocol, 27 extra-chromosomal integration events were identified, most likely caused by transposon excision and subsequent transposition into the delivered adenoviral vector genome. In total, this study provides a careful evaluation of the safety profile of adenovirus/Sleeping Beauty transposase hybrid-vectors. The obtained information will be useful when designing future preclinical studies utilizing hybrid-vectors in small and large animal models.

Safety Profile of the Newest Antiepileptic Drugs: A Curated Literature Review.

Science.gov (United States)

Palleria, Caterina; Cozza, Giuseppe; Khengar, Rajeshree; Libri, Vincenzo; De Sarro, Giovambattista

2017-01-01

Despite the introduction of new antiepileptic drugs (AEDs), the quality of life and therapeutic response for patients with epilepsy remain unsatisfactory. In addition, whilst several antiepileptic drugs (AEDs) have been approved and consequently marketed in recent years, little is known about their long-term safety and tolerability. Availability of the newest AEDs, characterized by improved pharmacokinetic profiles, has positively impacted the treatment approach for patients with partial seizures in clinical practice. However, the main cause of treatment failure is still poor patient compliance due to the occurrence of adverse drug reactions (ADRs) that lead to treatment withdrawal in about 25% of cases before achieving maximal efficacy, and is associated with increasing health care costs. In this Review, we conducted an online database search using Medline, PubMed, Embase, and the Cochrane Online Library to review the available studies highlighting the clinical relevance of side effects, pharmacological interactions, safety and tolerability of the newest AEDs: Brivaracetam (BRV), Cannabidiol (CBD), Eslicarbazepine acetate (ESL), Lacosamide (LCM), and Perampanel (PER). The principal benefit of the newest AEDs, in addition to reduced frequency and seizure severity, is the low number and severity of ADRs reported compared to more historic drugs. Early detection of ADRs could lead to an improvement in patients' quality of life, therefore it is important to monitor ADRs and to adequately perform post marketing surveillance in the clinical practice setting. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Long-term safety profile of belimumab plus standard therapy in patients with systemic lupus erythematosus.

Science.gov (United States)

Merrill, Joan T; Ginzler, Ellen M; Wallace, Daniel J; McKay, James D; Lisse, Jeffrey R; Aranow, Cynthia; Wellborne, Frank R; Burnette, Michael; Condemi, John; Zhong, Z John; Pineda, Lilia; Klein, Jerry; Freimuth, William W

2012-10-01

To evaluate the safety profile of long-term belimumab therapy combined with standard therapy for systemic lupus erythematosus (SLE) in patients with active disease. Patients who were randomized to receive intravenous placebo or belimumab 1, 4, or 10 mg/kg, plus standard therapy, and completed the initial 52-week double-blind treatment period were then allowed to enter a 24-week open-label extension phase. During the extension period, patients in the belimumab group either received the same dose or were switched to 10 mg/kg and patients in the placebo group were switched to belimumab 10 mg/kg. Patients who achieved a satisfactory response during the 24-week extension period were allowed to participate in the long-term continuation study of monthly belimumab 10 mg/kg. Adverse events (AEs) and abnormal laboratory results were analyzed per 100 patient-years in 1-year intervals. Of the 364 patients who completed the 52-week double-blind treatment period, 345 entered the 24-week extension, and 296 continued treatment with belimumab in the long-term continuation study. Safety data through 4 years of belimumab exposure (1,165 cumulative patient-years) are reported. Incidence rates of AEs, severe/serious AEs, infusion reactions, infections, malignancies, grades 3/4 laboratory abnormalities, and discontinuations due to AEs were stable or declined during 4-year belimumab exposure. The most common AEs included arthralgia, upper respiratory tract infection, headache, fatigue, and nausea. Serious infusion reactions were rare: only 1 occurred during the 4-year followup period. Rates of serious infection decreased from 5.9/100 patient-years to 3.4/100 patient-years, and no specific type of infection predominated. Belimumab added to standard therapy was generally well-tolerated over the 4-year treatment period in patients with SLE, which suggests that belimumab can be administered long term with an acceptable safety profile. Copyright © 2012 by the American College of Rheumatology.

Prehospital administration of P2Y12 inhibitors and early coronary reperfusion in primary PCI

DEFF Research Database (Denmark)

De Backer, Ole; Ratcovich, Hanna; Biasco, Luigi

2015-01-01

The newer oral P2Y12 inhibitors prasugrel and ticagrelor have been reported to be more potent and faster-acting antiplatelet agents than clopidogrel. This study aimed to investigate whether prehospital loading with prasugrel or ticagrelor improves early coronary reperfusion as compared to prehosp......The newer oral P2Y12 inhibitors prasugrel and ticagrelor have been reported to be more potent and faster-acting antiplatelet agents than clopidogrel. This study aimed to investigate whether prehospital loading with prasugrel or ticagrelor improves early coronary reperfusion as compared...... to prehospital loading with clopidogrel in a real-world ST-elevation myocardial infarction (STEMI) setting. Over a 70-month period, 3497 patients with on-going STEMI of less than 6 hours and without cardiac arrest or cardiogenic shock underwent primary percutaneous coronary intervention (PPCI) at our centre....... The primary endpoint of this study was the proportion of patients who did not meet the criteria for TIMI (Thrombolysis In Myocardial Infarction) flow grade 3 in the infarct-related artery at initial angiography before PPCI. Prehospital loading with prasugrel (n = 883) or ticagrelor (n = 491) did...

Safety and effectiveness of the new P2Y12r inhibitor agents vs clopidogrel in ACS patients according to the geographic area: East Asia vs Europe

NARCIS (Netherlands)

Giordana, Francesca; Montefusco, Antonio; D'Ascenzo, Fabrizio; Moretti, Claudio; Scarano, Silvia; Abu-Assi, Emad; Raposeiras-Roubín, Sergio; Henriques, Jose Paulo Simao; Saucedo, Jorge; González-Juanatey, José Ramón; Wilton, Stephen B.; Kikkert, Wouter J.; Nuñez-Gil, Iván; Ariza-Sole, Albert; Song, Xiantao; Alexopoulos, Dimitrios; Liebetrau, Christoph; Kawaji, Tetsuma; Huczek, Zenon; Nie, Shao-Ping; Fujii, Toshiharu; Correia, Luis; Kawashiri, Masa-Aki; García-Acuña, José María; Southern, Danielle; Alfonso, Emilio; Terol, Belén; Garay, Alberto; Zhang, Dongfeng; Chen, Yalei; Xanthopoulou, Ioanna; Osman, Neriman; Möllmann, Helge; Shiomi, Hiroki; Kowara, Michal; Filipiak, Krzysztof; Wang, Xiao; Yan, Yan; Fan, Jing-Yao; Ikari, Yuji; Nakahayshi, Takuya; Sakata, Kenji; Yamagishi, Masakazu; Kalpak, Oliver; Kedev, Sasko; Gaita, F.

2016-01-01

Background: In the setting of the Acute Coronary Syndrome (ACS), differences in response to prasugrel and ticagrelor between East Asian and European patients have not been investigated yet. Methods: This is a sub-analysis of the "BleeMACS registry". Patients admitted for ACS and underwent PCI from

Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches

Directory of Open Access Journals (Sweden)

Madureira AR

2016-08-01

Full Text Available Ana Raquel Madureira,1 Sara Nunes,2 Débora A Campos,1 João C Fernandes,2 Cláudia Marques,3 Monica Zuzarte,2 Beatriz Gullón,1 Luís M Rodríguez-Alcalá,1 Conceição Calhau,3,4 Bruno Sarmento,5–7 Ana Maria Gomes,1 Maria Manuela Pintado,1 Flávio Reis2 1Catholic University of Portugal, CBQF – Center for Biotechnology and Fine Chemistry – Associate Laboratory, Faculty of Biotechnology, Porto, Portugal; 2Laboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI, Faculty of Medicine, and CNC.IBILI Consortium, University of Coimbra, Coimbra, Portugal; 3Department of Biochemistry, Faculty of Medicine, University of Porto, Porto, Portugal; 4Center for Health Technology and Services Research (CINTESIS, Porto, Portugal; 5Department of Pharmaceutical Sciences, Institute of Health Sciences-North, CESPU, Gandra, Portugal; 6“I3S” Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal; 7INEB, Institute of Biomedical Engineering, University of Porto, Porto, Portugal Abstract: Rosmarinic acid (RA possesses several protective bioactivities that have attracted increasing interest by nutraceutical/pharmaceutical industries. Considering the reduced bioavailability after oral use, effective (and safe delivery systems are crucial to protect RA from gastrointestinal degradation. This study aims to characterize the safety profile of solid lipid nanoparticles produced with Witepsol and Carnauba waxes and loaded with RA, using in vitro and in vivo approaches, focused on genotoxicity and cytotoxicity assays, redox status markers, hematological and biochemical profile, liver and kidney function, gut bacterial microbiota, and fecal fatty acids composition. Free RA and sage extract, empty nanoparticles, or nanoparticles loaded with RA or sage extract (0.15 and 1.5 mg/mL were evaluated for cell (lymphocytes viability, necrosis and apoptosis, and antioxidant

Road safety performance indicators : country profiles. SafetyNet, Building the European Road Safety Observatory, Workpackage 3, Deliverable 3.7b.

NARCIS (Netherlands)

Riguelle, F. Eksler, V. Holló, P. Morsink, P. Gent, A. van Gitelman, V. Assum, T. & Rackliff, L.

2009-01-01

The EC 6th Framework Integrated Project SafetyNet aims to accelerate the availability and use of harmonised road safety data in Europe. Having such data available throughout Europe would be tremendously beneficial for road safety, since it would enable the evaluation of road safety measures, the

Meta-analysis of pemetrexed plus carboplatin doublet safety profile in first-line non-squamous non-small cell lung cancer studies.

Science.gov (United States)

Okamoto, Isamu; Schuette, Wolfgang H W; Stinchcombe, Thomas E; Rodrigues-Pereira, José; San Antonio, Belén; Chen, Jian; Liu, Jingyi; John, William J; Zinner, Ralph G

2017-05-01

This meta-analysis compared safety profiles (selected drug-related treatment-emergent adverse events [TEAEs]) of first-line pemetrexed plus carboplatin (PCb) area under the concentration-time curve 5 mg/min•mL (PCb5) or 6 mg/min•mL (PCb6), two widely used regimens in clinical practice for advanced non-squamous non-small cell lung cancer. All patients received pemetrexed 500 mg/m 2 every 21 days with either of two carboplatin doses for up to 4-6 cycles. Safety profiles of PCb doses were compared using three statistical analysis methods: frequency table analysis (FTA), generalized linear mixed effect model (GLMM), and the propensity score method. Efficacy outcomes of PCb5 and PCb6 regimens were summarized. A total of 486 patients mainly from the US, Europe, and East Asia were included in the analysis; 22% (n = 105) received PCb5 in one trial and 78% (n = 381) received PCb6 in four trials. The FTA comparison demonstrated that PCb5 vs PCb6 was associated with a statistically significantly lower incidence of TEAEs, including all-grade thrombocytopenia, anemia, fatigue, and vomiting, and grade 3/4 thrombocytopenia. In the GLMM analysis, PCb5 patients were numerically less likely to experience all-grade and grade 3/4 neutropenia, anemia, and thrombocytopenia. The propensity score regression analysis showed PCb5 group patients were significantly less likely than PCb6 group patients to experience all-grade hematologic TEAEs and grade 3/4 thrombocytopenia and anemia. After applying propensity score 1:1 matching, FTA analysis showed that the PCb5 group had significantly less all-grade and grade 3/4 hematologic toxicities. Overall efficacy outcomes, including overall survival, progression-free survival, and response rate, were similar between the two carboplatin doses. Acknowledging the limitations of this meta-analysis of five trials, heterogeneous in patient's characteristics and trial designs, the results show that the PCb5 regimen was generally associated

Gadobutrol for contrast-enhanced magnetic resonance imaging in elderly patients: review of the safety profile from clinical trial, post-marketing surveillance, and pharmacovigilance data

International Nuclear Information System (INIS)

Endrikat, J.; Schwenke, C.; Prince, M.R.

2015-01-01

Aim: To assess the safety of gadobutrol administration in elderly patients (≥65 years) by comparing the incidence of adverse drug reactions (ADRs) following gadobutrol-enhanced magnetic resonance imaging (MRI) procedures in elderly patients with that in adults aged 18–64 years. Materials and methods: Safety data on gadobutrol administration from clinical trials, post-marketing surveillance (PMS) studies, and pharmacovigilance reports were collected in three databases. In each dataset, absolute and relative frequencies of ADRs between age groups were analysed, along with odds ratios and 95% confidence intervals. Logistic regression was used to identify significant influencing factors on ADRs in the PMS and pharmacovigilance data. Results: Rates of reported ADRs were lower in elderly patients versus adults aged <65 years due to a reduced incidence of non-serious ADRs; this was statistically significant for the clinical trials and pharmacovigilance populations, with a trend in the PMS database. Serious ADRs occurred infrequently in the clinical trials and PMS populations (too low for statistical comparison), and pharmacovigilance data demonstrated a low incidence (<0.005%) in both age groups. Conclusions: This evaluation involving three large databases demonstrated no greater incidence of ADRs following gadobutrol-enhanced MRI in elderly patients (≥65 years) compared with younger adults, with gadobutrol having a favourable safety profile in both age groups. -- Highlights: •First dedicated safety study of an extracellular contrast agent in the elderly. •Elderly patients experience fewer non-serious ADRs than younger adults. •Gadobutrol has a favourable safety profile in both age groups

Evaluation of intestinal phosphate binding to improve the safety profile of oral sodium phosphate bowel cleansing.

Directory of Open Access Journals (Sweden)

Stef Robijn

Full Text Available Prior to colonoscopy, bowel cleansing is performed for which frequently oral sodium phosphate (OSP is used. OSP results in significant hyperphosphatemia and cases of acute kidney injury (AKI referred to as acute phosphate nephropathy (APN; characterized by nephrocalcinosis are reported after OSP use, which led to a US-FDA warning. To improve the safety profile of OSP, it was evaluated whether the side-effects of OSP could be prevented with intestinal phosphate binders. Hereto a Wistar rat model of APN was developed. OSP administration (2 times 1.2 g phosphate by gavage with a 12h time interval induced bowel cleansing (severe diarrhea and significant hyperphosphatemia (21.79 ± 5.07 mg/dl 6h after the second OSP dose versus 8.44 ± 0.97 mg/dl at baseline. Concomitantly, serum PTH levels increased fivefold and FGF-23 levels showed a threefold increase, while serum calcium levels significantly decreased from 11.29 ± 0.53 mg/dl at baseline to 8.68 ± 0.79 mg/dl after OSP. OSP administration induced weaker NaPi-2a staining along the apical proximal tubular membrane. APN was induced: serum creatinine increased (1.5 times baseline and nephrocalcinosis developed (increased renal calcium and phosphate content and calcium phosphate deposits on Von Kossa stained kidney sections. Intestinal phosphate binding (lanthanum carbonate or aluminum hydroxide was not able to attenuate the OSP induced side-effects. In conclusion, a clinically relevant rat model of APN was developed. Animals showed increased serum phosphate levels similar to those reported in humans and developed APN. No evidence was found for an improved safety profile of OSP by using intestinal phosphate binders.

Refactoring Real-Time Java Profiles

DEFF Research Database (Denmark)

Søndergaard, Hans; Thomsen, Bent; Ravn, Anders Peter

2011-01-01

Just like other software, Java profiles benefits from refactoring when they have been used and have evolved for some time. This paper presents a refactoring of the Real-Time Specification for Java (RTSJ) and the Safety Critical Java (SCJ) profile (JSR-302). It highlights core concepts and makes...

Investigation of chronic efficacy and safety profile of two potential anti-inflammatory bipyrazole-based compounds in experimental animals

Directory of Open Access Journals (Sweden)

Domiati S

2018-04-01

Full Text Available Souraya Domiati,1 Mohammed Mehanna,2,3 Hanan Ragab,4 Hania Nakkash Chmaisse,1 Ahmed El Mallah5 1Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Beirut Arab University, Beirut, Lebanon; 2Department of Pharmaceutical Technology, Faculty of Pharmacy, Beirut Arab University, Beirut, Lebanon; 3Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 4Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 5Department of Pharmacology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt Purpose: Although nonsteroidal anti-inflammatory drugs are widely used to treat a variety of disorders, their administration is associated with gastrointestinal side effects, acute kidney injury and liver enzymes’ elevation. Accordingly, researchers are encouraged to create novel agents with better safety profile. The aim of the current study was to evaluate the chronic efficacy and safety profile of two compounds previously proven to have acceptable acute anti-inflammatory and analgesic activities.Materials and methods: Doses were determined through formalin-induced mice paw edema-based dose–response curves. Granuloma weight was used to assess the chronic effect of the investigated compounds as compared to the vehicle and diclofenac representing the positive and the negative controls, respectively. Mice kidneys, livers and stomachs were histologically examined. Moreover, troponin I, alanine aminotransferase, aspartate aminotransferase, serum creatinine and blood urea nitrogen levels were measured. Results: The results highlight that the granulomas and exudates developed in mice after 7 days of treatment, with compound I and compound II were significantly lower than that of the negative control group. Moreover, compound I showed significantly better anti-inflammatory effect than diclofenac. Troponin level was undetected in all groups. Histopathological

Raising the profile of worker safety: highlights of the 2013 North American Agricultural Safety Summit.

Science.gov (United States)

Nelson, William J; Heiberger, Scott; Lee, Barbara C

2014-01-01

The 2013 North American Agricultural Safety Summit, an unprecedented gathering of industry leaders and safety experts, was held September 25-27 in Minneapolis, MN. Hosted by the industry-led Agricultural Safety and Health Council of America (ASHCA), there were 250 attendees, 82 speakers, 76 abstracts with poster presentations, along with "best practices" videos, genius bars sessions, learning stations, exhibits, breakfast roundtable topics, and receptions. The event was a mix of knowledge, inspiration and networking to enable participants to influence the adoption of safety practices in their home/work settings. Given the agriculture industry's commitment to feed nine billion people, the projected world population by 2050, it is imperative that producers and agribusiness strive to do it safely, humanely and sustainably. Evaluation feedback was very positive, indicating ASHCA's original objectives for the Summit were achieved.

Efficacy and Safety Profile of Diclofenac/Cyclodextrin and Progesterone/Cyclodextrin Formulations: A Review of the Literature Data.

Science.gov (United States)

Scavone, Cristina; Bonagura, Angela Colomba; Fiorentino, Sonia; Cimmaruta, Daniela; Cenami, Rosina; Torella, Marco; Fossati, Tiziano; Rossi, Francesco

2016-06-01

According to health technology assessment, patients deserve the best medicine. The development of drugs associated with solubility enhancers, such as cyclodextrins, represents a measure taken in order to improve the management of patients. Different drugs, such as estradiol, testosterone, dexamethasone, opioids, non-steroidal anti-inflammatories (NSAIDs; i.e. diclofenac), and progesterone are associated with cyclodextrins. Products containing the association of diclofenac/cyclodextrins are available for subcutaneous, intramuscular, and intravenous administration in doses that range from 25 to 75 mg. Medicinal products containing the association of progesterone/cyclodextrins are indicated for intramuscular and subcutaneous injection at a dose equal to 25 mg. The effects of cyclodextrins have been discussed in the solubility profile and permeability through biological membranes of drug molecules. A literature search was performed in order to give an overview of the pharmacokinetic characteristics, and efficacy and safety profiles of diclofenac/hydroxypropyl-β-cyclodextrin (HPβCD) and progesterone/HPβCD associations. The results of more than 20 clinical studies were reviewed. It was suggested that the new diclofenac/HPβCD formulation gives a rapid and effective response to acute pain and, furthermore, has pharmacokinetic and efficacy/safety profiles comparable to other medicinal products not containing cyclodextrins. One of the principal aspects of these new diclofenac formulations is that in lowering the dose (lower than 50 mg) the drugs could be more tolerable, especially in patients with comorbid conditions. Moreover, results of studies investigating the characteristics of progesterone and cyclodextrins showed that the new formulation (progesterone/HPβCD 25 mg solution) has the same bioavailability as other products containing progesterone. It is more rapidly absorbed and allows the achievement of peak plasma concentrations in a shorter time. Finally, the

Safety profile of the intravenous administration of brain-targeted stable nucleic acid lipid particles

Directory of Open Access Journals (Sweden)

Mariana Conceição

2016-03-01

Full Text Available In a clinical setting, where multiple administrations of the therapeutic agent are usually required to improve the therapeutic outcome, it is crucial to assess the immunogenicity of the administered nanoparticles. In this data work, we investigated the safety profile of the repeated intravenous administration of brain-targeted stable nucleic acid lipid particles (RVG-9r-targeted SNALPs. To evaluate local activation of the immune system, we performed analysis of mouse tissue homogenates and sections from cerebellum. To investigate peripheral activation of the immune system, we used serum of mice that were intravenously injected with RVG-9r-targeted SNALPs. These data are related and were discussed in the accompanying research article entitled “Intravenous administration of brain-targeted stable nucleic acid lipid particles alleviates Machado–Joseph disease neurological phenotype” (Conceição et al., in press [1].

Modeling pedestrian crossing speed profiles considering speed change behavior for the safety assessment of signalized intersections.

Science.gov (United States)

Iryo-Asano, Miho; Alhajyaseen, Wael K M

2017-11-01

Pedestrian safety is one of the most challenging issues in road networks. Understanding how pedestrians maneuver across an intersection is the key to applying countermeasures against traffic crashes. It is known that the behaviors of pedestrians at signalized crosswalks are significantly different from those in ordinary walking spaces, and they are highly influenced by signal indication, potential conflicts with vehicles, and intersection geometries. One of the most important characteristics of pedestrian behavior at crosswalks is the possible sudden speed change while crossing. Such sudden behavioral change may not be expected by conflicting vehicles, which may lead to hazardous situations. This study aims to quantitatively model the sudden speed changes of pedestrians as they cross signalized crosswalks under uncongested conditions. Pedestrian speed profiles are collected from empirical data and speed change events are extracted assuming that the speed profiles are stepwise functions. The occurrence of speed change events is described by a discrete choice model as a function of the necessary walking speed to complete crossing before the red interval ends, current speed, and the presence of turning vehicles in the conflict area. The amount of speed change before and after the event is modeled using regression analysis. A Monte Carlo simulation is applied for the entire speed profile of the pedestrians. The results show that the model can represent the pedestrian travel time distribution more accurately than the constant speed model. Copyright © 2017 Elsevier Ltd. All rights reserved.

Food safety knowledge and practices of abattoir and butchery shops and the microbial profile of meat in Mekelle City, Ethiopia

Science.gov (United States)

Haileselassie, Mekonnen; Taddele, Habtamu; Adhana, Kelali; Kalayou, Shewit

2013-01-01

Objective To assess the food safety knowledge and practices in meat handling, and to determine microbial load and pathogenic organisms in meat at Mekelle city. Methods A descriptive survey design was used to answer questions concerning the current status of food hygiene and sanitation practiced in the abattoir and butcher shops. Workers from the abattoir and butcher shops were interviewed through a structured questionnaire to assess their food safety knowledge. Bacterial load was assessed by serial dilution method and the major bacterial pathogens were isolated by using standard procedures. Results 15.4% of the abattoir workers had no health certificate and there was no hot water, sterilizer and cooling facility in the abattoir. 11.3% of the butchers didn't use protective clothes. There was a food safety knowledge gap within the abattoir and butcher shop workers. The mean values of bacterial load of abattoir meat, butcher shops and street meat sale was found to be 1.1×105, 5.6×105 and 4.3×106 cfu/g, respectively. The major bacterial pathogens isolated were Escherichia coli, Staphylococcus aureus and Bacillus cereus. Conclusions The study revealed that there is a reasonable gap on food safety knowledge by abattoir and butcher shop workers. The microbial profile was also higher compared to standards set by World Health Organization. Due attention should be given by the government to improve the food safety knowledge and the quality standard of meat sold in the city. PMID:23646306

Measurement of Food Safety Culture using Survey and Maturity Profiling Tools

OpenAIRE

Jespersen, Lone; Griffiths, Mansel; Maclaurin, Tanya; Chapman, Ben; Wallace, Carol A.

2016-01-01

Organizational culture is defined by dimensions and characteristics that can be used to measure food safety culture in food manufacturing through a food safety maturity model. Maturity models from quality, health care, and information technology have been used since early 1970 and this work presents a novel food safety culture maturity model with five capability areas and food safety pinpointed behaviours specific to functions and levels in a food manufacturing company. A survey tool linked t...

A predictable Java profile

DEFF Research Database (Denmark)

Bøgholm, Thomas; Hansen, Rene Rydhof; Ravn, Anders Peter

2009-01-01

A Java profile suitable for development of high integrity embedded systems is presented. It is based on event handlers which are grouped in missions and equipped with respectively private handler memory and shared mission memory. This is a result of our previous work on developing a Java profile......, and is directly inspired by interactions with the Open Group on their on-going work on a safety critical Java profile (JSR-302). The main contribution is an arrangement of the class hierarchy such that the proposal is a generalization of Real-Time Specification for Java (RTSJ). A further contribution...

Safety evaluation of zotepine for the treatment of schizophrenia.

Science.gov (United States)

Riedel, Michael; Musil, Richard; Seemüller, Florian; Spellmann, Ilja; Möller, Hans-Jürgen; Schennach-Wolff, Rebecca

2010-07-01

Atypical antipsychotics have become the first-line treatment for patients suffering from schizophrenia in the industrialized world. Given the frequent necessity of a life-long enduring antipsychotic treatment, the compounds' safety profile is of great importance for patients and caregivers. Zotepine is an antipsychotic with atypical properties and previous data have suggested a very favorable side effect profile. The aim of this review is to provide a broad knowledge base on the safety profile of zotepine deriving from currently available research results published in English medical databases. The focus of this research reports starts in the 1990s with zotepine's approval in Europe. This paper incorporates data on placebo-controlled studies of zotepine as well as studies with comparator compounds also beyond the diagnostic boarder of schizophrenia regarding zotepine's safety. The take home message of this safety evaluation of zotepine is that compared to typical compounds zotepine induces less extrapyramidal side effects; however, in terms of comparing zotepine's safety with other atypical antipsychotics more studies are needed to draw final conclusions.

Efficacy and Safety Profile of Tricyclo-DNA Antisense Oligonucleotides in Duchenne Muscular Dystrophy Mouse Model

Directory of Open Access Journals (Sweden)

Karima Relizani

2017-09-01

Full Text Available Antisense oligonucleotides (AONs hold promise for therapeutic splice-switching correction in many genetic diseases. However, despite advances in AON chemistry and design, systemic use of AONs is limited due to poor tissue uptake and sufficient therapeutic efficacy is still difficult to achieve. A novel class of AONs made of tricyclo-DNA (tcDNA is considered very promising for the treatment of Duchenne muscular dystrophy (DMD, a neuromuscular disease typically caused by frameshifting deletions or nonsense mutations in the gene-encoding dystrophin and characterized by progressive muscle weakness, cardiomyopathy, and respiratory failure in addition to cognitive impairment. Herein, we report the efficacy and toxicology profile of a 13-mer tcDNA in mdx mice. We show that systemic delivery of 13-mer tcDNA allows restoration of dystrophin in skeletal muscles and to a lower extent in the brain, leading to muscle function improvement and correction of behavioral features linked to the emotional/cognitive deficiency. More importantly, tcDNA treatment was generally limited to minimal glomerular changes and few cell necroses in proximal tubules, with only slight variation in serum and urinary kidney toxicity biomarker levels. These results demonstrate an encouraging safety profile for tcDNA, albeit typical of phosphorothiate AONs, and confirm its therapeutic potential for the systemic treatment of DMD patients. Keywords: antisense oligonucleotides, Duchenne muscular dystrophy, preclinical, splice switching, tcDNA-AONs

Safety Profile of Eslicarbazepine Acetate as Add-On Therapy in Adults with Refractory Focal-Onset Seizures: From Clinical Studies to 6 Years of Post-Marketing Experience.

Science.gov (United States)

Gama, Helena; Vieira, Mariana; Costa, Raquel; Graça, Joana; Magalhães, Luís M; Soares-da-Silva, Patrício

2017-12-01

Eslicarbazepine acetate was first approved in the European Union in 2009 as adjunctive therapy in adults with partial-onset seizures with or without secondary generalization. The objective of this study was to review the safety profile of eslicarbazepine acetate analyzing the data from several clinical studies to 6 years of post-marketing surveillance. We used a post-hoc pooled safety analysis of four phase III, double-blind, randomized, placebo-controlled studies (BIA-2093-301, -302, -303, -304) of eslicarbazepine acetate as add-on therapy in adults. Safety data of eslicarbazepine acetate in special populations of patients aged ≥65 years with partial-onset seizures (BIA-2093-401) and subjects with moderate hepatic impairment (BIA-2093-111) and renal impairment (BIA-2093-112) are also considered. The incidences of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and serious adverse events were analyzed. The global safety database of eslicarbazepine acetate was analyzed for all cases from post-marketing surveillance from 1 October, 2009 to 21 October, 2015. From a pooled analysis of four phase III studies, it was concluded that the incidence of treatment-emergent adverse events, treatment-emergent adverse events leading to discontinuation, and adverse drug reactions were dose dependent. Dizziness, somnolence, headache, and nausea were the most common treatment-emergent adverse events (≥10% of patients) and the majority were of mild-to-moderate intensity. No dose-dependent trend was observed for serious adverse events and individual serious adverse events were reported in less than 1% of patients. Hyponatremia was classified as a possibly related treatment-emergent adverse event in phase III studies (1.2%); however, after 6 years of post-marketing surveillance it represents the most frequently (10.2%) reported adverse drug reaction, with more than half of these cases occurring with eslicarbazepine acetate at

Control of the tokamak safety factor profile with time-varying constraints using MPC

International Nuclear Information System (INIS)

Maljaars, E.; Felici, F.; De Baar, M.R.; Geelen, P.J.M.; Steinbuch, M.; Van Dongen, J.; Hogeweij, G.M.D.

2015-01-01

A controller is designed for the tokamak safety factor profile that takes real-time-varying operational and physics limits into account. This so-called model predictive controller (MPC) employs a prediction model in order to compute optimal control inputs that satisfy the given limits. The use of linearized models around a reference trajectory results in a quadratic programming problem that can easily be solved online. The performance of the controller is analysed in a set of ITER L-mode scenarios simulated with the non-linear plasma transport code RAPTOR. It is shown that the controller can reduce the tracking error due to an overestimation or underestimation of the modelled transport, while making a trade-off between residual error and amount of controller action. It is also shown that the controller can account for a sudden decrease in the available actuator power, while providing warnings ahead of time about expected violations of operational and physics limits. This controller can be extended and implemented in existing tokamaks in the near future. (paper)

Real-Life Efficacy, Immunogenicity and Safety of Biosimilar Infliximab.

Science.gov (United States)

Vegh, Zsuzsanna; Kurti, Zsuzsanna; Lakatos, Peter L

2017-01-01

Recently, the use of biosimilar infliximab (IFX) in the treatment of inflammatory bowel diseases has become widespread in some European and non-European countries. Data on the efficacy, safety and immunogenicity from real-life cohorts are accumulating. The first reports showed similar outcomes in the induction and maintenance of remission, mucosal healing, safety and immunogenicity profile to the originator IFX. In the present review, we aimed to summarize the existing knowledge on the efficacy, safety and immunogenicity profile of biosimilar IFX reported from real-life cohorts. © 2017 S. Karger AG, Basel.

Tolerability and safety aspects of mirtazapine.

Science.gov (United States)

Nutt, David J

2002-06-01

The tolerability and safety profile of the noradrenergic and specific serotonergic antidepressant (NaSSA) mirtazapine reflects its unique pharmacological profile. The 5-HT(2) blocking effect contributes towards its anxiolytic effects and benefits on sleep, as well as preventing the sexual dysfunction that may occur with non-specific stimulation of the serotonin system by drugs such as the selective serotonin reuptake inhibitors (SSRIs). In addition, 5-HT(3) blockade by mirtazapine helps to prevent nausea and vomiting. Weight gain is the most commonly reported side-effect of mirtazapine, although there is evidence to suggest that this is not a significant problem during long-term treatment. In conclusion, mirtazapine has a good tolerability and safety profile that demonstrates several benefits over other antidepressants. Copyright 2002 John Wiley & Sons, Ltd.

Innovations in Post-Marketing Safety Research

NARCIS (Netherlands)

Stefánsdóttir, G.

2012-01-01

Safety surveillance is important during the entire life cycle of a drug. Pre-marketing trials have been shown to be ineffective in establishing the full safety profile of the drug, mainly due to their relatively small sample size and characteristics of the patients, which are usually younger and

Safety and Pharmacokinetic Profiles of Repeated-Dose Micafungin in Children and Adolescents Treated for Invasive Candidiasis

Science.gov (United States)

Benjamin, Daniel K.; Deville, Jaime G.; Azie, Nkechi; Kovanda, Laura; Roy, Mike; Wu, Chunzhang; Arrieta, Antonio

2013-01-01

Background Micafungin is an echinocandin with proven efficacy against a broad range of fungal infections, including those caused by Candida species. Objective To evaluate the safety and pharmacokinetics of once-daily 3 mg/kg and 4.5 mg/kg micafungin in children with proven, probable, or suspected invasive candidiasis. Methods Micafungin safety and pharmacokinetics were assessed in two Phase I, open-label, repeat-dose trials. In Study 2101, children aged 2–16 years were grouped by weight to receive 3 mg/kg (≥25 kg) or 4.5 mg/kg (<25 kg) intravenous micafungin for 10–14 days. In Study 2102, children aged 4 months to <2 years received 4.5 mg/kg micafungin. Study protocols were otherwise identical. Results Safety was analyzed in seventy-eight and nine children in Studies 2101 and 2102, respectively. Although adverse events were experienced by most children (2101: n = 62; 2102: n = 9), micafungin-related adverse events were less common (2101: n = 28; 2102: n = 1), and the number of patients discontinuing due to adverse events was low (2101: n = 4; 2102: n = 1). The most common micafungin-related adverse events were infusion-associated symptoms, pyrexia, and hypomagnesemia (Study 2101), and liver function abnormalities (Study 2102). The micafungin pharmacokinetic profile was similar to that seen in other studies conducted in children, but different than that observed in adults. Conclusions In this small cohort of children, once-daily doses of 3 mg/kg and 4.5 mg/kg micafungin were well tolerated. Pharmacokinetic data will be combined in a population pharmacokinetic analysis to support U.S. dosing recommendations in children. PMID:23958810

Developing patient safety in dentistry.

Science.gov (United States)

Pemberton, M N

2014-10-01

Patient safety has always been important and is a source of public concern. Recent high profile scandals and subsequent reports, such as the Francis report into the failings at Mid Staffordshire, have raised those concerns even higher. Mortality and significant morbidity associated with the practice of medicine has led to many strategies to help improve patient safety, however, with its lack of associated mortality and lower associated morbidity, dentistry has been slower at systematically considering how patient safety can be improved. Recently, several organisations, researchers and clinicians have discussed the need for a patient safety culture in dentistry. Strategies are available to help improve patient safety in healthcare and deserve further consideration in dentistry.

BWR AXIAL PROFILE

International Nuclear Information System (INIS)

Huffer, J.

2004-01-01

The purpose of this calculation is to develop axial profiles for estimating the axial variation in burnup of a boiling water reactor (BWR) assembly spent nuclear fuel (SNF) given the average burnup of an assembly. A discharged fuel assembly typically exhibits higher burnup in the center and lower burnup at the ends of the assembly. Criticality safety analyses taking credit for SNF burnup must account for axially varying burnup relative to calculations based on uniformly distributed assembly average burnup due to the under-burned tips. Thus, accounting for axially varying burnup in criticality analyses is also referred to as accounting for the ''end effect'' reactivity. The magnitude of the reactivity change due to ''end effect'' is dependent on the initial assembly enrichment, the assembly average burnup, and the particular axial profile characterizing the burnup distribution. The set of bounding axial profiles should incorporate multiple BWR core designs and provide statistical confidence (95 percent confidence that 95 percent of the population is bound by the profile) that end nodes are conservatively represented. The profiles should also conserve the overall burnup of the fuel assembly. More background on BWR axial profiles is provided in Attachment I

Profiles of bullying victimization, discrimination, social support, and school safety: Links with Latino/a youth acculturation, gender, depressive symptoms, and cigarette use.

Science.gov (United States)

Lorenzo-Blanco, Elma I; Unger, Jennifer B; Oshri, Assaf; Baezconde-Garbanati, Lourdes; Soto, Daniel

2016-01-01

Latino/a youth are at risk for symptoms of depression and cigarette smoking but this risk varies by acculturation and gender. To understand why some youth are at greater risk than others, we identified profiles of diverse community experiences (perceived discrimination, bullying victimization, social support, perceived school safety) and examined associations between profiles of community experience and depressive symptoms, cigarette smoking, acculturation, and gender. Data came from Project Red (Reteniendo y Entendiendo Diversidad para Salud), a school-based longitudinal study of acculturation among 1,919 Latino/a adolescents (52% female; 84% 14 years old; 87% U.S. born). Latent profile analysis (LPA) revealed 4 distinct profiles of community experience that varied by gender and acculturation. Boys were overrepresented in profile groups with high perceived discrimination, some bullying, and lack of positive experiences, while girls were overrepresented in groups with high bullying victimization in the absence and presence of other community experiences. Youth low on both U.S. and Latino/a cultural orientation described high perceived discrimination and lacked positive experiences, and were predominantly male. Profiles characterized by high perceived discrimination and /or high bullying victimization in the absence of positive experiences had higher levels of depressive symptoms and higher risk of smoking, relative to the other groups. Findings suggest that acculturation comes with diverse community experiences that vary by gender and relate to smoking and depression risk. Results from this research can inform the development of tailored intervention and prevention strategies to reduce depression and/or smoking for Latino/a youth. (c) 2016 APA, all rights reserved).

Neural network evaluation of tokamak current profiles for real time control

Science.gov (United States)

Wróblewski, Dariusz

1997-02-01

Active feedback control of the current profile, requiring real-time determination of the current profile parameters, is envisioned for tokamaks operating in enhanced confinement regimes. The distribution of toroidal current in a tokamak is now routinely evaluated based on external (magnetic probes, flux loops) and internal (motional Stark effect) measurements of the poloidal magnetic field. However, the analysis involves reconstruction of magnetohydrodynamic equilibrium and is too intensive computationally to be performed in real time. In the present study, a neural network is used to provide a mapping from the magnetic measurements (internal and external) to selected parameters of the safety factor profile. The single-pass, feedforward calculation of output of a trained neural network is very fast, making this approach particularly suitable for real-time applications. The network was trained on a large set of simulated equilibrium data for the DIII-D tokamak. The database encompasses a large variety of current profiles including the hollow current profiles important for reversed central shear operation. The parameters of safety factor profile (a quantity related to the current profile through the magnetic field tilt angle) estimated by the neural network include central safety factor, q0, minimum value of q, qmin, and the location of qmin. Very good performance of the trained neural network both for simulated test data and for experimental datais demonstrated.

Neural network evaluation of tokamak current profiles for real time control

International Nuclear Information System (INIS)

Wroblewski, D.

1997-01-01

Active feedback control of the current profile, requiring real-time determination of the current profile parameters, is envisioned for tokamaks operating in enhanced confinement regimes. The distribution of toroidal current in a tokamak is now routinely evaluated based on external (magnetic probes, flux loops) and internal (motional Stark effect) measurements of the poloidal magnetic field. However, the analysis involves reconstruction of magnetohydrodynamic equilibrium and is too intensive computationally to be performed in real time. In the present study, a neural network is used to provide a mapping from the magnetic measurements (internal and external) to selected parameters of the safety factor profile. The single-pass, feedforward calculation of output of a trained neural network is very fast, making this approach particularly suitable for real-time applications. The network was trained on a large set of simulated equilibrium data for the DIII-D tokamak. The database encompasses a large variety of current profiles including the hollow current profiles important for reversed central shear operation. The parameters of safety factor profile (a quantity related to the current profile through the magnetic field tilt angle) estimated by the neural network include central safety factor, q 0 , minimum value of q, q min , and the location of q min . Very good performance of the trained neural network both for simulated test data and for experimental datais demonstrated. copyright 1997 American Institute of Physics

Safety of bisphosphonates

DEFF Research Database (Denmark)

Pazianas, Michael; Abrahamsen, Bo

2011-01-01

and their safety profile has withstood the challenges of the harsh clinical reality and widespread use. Certainly, the esophageal or gastric irritation caused by the oral preparations is an established adverse effect, the risk of which can be reduced by the recommended routine of taking the medication. From...

Postmarketing cohort study to assess the safety profile of oral dexketoprofen trometamol for mild to moderate acute pain treatment in primary care.

Science.gov (United States)

Carne, Xavier; Rios, Jose; Torres, Ferran

2009-10-01

Recently, new concerns on the safety profile of nonsteroidal anti-inflammatory drugs (NSAIDs) have been raised by the European Medicines Agency (EMEA) and other regulatory authorities. The safety profile of oral dexketoprofen trometamol for the treatment of acute mild to moderate pain of different causes in actual conditions of use in the primary care setting was assessed. A prospective cohort study was designed to evaluate the tolerability of dexketoprofen compared with other commonly prescribed analgesics. Medications were given according to specifications in the summary of product characteristics. The intensity of pain was assessed at baseline and at days 1 and 7 of drug treatment using a 100-mm visual analog scale (VAS). Adverse events (AEs) were recorded. A total of 7,337 patients (median age [IQR] = 46 [33-61] years) were included in the study comparing dexketoprofen (n = 5,429), diclofenac (n = 485), ibuprofen (n = 479), paracetamol (n = 459), metamizole (n = 207), aceclofenac (n = 103), naproxen (n = 74), piroxicam (n = 69) and dexibuprofen (n = 32). The reasons for use were: musculoskeletal disorders, headache, dysmenorrhea and odontalgia. Treatment compliance was very high. Metamizole-paracetamol and dexketoprofen showed the lowest prevalence of AEs (2.7% and 3.6%, respectively), while aceclofenac-diclofenac showed the highest prevalence (8.2%) (P dexketoprofen, 1.57 (0.79-3.13) for ibuprofen and dexibuprofen, 2.31 (0.64-8.27) for naproxen, 2.63 (0.85-8.15) for piroxicam and 3.37 (1.87-6.06) for aceclofenac-diclofenac. These results confirm the safety of oral treatment with dexketoprofen in patients with acute pain of various etiologies observed in previous studies and support the use of dexketoprofen as a first-line drug for the approved therapeutic indications. Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.

Managing risk in healthcare: understanding your safety culture using the Manchester Patient Safety Framework (MaPSaF).

Science.gov (United States)

Parker, Dianne

2009-03-01

To provide sufficient information about the Manchester Patient Safety Framework (MaPSaF) to allow healthcare professionals to assess its potential usefulness. The assessment of safety culture is an important aspect of risk management, and one in which there is increasing interest among healthcare organizations. Manchester Patient Safety Framework offers a theory-based framework for assessing safety culture, designed specifically for use in the NHS. The framework covers multiple dimensions of safety culture, and five levels of safety culture development. This allows the generation of a profile of an organization's safety culture in terms of areas of relative strength and challenge, which can be used to identify focus issues for change and improvement. Manchester Patient Safety Framework provides a useful method for engaging healthcare professionals in assessing and improving the safety culture in their organization, as part of a programme of risk management.

Safety-analysis report for packaging (SARP) general-purpose heat-source module 750-Watt shipping container

International Nuclear Information System (INIS)

Whitney, M.A.; Burgan, C.E.; Blauvelt, R.K.; Zocher, R.W.; Bronisz, S.E.

1981-01-01

The SARP includes discussions of structural integrity, thermal resistance, radiation shielding and radiological safety, nuclear criticality safety, and quality control. Extensive tests and evaluations were performed to show that the container will function effectively with respect to all required standards and when subjected to normal transportation conditions and the sequence of four hypothetical accident conditions (free drop, puncture, thermal, and water immersion). In addition, a steady state temperature profile and radiation profile were measured using two heat sources that very closely resemble the GPHS. This gave an excellent representation of the GPHS temperature and radiation profile. A nuclear criticality safety analysis determined that all safety requirements are met

Motor carrier industry profile study : financial and operating performance profiles by industry segment, 2001-2002.

Science.gov (United States)

2004-09-01

This report profiles the motor carrier industry and its significant operating segments. It is one of a series of reports analyzing various aspects of the motor carrier industry. Other reports in the series focus on the safety performance of the indus...

Neural network evaluation of tokamak current profiles for real time control (abstract)

Science.gov (United States)

Wróblewski, Dariusz

1997-01-01

Active feedback control of the current profile, requiring real-time determination of the current profile parameters, is envisioned for tokamaks operating in enhanced confinement regimes. The distribution of toroidal current in a tokamak is now routinely evaluated based on external (magnetic probes, flux loops) and internal (motional Stark effect) measurements of the poloidal magnetic field. However, the analysis involves reconstruction of magnetohydrodynamic equilibrium and is too intensive computationally to be performed in real time. In the present study, a neural network is used to provide a mapping from the magnetic measurements (internal and external) to selected parameters of the safety factor profile. The single-pass, feedforward calculation of output of a trained neural network is very fast, making this approach particularly suitable for real-time applications. The network was trained on a large set of simulated equilibrium data for the DIII-D tokamak. The database encompasses a large variety of current profiles including the hollow current profiles important for reversed central shear operation. The parameters of safety factor profile (a quantity related to the current profile through the magnetic field tilt angle) estimated by the neural network include central safety factor, q0, minimum value of q, qmin, and the location of qmin. Very good performance of the trained neural network both for simulated test data and for experimental data is demonstrated.

Neural network evaluation of tokamak current profiles for real time control (abstract)

International Nuclear Information System (INIS)

Wroblewski, D.

1997-01-01

Active feedback control of the current profile, requiring real-time determination of the current profile parameters, is envisioned for tokamaks operating in enhanced confinement regimes. The distribution of toroidal current in a tokamak is now routinely evaluated based on external (magnetic probes, flux loops) and internal (motional Stark effect) measurements of the poloidal magnetic field. However, the analysis involves reconstruction of magnetohydrodynamic equilibrium and is too intensive computationally to be performed in real time. In the present study, a neural network is used to provide a mapping from the magnetic measurements (internal and external) to selected parameters of the safety factor profile. The single-pass, feedforward calculation of output of a trained neural network is very fast, making this approach particularly suitable for real-time applications. The network was trained on a large set of simulated equilibrium data for the DIII-D tokamak. The database encompasses a large variety of current profiles including the hollow current profiles important for reversed central shear operation. The parameters of safety factor profile (a quantity related to the current profile through the magnetic field tilt angle) estimated by the neural network include central safety factor, q 0 , minimum value of q, q min , and the location of q min . Very good performance of the trained neural network both for simulated test data and for experimental data is demonstrated. copyright 1997 American Institute of Physics

Study on Rail Profile Optimization Based on the Nonlinear Relationship between Profile and Wear Rate

Directory of Open Access Journals (Sweden)

Jianxi Wang

2017-01-01

Full Text Available This paper proposes a rail profile optimization method that takes account of wear rate within design cycle so as to minimize rail wear at the curve in heavy haul railway and extend the service life of rail. Taking rail wear rate as the object function, the vertical coordinate of rail profile at range optimization as independent variable, and the geometric characteristics and grinding depth of rail profile as constraint conditions, the support vector machine regression theory was used to fit the nonlinear relationship between rail profile and its wear rate. Then, the profile optimization model was built. Based on the optimization principle of genetic algorithm, the profile optimization model was solved to achieve the optimal rail profile. A multibody dynamics model was used to check the dynamic performance of carriage running on optimal rail profile. The result showed that the average relative error of support vector machine regression model remained less than 10% after a number of training processes. The dynamic performance of carriage running on optimized rail profile met the requirements on safety index and stability. The wear rate of optimized profile was lower than that of standard profile by 5.8%; the allowable carrying gross weight increased by 12.7%.

Radiation Safety for Sustainable Development

International Nuclear Information System (INIS)

2015-10-01

The objective of radiation safety is Assessments of Natural Radioactivity and its Radiological. The following topics were discussed during the conference: AFROSAFE Championing Radiation Safety in Africa, Radiation Calibration, and Development and Validation of a Laser Induced Breakdown Spectrometry Method for Cancer Detection and Characterization. Young Generation in NUCLEAR Initiative to Promote Nuclear Science and Technology, Radiation Protection Safety Culture and Application of Nuclear Techniques in Industry and the Environment were discuss. Rapid Chemometric X-Ray Fluorescence approaches for spectral Diagnostics of Cancer utilizing Tissue Trace Metals and Speciation profiles. Fundamental role of medical physics in Radiation Therapy

DIPS space exploration initiative safety

International Nuclear Information System (INIS)

Dix, T.E.

1991-01-01

The Dynamic Isotope Power Subsystem has been identified for potential applications for the Space Exploration Initiative. A qualitative safety assessment has been performed to demonstrate the overall safety adequacy of the Dynamic Isotope Power Subsystem for these applications. Mission profiles were defined for reference lunar and martian flights. Accident scenarios were qualitatively defined for all mission phases. Safety issues were then identified. The safety issues included radiation exposure, fuel containment, criticality, diversion, toxic materials, heat flux to the extravehicular mobility unit, and disposal. The design was reviewed for areas where safety might be further improved. Safety would be improved by launching the fuel separate from the rest of the subsystem on expendable launch vehicles, using a fuel handling tool during unloading of the hot fuel canister, and constructing a cage-like structure around the reversible heat removal system lithium heat pipes. The results of the safety assessment indicate that the DIPS design with minor modifications will produce a low risk concept

Safety profile of drugs used in the treatment of osteoporosis: a systematical review of the literature

Directory of Open Access Journals (Sweden)

M. Varenna

2013-10-01

Full Text Available The range of osteoporosis treatments is increasingly large and, like any disease, the pharmacological management of patients should involve a risk/benefit evaluation to attain the greatest reduction in risk of fracture with the lowest incidence of adverse events. The aim of this review is to critically appraise the literature about the safety issues of the main pharmacological treatments of osteoporosis. This document is the result of a consensus of experts based on a systematic review of regulatory documents, randomized controlled trials, metaanalyses, pharmacovigilance surveys and case series related to possible adverse drug reactions to osteoporosis treatment with calcium and vitamin D supplements, bisphosphonates, strontium ranelate, selective estrogen receptor modulators, denosumab, and teriparatide. As expected, randomized controlled trials showed only the most common adverse events due to the samples size and the short observation time. Case series and observational studies are able to provide data about uncommon side effects, but in some cases a sure cause-effect relationship needs still to be confirmed. Consistently with methodological limitations, the newer drugs have a tolerance profile that has not been fully explored yet. Osteoporosis treatments showed an overall good tolerance profile with rare serious adverse events that, however, must be well known by the clinician who prescribes these drugs. The concern about possible adverse events should be weighed against the reduction of morbidity and mortality associated with a significant fracture risk reduction.

Social network in patient safety: Social media visibility

Directory of Open Access Journals (Sweden)

Azucena Santillán García

2011-11-01

Full Text Available Internet social network (social media is a powerful communication tool, and its use is expanding significantly. This paper seeks to know the current state of visibility in online social networks of active citizen talking about patient safety. This is an observational cross-sectional study whose target population is the websites Facebook, Twitter and Tuenti in Spain. By three consecutive cuts social profiles were found using the searching terms “seguridad+paciente” and “safety+patient”. There were found 5 profiles on Facebook that met the search criteria, 6 on Twitter and none were found on Tuenti. It is concluded that although there is evidence of the rise of social networking, citizen network involved in patient safety appears not to be significantly represented within the social networks examined.

Safety profiles of Tripterygium wilfordii Hook F: a systematic review and meta-analysis

Directory of Open Access Journals (Sweden)

Chi Zhang

2016-11-01

Full Text Available Objective: Tripterygium wilfordii Hook F (TwHF is a widely used and effective treatment for inflammatory diseases. There have been concerns about its toxicity but no adequate synthesis of the evidence for adverse events (AEs. We aimed to undertake a clinically informative, systematic safety profile of TwHF.Methods: We undertook a systematic review and meta-analysis of experimental studies and observational studies. We searched electronic databases and conference abstracts. Safety outcomes were rates of common AEs. Results: We screened 4,137 abstracts for eligibility and included 594 studies in the analysis. The overall incidence of AEs was 26.7% (95% CI 24.8%, 28.8% in 23,256 TwHF users. The estimates did vary markedly when stratified by specific study types. The incidence of gastrointestinal symptoms, adverse reproductive outcomes, adverse skin reactions, hematologic events and cardiovascular events were 13.3% (95%CI 11.9%, 14.9%, 11.7% (95% CI 10.3%, 13.3%, 7.8% (95%CI 6.3%-9.5%, 6.5% (95%CI 5.7%-7.4% and 4.9% (95%CI 1.6%, 14.3%, respectively. The prevalence of irregular menstruation (IM was increased in patients taking TwHF compared with those given control (odds ratio [OR] 4.65, 95% CI 3.08 to 7.03. TwHF use has lower risk of weight gain (OR 0.12 [95%CI 0.04 to 0.39] and hair loss (OR 0.37 [95% CI 0.18 to 0.78]. Furthermore, long-term aspirin use (> 6 months has a higher AEs incidence (31.0% [95% CI 24.5%-38.5%].Conclusion: Our findings suggest that more than one in four patients who were taking TwHF had experienced AEs. A clear need exists for improved understanding of contributing risk factors, as well as of prevention and management strategies to improve patients' tolerance for TwHF.

Study on possibility of plasma current profile determination using an analytical model of tokamak equilibrium

International Nuclear Information System (INIS)

Moriyama, Shin-ichi; Hiraki, Naoji

1996-01-01

The possibility of determining the current profile of tokamak plasma from the external magnetic measurements alone is investigated using an analytical model of tokamak equilibrium. The model, which is based on an approximate solution of the Grad-Shafranov equation, can set a plasma current profile expressed with four free parameters of the total plasma current, the poloidal beta, the plasma internal inductance and the axial safety factor. The analysis done with this model indicates that, for a D-shaped plasma, the boundary poloidal magnetic field prescribing the external magnetic field distribution is dependent on the axial safety factor in spite of keeping the boundary safety factor and the plasma internal inductance constant. This suggests that the plasma current profile is reversely determined from the external magnetic analysis. The possibility and the limitation of current profile determination are discussed through this analytical result. (author)

Defining safety goals. 2. Basic Consideration on Defining Safety Goals

International Nuclear Information System (INIS)

Hakata, T.

2001-01-01

The purpose of this study is to develop basic safety goals that are rational and consistent for all nuclear facilities, including nuclear power plants and fuel cycle facilities. Basic safety goals (risk limits) by an index of radiation dose are discussed, which are based on health effects of detriment and fatality and risk levels presumably accepted by society. The contents of this paper are the personal opinions of the author. The desirable structure of safety goals is assumed to be 'basic safety goals plus specific safety goals (or supplemental safety goals) for each sort of facility, which reflects their characteristics'. The requisites of the basic safety goals must include (a) rational bases (scientific and social), (b) comprehensiveness (common to all sorts of nuclear facilities covering from normal to accidental conditions), and (c) applicability. To meet the requirements, the basic safety goals might have to be a risk profile expression by an index of radiation dose. The societal rationality is consideration of absolute risk levels (10 -6 or 10 -7 /yr) and/or relative risk factors (such as 0.1% of U.S. safety goals) that the general public accepts as tolerable. The following quantitative objectives are adopted in this study for protection of average individuals in the vicinity of a nuclear facility: 1. The additive annual radiation dose during normal operation must be -4 /yr (health detriment), 2x10 -6 /yr (latent cancer and severe hereditary effects), and 10 -7 /yr (acute fatality) from the statistics in Japan. The radiation effects on human beings are determined by recommendations of UNSCEAR (Ref. 1) and ICRP. The health effects considered are non-severe stochastic health detriment, i.e., detectable opacities of lens of eye (threshold 5 0.5 to 2 Sv), depression of hematopoiesis of bone marrow (0.5 Sv), and depression of reproductive capability (temporary sterility of testes ) (0.15 Sv). The LD 50/60 of acute fatality is ∼4 Sv, and fatalities by latent

Curcuma longa L. as a therapeutic agent in intestinal motility disorders. 2: Safety profile in mouse.

Science.gov (United States)

Micucci, Matteo; Aldini, Rita; Cevenini, Monica; Colliva, Carolina; Spinozzi, Silvia; Roda, Giulia; Montagnani, Marco; Camborata, Cecilia; Camarda, Luca; Chiarini, Alberto; Mazzella, Giuseppe; Budriesi, Roberta

2013-01-01

Curcuma extract exerts a myorelaxant effect on the mouse intestine. In view of a possible use of curcuma extract in motor functional disorders of the gastrointestinal tract, a safety profile study has been carried out in the mouse. Thirty mice were used to study the in vitro effect of curcuma on gallbladder, bladder, aorta and trachea smooth muscular layers and hearth inotropic and chronotropic activity. The myorelaxant effect on the intestine was also thoroughly investigated. Moreover, curcuma extract (200 mg/Kg/day) was orally administered to twenty mice over 28 days and serum liver and lipids parameters were evaluated. Serum, bile and liver bile acids qualitative and quantitative composition was were also studied. In the intestine, curcuma extract appeared as a not competitive inhibitor through cholinergic, histaminergic and serotoninergic receptors and showed spasmolytic effect on K(+) induced contraction at the level of L type calcium channels. No side effect was observed on bladder, aorta, trachea and heart when we used a dose that is effective on the intestine. An increase in gallbladder tone and contraction was observed. Serum liver and lipids parameters were normal, while a slight increase in serum and liver bile acids concentration and a decrease in bile were observed. Although these data are consistent with the safety of curcuma extract as far as its effect on the smooth muscular layers of different organs and on the heart, the mild cholestatic effect observed in absence of alteration of liver function tests must be further evaluated and the effective dose with minimal side effects considered.

Universal versus platelet reactivity assay-driven use of P2Y12 inhibitors in acute coronary syndrome patients: cost-effectiveness analyses for six European perspectives.

Science.gov (United States)

Coleman, Craig I; Limone, Brendan L

2014-01-01

Platelet reactivity assays (PRAs) can predict patients' likely response to clopidogrel. As ticagrelor and prasugrel are typically considered first-line agents for acute coronary syndrome in Europe, we assessed the cost-effectiveness of universal compared to PRA-driven selection of these agents. A Markov model was used to calculate five-year costs (2013£/€), quality-adjusted life-years and incremental cost-effectiveness ratios (ICERs) for one-year of universal ticagrelor or prasugrel (given to all) compared to each agents' corresponding PRA-driven strategy (ticagrelor/prasugrel in those with high platelet reactivity [HPR, >208 on the VerifyNow P2Y12 assay], others given generic clopidogrel). We assumed patients had their index event at 65-70 years of age and had a 42.7% incidence of HPR 24-48 hours post-revascularisation. The analysis was conducted from the perspective of six countries (France, Germany, Italy, Spain, the Netherlands and United Kingdom) and used a one-year cycle length. Event data for P2Y12 inhibitors were taken from multinational randomised trials and adjusted using country-specific epidemiologic data. Neither universal ticagrelor nor prasugrel were found to be cost-effective (all ICERs >40,250€ or £36,600/QALY) compared to their corresponding PRA-driven strategies in any of the countries evaluated. Results were sensitive to differences in P2Y12 Inhibitors costs and drug-specific relative risks of major adverse cardiac events. Monte Carlo simulation suggested universal ticagrelor or prasugrel were cost-effective in only 25-44% and 11-17% of 10,000 iterations compared to their respective PRA-driven strategies, when applying a willingness-to-pay threshold = €30,000 or £20,000/QALY. In conclusion, the universal use of newer P2Y12 inhibitors is not likely cost-effective compared to PRA-driven strategies.

A predictable Java profile - rationale and implementations

DEFF Research Database (Denmark)

Søndergaard, Hans; Bøgholm, Thomas; Hansen, Rene Rydhof

A Java profile suitable for development of high integrity embedded systems is presented. It is based on event handlers which are grouped in missions and equipped with respectively private handler memory and shared mission memory. This is a result of our previous work on developing a Java profile......, and is directly inspired by interactions with the Open Group on their on-going work on a safety critical Java profile (JSR-302). The main contribution is an arrangement of the class hierarchy such that the proposal is a generalization of Real-Time Specification for Java (RTSJ). A further contribution...

Active SMS-based influenza vaccine safety surveillance in Australian children.

Science.gov (United States)

Pillsbury, Alexis; Quinn, Helen; Cashman, Patrick; Leeb, Alan; Macartney, Kristine

2017-12-18

Australia's novel, active surveillance system, AusVaxSafety, monitors the post-market safety of vaccines in near real time. We analysed cumulative surveillance data for children aged 6 months to 4 years who received seasonal influenza vaccine in 2015 and/or 2016 to determine: adverse event following immunisation (AEFI) rates by vaccine brand, age and concomitant vaccine administration. Parent/carer reports of AEFI occurring within 3 days of their child receiving an influenza vaccine in sentinel immunisation clinics were solicited by Short Message Service (SMS) and/or email-based survey. Retrospective data from 2 years were combined to examine specific AEFI rates, particularly fever and medical attendance as a proxy for serious adverse events (SAE), with and without concomitant vaccine administration. As trivalent influenza vaccines (TIV) were funded in Australia's National Immunisation Program (NIP) in 2015 and quadrivalent (QIV) in 2016, respectively, we compared their safety profiles. 7402 children were included. Data were reported weekly through each vaccination season; no safety signals or excess of adverse events were detected. More children who received a concomitant vaccine had fever (7.5% versus 2.8%; p vaccine was associated with the highest increase in AEFI rates among children receiving a specified concomitant vaccine: 30.3% reported an AEFI compared with 7.3% who received an influenza vaccine alone (p safety profiles included low and expected AEFI rates (fever: 4.3% for TIV compared with 3.2% for QIV (p = .015); injection site reaction: 1.9% for TIV compared with 3.0% for QIV (p safety profile between brands. Active participant-reported data provided timely vaccine brand-specific safety information. Our surveillance system has particular utility in monitoring the safety of influenza vaccines, given that they may vary in composition annually. Copyright © 2017 Elsevier Ltd. All rights reserved.

164 original article profile of institutional infrastructure

African Journals Online (AJOL)

Dr Oboro VO

At this level is the most critical health services delivery point, with an ... Methods: The objectives of this study were to assess the universal precaution profile of primary health care .... Availability of safety training and monitoring schedule.

Phosphate binders for the treatment of hyperphosphatemia in chronic kidney disease patients on dialysis: a comparison of safety profiles.

Science.gov (United States)

Locatelli, Francesco; Del Vecchio, Lucia; Violo, Leano; Pontoriero, Giuseppe

2014-05-01

Hyperphosphatemia is common in the late stages of chronic kidney disease (CKD) and is associated with elevated parathormone levels, abnormal bone mineralization, extraosseous calcification and increased risk of cardiovascular events and death. Several classes of oral phosphate binders are available to help control phosphorus levels. Although effective at lowering serum phosphorus, they all have safety issues that need to be considered when selecting which one to use. This paper reviews the use of phosphate binders in patients with CKD on dialysis, with a focus on safety and tolerability. In addition to the more established agents, a new resin-based phosphate binder, colestilan, is discussed. Optimal phosphate control is still an unmet need in CKD. Nonetheless, we now have an extending range of phosphate binders available. Aluminium has potentially serious toxic risks. Calcium-based binders are still very useful but can lead to hypercalcemia and/or positive calcium balance and cardiovascular calcification. No long-term data are available for the new calcium acetate/magnesium combination product. Lanthanum is an effective phosphate binder, but there is insufficient evidence about possible long-term effects of tissue deposition. The resin-based binders, colestilan and sevelamer, appear to have profiles that would lead to less vascular calcification, and the main adverse events seen with these agents are gastrointestinal effects.

Patterns for Safety-Critical Java Memory Usage

DEFF Research Database (Denmark)

Rios Rivas, Juan Ricardo; Nilsen, Kelvin; Schoeberl, Martin

2012-01-01

Scoped memories are introduced in real-time Java profiles in order to make object allocation and deallocation time and space predictable. However, explicit scoping requires care from programmers when dealing with temporary objects, passing scope-allocated objects as arguments to methods, and retu......Scoped memories are introduced in real-time Java profiles in order to make object allocation and deallocation time and space predictable. However, explicit scoping requires care from programmers when dealing with temporary objects, passing scope-allocated objects as arguments to methods...... are illustrated by implementations in the safety-critical Java profile....

Country nuclear power profiles. 2000 ed

International Nuclear Information System (INIS)

2001-03-01

implemented and the profiles are supporting programmatic needs within the IAEA. It is noted that there also exist other less formal profiles on specific subjects of nuclear power in the Agency, e.g. Safety Profiles (NS Safety Co-ordination), Waste Management Profiles (NEFW), Fuel Cycle Profiles (NEFW)

RADWASS update. Radioactive Waste Safety Standards Programme

International Nuclear Information System (INIS)

Delattre, D.

2000-01-01

By the late 1980s, the issue of radioactive wastes and their management was becoming increasingly politically important. The IAEA responded by establishing a high profile family of safety standards, the Radioactive Waste Safety Standards (RADWASS). By this means, the IAEA intended to draw attention to the fact that well-established procedures for the safe management of radioactive wastes already were in place. The programme was intended to establish an ordered structure for safety documents on waste management and to ensure comprehensive coverage of all relevant subject areas. RADWASS documents are categorized under four subject areas - discharges, predisposal, disposal, and environmental restoration. The programme is overseen through a formalized review and approval mechanism that was established in 1996 for all safety standards activities. The Waste Safety Standards Committee (WASSC) is a standing body of senior regulatory officials with technical expertise in radioactive waste safety. To date, three Safety Requirements and seven Safety Guides have been issued

Monitoring product safety in the postmarketing environment.

Science.gov (United States)

Sharrar, Robert G; Dieck, Gretchen S

2013-10-01

The safety profile of a medicinal product may change in the postmarketing environment. Safety issues not identified in clinical development may be seen and need to be evaluated. Methods of evaluating spontaneous adverse experience reports and identifying new safety risks include a review of individual reports, a review of a frequency distribution of a list of the adverse experiences, the development and analysis of a case series, and various ways of examining the database for signals of disproportionality, which may suggest a possible association. Regulatory agencies monitor product safety through a variety of mechanisms including signal detection of the adverse experience safety reports in databases and by requiring and monitoring risk management plans, periodic safety update reports and postauthorization safety studies. The United States Food and Drug Administration is working with public, academic and private entities to develop methods for using large electronic databases to actively monitor product safety. Important identified risks will have to be evaluated through observational studies and registries.

Safety profile of dalfampridine extended release in multiple sclerosis: 5-year postmarketing experience in the United States

Directory of Open Access Journals (Sweden)

Jara M

2015-12-01

Full Text Available Michele Jara, Thomas Aquilina, Peter Aupperle, Adrian L Rabinowicz Acorda Therapeutics, Inc., Ardsley, NY, USA Background: Dalfampridine extended release tablets (dalfampridine-ER; prolonged-, modified, or sustained-release fampridine outside the US, 10 mg twice daily, was approved by the US Food and Drug Administration (FDA in January 2010 to improve walking in people with multiple sclerosis, as determined by an increase in walking speed. Objective: To provide a descriptive analysis of reported adverse events (AEs for commercially available dalfampridine-ER from March 2010 through March 31, 2015. Methods: Five-year postmarketing data for dalfampridine-ER were available from the exposure of approximately 107,000 patients in the US (103,700 patient-years. Commonly reported AEs (≥2% of all reported AEs and serious AEs were determined. The incidence of reported seizures was determined and the events were further investigated. Results: Among the 107,000 patients exposed to dalfampridine-ER (70% female; mean age 52.1, the most common AEs were dizziness (3.7%, insomnia (3.2%, balance disorder (3%, fall (2.4%, headache (2.4%, nausea (2.1%, and urinary tract infection (2%. Other common AEs were drug ineffectiveness (5.8%, gait disturbance (4.6%, and inappropriate dosing (3.1%. Serious AEs included rare anaphylactic reactions (five cases and drug hypersensitivity reactions (eight cases. A total of 657 seizure cases were reported (6.3/1,000 patient-years; of these, 324 were medically confirmed (3.1/1,000 patient-years. Incidence of reported seizures was stable over time. Duration of treatment prior to a seizure ranged from a single dose to >4 years; 12% of the seizures occurred within a week of starting treatment. Conclusion: The 5-year US postmarketing safety data of dalfampridine-ER is consistent with the safety profile observed in clinical trials. Incidence of reported seizures remained stable over time. Since commercial availability in March 2010, a

Ophthalmologic Baseline Characteristics and 2-Year Ophthalmologic Safety Profile of Pramipexole IR Compared with Ropinirole IR in Patients with Early Parkinson’s Disease

Directory of Open Access Journals (Sweden)

William Seiple

2016-01-01

Full Text Available Background. Parkinson’s disease (PD progressively affects dopaminergic neurotransmission and may affect retinal dopaminergic functions and structures. Objective. This 2-year randomized, open-label, parallel-group, flexible-dose study, NCT00144300, evaluated ophthalmologic safety profiles of immediate-release (IR pramipexole and ropinirole in patients with early idiopathic PD with ≤6 months’ prior dopamine agonist exposure and without preexisting major eye disorders. Methods. Patients received labeled IR regimens of pramipexole (n=121 or ropinirole (n=125 for 2 years. Comprehensive ophthalmologic assessments (COA included corrected acuity, Roth 28-color test, slit-lamp biomicroscopy, intraocular pressure, computerized visual field test, fundus photography, and electroretinography. Results. At baseline, we observed retinal pigmentary epithelium (RPE hypopigmentation not previously reported in PD patients. The estimated relative risk of 2-year COA worsening with pramipexole versus ropinirole was 1.07 (95% CI: 0.71–1.60. Mean changes from baseline in Unified Parkinson’s Disease Rating System parts II+III total scores (pramipexole: 1 year, −4.1±8.9, and 2 years, −0.7±10.1, and ropinirole: 1 year, −3.7±8.2, and 2 years, −1.7±10.5 and Hoehn–Yahr stage distribution showed therapeutic effects on PD symptoms. Safety profiles were consistent with labeling. Conclusions. The risk of retinal deterioration did not differ in early idiopathic PD patients receiving pramipexole versus ropinirole. RPE hypopigmentation at baseline was not previously reported in this population. This trial is registered with NCT00144300.

The profile of quantitative risk indicators in Krsko NPP

International Nuclear Information System (INIS)

Vrbanic, I.; Basic, I.; Bilic-Zabric, T.; Spiler, J.

2004-01-01

During the past decade strong initiative was observed which was aimed at incorporating information on risk into various aspects of operation of nuclear power plants. The initiative was observable in activities carried out by regulators as well as utilities and industry. It resulted in establishing the process, or procedure, which is often referred to as integrated decision making or risk informed decision making. In this process, engineering analyses and evaluations that are usually termed traditional and that rely on considerations of safety margins and defense in depth are supplemented by quantitative indicators of risk. Throughout the process, the plant risk was most commonly expressed in terms of likelihood of events involving damage to the reactor core and events with radiological releases to the environment. These became two commonly used quantitative indicators or metrics of plant risk (or, reciprocally, plant safety). They were evaluated for their magnitude (e.g. the expected number of events per specified time interval), as well as their profile (e.g. the types of contributing events). The information for quantitative risk indicators (to be used in risk informing process) is obtained from plant's probabilistic safety analyses or analyses of hazards. It is dependable on issues such as availability of input data or quality of model or analysis. Nuclear power plant Krsko has recently performed Periodic Safety Review, which was a good opportunity to evaluate and integrate the plant specific information on quantitative plant risk indicators and their profile. The paper discusses some aspects of quantitative plant risk profile and its perception.(author)

Applying principles from safety science to improve child protection.

Science.gov (United States)

Cull, Michael J; Rzepnicki, Tina L; O'Day, Kathryn; Epstein, Richard A

2013-01-01

Child Protective Services Agencies (CPSAs) share many characteristics with other organizations operating in high-risk, high-profile industries. Over the past 50 years, industries as diverse as aviation, nuclear power, and healthcare have applied principles from safety science to improve practice. The current paper describes the rationale, characteristics, and challenges of applying concepts from the safety culture literature to CPSAs. Preliminary efforts to apply key principles aimed at improving child safety and well-being in two states are also presented.

Impact of the Road Profile on Vehicle Deceleration

Directory of Open Access Journals (Sweden)

Vidas Žuraulis

2012-11-01

Full Text Available The article analyzes the impact of the longitudinal road profile on the efficiency of car braking estimated applying deceleration value. Different formulas are used for theoretical calculations, and therefore experimental brakes in different road slopes were performed to obtain the most accurate results. Deceleration, as one of the most important safety parameters, depends on the technical condition of the braking system, road conditions and structural and dynamic properties of the other car. Road alignments can significantly affect car manageability, because of weight transfer and extra track resistance, which may change the overall balance of the car and affect the nature of dynamic characteristics that may vary from certain critical values. The results of corrections to deceleration dependence on the road profile can be used for investigating traffic accidents, optimizing traffic control arrangements and implementing advanced systems for automotive active safety.

Safety and injury profile of conducted electrical weapons used by law enforcement officers against criminal suspects.

Science.gov (United States)

Bozeman, William P; Hauda, William E; Heck, Joseph J; Graham, Derrel D; Martin, Brian P; Winslow, James E

2009-04-01

Conducted electrical weapons such as the Taser are commonly used by law enforcement agencies. The safety of these weapons has been the subject of scrutiny and controversy; previous controlled studies in animals and healthy humans may not accurately reflect the risks of conducted electrical weapons used in actual conditions. We seek to determine the safety and injury profile of conducted electrical weapons used against criminal suspects in a field setting. This prospective, multicenter, observational trial tracked a consecutive case series of all conducted electrical weapon uses against criminal suspects at 6 US law enforcement agencies. Mandatory review of each conducted electrical weapon use incorporated physician review of police and medical records. Injuries were classified as mild, moderate, or severe according to a priori definitions. The primary outcome was a composite of moderate and severe injuries, termed significant injuries. Conducted electrical weapons were used against 1,201 subjects during 36 months. One thousand one hundred twenty-five subjects (94%) were men; the median age was 30 years (range 13 to 80 years). Mild or no injuries were observed after conducted electrical weapon use in 1,198 subjects (99.75%; 95% confidence interval 99.3% to 99.9%). Of mild injuries, 83% were superficial puncture wounds from conducted electrical weapon probes. Significant injuries occurred in 3 subjects (0.25%; 95% confidence interval 0.07% to 0.7%), including 2 intracranial injuries from falls and 1 case of rhabdomyolysis. Two subjects died in police custody; medical examiners did not find conducted electrical weapon use to be causal or contributory in either case. To our knowledge, these findings represent the first large, independent, multicenter study of conducted electrical weapon injury epidemiology and suggest that more than 99% of subjects do not experience significant injuries after conducted electrical weapon use.

A study on the impact of CYP2C19 genotype and platelet reactivity assay on patients undergoing PCI

Directory of Open Access Journals (Sweden)

P.C. Rath

2015-03-01

Conclusion: Clopidogrel resistance was observed to be 16.5% in our study population. PRA was useful in monitoring the efficacy of thienopyridines. By having this test, one can be safely maintained on clopidogrel in non-carriers, or with increased dose of clopidogrel in intermediate metabolizers or with newer drugs such as ticagrelor or prasugrel in poor metabolizers. Patients on ticagrelor and prasugrel identified as non-carriers of gene mutations for clopidogrel metabolism could be offered clopidogrel resulting in economic benefits to the patients. Patients at high risk of bleeding were also identified by the PRA.

Gadobutrol for contrast-enhanced magnetic resonance imaging in elderly patients: review of the safety profile from clinical trial, post-marketing surveillance, and pharmacovigilance data.

Science.gov (United States)

Endrikat, J; Schwenke, C; Prince, M R

2015-07-01

To assess the safety of gadobutrol administration in elderly patients (≥65 years) by comparing the incidence of adverse drug reactions (ADRs) following gadobutrol-enhanced magnetic resonance imaging (MRI) procedures in elderly patients with that in adults aged 18-64 years. Safety data on gadobutrol administration from clinical trials, post-marketing surveillance (PMS) studies, and pharmacovigilance reports were collected in three databases. In each dataset, absolute and relative frequencies of ADRs between age groups were analysed, along with odds ratios and 95% confidence intervals. Logistic regression was used to identify significant influencing factors on ADRs in the PMS and pharmacovigilance data. Rates of reported ADRs were lower in elderly patients versus adults aged statistically significant for the clinical trials and pharmacovigilance populations, with a trend in the PMS database. Serious ADRs occurred infrequently in the clinical trials and PMS populations (too low for statistical comparison), and pharmacovigilance data demonstrated a low incidence (<0.005%) in both age groups. This evaluation involving three large databases demonstrated no greater incidence of ADRs following gadobutrol-enhanced MRI in elderly patients (≥65 years) compared with younger adults, with gadobutrol having a favourable safety profile in both age groups. Copyright © 2015 The Royal College of Radiologists. All rights reserved.

The pharmacokinetics and safety profile of oral ganciclovir in combination with trimethoprim in HIV- and CMV-seropositive patients

Science.gov (United States)

Jung, Donald; AbdelHameed, Magdy H; Hunter, John; Teitelbaum, Philip; Dorr, Albert; Griffy, Kay

1999-01-01

Aims We investigated the pharmacokinetics and safety profile of oral ganciclovir coadministered with trimethoprim in HIV-and CMV-seropositive patients. Methods In an open-label, randomized, 3-way crossover study, 12 adult males received oral ganciclovir 1000 mg every 8h, oral trimethoprim 200 mg once daily, or both drugs concomitantly in a sequence of three 7-day treatment periods. Pharmacokinetic parameters were determined and adverse events recorded for each treatment. Results The presence of trimethoprim significantly decreased CLr (12.9%, P = 0.0068) and increased t1/2 (18.1%, P = 0.0378) of ganciclovir. However, these changes are unlikely to be clinically meaningful. There were no statistically significant changes in trimethoprim pharmacokinetic parameters in the presence of ganciclovir, with the exception of a 12.7% increase in Cmin. Ganciclovir was well tolerated when administered alone or in combination with trimethoprim. Conclusions There was no clinically significant pharmacokinetic interaction between oral ganciclovir and trimethoprim when coadministered. PMID:10215748

Pharmacokinetics, Safety and Cognitive Function Profile of Rupatadine 10, 20 and 40 mg in Healthy Japanese Subjects: A Randomised Placebo-Controlled Trial.

Directory of Open Access Journals (Sweden)

Jörg Täubel

Full Text Available Rupatadine is a marketed second generation antihistamine, with anti-PAF activity, indicated for symptomatic treatment of allergic rhinitis and urticaria. This study was conducted to evaluate the pharmacokinetics (PK, pharmacodynamics (PD, safety and tolerability of rupatadine in healthy Japanese subjects after single and multiple oral doses.In this randomised, double-blind, placebo-controlled study, 27 male and female healthy Japanese subjects were administered single and multiple escalating rupatadine dose of 10, 20 and 40 mg or placebo. Blood samples were collected at different time points for PK measurements and subjects were assessed for safety and tolerability. The effect of rupatadine on cognitive functioning was evaluated by means of computerized cognitive tests: rapid visual information processing (RVP, reaction time (RT, spatial working memory (SWM and visual analogue scales (VAS.Exposure to rupatadine as measured by Cmax and AUC was found to increase in a dose dependent manner over the dose range of 10-40 mg for both single and multiple dose administration. The safety assessments showed that all treatment related side effects were of mild intensity and there were no serious adverse events (SAEs or withdrawals due to treatment-emergent adverse events (TEAEs in this study. The therapeutic dose of rupatadine did not show any CNS impairment in any of the cognitive tests.This study demonstrated that rupatadine is safe and well tolerated by Japanese healthy subjects. The PK-PD profile confirmed previous experience with rupatadine.

Psychosocial influences on safety climate: evidence from community pharmacies.

Science.gov (United States)

Phipps, Denham L; Ashcroft, Darren M

2011-12-01

To examine the relationship between psychosocial job characteristics and safety climate. Cross-sectional survey. Community pharmacies in Great Britain. Participants A random sample of community pharmacists registered in Great Britain (n = 860). Survey instruments Effort-reward imbalance (ERI) indicator and Job Content Questionnaire (JCQ). Main outcome measures Pharmacy Safety Climate Questionnaire (PSCQ). The profile of scores from the ERI indicated a relatively high risk of adverse psychological effects. The profile of scores from the JCQ indicated both high demand on pharmacists and a high level of psychological and social resources to meet these demands. Path analysis confirmed a model in which the ERI and JCQ measures, as well as the type of pharmacy and pharmacist role, predicted responses to the PSCQ (χ(2)(36) = 111.38, p demand) accounted for the effect of job characteristics on safety climate ratings; each had differential effects on the PSCQ scales. The safety climate in community pharmacies is influenced by perceptions of job characteristics, such as the level of job demands and the resources available to meet these demands. Hence, any efforts to improve safety should take into consideration the effect of the psychosocial work environment on safety climate. In addition, there is a need to address the presence of work-related stressors, which have the potential to cause direct or indirect harm to staff and service users. The findings of the current study provide a basis for future research to improve the safety climate and well-being, both in the pharmacy profession and in other healthcare settings.

Diclofenac: an update on its mechanism of action and safety profile.

Science.gov (United States)

Gan, Tong J

2010-07-01

Diclofenac is a proven, commonly prescribed nonsteroidal anti-inflammatory drug (NSAID) that has analgesic, anti-inflammatory, and antipyretic properties, and has been shown to be effective in treating a variety of acute and chronic pain and inflammatory conditions. As with all NSAIDs, diclofenac exerts its action via inhibition of prostaglandin synthesis by inhibiting cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) with relative equipotency. However, extensive research shows the pharmacologic activity of diclofenac goes beyond COX inhibition, and includes multimodal and, in some instances, novel mechanisms of action (MOA). Literature retrieval was performed through PubMed/MEDLINE (through May 2009) using combinations of the terms diclofenac, NSAID, mechanism of action, COX-1, COX-2, and pharmacology. Reference citations resulting from publications identified in the literature search were reviewed when appropriate. This article reviews the established, putative, and emerging MOAs of diclofenac; compares the drug's pharmacologic and pharmacodynamic properties with other NSAIDs to delineate its potentially unique qualities; hypothesizes why it has been chosen for further recent formulation enhancement; and evaluates the potential effect of its MOA characteristics on safety. Research suggests diclofenac can inhibit the thromboxane-prostanoid receptor, affect arachidonic acid release and uptake, inhibit lipoxygenase enzymes, and activate the nitric oxide-cGMP antinociceptive pathway. Other novel MOAs may include the inhibition of substrate P, inhibition of peroxisome proliferator activated receptor gamma (PPARgamma), blockage of acid-sensing ion channels, alteration of interleukin-6 production, and inhibition of N-methyl-D-aspartate (NMDA) receptor hyperalgesia. The review was not designed to compare MOAs of diclofenac with other NSAIDs. Additionally, as the highlighted putative and emerging MOAs do not have clinical data to demonstrate that these models are

Assessment of the Safety of Some On-The-Shelf Canned Food ...

African Journals Online (AJOL)

There is also the possibility of these organisms posing food safety issues and pharmaceutical risks in case of possible out break, assayed through plasmid profiling of the culture-dependent isolates. A major concern in this study is the lack of adherence to food safety regulations. The products still been marketed on the ...

Drug safety evaluation of defibrotide.

Science.gov (United States)

Richardson, Paul G; Corbacioglu, Selim; Ho, Vincent Trien-Vinh; Kernan, Nancy A; Lehmann, Leslie; Maguire, Craig; Maglio, Michelle; Hoyle, Margaret; Sardella, Marco; Giralt, Sergio; Holler, Ernst; Carreras, Enric; Niederwieser, Dietger; Soiffer, Robert

2013-01-01

Hepatic veno-occlusive disease (VOD), also known as sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of chemotherapeutic conditioning used in preparation for hematopoietic stem-cell transplantation (SCT). Defibrotide (DF) has been shown in Phase II and III trials to improve complete response in patients with severe VOD (sVOD). None of the articles, to date, provide a comprehensive review of the safety of DF in VOD and/or a range of other conditions. This article reviews current clinical findings on DF, primarily in terms of safety for use in treatment and prophylaxis of VOD, and relevant safety data for its use in other diseases. The literature review was conducted using a PubMed search with the fixed term 'defibrotide' in combination with ≥ 1 of 'safety', 'veno-occlusive disease' (with and without 'treatment', 'prevention'), 'oncology', 'myeloma', 'microangiopathy', 'anti-thrombotic' and 'peripheral vascular disorder'. Related articles from the EBMT and ASH conference websites were also included. DF was well tolerated in majority of the studies. The safety profile of DF is largely favourable with toxicities comparable to control populations in the setting of SCT complicated by sVOD.

Safety profile of multielectrode-phased radiofrequency pulmonary vein ablation catheter and irrigated radiofrequency catheter.

Science.gov (United States)

Wasmer, K; Foraita, P; Leitz, P; Güner, F; Pott, C; Lange, P S; Eckardt, L; Mönnig, G

2016-01-01

Silent cerebral lesions with the multielectrode-phased radiofrequency (RF) pulmonary vein ablation catheter (PVAC(®)) have recently been investigated. However, comparative data on safety in relation to irrigated RF ablation are missing. One hundred and fifty consecutive patients (58 ± 12 years, 56 female) underwent first pulmonary vein isolation (PVI) for atrial fibrillation (61% paroxysmal) using PVAC(®) (PVAC). Procedure data as well as in-hospital complications were compared with 300 matched patients who underwent PVI using irrigated RF (iRF). Procedure duration (148 ± 63 vs. 208 ± 70 min; P drainage n = 0 vs. n = 6] occurred more frequently using iRF. Two patients in each group developed a TIA (1.3% vs. 0.6%). Of note, four of five thromboembolic events in the PVAC group (two TIAs and three transient ST elevations during ablation) occurred when all 10 electrodes were used for ablation. Pulmonary vein isolation using PVAC as a 'one-shot-system' has a comparable complication rate but a different risk profile. Pericardial effusion and tamponade occurred more frequently using iRF, whereas thromboembolic events were more prevalent using PVAC. Occurrence of clinically relevant thromboembolic events might be reduced by avoidance of electrode 1 and 10 interaction and uninterrupted anticoagulation, whereas contact force sensing for iRF might minimize pericardial effusion. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

PECULIARITIES OF CONSTRUCTION PROFILES OF SECURITY SYSTEMS OF INFORMATION SYSTEMS

Directory of Open Access Journals (Sweden)

Olga V. Lukinova

2015-01-01

Full Text Available Examines the specific issues of building functional and technological profiles of the security systems to ensure the safety of information systems in the paradigm of functional standardization; shows a view of the system of protection based on the model of OSE/RM; studied the composition and structure of the concept of "defense mechanism" for the purpose of profiling third instalment correction representation of the system of protection.

Investigational new drug safety reporting requirements for human drug and biological products and safety reporting requirements for bioavailability and bioequivalence studies in humans. Final rule.

Science.gov (United States)

2010-09-29

The Food and Drug Administration (FDA) is amending its regulations governing safety reporting requirements for human drug and biological products subject to an investigational new drug application (IND). The final rule codifies the agency's expectations for timely review, evaluation, and submission of relevant and useful safety information and implements internationally harmonized definitions and reporting standards. The revisions will improve the utility of IND safety reports, reduce the number of reports that do not contribute in a meaningful way to the developing safety profile of the drug, expedite FDA's review of critical safety information, better protect human subjects enrolled in clinical trials, subject bioavailability and bioequivalence studies to safety reporting requirements, promote a consistent approach to safety reporting internationally, and enable the agency to better protect and promote public health.

Desonide: a review of formulations, efficacy and safety.

Science.gov (United States)

Kahanek, Nr; Gelbard, Cg; Hebert, Aa

2008-07-01

Desonide is a low-potency topical corticosteroid that has been used for decades in the treatment of steroid-responsive dermatoses. The favorable safety profile of this topical agent makes it ideal for patients of all ages. This article provides a review of desonide's history, pharmacodynamic properties, vehicle technology, efficacy and safety. Randomized controlled trials, as well as open-label and non-comparative studies, case series and reports, experimental models, and data from the Galderma pharmacovigiliance program were reviewed in order to address the clinical efficacy and safety of desonide. Clinical efficacy and safety have been proven in multiple clinical trials. In addition to cream, lotion and ointment formulations, the recently developed hydrogel and foam preparations have increased desonide's versatility and patient tolerability.

Cardiovascular risk-benefit profile of sibutramine.

Science.gov (United States)

Scheen, A J

2010-01-01

Sibutramine is a combined norepinephrine and serotonin reuptake inhibitor used as an antiobesity agent to reduce appetite and promote weight loss in combination with diet and exercise. At a daily dose of 10-20 mg, it was initially considered to have a good safety profile, as it does not induce primary pulmonary hypertension or adverse effects on cardiac valves, in contrast to previous reports relating to some other antiobesity agents. However, it exerts disparate effects on cardiovascular risk factors. On the one hand, sibutramine may have antiatherogenic activities, as it improves insulin resistance, glucose metabolism, dyslipidemia, and inflammatory markers, with most of these effects resulting from weight loss rather than from an intrinsic effect of the drug. On the other hand, because of its specific mode of action, sibutramine exerts a peripheral sympathomimetic effect, which induces a moderate increase in heart rate and attenuates the reduction in BP attributable to weight loss or even slightly increases BP. It may also prolong the QT interval, an effect that could induce arrhythmias. Because of these complex effects, it is difficult to conclude what the final impact of sibutramine on cardiovascular outcomes might be. Sibutramine has been shown to exert favorable effects on some surrogate cardiovascular endpoints such as reduction of left ventricular hypertrophy and improvement of endothelial dysfunction. A good cardiovascular safety profile was demonstrated in numerous 1- to 2-year controlled trials, in both diabetic and nondiabetic well selected patients, as well as in several observational studies. However, since 2002, several cardiovascular adverse events (hypertension, tachycardia, arrhythmias, and myocardial infarction) have been reported in sibutramine-treated patients. This led to a contraindication of the use of this antiobesity agent in patients with established coronary heart disease, previous stroke, heart failure, or cardiac arrhythmias. SCOUT

Diclofenac topical solution compared with oral diclofenac: a pooled safety analysis

Directory of Open Access Journals (Sweden)

Roth SH

2011-06-01

Full Text Available Sanford H Roth1, Philip Fuller21Arizona Research and Education, Arthritis Laboratory, Arizona State University, Phoenix, AZ, USA; 2Medical Affairs, Covidien, Hazelwood, MO, USABackground: Topical nonsteroidal anti-inflammatory drug (NSAID formulations, which produce less systemic exposure compared with oral formulations, are an option for the management of osteoarthritis (OA. However, the overall safety and efficacy of these agents compared with oral or systemic therapy remains controversial.Methods: Two 12-week, double-blind, double-dummy, randomized, controlled, multicenter studies compared the safety and efficacy profiles of diclofenac topical solution (TDiclo with oral diclofenac (ODiclo. Each study independently showed that TDiclo had similar efficacy to ODiclo. To compare the safety profiles of TDiclo and ODiclo, a pooled safety analysis was performed for 927 total patients who had radiologically confirmed symptomatic OA of the knee. This pooled analysis included patients treated with TDiclo, containing 45.5% dimethyl sulfoxide (DMSO, and those treated with ODiclo. Safety assessments included monitoring of adverse events (AEs, recording of vital signs, dermatologic evaluation of the study knee, and clinical laboratory evaluation.Results: AEs occurred in 312 (67.1% patients using TDiclo versus 298 (64.5% of those taking ODiclo. The most common AE with TDiclo was dry skin at the application site (24.1% vs 1.9% with ODiclo; P < 0.0001. Fewer gastrointestinal (25.4% vs 39.0%; P < 0.0001 and cardiovascular (1.5% vs 3.5%; P = 0.055 AEs occurred with TDiclo compared with ODiclo. ODiclo was associated with significantly greater increases in liver enzymes and creatinine, and greater decreases in creatinine clearance and hemoglobin (P < 0.001 for all.Conclusions: These findings suggest that TDiclo represents a useful alternative to oral NSAID therapy in the management of OA, with a more favorable safety profile.Keywords: diclofenac, gastropathy

2011 Annual Meeting of the Safety Pharmacology Society: an overview.

Science.gov (United States)

Cavero, Icilio

2012-03-01

The keynote address of 2011 Annual Meeting of the Safety Pharmacology Society examined the known and the still to be known on drug-induced nephrotoxicity. The nominee of the Distinguished Service Award Lecture gave an account of his career achievements particularly on the domain of chronically instrumented animals for assessing cardiovascular safety. The value of Safety Pharmacology resides in the benefits delivered to Pharma organizations, regulators, payers and patients. Meticulous due diligence concerning compliance of Safety Pharmacology studies to best practices is an effective means to ensure that equally stringent safety criteria are applied to both in-licensed and in-house compounds. Innovative technologies of great potential for Safety Pharmacology presented at the meeting are organs on chips (lung, heart, intestine) displaying mechanical and biochemical features of native organs, electrical field potential (MEA) or impedance (xCELLigence Cardio) measurements in human induced pluripotent stem cell-derived cardiomyocytes for unveiling cardiac electrophysiological and mechanical liabilities, functional human airway epithelium (MucilAir™) preparations with unique 1-year shelf-life for acute and chronic in vitro evaluation of drug efficacy and toxicity. Custom-designed in silico and in vitro assay platforms defining the receptorome space occupied by chemical entities facilitate, throughout the drug discovery phase, the selection of candidates with optimized safety profile on organ function. These approaches can now be complemented by advanced computational analysis allowing the identification of compounds with receptorome, or clinically adverse effect profiles, similar to those of the drug candidate under scrutiny for extending the safety assessment to potential liability targets not captured by classical approaches. Nonclinical data supporting safety can be quite reassuring for drugs with a discovered signal of risk. However, for marketing authorization

Refractive outcomes of an advanced aspherically optimized profile for myopia corrections by LASIK: a retrospective comparison with the standard aspherically optimized profile

Directory of Open Access Journals (Sweden)

Meyer B

2015-02-01

Full Text Available Bertram Meyer,1 Georg Sluyterman van Langeweyde,2 Matthias Wottke2 1Augencentrum Köln, Cologne, Germany; 2Carl Zeiss Meditec AG, Jena, Germany Purpose: A retrospective comparison of refractive outcomes of a new, aspherically optimized profile with an enhanced energy correction feature (Triple-A and the conventionally used aspherically optimized profile (ASA, or aberration smart ablation for correction of low-to-high myopia.Setting: Augen-OP-Centrum, Cologne, GermanyDesign: Retrospective nonrandomized comparative studyMethods: A central database at the Augen-OP-Centrum was used to gather retrospective data for low-to-high myopia (up to -10 D. One hundred and seven eyes (56 patients were treated with the ASA profile, and 79 eyes (46 patients were treated with the Triple-A profile. Postoperative outcomes were evaluated at 1 month, 3 months, 6 months, and 1 year follow-up time points.Results: The Triple-A profile showed better predictability indicated by a significantly lower standard deviation of residuals (0.32–0.34 vs 0.36–0.44, Triple-A vs ASA in the 6-month to 1-year period. The Triple-A group had better stability across all time intervals and achieved better postoperative astigmatism improvements with significantly lower scatter. This group achieved better safety at 1 year, with 100% of eyes showing no change or gain in Snellen lines, compared with 97% in the ASA group. A better safety index was observed for the Triple-A group at later time points. The Triple-A group had a better efficacy index and a higher percentage of eyes with an uncorrected Snellen visual acuity of 20/20 or greater at all investigated follow-up time points.Conclusion: The new aspherically optimized Triple-A profile can safely and effectively correct low-to-high myopia. It has demonstrated superiority over the ASA profile in most refractive outcomes. Keywords: Triple-A, wavefront measurements, corneal aberrations, corneal asphericity, ablation profile

Transarterial Chemoembolization for Hepatocellular Carcinoma with a New Generation of Beads: Clinical–Radiological Outcomes and Safety Profile

Energy Technology Data Exchange (ETDEWEB)

Spreafico, Carlo, E-mail: carlo.spreafico@istitutotumori.mi.it; Cascella, Tommaso, E-mail: tommaso.cascella@istitutotumori.mi.it [Fondazione Istituto Tumori, Department of Radiology (Italy); Facciorusso, Antonio, E-mail: antonio.facciorusso@istitutotumori.mi.it; Sposito, Carlo, E-mail: carlo.sposito@istitutotumori.mi.it [Fondazione Istituto Tumori, Department of Liver Surgery and Transplant (Italy); Rodolfo, Lanocita, E-mail: rodolfo.lanocita@istitutotumori.mi.it; Morosi, Carlo, E-mail: carlo.morosi@istitutotumori.mi.it; Civelli, Enrico M., E-mail: enrico.civelli@istitutotumori.mi.it; Vaiani, Marta, E-mail: marta.vaiani@istitutotumori.mi.it [Fondazione Istituto Tumori, Department of Radiology (Italy); Bhoori, Sherrie, E-mail: sherrie.bhoori@istitutotumori.mi.it [Fondazione Istituto Tumori, Department of Liver Surgery and Transplant (Italy); Pellegrinelli, Alessandro, E-mail: alessandro.pellegrinelli@istitutotumori.mi.it [Fondazione Istituto Tumori, Department of Pathology (Italy); Marchianò, Alfonso, E-mail: alfonso.marchiano@istitutotumori.mi.it [Fondazione Istituto Tumori, Department of Radiology (Italy); Mazzaferro, Vincenzo, E-mail: vincenzo.mazzaferro@istitutotumori.mi.it [Fondazione Istituto Tumori, Department of Liver Surgery and Transplant (Italy)

2015-02-15

PurposeTo evaluate the short-term safety and efficacy of the new generation of 70–150 µm drug-eluting beads (M1 DEB) in patients with hepatocellular carcinoma undergoing transarterial chemoembolization (TACE) as a primary therapy or as a bridge to liver transplantation (LT).MethodsForty-five consecutive patients underwent TACE with M1 DEB loaded with doxorubicin (DEBDOX/M1). Clinical data were recorded at 12, 24, and 48 h, 7 and 30 days after treatment. Response was assessed by computed tomographic scan according to the modified response evaluation criteria in solid tumors criteria, and a second DEBDOX/M1 TACE was scheduled within 6 weeks in case of a noncomplete response.ResultsAll patients had well-compensated cirrhosis (97.7 % Child A, 44.4 % hepatitis C virus, median age 61 years). Twenty patients (44.4 %) had Barcelona Clinic for Liver Cancer class B disease; the median number of nodules and their sum of diameters were 2 (range 1–6) and 43 mm (range 10–190), respectively. The mean number of TACE procedures per patient was 1.4. Objective response rate (complete + partial response) was 77.7 % with a median time to best response of 3 months (95 % confidence interval 2–4). In 13 patients, DEBDOX/M1 TACE served as a bridge/downstaging to LT/surgery. Pathology showed that more than 90 % necrosis was achieved in 10 of 28 nodules. DEBDOX/M1 TACE was well tolerated, and the grade 3/4 adverse event rate was low (1 of 65 procedures).ConclusionDEBDOX/M1 TACE is an effective procedure with a favorable safety profile and promising results in terms of objective response rate, tumor downstaging, and necrosis.

EVALUATION OF COST-EFFECTIVENESS OF PLATELET REACTIVITY ANALYSIS USING THE VERIFYNOW P2Y12 ASSAY IN PATIENTS AFTER ACUTE CORONARY SYNDROME

Directory of Open Access Journals (Sweden)

A. V. Rudakova

2015-09-01

Full Text Available Dual antiplatelet therapy, including clopidogrel and aspirin, in a significant share of patients after acute coronary syndrome (ACS is characterized by high level of platelet reactivity, which is associated with an increased incidence of cardiovascular events. Perhaps it will make reasonable the prescription of new antiplatelet drugs, particularly the combination of ticagrelor with aspirin.Aim. To assess the cost-effectiveness of VerifyNow P2Y12 platelet reactivity testing in patients after ACS.Material and methods. The analysis was performed for patients aged 55 years after ACS by modeling based on the results of the PLATO trial considering Russian epidemiological data. The time horizon of simulation was 5 years. It was assumed that the patients were receiving either generic clopidogrel or ticagrelor for 1 year, or before maintenance treatment VerifyNow P2Y12 assay had been performed, and the patients with platelet reactivity index >230 24-48 hours after ACS were receiving ticagrelor and the remaining patients - generic clopidogrel. It was expected that after 1 year the patients would discontinue treatment with clopidogrel or ticagrelor, and hereafter additional therapeutic effect of their use would be absent. The costs of antiplatelet agents in the reference case corresponded to the weighted average price of public procurement in 2013 in Russia. The costs of treatment of complications corresponded to the compulsory health insurance rates for St. Petersburg in 2014. The cost and life expectancy were discounted at 3.5% per year.Results. The platelet reactivity test and the prescription by its results of the combination of clopidogrel plus aspirin or ticagrelor plus aspirin can prevent 5 myocardial infarction and 6 deaths per 1000 patients additionally as compared with the prescription of clopidogrel plus aspirin combination to all patients. The costs for one additional year of life as compared with the combination of clopidogrel plus aspirin

Algorithm Validation of the Current Profile Reconstruction of EAST Based on Polarimeter/Interferometer

International Nuclear Information System (INIS)

Qian Jinping; Ren Qilong; Wan Baonian; Liu Haiqin; Zeng Long; Luo Zhengping; Chen Dalong; Shi Tonghui; Sun Youwen; Shen Biao; Xiao Bingjia; Lao, L. L.; Hanada, K.

2015-01-01

The method of plasma current profile reconstruction using the polarimeter/interferometer (POINT) data from a simulated equilibrium is explored and validated. It is shown that the safety factor (q) profile can be generally reconstructed from the external magnetic and POINT data. The reconstructed q profile is found to reasonably agree with the initial equilibriums. Comparisons of reconstructed q and density profiles using the magnetic data and the POINT data with 3%, 5% and 10% random errors are investigated. The result shows that the POINT data could be used to a reasonably accurate determination of the q profile. (fusion engineering)

Contribution of operating feedback to probabilistic safety studies

International Nuclear Information System (INIS)

Guio, J.M. de; Lannoy, A.

1992-03-01

This paper presents the method used for PWR unit operation feedback analysis and its contribution to probabilistic safety studies. The targets were as follows: - use of failure data banks to assess reliability parameters, - use of event data banks to identify and quantify main system initiating events, - determination of a standard operating profile. These studies, performed in the context of nuclear power plant safety programs, prove useful not only to safety engineers but also to equipment experts, designers, operators and maintenance specialists. They constitute basic data for studies in all these areas or the departure point for new investigations. (authors). 3 figs., 3 tabs., 3 refs

Advanced Range Safety System for High Energy Vehicles

Science.gov (United States)

Claxton, Jeffrey S.; Linton, Donald F.

2002-01-01

The advanced range safety system project is a collaboration between the National Aeronautics and Space Administration and the United States Air Force to develop systems that would reduce costs and schedule for safety approval for new classes of unmanned high-energy vehicles. The mission-planning feature for this system would yield flight profiles that satisfy the mission requirements for the user while providing an increased quality of risk assessment, enhancing public safety. By improving the speed and accuracy of predicting risks to the public, mission planners would be able to expand flight envelopes significantly. Once in place, this system is expected to offer the flexibility of handling real-time risk management for the high-energy capabilities of hypersonic vehicles including autonomous return-from-orbit vehicles and extended flight profiles over land. Users of this system would include mission planners of Space Launch Initiative vehicles, space planes, and other high-energy vehicles. The real-time features of the system could make extended flight of a malfunctioning vehicle possible, in lieu of an immediate terminate decision. With this improved capability, the user would have more time for anomaly resolution and potential recovery of a malfunctioning vehicle.

Safety culture perceptions of pharmacists in Malaysian hospitals and health clinics: a multicentre assessment using the Safety Attitudes Questionnaire

Science.gov (United States)

Samsuri, Srima Elina; Pei Lin, Lua; Fahrni, Mathumalar Loganathan

2015-01-01

Objective To assess the safety attitudes of pharmacists, provide a profile of their domains of safety attitude and correlate their attitudes with self-reported rates of medication errors. Design A cross-sectional study utilising the Safety Attitudes Questionnaire (SAQ). Setting 3 public hospitals and 27 health clinics. Participants 117 pharmacists. Main outcome measure(s) Safety culture mean scores, variation in scores across working units and between hospitals versus health clinics, predictors of safety culture, and medication errors and their correlation. Results Response rate was 83.6% (117 valid questionnaires returned). Stress recognition (73.0±20.4) and working condition (54.8±17.4) received the highest and lowest mean scores, respectively. Pharmacists exhibited positive attitudes towards: stress recognition (58.1%), job satisfaction (46.2%), teamwork climate (38.5%), safety climate (33.3%), perception of management (29.9%) and working condition (15.4%). With the exception of stress recognition, those who worked in health clinics scored higher than those in hospitals (psafety culture. As perceptions improved, the number of medication errors reported decreased. Group-specific interventions that target specific domains are necessary to improve the safety culture. PMID:26610761

Fatty Acid Profile and Physicochemical Properties of Landolphia ...

African Journals Online (AJOL)

Purpose: To elucidate lipid profile of Landolphia owariensis P. Beauv stringy seed oil, the bulk physicochemical properties of its neutral lipid (NL), and also to ascertain its nutritional properties, safety and industrial applications. Methods: The neutral lipid was recovered by macerating 500 g of L. owariensis stringy seed pulp ...

Analysis of the safety and pharmacodynamics of human fibrinogen concentrate in animals

International Nuclear Information System (INIS)

Beyerle, Andrea; Nolte, Marc W.; Solomon, Cristina; Herzog, Eva; Dickneite, Gerhard

2014-01-01

Fibrinogen, a soluble 340 kDa plasma glycoprotein, is critical in achieving and maintaining hemostasis. Reduced fibrinogen levels are associated with an increased risk of bleeding and recent research has investigated the efficacy of fibrinogen concentrate for controlling perioperative bleeding. European guidelines on the management of perioperative bleeding recommend the use of fibrinogen concentrate if significant bleeding is accompanied by plasma fibrinogen levels less than 1.5–2.0 g/l. Plasma-derived human fibrinogen concentrate has been available for therapeutic use since 1956. The overall aim of the comprehensive series of non-clinical investigations presented was to evaluate i) the pharmacodynamic and pharmacokinetic characteristics and ii) the safety and tolerability profile of human fibrinogen concentrate Haemocomplettan P® (RiaSTAP®). Pharmacodynamic characteristics were assessed in rabbits, pharmacokinetic parameters were determined in rabbits and rats and a safety pharmacology study was performed in beagle dogs. Additional toxicology tests included: single-dose toxicity tests in mice and rats; local tolerance tests in rabbits; and neoantigenicity tests in rabbits and guinea pigs following the introduction of pasteurization in the manufacturing process. Human fibrinogen concentrate was shown to be pharmacodynamically active in rabbits and dogs and well tolerated, with no adverse events and no influence on circulation, respiration or hematological parameters in rabbits, mice, rats and dogs. In these non-clinical investigations, human fibrinogen concentrate showed a good safety profile. This data adds to the safety information available to date, strengthening the current body of knowledge regarding this hemostatic agent. - Highlights: • A comprehensive series of pre-clinical investigations of human fibrinogen concentrate. • Human fibrinogen concentrate was shown to be pharmacodynamically active. • Human fibrinogen concentrate was well tolerated

Analysis of the safety and pharmacodynamics of human fibrinogen concentrate in animals

Energy Technology Data Exchange (ETDEWEB)

Beyerle, Andrea, E-mail: andrea.beyerle@cslbehring.com [CSL Behring GmbH, Preclinical Research and Development, Marburg (Germany); Nolte, Marc W. [CSL Behring GmbH, Preclinical Research and Development, Marburg (Germany); Solomon, Cristina [CSL Behring GmbH, Medical Affairs, Marburg (Germany); Department of Anaesthesiology, Perioperative Medicine and General Intensive Care, Paracelsus Medical University, Salzburg (Austria); Herzog, Eva; Dickneite, Gerhard [CSL Behring GmbH, Preclinical Research and Development, Marburg (Germany)

2014-10-01

Fibrinogen, a soluble 340 kDa plasma glycoprotein, is critical in achieving and maintaining hemostasis. Reduced fibrinogen levels are associated with an increased risk of bleeding and recent research has investigated the efficacy of fibrinogen concentrate for controlling perioperative bleeding. European guidelines on the management of perioperative bleeding recommend the use of fibrinogen concentrate if significant bleeding is accompanied by plasma fibrinogen levels less than 1.5–2.0 g/l. Plasma-derived human fibrinogen concentrate has been available for therapeutic use since 1956. The overall aim of the comprehensive series of non-clinical investigations presented was to evaluate i) the pharmacodynamic and pharmacokinetic characteristics and ii) the safety and tolerability profile of human fibrinogen concentrate Haemocomplettan P® (RiaSTAP®). Pharmacodynamic characteristics were assessed in rabbits, pharmacokinetic parameters were determined in rabbits and rats and a safety pharmacology study was performed in beagle dogs. Additional toxicology tests included: single-dose toxicity tests in mice and rats; local tolerance tests in rabbits; and neoantigenicity tests in rabbits and guinea pigs following the introduction of pasteurization in the manufacturing process. Human fibrinogen concentrate was shown to be pharmacodynamically active in rabbits and dogs and well tolerated, with no adverse events and no influence on circulation, respiration or hematological parameters in rabbits, mice, rats and dogs. In these non-clinical investigations, human fibrinogen concentrate showed a good safety profile. This data adds to the safety information available to date, strengthening the current body of knowledge regarding this hemostatic agent. - Highlights: • A comprehensive series of pre-clinical investigations of human fibrinogen concentrate. • Human fibrinogen concentrate was shown to be pharmacodynamically active. • Human fibrinogen concentrate was well tolerated

The safety and effectiveness profile of eldecalcitol in a prospective, post-marketing observational study in Japanese patients with osteoporosis: interim report.

Science.gov (United States)

Saito, Hitoshi; Kakihata, Hiroyuki; Nishida, Yosuke; Yatomi, Sawako; Nihojima, Shigeru; Kobayashi, Yumiko; Tabata, Hidehiro; Nomura, Makoto

2017-07-01

This large-scale post-marketing surveillance study was conducted to assess the safety and effectiveness of eldecalcitol treatment in patients with osteoporosis in a Japanese clinical setting. A total of 3567 patients with osteoporosis were enrolled and received eldecalcitol 0.75 μg/day for 12 months. For this interim report, 3285 patients were eligible for analysis. Mean age was 74.9 ± 8.7 years; 86.8 % (2854/3285) were women. There were 142 reported adverse drug reactions (ADRs) in 129 patients (3.92 % of the total 3285 patients): the most common were hypercalcemia and increased blood calcium (0.88 %), renal impairment (0.27 %), abdominal discomfort (0.24 %), constipation (0.24 %), and pruritus (0.24 %). The incidence of ADRs was 5.10 % in men and 3.74 % in women. Although 10 serious ADRs were reported in 9 patients (0.27 %), no clinically significant safety issues were identified. Incidence of hypercalcemia or increased blood calcium was 8.47 % in patients with renal impairment and only 0.74 % in patients without renal impairment. At last observation, the incidence of new vertebral and nonvertebral fractures was 2.44 % and 1.70 %, respectively. There was a significant increase in bone mineral density at the lumbar spine and distal radius. The bone turnover markers BAP, serum NTX, urinary NTX, and TRACP-5b were suppressed by eldecalcitol treatment in both sexes. In conclusion, consistent with the findings of the phase III pivotal clinical trial, eldecalcitol was shown to have a favorable safety profile and effectiveness in Japanese patients with osteoporosis. However, periodic measurements of serum calcium were required to prevent occurrence of hypercalcemia during eldecalcitol treatment, especially in patients with renal impairment.

Use of a risk characterisation approach to contextualise the safety profile of new rheumatoid arthritis treatments: a case study using tofacitinib.

Science.gov (United States)

Curtis, Jeffrey R; Zhang, Richard; Krishnaswami, Sriram; Anisfeld, Andrew; Chen, Yan; Strengholt, Sander; Chen, Connie; Geier, Jamie

2017-03-01

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). To characterise the relative safety profile of tofacitinib to biologic disease-modifying antirheumatic drugs (bDMARDs), the accrued patient-years (pt-yrs) of exposure needed in an RA clinical trial programme to detect a potential increase in risk of specific adverse events (AEs) was determined. This case study/framework was constructed on the pt-yrs' accrual within pooled phase (P)1, P2 and P3, as well as long-term extension, studies of tofacitinib in RA (March 2015 data-cut) and published AE incidence rates for bDMARDs. Sample size calculations were based on a Poisson distribution to estimate pt-yrs' exposure required for 90 % probability that the lower bound of the 95 % confidence interval for tofacitinib/bDMARD would be >1, assuming that tofacitinib rates were 1.2×/1.5×/2.0× greater than comparator rates. AE rates for bDMARDs were derived from sources intended to optimise similarity with the tofacitinib database in terms of baseline characteristics, study duration and follow-up. Based on the tofacitinib exposure accrued (19,406 pt-yrs), data were sufficient (90 % probability) to detect potential differences over external bDMARD comparator rates in serious infections (≥1.2×), malignancies (excluding non-melanoma skin cancer [NMSC]), NMSC, major adverse cardiovascular events (MACE) and lymphoma (each ≥1.5×), as well as opportunistic infections and gastrointestinal perforations (≥2×), should they exist. This risk characterisation approach can support the comparative safety of new RA medications. To date, tofacitinib safety appears similar to approved published data from bDMARDs with respect to serious infections, malignancies (excluding NMSC), NMSC, MACE, lymphoma, opportunistic infections and gastrointestinal perforations.

Nonclinical safety of mavrilimumab, an anti-GMCSF receptor alpha monoclonal antibody, in cynomolgus monkeys: Relevance for human safety

Energy Technology Data Exchange (ETDEWEB)

Ryan, Patricia C., E-mail: ryanp@medimmune.com [MedImmune, LLC, Gaithersburg, MD (United States); Sleeman, Matthew A. [MedImmune, LLC, Cambridge (United Kingdom); Rebelatto, Marlon [MedImmune, LLC, Gaithersburg, MD (United States); Wang, Bing; Lu, Hong [MedImmune, LLC, Moutain View, CA (United States); Chen, Xiaomin [Novartis, East Hanover, NJ (United States); Wu, Chi-Yuan [MedImmune, LLC, Moutain View, CA (United States); Hinrichs, Mary Jane; Roskos, Lorin [MedImmune, LLC, Gaithersburg, MD (United States); Towers, Heidi [MedImmune, LLC, Cambridge (United Kingdom); McKeever, Kathleen; Dixit, Rakesh [MedImmune, LLC, Gaithersburg, MD (United States)

2014-09-01

Mavrilimumab (CAM-3001) is an investigational human IgG4 monoclonal antibody (MAb) targeting GM-CSF receptor alpha which is currently being developed for the treatment of RA. GM-CSF plays a central role in the pathogenesis of rheumatoid arthritis (RA) through the activation, differentiation, and survival of macrophages and neutrophils. To support clinical development, the nonclinical safety of mavrilimumab was evaluated in several studies with cynomolgus monkeys as the pharmacologically relevant species. Comprehensive toxicity parameters were assessed in each study, and treatment duration ranged from 4 to 26 weeks. Mavrilimumab has an acceptable safety profile in monkeys with no changes in any parameters other than microscopic findings in lung. In several studies, minimal accumulation of foamy alveolar macrophages was observed. This finding was only seen in studies of at least 11 weeks duration, was reversible following a dose-free recovery period and was considered non-adverse. At higher dose levels (≥ 30 mg/kg/week), in a 26-week repeat-IV dose study, the presence of lung foreign material, cholesterol clefts, and granulomatous inflammation was also observed in a few animals and was considered adverse. The dose- and time-related accumulation of foamy macrophages in lung following exposure to mavrilimumab observed in several NHP studies was expected based upon the known role of GM-CSFRα signaling in the function of alveolar macrophages. Overall, a clean no-observed-adverse-effect-level (NOAEL) without any effects in lung was established and provided adequate clinical safety margins. In clinical studies in RA patients, mavrilimumab has demonstrated good clinical activity with adequate safety to support further clinical development. A Phase 2b study of mavrilimumab in subjects with RA is in progress. - Highlights: • Mavrilimumab is a MAB targeting GM-CSFRα being developed for RA therapy. • Mavrilimumab has an acceptable safety profile in cynomolgus monkeys. �

Nonclinical safety of mavrilimumab, an anti-GMCSF receptor alpha monoclonal antibody, in cynomolgus monkeys: Relevance for human safety

International Nuclear Information System (INIS)

Ryan, Patricia C.; Sleeman, Matthew A.; Rebelatto, Marlon; Wang, Bing; Lu, Hong; Chen, Xiaomin; Wu, Chi-Yuan; Hinrichs, Mary Jane; Roskos, Lorin; Towers, Heidi; McKeever, Kathleen; Dixit, Rakesh

2014-01-01

Mavrilimumab (CAM-3001) is an investigational human IgG4 monoclonal antibody (MAb) targeting GM-CSF receptor alpha which is currently being developed for the treatment of RA. GM-CSF plays a central role in the pathogenesis of rheumatoid arthritis (RA) through the activation, differentiation, and survival of macrophages and neutrophils. To support clinical development, the nonclinical safety of mavrilimumab was evaluated in several studies with cynomolgus monkeys as the pharmacologically relevant species. Comprehensive toxicity parameters were assessed in each study, and treatment duration ranged from 4 to 26 weeks. Mavrilimumab has an acceptable safety profile in monkeys with no changes in any parameters other than microscopic findings in lung. In several studies, minimal accumulation of foamy alveolar macrophages was observed. This finding was only seen in studies of at least 11 weeks duration, was reversible following a dose-free recovery period and was considered non-adverse. At higher dose levels (≥ 30 mg/kg/week), in a 26-week repeat-IV dose study, the presence of lung foreign material, cholesterol clefts, and granulomatous inflammation was also observed in a few animals and was considered adverse. The dose- and time-related accumulation of foamy macrophages in lung following exposure to mavrilimumab observed in several NHP studies was expected based upon the known role of GM-CSFRα signaling in the function of alveolar macrophages. Overall, a clean no-observed-adverse-effect-level (NOAEL) without any effects in lung was established and provided adequate clinical safety margins. In clinical studies in RA patients, mavrilimumab has demonstrated good clinical activity with adequate safety to support further clinical development. A Phase 2b study of mavrilimumab in subjects with RA is in progress. - Highlights: • Mavrilimumab is a MAB targeting GM-CSFRα being developed for RA therapy. • Mavrilimumab has an acceptable safety profile in cynomolgus monkeys. �

A network meta-analysis of randomized controlled trials for comparing the effectiveness and safety profile of treatments with marketing authorization for relapsing multiple sclerosis.

Science.gov (United States)

Hadjigeorgiou, G M; Doxani, C; Miligkos, M; Ziakas, P; Bakalos, G; Papadimitriou, D; Mprotsis, T; Grigoriadis, N; Zintzaras, E

2013-12-01

The relative effectiveness and safety profile of the treatments with marketing authorization for relapsing multiple sclerosis (MS) are not well known because randomized controlled trials with head-to-head comparisons between these treatments do not exist. Thus, a network of multiple-treatments meta-analysis was performed using four clinical outcomes: 'patients free of relapse', 'patients without disease progression', 'patients without MRI progression' and 'patients with adverse events'. Randomized controlled trials (RCTs) on MS were systematically searched in PubMed and Cochrane Central Register of Controlled Trial. The network analysis performed pairwise comparisons between the marketed treatments (Betaferon 250mcg, Avonex 30mcg, Rebif 44mcg, Rebif 22mcg, Aubagio 7 mg, Aubagio 14 mg, Copaxone 20 mg, Tysabri 300 mg, Gilenya 0·5 mg and Novantrone 12 mg/m(2)) using direct and indirect analyses. The analysis included 48 articles, involving 20 455 patients with MS. The direct analysis showed better response for more than one outcome for Gilenya compared with Avonex ('patients free of relapse' and 'patients without MRI progression') and for Betaferon compared with Avonex ('patients without disease progression' and 'patients without MRI progression'). The indirect analysis indicated that Tysabri may have better relative effectiveness compared with the other treatments for two outcomes: 'patients free of relapse' and 'patients without MRI progression'. Regarding 'patients with adverse events', no data were available for all comparisons to make fair inferences. This was an attempt, for the first time, to compare the efficacy and safety profile of existing approved treatments for relapsing MS. Although some treatments have shown better response, the results of the network analysis should be interpreted with caution because of the lack of RCTs with head-to-head comparisons between treatments. © 2013 John Wiley & Sons Ltd.

Long-term efficacy and safety of tacalcitol ointment in patients with chronic plaque psoriasis.

NARCIS (Netherlands)

Kerkhof, P.C.M. van de; Berth-Jones, J.; Griffiths, C.E.; Harrison, P.V.; Honigsmann, H.; Marks, R.; Roelandts, R.; Schopf, E.; Trompke, C.

2002-01-01

BACKGROUND: As psoriasis patients often require continuous treatment optimal therapy has to provide efficacy and a good safety profile over the long term. OBJECTIVES: The aim of this multicentre study was to assess the efficacy, safety and tolerability of tacalcitol (4 microg g(-1)) ointment

Effectiveness of new antiplatelets in the prevention of recurrent myocardial infarction.

Science.gov (United States)

Grimaldi-Bensouda, Lamiae; Danchin, Nicolas; Dallongeville, Jean; Falissard, Bruno; Furber, Alain; Cottin, Yves; Bonello, Laurent; Morel, Olivier; Leclercq, Florence; Puymirat, Etienne; Ghanem, Fahmi; Delarche, Nicolas; Benichou, Jacques; Abenhaim, Lucien

2018-03-13

To compare ticagrelor and prasugrel with clopidogrel for recurrent fatal and non-fatal myocardial infarction (reMI) in real-life conditions. Case-referent study using the Pharmacoepidemiological General Research eXtension (PGRx)-acute coronary syndrome (ACS) registry. Cases were patients with reMI from a cohort with index ACS or external to the cohort (same sites). Referents from the cohort, without recurrent event, were matched on index ACS type and date, age and sex with reMI cases. Multivariate conditional logistic regression assessed the OR (95% CI) for reMI associated with ticagrelor and prasugrel vs clopidogrel, adjusted for aspirin use and cardiovascular risk factors. 1047 cases and 2234 matched referents were included. Compared with clopidogrel, ticagrelor and prasugrel were associated with respective ORs of 0.65 (95% CI 0.52 to 0.81) and 0.71 (95% CI 0.53 to 0.96) for reMI occurrence. ORs for ticagrelor and prasugrel vs clopidogrel were: 0.50 (95% CI 0.38 to 0.67) and 0.66 (95% CI 0.45 to 0.95), 0.39 (95% CI 0.24 to 0.62) and 0.44 (95% CI 0.26 to 0.75), 0.63 (95% CI 0.43 to 0.92) and 1.20 (95% CI 0.69 to 2.07), 1.11 (95% CI 0.72 to 1.72) and 0.82 (95% CI 0.44 to 1.54) when index ACS was a first MI, a first ST-elevated MI (STEMI), a first non-STEMI and a recurrent ACS, respectively, and 0.63 (95% CI 0.45 to 0.87) and 0.77 (95% CI 0.41 to 1.45) forpatients aged ≥70 years. This real-world study showed a significant reduction of reMI with new antiplatelets compared with clopidogrel, ticagrelor being associated with a greater decrease of risk notably for first, either STEMI or non-STEMI. The larger magnitude of effect may be attributed to potential residual confounding or higher effectiveness compared with efficacy reported in trials (EMA Post Authorisation Study Registry Number EUPAS5905). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless

Antiplatelet drug selection in PCI to vein grafts in patients with acute coronary syndrome and adverse clinical outcomes: Insights from the British Cardiovascular Intervention Society database.

Science.gov (United States)

Sirker, Alex; Kwok, Chun Shing; Kontopantelis, Evangelos; Johnson, Tom; Freeman, Philip; de Belder, Mark A; Ludman, Peter; Zaman, Azfar; Mamas, Mamas A

2018-01-22

This study aims to evaluate outcomes associated with different P2Y12 agents in Saphenous Vein graft (SVG) percutaneous coronary intervention (PCI). SVG PCI is associated with greater risks of ischemic complications, compared with native coronary PCI. Outcomes associated with the use of potent P2Y12 blocking drugs, Prasugrel and Ticagrelor, in SVG PCI are unknown. Patients included in the study underwent SVG PCI in the United Kingdom between 2007 and 2014 for acute coronary syndrome and were grouped by P2Y12 antiplatelet use. In-hospital major adverse cardiac events, major bleeding and 30-day and 1-year mortality were examined. Multiple imputations with chained equations to impute missing data were used. Adjustment for baseline imbalances was performed using (1) multiple logistic regression (MLR) and (separately) (2) propensity score matching (PSM). Data weres analyzed from 8,119 patients and most cases were treated with Clopidogrel (n = 7,401), followed by Ticagrelor (n = 497) and Prasugrel (n = 221). In both MLR and PSM models, there was no significant evidence to suggest that either Prasugrel or Ticagrelor was associated with significantly lower 30-day mortality compared with Clopidogrel. The odds ratios reported from the multivariable analysis were 1.22 (95% CI: 0.60-2.51) for Prasugrel vs. Clopidogrel and 0.48 (95% CI: 0.20-1.16) for Ticagrelor vs. Clopidogrel. No significant differences were seen for in-hospital ischemic or bleeding events. Our real world national study provides no clear evidence to indicate that use of potent P2Y12 blockers in SVG PCI is associated with improved clinical outcomes. © 2018 Wiley Periodicals, Inc.

Optimized profiles for improved confinement and stability in the Dill-D tokamak

International Nuclear Information System (INIS)

Taylor, T.S.; St John, H.; Turnbull, A.D.

1994-01-01

Simultaneous achievement of high energy confinement, τ E , and high plasma beta, β, leads to an economically attractive compact tokamak fusion reactor. High confinement enhancement, H τ E /τ E -ITER89P 4, and high normalized beta β N β/(I/aB) = 6%-m-T/MA. have been obtained in DIII-D experimental discharges. These improved confinement and/or improved stability limits are observed in several DIII-D high performance operational regimes: VH-mode, high l i H-mode, second stable core, and high beta poloidal. We have identified several important features of the improved performance in these discharges: details of the plasma shape, toroidal rotation or ExB flow profile, q profile and current density profile, and pressure profile. From our improved physics understanding of these enhanced performance regimes, we have developed operational scenarios which maintain the essential features of the improved confinement and which increase the stability limits using localized current profile control. The stability limit is increased by modifying the interior safety factor profile to be nonmonotonic with high central q, while maintaining the edge current density consistent with the improved transport regimes and the high edge bootstrap current. We have calculated high beta equilibria with β N 6.5, stable to ideal n=1 kinks and stable to ideal ballooning modes. The safety factor at the 95% flux surface is 6, the central q value is 3.9 and the minimum in q is 2.6. The current density profile is maintained by the natural profile of the bootstrap current, and a modest amount of electron cyclotron current drive. (Author)

Optimized profiles for improved confinement and stability in the DIII-D tokamak

International Nuclear Information System (INIS)

Taylor, T.S.; St. John, H.; Turnbull, A.D.

1995-02-01

Simultaneous achievement of high energy confinement, τ E , and high plasma beta, β, leads to an economically attractive compact tokamak fusion reactor. High confinement enhancement, H = τ E /τ E-ITER89P = 4, and high normalized beta β N = β/(I/aB) = 6%-m-T/MA, have been obtained in DIII-D experimental discharges. These improved confinement and/or improved stability limits are observed in several DIII-D high performance operational regimes: VH-mode, high ell i H-mode, second stable core, and high beta poloidal. The authors have identified several important features of the improved performance in these discharges: details of the plasma shape, toroidal rotation or ExB flow profile, q profile and current density profile, and pressure profile. From the improved physics understanding of these enhanced performance regimes, they have developed operational scenarios which maintain the essential features of the improved confinement and which increase the stability limits using localized current profile control. The stability limit is increased by modifying the interior safety factor profile to be nonmonotonic with high central q, while maintaining the edge current density consistent with the improved transport regimes and the high edge bootstrap current. They have calculated high beta equilibria with β N = 6.5, stable to ideal n = 1 kinks and stable to ideal ballooning modes. The safety factor at the 95% flux surface is 6, the central q value is 3.9 and the minimum in q is 2.6. The current density profile is maintained by the natural profile of the bootstrap current, and a modest amount of electron cyclotron current drive

Yield and Safety Profile of Ultrasound Guided Fine Needle Aspiration Cytology (FNAC) of Lymph Nodes

International Nuclear Information System (INIS)

Sattar, A.; Wahab, S.; Javed, A.; Shamim, S. H.

2016-01-01

Objective: To determine the re-biopsy rate, positive yield and safety profile of ultrasound guided fine needle aspiration cytology (FNAC) in cervical lymph nodes in terms of its complications and repeat procedures. Study Design: An analytical study. Place and Duration of Study: Department of Vascular and Interventional Radiology, Dow University Hospital, Dow University of Health Sciences, Karachi, from June to December 2013. Methodology: Eighty neck swellings, which were found to be lymph nodes on ultrasound, underwent ultrasound guided FNAC, from outpatients. Lymph nodes which were included in the study were those that were not easily palpable, located near major blood vessels, where patient refused of direct palpation and wanted image guided FNAC, those directly sent by physician for image guided FNAC and where blind biopsy remained inconclusive. Patients who refused on explanation or did not give consent were excluded. Complications and repeat biopsy were noted. Result: This study consisted of 80 cases, of which 51 cases (63.75 percentage) were female and 29 cases (36.25 percentage) were male. Repeat biopsy was required in 1 case (1.6 percentage). There were no procedure-related complications. A total of 44 cases (55 percentage) revealed evidence suggesting or confirming the existence of tuberculosis. Rest of the others showed other benign lesions, reactive lymphadenopathy and malignancy. Conclusion: Ultrasound guided FNAC is a safe procedure with low re-biopsy rate that aids diagnosis. The predominant cause of cervical lymphadenopathy in this study was tuberculous lymphadenitis. (author)

Pre-Exposure Prophylaxis for HIV Prevention: Safety Concerns.

Science.gov (United States)

Tetteh, Raymond A; Yankey, Barbara A; Nartey, Edmund T; Lartey, Margaret; Leufkens, Hubert G M; Dodoo, Alexander N O

2017-04-01

Available evidence supports the efficacy of pre-exposure prophylaxis (PrEP) in decreasing the incidence of human immunodeficiency virus (HIV) infection among high-risk individuals, especially when used in combination with other behavioural preventive methods. Safety concerns about PrEP present challenges in the implementation and use of PrEP. The aim of this review is to discuss safety concerns observed in completed clinical trials on the use of PrEP. We performed a literature search on PrEP in PubMed, global advocacy for HIV prevention (Aids Vaccine Advocacy Coalition) database, clinical trials registry " http://www.clinicaltrials.gov " and scholar.google, using combination search terms 'pre-exposure prophylaxis', 'safety concerns in the use of pre-exposure prophylaxis', 'truvada use as PrEP', 'guidelines for PrEP use', 'HIV pre-exposure prophylaxis' and 'tenofovir' to identify clinical trials and literature on PrEP. We present findings associated with safety issues on the use of PrEP based on a review of 11 clinical trials on PrEP with results on safety and efficacy as at April 2016. We also reviewed findings from routine real-life practice reports. The pharmacological intervention for PrEP was tenofovir disoproxil fumarate/emtricitabine in a combined form as Truvada ® or tenofovir as a single entity. Both products are efficacious for PrEP and seem to have a good safety profile. Regular monitoring is recommended to prevent long-term toxic effects. The main adverse effects observed with PrEP are gastrointestinal related; basically mild to moderate nausea, vomiting and diarrhea. Other adverse drug effects worth monitoring are liver enzymes, renal function and bone mineral density. PrEP as an intervention to reduce HIV transmission appears to have a safe benefit-risk profile in clinical trials. It is recommended for widespread use but adherence monitoring and real-world safety surveillance are critical in the post-marketing phase to ensure that the benefits

Safety culture perceptions of pharmacists in Malaysian hospitals and health clinics: a multicentre assessment using the Safety Attitudes Questionnaire.

Science.gov (United States)

Samsuri, Srima Elina; Pei Lin, Lua; Fahrni, Mathumalar Loganathan

2015-11-26

To assess the safety attitudes of pharmacists, provide a profile of their domains of safety attitude and correlate their attitudes with self-reported rates of medication errors. A cross-sectional study utilising the Safety Attitudes Questionnaire (SAQ). 3 public hospitals and 27 health clinics. 117 pharmacists. Safety culture mean scores, variation in scores across working units and between hospitals versus health clinics, predictors of safety culture, and medication errors and their correlation. Response rate was 83.6% (117 valid questionnaires returned). Stress recognition (73.0±20.4) and working condition (54.8±17.4) received the highest and lowest mean scores, respectively. Pharmacists exhibited positive attitudes towards: stress recognition (58.1%), job satisfaction (46.2%), teamwork climate (38.5%), safety climate (33.3%), perception of management (29.9%) and working condition (15.4%). With the exception of stress recognition, those who worked in health clinics scored higher than those in hospitals (pculture. As perceptions improved, the number of medication errors reported decreased. Group-specific interventions that target specific domains are necessary to improve the safety culture. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The Public Safety Impact of Community Notification Laws: Rearrest of Convicted Sex Offenders

Science.gov (United States)

Freeman, Naomi J.

2012-01-01

Sex offender management is one of the highest-profile issues in public safety today. Although states have enacted community notification laws as a means to protect communities from sexual offending, limited research has been conducted to examine the impact of these laws on public safety. As such, this study used a quasi-experimental design to…

Impact of biomarker development on drug safety assessment

International Nuclear Information System (INIS)

Marrer, Estelle; Dieterle, Frank

2010-01-01

Drug safety has always been a key aspect of drug development. Recently, the Vioxx case and several cases of serious adverse events being linked to high-profile products have increased the importance of drug safety, especially in the eyes of drug development companies and global regulatory agencies. Safety biomarkers are increasingly being seen as helping to provide the clarity, predictability, and certainty needed to gain confidence in decision making: early-stage projects can be stopped quicker, late-stage projects become less risky. Public and private organizations are investing heavily in terms of time, money and manpower on safety biomarker development. An illustrative and 'door opening' safety biomarker success story is the recent recognition of kidney safety biomarkers for pre-clinical and limited translational contexts by FDA and EMEA. This milestone achieved for kidney biomarkers and the 'know how' acquired is being transferred to other organ toxicities, namely liver, heart, vascular system. New technologies and molecular-based approaches, i.e., molecular pathology as a complement to the classical toolbox, allow promising discoveries in the safety biomarker field. This review will focus on the utility and use of safety biomarkers all along drug development, highlighting the present gaps and opportunities identified in organ toxicity monitoring. A last part will be dedicated to safety biomarker development in general, from identification to diagnostic tests, using the kidney safety biomarkers success as an illustrative example.

Discovery of safety biomarkers for atorvastatin in rat urine using mass spectrometry based metabolomics combined with global and targeted approach

International Nuclear Information System (INIS)

Kumar, Bhowmik Salil; Lee, Young-Joo; Yi, Hong Jae; Chung, Bong Chul; Jung, Byung Hwa

2010-01-01

In order to develop a safety biomarker for atorvastatin, this drug was orally administrated to hyperlipidemic rats, and a metabolomic study was performed. Atorvastatin was given in doses of either 70 mg kg -1 day -1 or 250 mg kg -1 day -1 for a period of 7 days (n = 4 for each group). To evaluate any abnormal effects of the drug, physiological and plasma biochemical parameters were measured and histopathological tests were carried out. Safety biomarkers were derived by comparing these parameters and using both global and targeted metabolic profiling. Global metabolic profiling was performed using liquid chromatography/time of flight/mass spectrometry (LC/TOF/MS) with multivariate data analysis. Several safety biomarker candidates that included various steroids and amino acids were discovered as a result of global metabolic profiling, and they were also confirmed by targeted metabolic profiling using gas chromatography/mass spectrometry (GC/MS) and capillary electrophoresis/mass spectrometry (CE/MS). Serum biochemical and histopathological tests were used to detect abnormal drug reactions in the liver after repeating oral administration of atorvastatin. The metabolic differences between control and the drug-treated groups were compared using PLS-DA score plots. These results were compared with the physiological and plasma biochemical parameters and the results of a histopathological test. Estrone, cortisone, proline, cystine, 3-ureidopropionic acid and histidine were proposed as potential safety biomarkers related with the liver toxicity of atorvastatin. These results indicate that the combined application of global and targeted metabolic profiling could be a useful tool for the discovery of drug safety biomarkers.

Discovery of safety biomarkers for atorvastatin in rat urine using mass spectrometry based metabolomics combined with global and targeted approach

Energy Technology Data Exchange (ETDEWEB)

Kumar, Bhowmik Salil [Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650 (Korea, Republic of); University of Science and Technology, (305-333) 113 Gwahangno, Yuseong-gu, Daejeon (Korea, Republic of); Lee, Young-Joo; Yi, Hong Jae [College of Pharmacy, Kyung Hee University, Hoegi-dong, Dongdaemun-gu, Seoul 130-791 (Korea, Republic of); Chung, Bong Chul [Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650 (Korea, Republic of); Jung, Byung Hwa, E-mail: jbhluck@kist.re.kr [Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650 (Korea, Republic of); University of Science and Technology, (305-333) 113 Gwahangno, Yuseong-gu, Daejeon (Korea, Republic of)

2010-02-19

In order to develop a safety biomarker for atorvastatin, this drug was orally administrated to hyperlipidemic rats, and a metabolomic study was performed. Atorvastatin was given in doses of either 70 mg kg{sup -1} day{sup -1} or 250 mg kg{sup -1} day{sup -1} for a period of 7 days (n = 4 for each group). To evaluate any abnormal effects of the drug, physiological and plasma biochemical parameters were measured and histopathological tests were carried out. Safety biomarkers were derived by comparing these parameters and using both global and targeted metabolic profiling. Global metabolic profiling was performed using liquid chromatography/time of flight/mass spectrometry (LC/TOF/MS) with multivariate data analysis. Several safety biomarker candidates that included various steroids and amino acids were discovered as a result of global metabolic profiling, and they were also confirmed by targeted metabolic profiling using gas chromatography/mass spectrometry (GC/MS) and capillary electrophoresis/mass spectrometry (CE/MS). Serum biochemical and histopathological tests were used to detect abnormal drug reactions in the liver after repeating oral administration of atorvastatin. The metabolic differences between control and the drug-treated groups were compared using PLS-DA score plots. These results were compared with the physiological and plasma biochemical parameters and the results of a histopathological test. Estrone, cortisone, proline, cystine, 3-ureidopropionic acid and histidine were proposed as potential safety biomarkers related with the liver toxicity of atorvastatin. These results indicate that the combined application of global and targeted metabolic profiling could be a useful tool for the discovery of drug safety biomarkers.

Evaluating the U.S. Food Safety Modernization Act Produce Safety Rule Standard for Microbial Quality of Agricultural Water for Growing Produce

NARCIS (Netherlands)

Havelaar, Arie H; Vazquez, Kathleen M; Topalcengiz, Zeynal; Muñoz-Carpena, Rafael; Danyluk, Michelle D

2017-01-01

The U.S. Food and Drug Administration (FDA) has defined standards for the microbial quality of agricultural surface water used for irrigation. According to the FDA produce safety rule (PSR), a microbial water quality profile requires analysis of a minimum of 20 samples for Escherichia coli over 2 to

Child and youth care workers: Profile, nutrition knowledge and food ...

African Journals Online (AJOL)

CCWs (N = 40) employed permanently or part-time were included. Convenience purposive sampling of the CCWs was undertaken. A structured self-administered questionnaire, developed and tested for this purpose, was used to gather information on the profile, nutrition knowledge, food safety and hygiene practices.

Safety and pharmacokinetic profile of fixed-dose ivermectin with an innovative 18mg tablet in healthy adult volunteers.

Directory of Open Access Journals (Sweden)

Jose Muñoz

2018-01-01

Full Text Available Ivermectin is a pivotal drug for the control of onchocerciasis and lymphatic filariasis, which is increasingly identified as a useful drug for the control of other Neglected Tropical Diseases. Its role in the treatment of soil transmitted helminthiasis through improved efficacy against Trichuris trichiura in combination with other anthelmintics might accelerate the progress towards breaking transmission. Ivermectin is a derivative of Avermectin B1, and consists of an 80:20 mixture of the equipotent homologous 22,23 dehydro B1a and B1b. Pharmacokinetic characteristics and safety profile of ivermectin allow to explore innovative uses to further expand its utilization through mass drug administration campaigns to improve coverage rates. We conducted a phase I clinical trial with 54 healthy adult volunteers who sequentially received 2 experimental treatments using a new 18 mg ivermectin tablet in a fixed-dose strategy of 18 and 36 mg single dose regimens, compared to the standard, weight based 150–200 μg/kg, regimen. Volunteers were recruited in 3 groups based on body weight. Plasma concentrations of ivermectin were measured through HPLC up to 168 hours post treatment. Safety data showed no significant differences between groups and no serious adverse events: headache was the most frequent adverse event in all treatment groups, none of them severe. Pharmacokinetic parameters showed a half-life between 81 and 91 h in the different treatment groups. When comparing the systemic bioavailability (AUC0t and Cmax of the reference product (WA-ref with the other two study groups using fixed doses, we observed an overall increase in AUC0t and Cmax for the two experimental treatments of 18 mg and 36 mg. Body mass index (BMI and weight were associated with t1/2 and V/F, probably reflecting the high liposolubility of IVM with longer retention times proportional to the presence of more adipose tissue. Systemic exposure to ivermectin (AUC0t or Cmax was not

Novel agents for anti-platelet therapy

Directory of Open Access Journals (Sweden)

Ji Xuebin

2011-11-01

Full Text Available Abstract Anti-platelet therapy plays an important role in the treatment of patients with thrombotic diseases. The most commonly used anti-platelet drugs, namely, aspirin, ticlopidine, and clopidogrel, are effective in the prevention and treatment of cardio-cerebrovascular diseases. Glycoprotein IIb/IIIa antagonists (e.g., abciximab, eptifibatide and tirofiban have demonstrated good clinical benefits and safety profiles in decreasing ischemic events in acute coronary syndrome. However, adverse events related to thrombosis or bleeding have been reported in cases of therapy with glycoprotein IIb/IIIa antagonists. Cilostazol is an anti-platelet agent used in the treatment of patients with peripheral ischemia, such as intermittent claudication. Presently, platelet adenosine diphosphate P2Y(12 receptor antagonists (e.g., clopidogrel, prasugrel, cangrelor, and ticagrelor are being used in clinical settings for their pronounced protective effects. The new protease-activated receptor antagonists, vorapaxar and atopaxar, potentially decrease the risk of ischemic events without significantly increasing the rate of bleeding. Some other new anti-platelet drugs undergoing clinical trials have also been introduced. Indeed, the number of new anti-platelet drugs is increasing. Consequently, the efficacy of these anti-platelet agents in actual patients warrants scrutiny, especially in terms of the hemorrhagic risks. Hopefully, new selective platelet inhibitors with high anti-thrombotic efficiencies and low hemorrhagic side effects can be developed.

Application of Feedback System Control Optimization Technique in Combined Use of Dual Antiplatelet Therapy and Herbal Medicines

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Wang Liu

2018-05-01

Full Text Available Aim: Combined use of herbal medicines in patients underwent dual antiplatelet therapy (DAPT might cause bleeding or thrombosis because herbal medicines with anti-platelet activities may exhibit interactions with DAPT. In this study, we tried to use a feedback system control (FSC optimization technique to optimize dose strategy and clarify possible interactions in combined use of DAPT and herbal medicines.Methods: Herbal medicines with reported anti-platelet activities were selected by searching related references in Pubmed. Experimental anti-platelet activities of representative compounds originated from these herbal medicines were investigated using in vitro assay, namely ADP-induced aggregation of rat platelet-rich-plasma. FSC scheme hybridized artificial intelligence calculation and bench experiments to iteratively optimize 4-drug combination and 2-drug combination from these drug candidates.Results: Totally 68 herbal medicines were reported to have anti-platelet activities. In the present study, 7 representative compounds from these herbal medicines were selected to study combinatorial drug optimization together with DAPT, i.e., aspirin and ticagrelor. FSC technique first down-selected 9 drug candidates to the most significant 5 drugs. Then, FSC further secured 4 drugs in the optimal combination, including aspirin, ticagrelor, ferulic acid from DangGui, and forskolin from MaoHouQiaoRuiHua. Finally, FSC quantitatively estimated the possible interactions between aspirin:ticagrelor, aspirin:ferulic acid, ticagrelor:forskolin, and ferulic acid:forskolin. The estimation was further verified by experimentally determined Combination Index (CI values.Conclusion: Results of the present study suggested that FSC optimization technique could be used in optimization of anti-platelet drug combinations and might be helpful in designing personal anti-platelet therapy strategy. Furthermore, FSC analysis could also identify interactions between different

Current density profile inside q=1 on Tore Supra

International Nuclear Information System (INIS)

Joffrin, E.; Desgranges, C.; Sabot, R.; Dubois, M.A.

1995-01-01

The Tore Supra polarimeter used to measure the poloidal field distribution is described. The current density profiles are computed in two different ways using the interferometric and polarimetric data in conjunction with the magnetic data and the location of the inversion radius determined by the soft X-ray camera. The current density inside the q=1 surface is investigated for normal and monster sawteeth. Its variation are also measured by the polarimeter and compared with that predicted by the current diffusion equation assuming complete reconnection. Finally, the safety factor profile is compared with that obtained with the striation data of the pellet ablation. The results of the evolution of the q profile during sawteeth are in good agreement with those obtained in other devices. (author) 9 refs.; 4 figs

Oil characteristics and fatty acid profile of seeds from three varieties ...

African Journals Online (AJOL)

Oil characteristics and fatty acid profile of seeds from three varieties of date palm ... of oils, as indicators of the quality and safety, and oxidative status of edible oils, ... industry, these data suggest that the potential applications of date seed oil for ...

Comparison of the Safety of Seven Iodinated Contrast Media

Science.gov (United States)

Seong, Jong-Mi; Choi, Nam-Kyong; Lee, Joongyub; Chang, Yoosoo; Kim, Ye-Jee; Yang, Bo Ram; Jin, Xue-Mei; Kim, Ju-Young

2013-01-01

We aimed to determine the characteristic adverse events (AEs) of iodinated contrast media (IOCM) and to compare the safety profiles of different IOCM. This study used the database of AEs reports submitted by healthcare professionals from 15 Regional Pharmacovigilance Centers between June 24, 2009 and December 31, 2010 in Korea. All reports of IOCM, including iopromide, iohexol, iopamidol, iomeprol, ioversol, iobitridol and iodixanol, were analyzed. Safety profiles were compared between different IOCM at the system organ level using the proportional reporting ratio (PRR) and 95% confidence interval (95% CI). Among a total of 48,261 reports, 6,524 (13.5%) reports were related to the use of IOCM. Iopromide (45.5%), iohexol (16.9%), iopamidol (14.3%) and iomeprol (10.3%) were identified as frequently reported media. 'Platelet, bleeding & clotting disorders' (PRR, 29.6; 95%CI, 1.9-472.6) and 'urinary system disorders' (PRR, 22.3; 95% CI, 17.1-29.1) were more frequently reported for iodixanol than the other IOCM. In conclusion, the frequency of AEs by organ class was significantly different between individual media. These differences among different IOCM should be considered when selecting a medium among various IOCM and when monitoring patients during and after its use to ensure optimum usage and patient safety. PMID:24339697

Safety Issues Concerning the Medical Use of Cannabis and Cannabinoids

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Mark A Ware

2005-01-01

Full Text Available Safety issues are a major barrier to the use of cannabis and cannabinoid medications for clinical purposes. Information on the safety of herbal cannabis may be derived from studies of recreational cannabis use, but cannabis exposure and effects may differ widely between medical and recreational cannabis users. Standardized, quality-controlled cannabinoid products are available in Canada, and safety profiles of approved medications are available through the Canadian formulary. In the present article, the evidence behind major safety issues related to cannabis use is summarized, with the aim of promoting informed dialogue between physicians and patients in whom cannabinoid therapy is being considered. Caution is advised in interpreting these data, because clinical experience with cannabinoid use is in the early stages. There is a need for long-term safety monitoring of patients using cannabinoids for a wide variety of conditions, to further guide therapeutic decisions and public policy.

Efficacy and safety of adalimumab in ankylosing spondylitis

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Mounach A

2014-08-01

Full Text Available Aziza Mounach, Abdellah El MaghraouiRheumatology Department, Military Hospital Mohammed V, Rabat, MoroccoAbstract: Ankylosing spondylitis (AS is the most common and most severe subtype of spondyloarthritis. It also may be an outcome of any of the other spondyloarthritis subtypes. AS preferentially affects the sacroiliac joints and the tip of the column, with a tendency to later ankylosis. Peripheral joints, enthesis, and other extra-articular involvement may be observed. Tumor necrosis factor (TNF inhibitors are now well-established, effective drugs in the treatment of AS symptoms. Adalimumab, which is a fully human monoclonal antibody that binds to and neutralizes TNF, has demonstrated efficacy in treating AS symptoms, including axial involvement, peripheral arthritis, enthesitis, uveitis, gut involvement, and psoriasis. Furthermore, adalimumab has showed an overall acceptable safety profile. In this paper, we review the efficacy and safety profile of adalimumab in the treatment of AS, and discuss its differences from the other anti-TNF drugs reported in the literature.Keywords: ankylosing spondylitis, spondyloarthritis, adalimumab, tumor necrosis factor-α

Profile control simulations and experiments on TCV : A controller test environment and results using a model-based predictive controller

NARCIS (Netherlands)

Maljaars, E.; Felici, F.; Blanken, T.C.; Galperti, C.; Sauter, O.; de Baar, M.R.; Carpanese, F.; Goodman, T.P.; Kim, D.; Kim, S.H.; Kong, M.G.; Mavkov, B.; Merle, A.; Moret, J.M.; Nouailletas, R.; Scheffer, M.; Teplukhina, A.A.; Vu, N.M.T.

2017-01-01

The successful performance of a model predictive profile controller is demonstrated in simulations and experiments on the TCV tokamak, employing a profile controller test environment. Stable high-performance tokamak operation in hybrid and advanced plasma scenarios requires control over the safety

Profile control simulations and experiments on TCV: a controller test environment and results using a model-based predictive controller

NARCIS (Netherlands)

Maljaars, B.; Felici, F.; Blanken, T. C.; Galperti, C.; Sauter, O.; de Baar, M. R.; Carpanese, F.; Goodman, T. P.; Kim, D.; Kim, S. H.; Kong, M.; Mavkov, B.; Merle, A.; Moret, J.; Nouailletas, R.; Scheffer, M.; Teplukhina, A.; Vu, T.

2017-01-01

The successful performance of a model predictive profile controller is demonstrated in simulations and experiments on the TCV tokamak, employing a profile controller test environment. Stable high-performance tokamak operation in hybrid and advanced plasma scenarios requires control over the safety

Plutonium, americium, and uranium concentrations in Nevada Test Site soil profiles

International Nuclear Information System (INIS)

Essington, E.H.; Gilbert, R.O.; Eberhardt, L.L.; Fowler, E.B.

1975-01-01

Many soil profile samples were collected by the Nevada Applied Ecology Group from five nuclear safety test sites on the Nevada Test Site and Tonopah Test Range in Nevada, U.S.A. The profile samples were analyzed for 239 Pu, 240 Pu, 241 Am, and in some cases 235 U and 238 U, in order to estimate the depth of radionuclide penetration and level of contamination at specific sampling depths after an extended period of time since deposition on the surface. Nearly 70 individual profiles were examined. About one-half of the profiles exhibited a smooth leaching pattern with more than 95 percent of the plutonium in the top 5 cm. Other profile patterns are discussed relative to mechanical disturbance of the profile after the initial deposition, accumulation of plutonium in specific zones within the soil profile, and occurrence of large amounts of plutonium in the deepest parts of the soil profile. The implications of these observations are discussed with respect to redistribution of radioactivity by wind, water, and burrowing animals, ingestion by burrowing and grazing animals, uptake by vegetation, and cleanup operations. (auth)

Evaluation of Patient Safety Culture and Organizational Culture as a Step in Patient Safety Improvement in a Hospital in Jakarta, Indonesia

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Afrisya Iriviranty

2016-07-01

Full Text Available Introduction: Establishment of patient safety culture is the first step in the improvement of patient safety. As such, assessment of patient safety culture in hospitals is of paramount importance. Patient safety culture is an inherent component of organizational culture, so that the study of organizational culture is required in developing patient safety. This study aimed to evaluate patient safety culture among the clinical staff of a hospital in Jakarta, Indonesia and identify organizational culture profile. Materials and Methods: This cross-sectional, descriptive, qualitative study was conducted in a hospital in Jakarta, Indonesia in 2014. Sample population consisted of nurses, midwives, physicians, pediatricians, obstetrics and gynecology specialists, laboratory personnel, and pharmacy staff (n=152. Data were collected using the Hospital Survey on Patient Safety Culture developed by the Agency for Healthcare Research and Quality (AHRQ and Organizational Culture Assessment Instrument (OCAI. Results: Teamwork within units” was the strongest dimension of patient safety culture (91.7%, while “staffing” and “non-punitive response to error” were the weakest dimensions (22.7%. Moreover, clan culture was the most dominant type of organizational culture in the studied hospital. This culture serves as a guide for the changes in the healthcare organization, especially in the development of patient safety culture. Conclusion: According to the results of this study, healthcare providers were positively inclined toward the patient safety culture within the organization. As such, the action plan was designed through consensus decision-making and deemed effective in articulating patient safety in the vision and mission of the organization.

Aliskiren: a clinical profile

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Roland E Schmieder

2006-06-01

Full Text Available Aliskiren is a novel oral antihypertensive agent, and the first in the new class of direct renin inhibitors. Here we review the key criteria that a new antihypertensive drug should possess, notably effective blood pressure lowering as monotherapy and combination therapy, 24-hour blood pressure control, safety and tolerability, end-organ protective effects, minimal drug interaction and efficacy during long-term use.Aliskiren fulfils key criteria for a new antihypertensive agent.The drug demonstrates effective blood lowering in a number of studies as monotherapy and in combination with a thiazide diuretic (hydrochlorothiazide, an angiotensin-converting enzyme inhibitor (ramipril and a calcium channel blocker (amlodipine. Other studies applying ambulatory blood pressure monitoring show that aliskiren maintains blood pressure control for more than 24 hours. Aliskiren, 150 mg and 300 mg have demonstrated a placebo-like safety and tolerability profile, with no interactions with a wide range of commonly used drugs. Three studies (AVOID, ALOFT and ALLAY are ongoing properties. with aliskiren to assess end-organ protective properties.

Review of Post-Marketing Safety Data on Tapentadol, a Centrally Acting Analgesic.

Science.gov (United States)

Stollenwerk, Ariane; Sohns, Melanie; Heisig, Fabian; Elling, Christian; von Zabern, Detlef

2018-01-01

Tapentadol is a centrally acting analgesic that has been available for the management of acute and chronic pain in routine clinical practice since 2009. This is the first integrated descriptive analysis of post-marketing safety data following the use of tapentadol in a broad range of pain conditions relating to the topics overall safety, dose administration above approved dosages, administration during pregnancy, serotonin syndrome, respiratory depression, and convulsion. The data analyzed pertain to spontaneous reports from healthcare and non-healthcare professionals and were put in the context of safety information known from interventional and non-interventional trials. The first years of routine clinical practice experience with tapentadol have confirmed the tolerability profile that emerged from the clinical trials. Moreover, the reporting of expected side effects such as respiratory depression and convulsion was low and no major risks were identified. The evaluation of available post-marketing data did not confirm the theoretical risk of serotonin syndrome nor did it reveal unexpected side effects with administration of higher than recommended doses. More than 8 years after its first introduction, the favorable overall safety profile of tapentadol in the treatment of various pain conditions is maintained in the general population. Grünenthal GmbH.

Stationary density profiles in the Alcator C-mod tokamak

International Nuclear Information System (INIS)

Kesner, J.; Ernst, D.; Hughes, J.; Mumgaard, R.; Shiraiwa, S.; Whyte, D.; Scott, S.

2012-01-01

In the absence of an internal particle source, plasma turbulence will impose an intrinsic relationship between an inwards pinch and an outwards diffusion resulting in a stationary density profile. The Alcator C-mod tokamak utilizes RF heating and current drive so that fueling only occurs in the vicinity of the separatrix. Discharges that transition from L-mode to I-mode are seen to maintain a self-similar stationary density profile as measured by Thomson scattering. For discharges with negative magnetic shear, an observed rise of the safety factor in the vicinity of the magnetic axis appears to be accompanied by a decrease of electron density, qualitatively consistent with the theoretical expectations.

Observational Pharmacoepidemiology in the Drug Safety and Effectiveness Evaluation

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José Cabrita

2017-04-01

Full Text Available Observational epidemiological studies have been used in the medicines context for more than 40 years, contributing to characterize drug use patterns and safety, efficacy and effectiveness profiles. Its use has been increased in recognition of the clinical trials limitations to assess the therapeutic and iatrogenic potential of the medicines after its commercialization. The evolution of the regulatory framework for pharmacovigilance, requiring post-marketing studies, post-authorization safety studies (PASS and the post-authorization efficacy studies (PAES to approve certain drugs, reinforced the importance of observational pharmacoepidemiology for the characterization of the medicines safety and effectiveness profiles. Pharmacoepidemiological research can be carried out from field studies designed to obtain the necessary information or in databases with health records of population samples that already contain the information. This 2nd option is more efficient and more and more frequent. Although, observational research from field studies continues to have its space, the increasing availability of databases allowed a new development to observational pharmacoepidemiology. Indeed, access to automated records databases with up-to-date information on medical prescriptions and global health care to representative population samples with long follow-up periods is a valuable tool for the study of drug use patterns and therapeutic and iatrogenic potential in routine clinical practice. In this context, observational pharmacoepidemiology reinforces its role as a scientific area particularly suitable for evaluating the safety and the effectiveness of the medicines in the “real world”, making a relevant contribution to overcome the gap in translating the evidence from the clinical trials for clinical practice.

Safety update on the use of recombinant activated factor VII in approved indications.

Science.gov (United States)

Neufeld, Ellis J; Négrier, Claude; Arkhammar, Per; Benchikh el Fegoun, Soraya; Simonsen, Mette Duelund; Rosholm, Anders; Seremetis, Stephanie

2015-06-01

This updated safety review summarises the large body of safety data available on the use of recombinant activated factor VII (rFVIIa) in approved indications: haemophilia with inhibitors, congenital factor VII (FVII) deficiency, acquired haemophilia and Glanzmann's thrombasthenia. Accumulated data up to 31 December 2013 from clinical trials as well as post-marketing data (registries, literature reports and spontaneous reports) were included. Overall, rFVIIa has shown a consistently favourable safety profile, with no unexpected safety concerns, in all approved indications. No confirmed cases of neutralising antibodies against rFVIIa have been reported in patients with congenital haemophilia, acquired haemophilia or Glanzmann's thrombasthenia. The favourable safety profile of rFVIIa can be attributed to the recombinant nature of rFVIIa and its localised mechanism of action at the site of vascular injury. Recombinant FVIIa activates factor X directly on the surface of activated platelets, which are present only at the site of injury, meaning that systemic activation of coagulation is avoided and the risk of thrombotic events (TEs) thus reduced. Nonetheless, close monitoring for signs and symptoms of TE is warranted in all patients treated with any pro-haemostatic agent, including rFVIIa, especially the elderly and any other patients with concomitant conditions and/or predisposing risk factors to thrombosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

NASA's Software Safety Standard

Science.gov (United States)

Ramsay, Christopher M.

2007-01-01

NASA relies more and more on software to control, monitor, and verify its safety critical systems, facilities and operations. Since the 1960's there has hardly been a spacecraft launched that does not have a computer on board that will provide command and control services. There have been recent incidents where software has played a role in high-profile mission failures and hazardous incidents. For example, the Mars Orbiter, Mars Polar Lander, the DART (Demonstration of Autonomous Rendezvous Technology), and MER (Mars Exploration Rover) Spirit anomalies were all caused or contributed to by software. The Mission Control Centers for the Shuttle, ISS, and unmanned programs are highly dependant on software for data displays, analysis, and mission planning. Despite this growing dependence on software control and monitoring, there has been little to no consistent application of software safety practices and methodology to NASA's projects with safety critical software. Meanwhile, academia and private industry have been stepping forward with procedures and standards for safety critical systems and software, for example Dr. Nancy Leveson's book Safeware: System Safety and Computers. The NASA Software Safety Standard, originally published in 1997, was widely ignored due to its complexity and poor organization. It also focused on concepts rather than definite procedural requirements organized around a software project lifecycle. Led by NASA Headquarters Office of Safety and Mission Assurance, the NASA Software Safety Standard has recently undergone a significant update. This new standard provides the procedures and guidelines for evaluating a project for safety criticality and then lays out the minimum project lifecycle requirements to assure the software is created, operated, and maintained in the safest possible manner. This update of the standard clearly delineates the minimum set of software safety requirements for a project without detailing the implementation for those

A comparative safety review between GLP-1 receptor agonists and SGLT2 inhibitors for diabetes treatment.

Science.gov (United States)

Consoli, Agostino; Formoso, Gloria; Baldassarre, Maria Pompea Antonia; Febo, Fabrizio

2018-03-01

Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium glucose cotransporter 2 inhibitors (SGLT2i) are of particular interest in type 2 diabetes treatment strategies, due to their efficacy in reducing HbA1c with a low risk of hypoglycaemia, to their positive effects on body weight and blood pressure and in light of their effects on cardiovascular risk and on nephroprotection emerged from the most recent cardiovascular outcome trials. Since it is therefore very likely that GLP-1RA and SGLT2i use will become more and more common, it is more and more important to gather and discuss information about their safety profile. Area Covered: adverse events and the safety concerns most often emerged in trials with GLP-1RA namely, exenatide long acting release (LAR), dulaglutide, liraglutide, semaglutide, lixisenatide or SGLT2i, namely empagliflozin, dapagliflozin, canagliflozin and SGLT2i with an attempt at comparing the safety profiles of molecules of these two classes. Expert opinion: GLP-1RA and SGLT2i, although each associated with different specific side effects, share a 'similar' safety profile and are both drugs relatively easy to handle. The potentially complementary mechanisms of action, the cardio and nephroprotective effects demonstrated by molecules of both classes, make these drugs potentially useful even in add on to each other.

Toroidal equilibrium and radial profiles from magnetic measurements in Extrap T1

International Nuclear Information System (INIS)

Brunsell, Per; Jin Li; Tennfors, Einar

1991-01-01

The toroidal equilibrium position in the Extrap T1 toroidal Z-pinch is studied by measuring the currents induced in the external octupole field rings. Radial profiles are obtained by an internal magnetic coil array. From the magnetic field, profiles of current density, plasma pressure, safety factor, resistivity and input power density are deduced. A polynomial model is developed to simulate the measured profiles. The classical ion heat conduction losses in Extrap discharges are calculated using this model and compared to the power input. for polynomials matched to magnetic field profiles measured in present experiments, these losses are small. By varying the coefficients of the polynomials, a region is found where the power input can balance the classical heat conduction losses at higher values of Θ and β o . (Author)

Protectionism or Legitimate Regulations: What can Trade Partners Expect from the New US Food Safety Regime?

OpenAIRE

Nakuja, T.; Kerr, William A.

2013-01-01

In January 2011, the US passed the Food Safety Modernization Act (FSMA) which represents a major legislative initiative to revise and strengthen the regulatory regime pertaining to foodborne illness and contamination. The tightening of the regulatory regime was justified on the basis of a number of high-profile foodborne disease incidents, which are claimed to have undermined public confidence in the US food safety system. While tightening food safety regulations inevitably increase barriers ...

Advances in Predictive Toxicology for Discovery Safety through High Content Screening.

Science.gov (United States)

Persson, Mikael; Hornberg, Jorrit J

2016-12-19

High content screening enables parallel acquisition of multiple molecular and cellular readouts. In particular the predictive toxicology field has progressed from the advances in high content screening, as more refined end points that report on cellular health can be studied in combination, at the single cell level, and in relatively high throughput. Here, we discuss how high content screening has become an essential tool for Discovery Safety, the discipline that integrates safety and toxicology in the drug discovery process to identify and mitigate safety concerns with the aim to design drug candidates with a superior safety profile. In addition to customized mechanistic assays to evaluate target safety, routine screening assays can be applied to identify risk factors for frequently occurring organ toxicities. We discuss the current state of high content screening assays for hepatotoxicity, cardiotoxicity, neurotoxicity, nephrotoxicity, and genotoxicity, including recent developments and current advances.

Estimation of left-turning vehicle maneuvers for the assessment of pedestrian safety at intersections

Directory of Open Access Journals (Sweden)

Wael K.M. Alhajyaseen

2012-07-01

Full Text Available Improving pedestrian safety at intersections remains a critical issue. Although several types of safety countermeasures, such as reforming intersection layouts, have been implemented, methods have not yet been established to quantitatively evaluate the effects of these countermeasures before installation. One of the main issues in pedestrian safety is conflicts with turning vehicles. This study aims to develop an integrated model to represent the variations in the maneuvers of left-turners (left-hand traffic at signalized intersections that dynamically considers the vehicle reaction to intersection geometry and crossing pedestrians. The proposed method consists of four empirically developed stochastic sub-models, including a path model, free-flow speed profile model, lag/gap acceptance model, and stopping/clearing speed profile model. Since safety assessment is the main objective driving the development of the proposed model, this study uses post-encroachment time (PET and vehicle speed at the crosswalk as validation parameters. Preliminary validation results obtained by Monte Carlo simulation show that the proposed integrated model can realistically represent the variations in vehicle maneuvers as well as the distribution of PET and vehicle speeds at the crosswalk.

Profiling high-frequency accident locations using association rules

OpenAIRE

GEURTS, Karolien; WETS, Geert; BRIJS, Tom; VANHOOF, Koen

2003-01-01

In Belgium, traffic safety is currently one of the government's highest priorities. Identifying and profiling black spots and black zones in terms of accident related data and location characteristics must provide new insights into the complexity and causes of road accidents, which, in ram, provide valuable input for government actions. In this paper, association rules are used to identify accident circumstances that frequently occur together at high frequency accident locations. Furthermore...

Dietary feeding of flavokawain A, a Kava chalcone, exhibits a satisfactory safety profile and its association with enhancement of phase II enzymes in mice

Directory of Open Access Journals (Sweden)

Xuesen Li

2014-01-01

Full Text Available Flavokawain A (FKA, a major chalcone in the Kava plant, has recently demonstrated promising anti-cancer activities. A systematic evaluation of FKA's safety profile has not been reported before. In this study, male FVB/N mice were fed with an AIN-76A diet or AIN-76A diet supplemented with 0.6% (6 g/kg food FKA or 0.6% commercial kava root extract (KRE for three weeks. Dietary feeding of FKA did not affect food consumption and body weight. Histopathological examination of liver, kidney, colon, lung, heart, spleen, and thymus revealed no signs of FKA-induced toxicity. Biochemical serum analysis and histological examination confirmed normal organ function in FKA-treated mice. The cytotoxicity profile showed FKA had minimal side effects on bone marrow and small intestinal epithelial cells compared with Adriamycin. In addition, oral feeding of FKA increased activities of both glutathione S-transferase and quinone reductase in the liver, lung, prostate and bladder tissues of mice. In comparison, dietary feeding of 0.6% KRE increased liver/body weight ratio and decreased spleen, thymus, and testis/body weight ratios, as well as induced nodular proliferation in liver tissues. Therefore, dietary feeding FKA showed no adverse effects on major organ function and homeostasis in mice, suggesting the potential of FKA for chemoprevention study of human cancers.

Safety of nifedipine GITS in stable angina: The ACTION trial

NARCIS (Netherlands)

P. Poole-Wilson (Philip); B.A. Kirwan (Bridget Anne); Z. Vokó (Zoltán); S. de Brouwer (Sophie); F.J. van Dalen (Frederik); J. Lubsen (Jacob)

2006-01-01

textabstractAim: We describe the safety profile of nifedipine GITS as assessed from adverse events reported in the ACTION trial in which 7,665 patients with stable, symptomatic coronary artery disease were randomly assigned nifedipine GITS or placebo and followed for a mean of 4.9 years. Methods:

Students' Perceptions of Safety at School after Sandy Hook

Science.gov (United States)

Fisher, Benjamin W.; Nation, Maury; Nixon, Carol T.; McIlroy, Sarah

2017-01-01

High profile school shootings have served as pivotal events for developing policies to promote student safety. Although previous studies indicate that exposure to violence is associated with feeling unsafe at school and poorer academic and psychosocial outcomes, research on the relationship between widely publicized acts of school violence and…

Safety of treatment options for spondyloarthritis: a narrative review.

Science.gov (United States)

D'Angelo, Salvatore; Carriero, Antonio; Gilio, Michele; Ursini, Francesco; Leccese, Pietro; Palazzi, Carlo

2018-05-01

Spondyloarthritis (SpA) are chronic inflammatory diseases with overlapping pathogenic mechanisms and clinical features. Treatment armamentarium against SpA includes non-steroidal anti-inflammatory drugs, glucocorticoids, conventional disease-modifying antirheumatic drugs (DMARDs, including sulfasalazine, methotrexate, leflunomide, cyclosporine), targeted synthetic DMARDs (apremilast) and biological DMARDs (TNF inhibitors, anti-IL 12/23 and anti-IL-17 agents). Areas covered: A narrative review of published literature on safety profile of available SpA treatment options was performed. Readers will be provided with a comprehensive overview on frequent and rare adverse events associated with each drug listed in current SpA treatment recommendations. Expert opinion: The overall safety profile of such molecules is good and serious adverse events are rare but need to be promptly recognized and treated. However, the monitoring of adverse events is a major challenge for clinicians because it is not adequately addressed by current treatment recommendations. A tailored treatment is crucial and rheumatologists must accurately select patients in order to identify those more susceptible to develop adverse events.

Safety, Efficacy, and Patient Acceptability of Everolimus in the Treatment of Breast Cancer.

Science.gov (United States)

Lousberg, Laurence; Jerusalem, Guy

2016-01-01

Everolimus combined with exemestane is an important treatment option for patients suffering from estrogen receptor-positive, human epidermal growth factor receptor 2-negative, advanced breast cancer (ABC) who have been previously treated with a nonsteroidal aromatase inhibitor (NSAI). After presentation of phase III registration trial BOLERO-2, several phase IIIb trials have been started to evaluate this regimen in a more real-world setting. Here, we review the efficacy and safety data published or presented at selected international meetings. These studies confirmed the outcome observed in the BOLERO-2 trial. Patient acceptance rate is also discussed by focusing on the permanent everolimus discontinuation rate in these trials. Factors influencing the safety profile are also reported, including the impact of age. The optimal sequence of combined therapy approaches associating targeted and endocrine therapy (ET) has yet to be determined as new treatment options such as cyclin-dependent kinase inhibitors become available. However, everolimus-exemestane remains an important treatment option with a major impact on progression-free survival (PFS) and an acceptable safety profile.

Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review

Science.gov (United States)

Solmi, Marco; Murru, Andrea; Pacchiarotti, Isabella; Undurraga, Juan; Veronese, Nicola; Fornaro, Michele; Stubbs, Brendon; Monaco, Francesco; Vieta, Eduard; Seeman, Mary V; Correll, Christoph U; Carvalho, André F

2017-01-01

Since the discovery of chlorpromazine (CPZ) in 1952, first-generation antipsychotics (FGAs) have revolutionized psychiatric care in terms of facilitating discharge from hospital and enabling large numbers of patients with severe mental illness (SMI) to be treated in the community. Second-generation antipsychotics (SGAs) ushered in a progressive shift from the paternalistic management of SMI symptoms to a patient-centered approach, which emphasized targets important to patients – psychosocial functioning, quality of life, and recovery. These drugs are no longer limited to specific Diagnostic and Statistical Manual of Mental Disorders (DSM) categories. Evidence indicates that SGAs show an improved safety and tolerability profile compared with FGAs. The incidence of treatment-emergent extrapyramidal side effects is lower, and there is less impairment of cognitive function and treatment-related negative symptoms. However, treatment with SGAs has been associated with a wide range of untoward effects, among which treatment-emergent weight gain and metabolic abnormalities are of notable concern. The present clinical review aims to summarize the safety and tolerability profile of selected FGAs and SGAs and to link treatment-related adverse effects to the pharmacodynamic profile of each drug. Evidence, predominantly derived from systematic reviews, meta-analyses, and clinical trials of the drugs amisulpride, aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, ziprasidone, CPZ, haloperidol, loxapine, and perphenazine, is summarized. In addition, the safety and tolerability profiles of antipsychotics are discussed in the context of the “behavioral toxicity” conceptual framework, which considers the longitudinal course and the clinical and therapeutic consequences of treatment-emergent side effects. In SMI, SGAs with safer metabolic profiles should ideally be prescribed

[Profile of silodosin].

Science.gov (United States)

Montorsi, Francesco

2013-01-01

Silodosin is a highly selective alpha1A-adrenoceptor antagonist approved for the treatment of the signs and symptoms of benign prostatic hyperplasia. Its clinical pharmacology profile offers a number of advantages, including uroselectivity, once-daily (QD) dosing, a standard dose of 8 mg QD that does not need to be adjusted according to age, and the feasibility of concomitant treatment with phosphodiesterase type 5 (PDE5) inhibitors and antihypertensive agents. Three phase 3 double-blind, randomised trials using the dosage regimen of 8 mg QD in > 800 patients have shown that silodosin is significantly more effective than placebo (p nocturia (p = 0.03). Safety data collected in 1581 patients exposed to chronic treatment with silodosin 8 mg QD have shown that the drug is safe and well tolerated. As was to be expected with a uroselective compound, cardiovascular effects have been minimal. The most common adverse reaction is "retrograde ejaculation" (anejaculation), which led to treatment discontinuation in only 3.9% of patients. The rare, drug class-related safety issue of intraocular floppy iris syndrome can be satisfactorily managed by warning patients simply to inform their ophthalmologist that they are or were on treatment with an alpha1-adrenoceptor blocker.

Insights from the U.S. department of Energy plant safety evaluation program of VVER and RBMK reactors

International Nuclear Information System (INIS)

Petri, M.C.; Binder, J.L.; Pasedag, W.F.

2001-01-01

Throughout the years 1990 the U.S. Department of Energy has worked build capability in countries of the former Soviet Union to assess the safety of their VVER and RBMK reactors. Through this Plant Safety Evaluation Program, deterministic and probabilistic analyses have been used to provide a documented plant risk profile to support safe plant operation and to set priorities for safety upgrades. Work has been sponsored at thirteen nuclear power plant sites in eight countries. The Plant Safety Evaluation Program has resulted in immediate and long-term safety benefits for the Soviet-designed nuclear plants. (author)

Modern diaper performance: construction, materials, and safety review.

Science.gov (United States)

Dey, Swatee; Kenneally, Dianna; Odio, Mauricio; Hatzopoulos, Ioannis

2016-07-01

A review of the literature on diapers and diaper rash reveals that many clinicians are unfamiliar with modern diaper construction and materials as well as diaper safety testing methods. Typical modern diapers do not contain ingredients of concern such as latex and disperse dyes, but use ingredients such as spandex and pigments with a favorable safety profile. Today's disposable diaper is a high performance product whose carefully designed layers and liners provide optimal urine and feces absorption and an ever more clothing-like and comfortable fit. This is possible due to a variety of specialized polymer materials that provide optimal absorption of urine and feces, thereby minimizing skin exposure. © 2016 The International Society of Dermatology.

Viewpoint: "underutilisation of novel antiplatelet agents--myths, generics, and economics".

Science.gov (United States)

Serebruany, V L; Fortmann, S D

2014-07-03

Two oral antiplatelet agents have been recently introduced for acute coronary syndromes indication providing alternatives for dual therapy with aspirin and clopidogrel. In fact, worldwide prasugrel has been on the market for four years, and ticagrelor for over two years. Despite declared benefits over clopidogrel, including hypothetical cost saving advantages, in real life, the clinical utilisation of both agents is small. Generic clopidogrel, and price differences are claimed as major obstacles to prevent broader prasugrel and ticagrelor use. However, these economic difficulties are barely supported by available evidence, and served mostly to protect questionable management spending, as an exuse to explain why in reality cardiologists are so sceptical about both novel agents, and to convince the sharehoders that their money is not wasted, misleading the owners with regard to future success. Importantly, brand Plavix® is used worldwide 5-10 times more often than new agents, despite heavy generic competition. The future of prasugrel outside Japan, where much lower reasonable dose will be used is not impressive due to lack of further outcome studies, negative results of the latest trials, and less than four years left before patent expiration. The fate of ticagrelor will depend on verification of deaths numbers in the ongoing United States Department of Justice PLATO investigation, and confirmation of the mortality benefit in the PEGASUS TIMI-54 trial.

Risk perception, safety goals and regulatory decision-making

International Nuclear Information System (INIS)

Hoegberg, Lars

1998-01-01

Deciding on 'how safe is safe enough?' includes value judgements with implications of an ethical and political nature. As regulators are accountable to governments, parliaments and the general public, regulatory decision-making should be characterized by transparency with respect to how such value judgements are reflected in risk assessments and regulatory decisions. Some approaches in this respect are discussed in the paper, based on more than fifteen years of experience in nuclear regulatory decision-making. Issues discussed include: (1) risk profiles and safety goals associated with severe reactor accidents--individual health risks, societal risks and risk of losing investments; (2) risk profile-based licensing of the Swedish SFR final disposal facility for low and intermediate level radioactive waste

Facilitating improved road safety based on increased knowledge about driving behaviour and profiling sub-groups of drivers

DEFF Research Database (Denmark)

Martinussen, Laila Marianne

The aim of the Ph.D. study presented in this thesis was to facilitate improved road safety through increased understanding of methods used to measure driving behaviour, and through increased knowledge about driving behaviour in sub-groups of drivers. More specifically, the usefulness of the Driver...... with underlying mechanisms of lack of focus, emotional stress, recklessness and confusion, and hence it is highly important to further explore means to making drivers become more focused or attentive when driving, and to deal with emotional responses in traffic like impatience and frustration (Article 1). 2......, indicating that the problem lies in the drivers’ attitudes towards safety (Article 3). 6. It is indicated that rather than viewing safety and risk as two ends of a continuum, safety and risk should be understood as two separate constructs, with different underlying motives. Therefore it is suggested...

Profiling high frequency accident locations using associations rules

OpenAIRE

GEURTS, Karolien; WETS, Geert; BRIJS, Tom; VANHOOF, Koen

2002-01-01

In Belgium, traffic safety is currently one of the government’s highest priorities. Identifying and profiling black spots and black zones in terms of accident related data and location characteristics must provide new insights into the complexity and causes of road accidents which, in turn, provide valuable input for government actions. In this paper, association rules are used to identify accident circumstances that frequently occur together at high frequency accident locations. Furthermore,...

Safety and tolerability of extended-release niacin-laropiprant: Pooled analyses for 11,310 patients in 12 controlled clinical trials.

Science.gov (United States)

McKenney, James; Bays, Harold; Gleim, Gilbert; Mitchel, Yale; Kuznetsova, Olga; Sapre, Aditi; Sirah, Waheeda; Maccubbin, Darbie

2015-01-01

The Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) showed that adding extended-release niacin-laropiprant (ERN-LRPT) to statin provided no incremental cardiovascular benefit vs placebo (PBO). ERN-LRPT was also associated with an excess of serious adverse experiences (AEs), some of which were unexpected (infections and bleeding). These findings led to the withdrawal of ERN-LRPT from all markets. We examined the safety profile of ERN-LRPT vs the comparators ERN alone and statins in the ERN-LRPT development program to assess whether similar safety signals were observed to those seen in HPS-THRIVE and whether these might be attributed to ERN or LRPT. Postrandomization safety data from 12 clinical studies, 12 to 52 weeks in duration and involving 11,310 patients, were analyzed across 3 treatments: (1) ERN-LRPT; (2) ERN-NSP (ERN, Merck & Co, Inc or Niaspan [NSP], Abbott Laboratories); and (3) statin-PBO (statin or PBO). The safety profiles of ERN-LRPT and ERN-NSP were similar, except for less flushing with ERN-LRPT. Nonflushing AEs reported more frequently with ERN-LRPT or ERN-NSP than with statin-PBO were mostly nonserious and typical of niacin (nausea, diarrhea, and increased blood glucose). There was no evidence for an increased risk of serious AEs related to diabetes, muscle, infection, or bleeding. Pooled data from 11,310 patients revealed that, except for reduced flushing, the safety profile of ERN-LRPT was similar to that of ERN-NSP; LRPT did not appear to adversely affect the side-effect profile of ERN. The inability to replicate the unexpected AE findings in HPS2-THRIVE could be because of the smaller sample size and substantially shorter duration of these studies. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

The safety of available and emerging options for emergency contraception.

Science.gov (United States)

Lee, Jessica K; Schwarz, Eleanor Bimla

2017-10-01

Emergency contraception (EC) is a way to significantly reduce the chance of becoming pregnant after an episode of unprotected intercourse. Considerable data support the safety of all available and emerging options for EC. Areas covered: This review presents a comprehensive summary of the literature regarding the safety of EC as well as directions for further study. PubMed was searched for all relevant studies published prior to June 2017. Expertopinion: All available methods of EC (i.e., ulipristal acetate pills, levonorgestrel pills, and the copper-IUD), carry only mild side effects and serious adverse events are essentially unknown. The copper IUD has the highest efficacy of EC methods. Given the excellent safety profiles of mifepristone and the levonorgestrel IUD, research is ongoing related to use of these products for EC.

Issues in the management of acute agitation: how much current guidelines consider safety?

Directory of Open Access Journals (Sweden)

Bruno ePacciardi

2013-05-01

Full Text Available Agitated behavior constitutes up to 10% of emergency psychiatric interventions. Pharmacological tranquilization is often used as a valid treatment for agitation but a strong evidence base does not underpin it. Available literature shows different recommendations, supported by research data, theoretical considerations or clinical experience. Rapid tranquilization is mainly based on parenteral drug treatment and the few existing guidelines on this topic, when suggesting the use of first generation antipsychotics and benzodiazepines, include drugs with questionable tolerability profile such as chlorpromazine, haloperidol, midazolam and lorazepam. In order to systematically evaluate safety concerns related to the adoption of such guidelines, we reviewed them independently from principal diagnosis while examining tolerability data for suggested treatments. There is a growing evidence about safety profile of second generation antipsychotics for rapid tranquilization but further controlled studies providing definitive data in this area are urgently needed.

Viewpoint: Central adjudication of myocardial infarction in outcome-driven clinical trials--common patterns in TRITON, RECORD, and PLATO?

Science.gov (United States)

Serebruany, Victor L; Atar, Dan

2012-09-01

Central adjudication in randomised controlled outcome-driven trials represents a traditional approach to maintain data integrity by applying uniformed rules for assessment of clinical events. It was the purpose of this investigation to determine the patterns of myocardial infarction (MI) adjudication in the TRITON, RECORD, and PLATO trials. We were matching centrally-adjudicated MI's (CAMI's) from the official trial publication with the site-reported MI (SRMI's) count from the Food and Drug Administration's secondary analyses for the investigational compounds prasugrel (TRITON), rosiglitazone (RECORD), and ticagrelor (PLATO). CAMI numbers showed a remarkable discrepancy to SRMI's by more than a doubling of the difference: from 72 to 145 events in TRITON favoring prasugrel (from a hazard ratio [HR]=0.76, p=0.08; to a HR=0.76, p<0.001), and from 44 to 89 events in favour of ticagrelor in PLATO (from a HR=0.94, p=0.095; to a HR=0.84, p<0.001). In contrast, in the RECORD trial, the CAMI count was less than the SRMI count (from 24 to 8 events, from a HR=1.42, p=0.93; to a HR=1.14, p=0.96), in this case diminishing cardiovascular hazards in favour of rosiglitazone. In conclusion, central adjudication in the TRITON, the RECORD, and the PLATO trial turned out to have a critical impact on study outcomes. Trial publications should in the future include site-reported major efficacy and safety endpoints to preserve data integrity. The regulatory authorities should consider independent audits when there is a major disagreement between centrally adjudicated and site reported events influencing the results of a major clinical trial.

Safety Profile of Meswak Root Extract on Liver, Kidney, Sexual Hormones and Hematological Parameters of Rats

Directory of Open Access Journals (Sweden)

Abeer Y. IBRAHIM

2012-02-01

Full Text Available This study was conducted to investigate the safety profile of Salvadora persica (Salvadoraceae aqueous alcoholic root extract by carrying out acute and sub-chronic toxicity assessment in order to find out any side effect of the traditionally using of these root sticks. Regarding to acute toxicity test, mice were administered the extract up to 5 g kg-1, intraperitoneally. Animals were then observed for behavioural changes; signs of toxicity, and mortality within 24 h. Surviving mice were monitored for 7 days for signs of delayed toxicity. In the sub-chronic toxicity test, rats were daily treated with the extract at a dose of 400 mg kg-1 intraperitoneally, for 30 days. At the end of the test period, hematological and biochemical parameters were determined in blood and serum samples with determination of vital organs weights. In the acute toxicity test, the extract was practically non-toxic showing no mortality and visible signs of delayed toxicity. The LD50, given intraperitoneally, was estimated to be 4 g kg-1. Administration of extract (at a dose of 400 mg Kg-1 b.wt. to male and female rats for 30 days did not produce any significant (P < 0.05 effect on hematological and most biochemical parameters also vital organs weights. The root extract showed adverse effects on sexual hormones, by increasing estrogen secretion and reducing testosterone level in male rats. At the same time, the extract reduces progesterone level in female satellite group. Overall, Meswak aqueous extract is safe concerning liver and kidney functions and hematological assessments; however, it induces reversal effect on sexual hormones levels determined in sera.

Nonclinical safety strategies for stem cell therapies

Energy Technology Data Exchange (ETDEWEB)

Sharpe, Michaela E., E-mail: michaela_sharpe@yahoo.com [Investigative Toxicology, Drug Safety Research and Development, Pfizer Ltd, Ramsgate Road, Sandwich, CT13 9NJ (United Kingdom); Morton, Daniel [Exploratory Drug Safety, Drug Safety Research and Development, Pfizer Inc, Cambridge, 02140 (United States); Rossi, Annamaria [Investigative Toxicology, Drug Safety Research and Development, Pfizer Ltd, Ramsgate Road, Sandwich, CT13 9NJ (United Kingdom)

2012-08-01

Recent breakthroughs in stem cell biology, especially the development of the induced pluripotent stem cell techniques, have generated tremendous enthusiasm and efforts to explore the therapeutic potential of stem cells in regenerative medicine. Stem cell therapies are being considered for the treatment of degenerative diseases, inflammatory conditions, cancer and repair of damaged tissue. The safety of a stem cell therapy depends on many factors including the type of cell therapy, the differentiation status and proliferation capacity of the cells, the route of administration, the intended clinical location, long term survival of the product and/or engraftment, the need for repeated administration, the disease to be treated and the age of the population. Understanding the product profile of the intended therapy is crucial to the development of the nonclinical safety study design.

Nonclinical safety strategies for stem cell therapies

International Nuclear Information System (INIS)

Sharpe, Michaela E.; Morton, Daniel; Rossi, Annamaria

2012-01-01

Recent breakthroughs in stem cell biology, especially the development of the induced pluripotent stem cell techniques, have generated tremendous enthusiasm and efforts to explore the therapeutic potential of stem cells in regenerative medicine. Stem cell therapies are being considered for the treatment of degenerative diseases, inflammatory conditions, cancer and repair of damaged tissue. The safety of a stem cell therapy depends on many factors including the type of cell therapy, the differentiation status and proliferation capacity of the cells, the route of administration, the intended clinical location, long term survival of the product and/or engraftment, the need for repeated administration, the disease to be treated and the age of the population. Understanding the product profile of the intended therapy is crucial to the development of the nonclinical safety study design.

Profile of vildagliptin in type 2 diabetes: efficacy, safety, and patient acceptability

Directory of Open Access Journals (Sweden)

Pan CY

2013-05-01

Full Text Available CY Pan,1 XL Wang21Chinese PLA General Hospital, Beijing, People's Republic of China; 2Medical Affairs Department, Beijing Novartis Pharma Co, Ltd, Beijing, People's Republic of ChinaAbstract: Vildagliptin is a selective and potent dipeptidyl peptidase-4 inhibitor that improves glycemic control by inhibiting the degradation of both endogenous glucagon-like peptide-1 and glucose-dependent insulinotropic peptide. This article is a comprehensive review of the safety and efficacy of vildagliptin in patients with type 2 diabetes. Clinical evidence has proven that it effectively decreases hemoglobin A1c with a low risk of hypoglycemia and is weight neutral. The addition of vildagliptin to metformin improves glucose control and significantly reduces gastrointestinal adverse events, particularly in patients inadequately controlled with metformin monotherapy. Its long-term advantages include preservation of β-cell function, reduction in total cholesterol, decrease in fasting lipolysis in adipose tissue, and triglyceride storage in non-fat tissues. Vildagliptin is well tolerated with a low incidence of AEs, and it does not increase the risk of cardiovascular/cerebrovascular (CCV events. It can be taken before or after meals, and has little drug interaction, thus it will be well accepted.Keywords: dipeptidyl peptidase-4, incretin hormones, vildagliptin, efficacy, safety, patient acceptability

1D profiling using highly dispersive guided waves

International Nuclear Information System (INIS)

Volker, Arno; Zon, Tim van; Enthoven, Daniel; Verburg, Wesley

2015-01-01

Corrosion is one of the industries major issues regarding the integrity of assets. Currently inspections are conducted at regular intervals to ensure a sufficient integrity level of these assets. Cost reduction while maintaining a high level of reliability and safety of installations is a major challenge. There are many situations where the actual defect location is not accessible, e.g., a pipe support or a partially buried pipe. Guided wave tomography has been developed to reconstruct the wall thickness. In case of bottom of the line corrosion, i.e., a single corrosion pit, a simpler approach may be followed. Data is collected in a pit-catch configuration at the 12 o'clock position using highly dispersive guided waves. The phase spectrum is used to invert for a wall thickness profile in the circumferential direction, assuming a Gaussian defect profile. An EMAT sensor design has been made to measure at the 12 o'clock position of a pipe. The concept is evaluated on measured data, showing good sizing capabilities on a variety simple defect profiles

Patient safety: Safety culture and patient safety ethics

DEFF Research Database (Denmark)

Madsen, Marlene Dyrløv

2006-01-01

,demonstrating significant, consistent and sometimes large differences in terms of safety culture factors across the units participating in the survey. Paper 5 is the results of a study of the relation between safety culture, occupational health andpatient safety using a safety culture questionnaire survey......Patient safety - the prevention of medical error and adverse events - and the initiative of developing safety cultures to assure patients from harm have become one of the central concerns in quality improvement in healthcare both nationally andinternationally. This subject raises numerous...... challenging issues of systemic, organisational, cultural and ethical relevance, which this dissertation seeks to address through the application of different disciplinary approaches. The main focus of researchis safety culture; through empirical and theoretical studies to comprehend the phenomenon, address...

Gene expression profiling for food safety assessment: examples in potato and maize

CSIR Research Space (South Africa)

Van Dijk, JP

2010-01-01

Full Text Available Northumberlan Brummeria GMO Food safety Food specifi can of samplin input system, but also different cultivars of the same crop species, including genetically modified ones. A n tool e in th larger blotting at a particular position is a measure... of transcriptomics, proteomics and metabolomics for the detection of undesirable side effects of genetically modifying plants (Cellini et al., 2004); http://www.entransfood.nl/RTDprojects/GMO- CARE/GMOCARE.html; http...

Supplementary safety system 1/4 scale testing

Energy Technology Data Exchange (ETDEWEB)

Garrett, R.L.; Paik, I.K.

1993-09-01

During the course of updating the K-Reactor Safety Analysis Report Chapter 15 in 1990, it was identified that the current Supplementary Safety System (SSS) may not be adequate in protecting the reactor during the process water pump coastdown initiated by a loss of AC power when the safety rods are assumed to fail. A SSS modification project was initiated to add an additional ink injection pathway near the pump suction. In addition, the Department of Energy raised a question on the thermal buoyancy effects on moderator flow pattern and ink dispersion in the moderator space. The development and documentation of a two-dimensional code called MODFLOW was undertaken to describe the problem. This report discusses the results of the moderator flow and ink (Gadolinium Poison Solution - GPS) dispersion tests designed to provide qualified data for validation and benchmarking of the MODFLOW computer code with the secondary objectives being the development of concentration profiles and video footage of simulated GPS dispersion under steady-state and transient flow conditions.

Prasugrel (Efient®) with percutaneous coronary intervention for treating acute coronary syndromes (review of TA182): systematic review and economic analysis.

Science.gov (United States)

Greenhalgh, Janette; Bagust, Adrian; Boland, Angela; Dwan, Kerry; Beale, Sophie; Fleeman, Nigel; McEntee, Joanne; Dundar, Yenal; Richardson, Marty; Fisher, Michael

2015-04-01

Acute coronary syndromes (ACSs) are life-threatening conditions associated with acute myocardial ischaemia. There are three main types of ACS: ST segment elevation myocardial infarction (STEMI), non-ST segment elevation myocardial infarction (NSTEMI) and unstable angina (UA). One treatment for ACS is percutaneous coronary intervention (PCI) plus adjunctive treatment with antiplatelet drugs. Dual therapy antiplatelet treatment [aspirin plus either prasugrel (Efient(®), Daiichi Sankyo Company Ltd UK/Eli Lilly and Company Ltd), clopidogrel or ticagrelor (Brilique(®), AstraZeneca)] is standard in UK clinical practice. Prasugrel is the focus of this review. The remit is to appraise the clinical effectiveness and cost-effectiveness of prasugrel within its licensed indication for the treatment of ACS with PCI and is a review of National Institute for Health and Care Excellence technology appraisal TA182. Four electronic databases (MEDLINE, EMBASE, The Cochrane Library, PubMed) were searched from database inception to June 2013 for randomised controlled trials (RCTs) and to August 2013 for economic evaluations comparing prasugrel with clopidogrel or ticagrelor in ACS patients undergoing PCI. Clinical outcomes included non-fatal and fatal cardiovascular (CV) events, adverse effects of treatment and health-related quality of life (HRQoL). Cost-effectiveness outcomes included incremental cost per life-year gained and incremental cost per quality-adjusted life-year (QALY) gained. An independent economic model assessed four mutually exclusive subgroups: ACS patients treated with PCI for STEMI and with and without diabetes mellitus and ACS patients treated with PCI for UA or NSTEMI and with and without diabetes mellitus. No new RCTs were identified beyond that reported in TA182. TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel Thrombolysis in Myocardial Infarction 38) compared prasugrel with clopidogrel in ACS

An open, randomized, parallel-group study to compare the efficacy and safety profile of inhaled human insulin (Exubera) with glibenclamide as adjunctive therapy in patients with type 2 diabetes poorly controlled on metformin

DEFF Research Database (Denmark)

Barnett, AH; Dreyer, M; Lange, Peter

2006-01-01

OBJECTIVE: To compare the efficacy and safety profile of adding inhaled human insulin (INH) (Exubera) or glibenclamide to metformin monotherapy in patients with poorly controlled type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted an open-label, parallel, 24-week multicenter trial. Patients...... associated clinical manifestations. CONCLUSIONS: In patients with type 2 diabetes poorly controlled on metformin, adding INH or glibenclamide was similarly effective in improving glycemic control, and both were well tolerated. A predefined subgroup with very high A1C (>9.5%) was more effectively treated...

Nonclinical Profile of BLZ-100, a Tumor-Targeting Fluorescent Imaging Agent.

Science.gov (United States)

Parrish-Novak, Julia; Byrnes-Blake, Kelly; Lalayeva, Narine; Burleson, Stefanie; Fidel, Janean; Gilmore, Rhonda; Gayheart-Walsten, Pamela; Bricker, Gregory A; Crumb, William J; Tarlo, K S; Hansen, Stacey; Wiss, Valorie; Malta, Errol; Dernell, William S; Olson, James M; Miller, Dennis M

BLZ-100 is a single intravenous use, fluorescent imaging agent that labels tumor tissue to enable more complete and precise surgical resection. It is composed of a chlorotoxin peptide covalently bound to the near-infrared fluorophore indocyanine green. BLZ-100 is in clinical development for intraoperative visualization of human tumors. The nonclinical safety and pharmacokinetic (PK) profile of BLZ-100 was evaluated in mice, rats, canines, and nonhuman primates (NHP). Single bolus intravenous administration of BLZ-100 was well tolerated, and no adverse changes were observed in cardiovascular safety pharmacology, PK, and toxicology studies in rats and NHP. The single-dose no-observed-adverse-effect-levels (NOAELs) were 7 mg (28 mg/kg) in rats and 60 mg (20 mg/kg) in NHP, corresponding to peak concentration values of 89 400 and 436 000 ng/mL and area-under-the-curve exposure values of 130 000 and 1 240 000 h·ng/mL, respectively. Based on a human imaging dose of 3 mg, dose safety margins are >100 for rat and monkey. BLZ-100 produced hypersensitivity reactions in canine imaging studies (lethargy, pruritus, swollen muzzle, etc). The severity of the reactions was not dose related. In a follow-up study in dogs, plasma histamine concentrations were increased 5 to 60 minutes after BLZ-100 injection; this coincided with signs of hypersensitivity, supporting the conclusion that the reactions were histamine based. Hypersensitivity reactions were not observed in other species or in BLZ-100 human clinical studies conducted to date. The combined imaging, safety pharmacology, PK, and toxicology studies contributed to an extensive initial nonclinical profile for BLZ-100, supporting first-in-human clinical trials.

A 6-week, multicentre, randomised, double-blind, double-dummy, active-controlled, clinical safety study of lumiracoxib and rofecoxib in osteoarthritis patients

Directory of Open Access Journals (Sweden)

Yu Sue

2008-09-01

Full Text Available Abstract Background Lumiracoxib is a selective cyclooxygenase-2 inhibitor effective in the treatment of osteoarthritis (OA with a superior gastrointestinal (GI safety profile as compared to traditional non-steroidal anti-inflammatory drugs (NSAIDs, ibuprofen and naproxen. This safety study compared the GI tolerability, the blood pressure (BP profile and the incidence of oedema with lumiracoxib and rofecoxib in the treatment of OA. Rofecoxib was withdrawn worldwide due to an associated increased risk of CV events and lumiracoxib has been withdrawn from Australia, Canada, Europe and a few other countries following reports of suspected adverse liver reactions. Methods This randomised, double-blind study enrolled 309 patients (aged greater than or equal to 50 years with primary OA across 51 centres in Europe. Patients were randomly allocated to receive either lumiracoxib 400 mg od (four times the recommended dose in OA (n = 154 or rofecoxib 25 mg od (n = 155. The study was conducted for 6 weeks and assessments were performed at Weeks 3 and 6. The primary safety measures were the incidence of predefined GI adverse events (AEs and peripheral oedema. The secondary safety measures included effect of treatment on the mean sitting systolic and diastolic blood pressure (msSBP and msDBP. Tolerability of lumiracoxib 400 mg was assessed by the incidence of AEs. Results Lumiracoxib and rofecoxib displayed similar GI safety profiles with no statistically significant difference in predefined GI AEs between the two groups (43.5% vs. 37.4%, respectively. The incidence and severity of individual predefined GI AEs was comparable between the two groups. The incidence of peripheral oedema was low and identical in both the groups (n = 9, 5.8%. Only one patient in the lumiracoxib group and three patients in the rofecoxib group had a moderate or severe event. At Week 6 there was a significantly lower msSBP and msDBP in the lumiracoxib group compared to the rofecoxib

A Pharmacovigilance Study in First Episode of Psychosis: Psychopharmacological Interventions and Safety Profiles in the PEPs Project.

Science.gov (United States)

Bioque, Miquel; Llerena, Adrián; Cabrera, Bibiana; Mezquida, Gisela; Lobo, Antonio; González-Pinto, Ana; Díaz-Caneja, Covadonga M; Corripio, Iluminada; Aguilar, Eduardo J; Bulbena, Antoni; Castro-Fornieles, Josefina; Vieta, Eduard; Lafuente, Amàlia; Mas, Sergi; Parellada, Mara; Saiz-Ruiz, Jerónimo; Cuesta, Manuel J; Bernardo, Miguel

2016-04-01

The characterization of the first episode of psychosis and how it should be treated are principal issues in actual research. Realistic, naturalistic studies are necessary to represent the entire population of first episode of psychosis attended in daily practice. Sixteen participating centers from the PEPs project recruited 335 first episode of psychosis patients, aged 7 to 35 years. This article describes and discusses the psychopharmacological interventions and safety profiles at baseline and during a 60-day pharmacovigilance period. The majority of first episode of psychosis patients received a second-generation antipsychotic (96.3%), orally (95%), and in adjusted doses according to the product specifications (87.2%). A total of 24% were receiving an antipsychotic polytherapy pattern at baseline, frequently associated with lower or higher doses of antipsychotics than the recommended ones. Eight patients were taking clozapine, all in monotherapy. Males received higher doses of antipsychotic (P=.043). A total of 5.2% of the patients were being treated with long-acting injectable antipsychotics; 12.2% of the patients received anticholinergic drugs, 12.2% antidepressants, and 13.7% mood stabilizers, while almost 40% received benzodiazepines; and 35.52% reported at least one adverse drug reaction during the pharmacovigilance period, more frequently associated with higher antipsychotic doses and antipsychotic polytherapy (85.2% vs 45.5%, Psecurity issues, support future research of determinate pharmacological strategies for the treatment of early phases of psychosis, such as the role of clozapine, long-acting injectable antipsychotics, antipsychotic combination, and the use of benzodiazepines. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Lower hybrid wave accessibility as a means for current profile control

International Nuclear Information System (INIS)

Briffod, G.; Gormezano, C.; Parlange, F.; Van Houtte, D.

1986-01-01

Powerful ICRH experiments on JET and Neutral Beam Injection of various species on TFTR have recently confirmed the insensitivity of the temperature and safety factor profile shapes to the heating profile and the important role played by the sawtooth activity on the overall performances. In order to overcome these limitations, we propose in this paper, in a Tokamak operating at constant plasma current: to control the resistive part of the current by driving an H.F. current by Lower Hybrid Wave. To act on the current profile, with the constraint that q(o) > 1 by controlling the wave penetration. Constant plasma current Tokamak discharges in which a part of the current is driven by L.H.W. have been extensively studied on PETULA and this mode of operation has proven to be very efficient in stabilizing the sawtooth and M.H.D. activity

Safety and efficacy of elbasvir and grazoprevir for treatment of hepatitis C.

Science.gov (United States)

Carrion, Andres F; Martin, Paul

2016-06-01

The combination of elbasvir and grazoprevir in a single co-formulated tablet is highly effective for treatment of hepatitis C virus (HCV) infection. This regimen affords profound inhibition of NS3/4A protease and NS5A activity, resulting in potent activity against HCV genotypes 1, 4, and 6 with high rates of sustained virological response. This review covers the mechanism of action, pharmacokinetics, clinical applications, efficacy and safety profile of elbasvir/grazoprevir including special populations such as individuals with compensated and decompensated cirrhosis, HCV/HIV co-infection, advanced chronic kidney disease, and those that previously failed antiviral therapy. Elbasvir/grazoprevir is an effective antiviral regimen for treatment of genotypes 1 and 4 and has a very favorable safety profile based on extensive data from several pre-licensure clinical trials that included patient subgroups at increased risk of toxicity. This regimen is currently the only one licensed for use in individuals with advanced chronic kidney disease requiring hemodialysis.

Defining safety culture and the nexus between safety goals and safety culture. 4. Enhancing Safety Culture Through the Establishment of Safety Goals

International Nuclear Information System (INIS)

Tateiwa, Kenji; Miyata, Koichi; Yahagi, Kimitoshi

2001-01-01

Safety culture is the perception of each individual and organization of a nuclear power plant that safety is the first priority, and at Tokyo Electric Power Company (TEPCO), we have been practicing it in everyday activities. On the other hand, with the demand for competitiveness of nuclear power becoming even more intense these days, we need to pursue efficient management while maintaining the safety level at the same time. Below, we discuss how to achieve compatibility between safety culture and efficient management as well as enhance safety culture. Discussion at Tepco: safety culture-nurturing activities such as the following are being implemented: 1. informing the employees of the 'Declaration of Safety Promotion' by handing out brochures and posting it on the intranet home page; 2. publishing safety culture reports covering stories on safety culture of other industry sectors, recent movements on safety culture, etc.; 3. conducting periodic questionnaires to employees to grasp how deeply safety culture is being established; 4. carrying out educational programs to learn from past cases inside and outside the nuclear industry; 5. committing to common ownership of information with the public. The current status of safety culture in Japan sometimes seems to be biased to the quest of ultimate safety; rephrasing it, there have been few discussions regarding the sufficiency of the quantitative safety level in conjunction with the safety culture. Safety culture is one of the most crucial foundations guaranteeing the plant's safety, and for example, the plant safety level evaluated by probabilistic safety assessment (PSA) could be said to be valid only on the ground that a sound and sufficient safety culture exists. Although there is no doubt that the safety culture is a fundamental and important attitude of an individual and organization that keeps safety the first priority, the safety culture in itself should not be considered an obstruction to efforts to implement

Overall safety profile and effectiveness of tramadol hydrochloride/acetaminophen in patients with chronic noncancer pain in Japanese real-world practice.

Science.gov (United States)

Yoshizawa, K; Kawai, K; Fujie, M; Suzuki, J; Ogawa, Y; Yajima, T; Yokomori, J

2015-11-01

To evaluate the overall safety profile and clinical effectiveness of tramadol hydrochloride/acetaminophen (TA) combination tablets in Japanese patients with chronic noncancer pain unrelieved by non-opioid drugs for up to 12 weeks in real-world practice. This survey was a multicenter, prospective, longitudinal registry on the use of TA as a newly initiated pain treatment for chronic noncancer pain incurable by non-opioid analgesics that was conducted under the Good Post Marketing Study Practice regulation controlled by the Japan Ministry of Health, Labor and Welfare. Collected data included socio-demographics, treatment information, incidence of adverse drug reactions (ADRs), numerical rating scale for intensity of pain, EuroQol-5D (EQ-5D) scale, and physician's global impression (PGI) during the 12 week observation period. A total of 1316 patients were registered. ADRs were reported in 259 patients (20.5%); most events were nonserious (99.4%), including nausea (n = 87 [6.9%]), constipation (n = 63 [5.0%]), dizziness and somnolence (n = 29 [2.3%] each), and vomiting (n = 21 [1.7%]). No event related to drug dependence or respiratory depression was reported. In addition, 82.8% of patients showed acceptable effectiveness based on PGI at Week 4. Numerical rating scale for intensity of pain and EQ-5D utility scores were improved by -2.7 (SD 2.3) and 0.16 (SD 0.20) at Week 4, respectively, and the improvement was maintained until Week 12. This is a first report to evaluate the risk-benefit profile of TA in Japanese real-world practice using large size registry data. It is suggested that the favorable risk-benefit balance of TA was confirmed for patients with chronic noncancer pain unrelieved by non-opioid drugs in real-world practice. Limitations of this study were those inherent to open-label and non-interventional study designs. This registry survey is registered at umin.ac.jp (identifier: UMIN000015901).

Need for an "integrated safety assessment" of GMOs, linking food safety and environmental considerations.

Science.gov (United States)

Haslberger, Alexander G

2006-05-03

information. An integrated assessment might help to focus and save capacities in highly technical areas such as molecular characterization or profiling, which are often necessary for both assessments. In the area of establishing international standards for traded foods, such as for the newly created Standards in Trade and Development Facility (STDF), an integrated assessment might help in the consideration of important environmental aspects involved in health and food safety. Furthermore, an established integrated view on GMOs may create greater consumer confidence in the technology.

Modeling of passengers' safety perception for buses on mountainous roads.

Science.gov (United States)

Khoo, Hooi Ling; Ahmed, Muaid

2018-04-01

This study had developed a passenger safety perception model specifically for buses taking into consideration the various factors, namely driver characteristics, environmental conditions, and bus characteristics using Bayesian Network. The behaviour of bus driver is observed through the bus motion profile, measured in longitudinal, lateral, and vertical accelerations. The road geometry is recorded using GPS and is computed with the aid of the Google map while the perceived bus safety is rated by the passengers in the bus in real time. A total of 13 variables were derived and used in the model development. The developed Bayesian Network model shows that the type of bus and the experience of the driver on the investigated route could have an influence on passenger's perception of their safety on buses. Road geometry is an indirect influencing factor through the driver's behavior. The findings of this model are useful for the authorities to structure an effective strategy to improve the level of perceived bus safety. A high level of bus safety will definitely boost passenger usage confidence which will subsequently increase ridership. Copyright © 2018 Elsevier Ltd. All rights reserved.

Using resources for scientific-driven pharmacovigilance: from many product safety documents to one product safety master file.

Science.gov (United States)

Furlan, Giovanni

2012-08-01

Current regulations require a description of the overall safety profile or the specific risks of a drug in multiple documents such as the Periodic and Development Safety Update Reports, Risk Management Plans (RMPs) and Signal Detection Reports. In a resource-constrained world, the need for preparing multiple documents reporting the same information results in shifting the focus from a thorough scientific and medical evaluation of the available data to maintaining compliance with regulatory timelines. Since the aim of drug safety is to understand and characterize product issues to take adequate risk minimization measures rather than to comply with bureaucratic requirements, there is the need to avoid redundancy. In order to identify core drug safety activities that need to be undertaken to protect patient safety and reduce the number of documents reporting the results of these activities, the author has reviewed the main topics included in the drug safety guidelines and templates. The topics and sources that need to be taken into account in the main regulatory documents have been found to greatly overlap and, in the future, as a result of the new Periodic Safety Update Report structure and requirements, in the author's opinion this overlap is likely to further increase. Many of the identified inter-document differences seemed to be substantially formal. The Development Safety Update Report, for example, requires separate presentation of the safety issues emerging from different sources followed by an overall evaluation of each safety issue. The RMP, instead, requires a detailed description of the safety issues without separate presentation of the evidence derived from each source. To some extent, however, the individual documents require an in-depth analysis of different aspects; the RMP, for example, requires an epidemiological description of the indication for which the drug is used and its risks. At the time of writing this article, this is not specifically

Safety and Efficacy of D-Tagatose in Glycemic Control in Subjects with Type 2 Diabetes

OpenAIRE

Ensor, Mark; Banfield, Amy B.; Smith, Rebecca R.; Williams, Jarrod; Lodder, Robert A.

2014-01-01

The primary objectives of this study were to evaluate the treatment effect of D-tagatose on glycemic control, determined by a statistically significant decrease in hemoglobin A1c (HbA1c), and safety profile of D-tagatose compared to placebo. The secondary objectives were to evaluate the treatment effects on fasting blood glucose, insulin, lipid profiles, changes in BMI, and the proportion of subjects achieving HbA1c targets of

Efficacy and safety of tofacitinib in patients with active rheumatoid arthritis: review of key Phase 2 studies.

Science.gov (United States)

Fleischmann, Roy; Kremer, Joel; Tanaka, Yoshiya; Gruben, David; Kanik, Keith; Koncz, Tamas; Krishnaswami, Sriram; Wallenstein, Gene; Wilkinson, Bethanie; Zwillich, Samuel H; Keystone, Edward

2016-12-01

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Here, the safety and efficacy data from five Phase 2 studies of tofacitinib in patients with RA are summarized. Tofacitinib 1-30 mg twice daily was investigated, as monotherapy and in combination with methotrexate, in patients with RA. Tofacitinib 20 mg once daily was investigated in one study. Tofacitinib 5 and 10 mg twice daily were selected for investigation in Phase 3 studies; therefore, the efficacy and safety of tofacitinib 5 and 10 mg twice daily in Phase 2 studies are the focus of this review. Tofacitinib ≥ 5 mg twice daily was efficacious in a dose-dependent manner, with statistically significant and clinically meaningful reductions in the signs and symptoms of RA and patient-reported outcomes. The safety profile was consistent across studies. The efficacy and safety profile of tofacitinib in Phase 2 studies supported its further investigation and the selection of tofacitinib 5 mg twice daily and tofacitinib 10 mg twice daily for evaluation in Phase 3 studies. © 2016 The Authors. International Journal of Rheumatic Diseases published by Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Safety of Factor XIII Concentrate: Analysis of More than 20 Years of Pharmacovigilance Data

Science.gov (United States)

Solomon, Cristina; Korte, Wolfgang; Fries, Dietmar; Pendrak, Inna; Joch, Christine; Gröner, Albrecht; Birschmann, Ingvild

2016-01-01

Background Plasma-derived factor XIII (FXIII) concentrate is an effective treatment for FXIII deficiency. We describe adverse drug reactions (ADRs) reported during pharmacovigilance monitoring of Fibrogammin®/Corifact® and review published safety data. Methods Postmarketing safety reports recorded by CSL Behring from June 1993 to September 2013 were analyzed. Clinical studies published during the same period were also reviewed. Results Commercial data indicated that 1,653,450,333 IU FXIII concentrate were distributed over the review period, equivalent to 1,181,036 doses for a 70 kg patient. 75 cases were reported (one/15,700 standard doses or 22,046,000 IU). Reports of special interest included 12 cases of possible hypersensitivity reactions (one/98,400 doses or 137,787,500 IU), 7 with possible thromboembolic events (one/168,700 doses or 236,207,200 IU), 5 of possible inhibitor development (one/236,200 doses or 330,690,100 IU), and 20 of possible pathogen transmission (one/59,100 doses or 82,672,500 IU). 19 pathogen transmission cases involved viral infection; 4 could not be analyzed due to insufficient data, but for all others a causal relationship to the product was assessed as unlikely. A review of published literature revealed a similar safety profile. Conclusion Assessment of ADRs demonstrated that FXIII concentrate carries a low risk of ADRs across various clinical situations, suggesting a favorable safety profile. PMID:27781024

Low-profile stent system for treatment of atherosclerotic renal artery stenosis : The GREAT trial

NARCIS (Netherlands)

Sapoval, Marc; Zahringer, Markus; Pattynama, Peter; Rabbia, Claudio; Vignali, Claudio; Maleux, Geert; Boyer, Louis; Szczerbo-Trojanowska, Malgorzata; Jaschke, Werner; Hafsahl, Geir; Downes, Mark; Beregi, Jean Paul; Veeger, Nic; Talen, Aly

PURPOSE: The Palmaz Genesis Peripheral Stainless Steel Balloon Expandable Stent in Renal Artery Treatment (GREAT) Trial was designed to assess the safety and performance of a low-profile stent for the treatment of obstructive renal artery disease by looking at 6-month renal artery patency uniformly

Diagnostic development for current density profile control at KSTAR

Energy Technology Data Exchange (ETDEWEB)

Ko, J., E-mail: jinseok@nfri.re.kr [National Fusion Research Institute, Daejeon 34133 (Korea, Republic of); University of Science and Technology, Daejeon 34113 (Korea, Republic of); Chung, J. [National Fusion Research Institute, Daejeon 34133 (Korea, Republic of); Messmer, M.C.C. [Department of Applied Physics, Eindhoven University of Technology, Eindhoven (Netherlands)

2016-11-01

Highlights: • The motional Stark effect (MSE) diagnostic installed at KSTAR. • Engineering challenges and solutions on the design and fabrication of the front optics housing and filter modules. • Characterization of the bandpass filters and the responses to polarized light. - Abstract: The current density profile diagnostics are critical for the control of the steady-state burning plasma operations. A multi-channel motional Stark effect (MSE) diagnostic system has been implemented for the measurements of the internal magnetic field structures that constrain the magnetic equilibrium reconstruction to accurately produce the tokamak safety factor and current density profiles for the Korea Superconducting Tokamak Advanced Research (KSTAR). This work presents the design and fabrication of the front optics and the filter modules and the calibration activities for the MSE diagnostic at KSTAR.

The Sensitivity Analysis of Axial Pressure Tube Creep Profile for Dryout Power in PHWR

Energy Technology Data Exchange (ETDEWEB)

Ryu, Euiseung; Kim, Youngae [KHNP CRI, Daejeon (Korea, Republic of)

2016-10-15

The Stern Laboratory performed the CHF tests with only one axial pressure tube creep profile per 3.3%, 5.1% peak crept channel and made CHF correlation including creep factor from the CHF test results. Wolsong nuclear power plants also have utilized the same CHF correlation derived by CNL. Pressure tube diameter creep rate is function of fast neutron, coolant temperature, and coolant pressure in a channel. It means that various axial pressure tube creep profiles exist in PHWR due to the history of operating conditions. Usually, CHF correlation is used during ROP(Regional Overpower Protection) Trip Setpoint Analysis or Safety Analysis in PHWR. The sensitivity analysis for CHF effects using various creep profiles is needed. This paper summarizes the comparison results of dryout power between CHF test creep profile and estimated creep profiles of Wolsong units. The effect of axial pressure tube creep profile for dryout power in fuel channel is evaluated by using Stern Lab. CHF test creep profile and 380 channel creep profiles of Wolsong. The dryout powers at 3.3% and 5.1% test conditions are slightly smaller when using 380 Wolsong channels creep profiles. These also show that the simulated dryout powers maintain consistency regardless of flow conditions.

[Safety and efficacy of ketamine for pain relief].

Science.gov (United States)

Niesters, Marieke; Dahan, Albert; van Kleef, Maarten

2016-01-01

Intravenous ketamine treatment is frequently used for the management of chronic pain, especially in those patients who do not benefit from other therapies. In this commentary we discuss the efficacy of ketamine for relief of chronic pain and ketamine's safety profile. A review of the literature indicates that only a few studies show that intravenous ketamine has analgesic effects that persist beyond the infusion period, an effect that occurs in about two-thirds of patients. Ketamine has multiple safety issues, ranging from psychotomimetic and schizotypal symptoms, sympathetic stimulation, tachycardia and hypertension, and damage to the liver and the urogenital tract. Damage to the urogenital tract seems to be restricted to individuals who chronically abuse ketamine. We indicate the need for large randomized trials in which ketamine is compared with an 'active' placebo.

Measuring the safety culture in a hospital setting: a concept whose time has come?

Science.gov (United States)

Robb, Gillian; Seddon, Mary

2010-05-14

Getting the right 'patient safety culture' is thought to be an important component in improving patient safety in hospitals, however there is a lack of clarity in how best to measure and improve it, and whether such improvement actually translates to better patient outcomes. This paper reflects on the Counties Manukau District Health Board (CMDHB) experience with a patient safety survey and attempts to answer questions other organisations may ask when deciding whether to invest in such survey. A literature search was undertaken to identify valid and reliable patient safety culture survey tools. These were reviewed with respect to how best to interpret and use the results. If hospitals decide to undertake a patient safety culture survey, the recommended survey tools are the Safety Attitudes Questionnaire (SAQ) and the Hospital Survey on Patient Safety (HSOPS). Both have been widely used and have sound and comprehensive psychometrics. Only the SAQ has established links with patient safety outcomes such as reduced healthcare associated infections. Surveys can provide some insights into the patient safety culture within an organisation, but the opportunity costs of undertaking a survey should be carefully considered. Much of their value lies in raising the profile of patient safety and promoting conversations; making patient safety 'the way we do business around here'.

Coronary artery bypass grafting-related bleeding complications in patients treated with dual antiplatelet treatment

NARCIS (Netherlands)

Tomšič, Anton; Schotborgh, Mark A.; Manshanden, Johan S. J.; Li, Wilson W. L.; de Mol, Bas A. J. M.

2016-01-01

To evaluate the relationship between the timing of either ticagrelor or clopidogrel discontinuation and bleeding-related complications in patients undergoing isolated on-pump coronary artery bypass grafting (CABG). Between January 2012 and December 2014, 705 consecutive patients underwent isolated

Coronary artery bypass grafting-related bleeding complications in patients treated with dual antiplatelet treatment.

NARCIS (Netherlands)

Tomsic, A.; Schotborgh, M.A.; Manshanden, J.S.; Li, W.W.L.; Mol, B.A. de

2016-01-01

OBJECTIVES: To evaluate the relationship between the timing of either ticagrelor or clopidogrel discontinuation and bleeding-related complications in patients undergoing isolated on-pump coronary artery bypass grafting (CABG). METHODS: Between January 2012 and December 2014, 705 consecutive patients

Recurrent Acute Respiratory Infections in Children: Effectiveness and Safety of Phytotherapy

Directory of Open Access Journals (Sweden)

V. P. Vavilova

2015-01-01

Full Text Available Recurrent respiratory infections in children lead to physical development disorders, formation of chronic nidi of infection, failure of adaptive mechanisms and degradation o immunobiological resisting barriers; this causes development of new diseases. Results of the presented non interventional clinical study confirm high safety profile and effectiveness of a therapeutic phytopreparation for recurrent respiratory infections. 

Clinical Safety and Tolerability of Vildagliptin - Insights from Randomised Trials, Observational Studies and Post-marketing Surveillance.

Science.gov (United States)

Mathieu, Chantal; Kozlovski, Plamen; Paldánius, Päivi M; Foley, James E; Modgill, Vikas; Evans, Marc; Serban, Carmen

2017-08-01

Vildagliptin is one of the most extensively studied dipeptidyl peptidase-4 (DPP-4) inhibitors in terms of its clinical utility. Over the last decade, a vast panorama of evidence on the benefit-risk profile of vildagliptin has been generated in patients with type 2 diabetes mellitus (T2DM). In this article, we review the cumulative evidence on the safety of vildagliptin from the clinical development programme, as well as reports of rare adverse drug reactions detected during the post-marketing surveillance of the drug. Across clinical studies, the overall safety and tolerability profile of vildagliptin was similar to placebo, and it was supported by real-world data in a broad population of patients with T2DM, making DPP-4 inhibitors, like vildagliptin, a safe option for managing patients with T2DM.

Development of a Quality and Safety Competency Curriculum for Radiation Oncology Residency: An International Delphi Study

International Nuclear Information System (INIS)

Adleman, Jenna; Gillan, Caitlin; Caissie, Amanda; Davis, Carol-Anne; Liszewski, Brian; McNiven, Andrea; Giuliani, Meredith

2017-01-01

Purpose: To develop an entry-to-practice quality and safety competency profile for radiation oncology residency. Methods and Materials: A comprehensive list of potential quality and safety competency items was generated from public and professional resources and interprofessional focus groups. Redundant or out-of-scope items were eliminated through investigator consensus. Remaining items were subjected to an international 2-round modified Delphi process involving experts in radiation oncology, radiation therapy, and medical physics. During Round 1, each item was scored independently on a 9-point Likert scale indicating appropriateness for inclusion in the competency profile. Items indistinctly ranked for inclusion or exclusion were re-evaluated through web conference discussion and reranked in Round 2. Results: An initial 1211 items were compiled from 32 international sources and distilled to 105 unique potential quality and safety competency items. Fifteen of the 50 invited experts participated in round 1: 10 radiation oncologists, 4 radiation therapists, and 1 medical physicist from 13 centers in 5 countries. Round 1 rankings resulted in 80 items included, 1 item excluded, and 24 items indeterminate. Two areas emerged more prominently within the latter group: change management and human factors. Web conference with 5 participants resulted in 9 of these 24 items edited for content or clarity. In Round 2, 12 participants rescored all indeterminate items resulting in 10 items ranked for inclusion. The final 90 enabling competency items were organized into thematic groups consisting of 18 key competencies under headings adapted from Deming's System of Profound Knowledge. Conclusions: This quality and safety competency profile may inform minimum training standards for radiation oncology residency programs.

Development of a Quality and Safety Competency Curriculum for Radiation Oncology Residency: An International Delphi Study

Energy Technology Data Exchange (ETDEWEB)

Adleman, Jenna [Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Gillan, Caitlin [Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Caissie, Amanda [Department of Radiation Oncology, Dalhousie University, Halifax, Nova Scotia (Canada); Saint John Regional Hospital, Saint John, New Brunswick (Canada); Davis, Carol-Anne [Department of Radiation Oncology, Dalhousie University, Halifax, Nova Scotia (Canada); Nova Scotia Cancer Centre, Halifax, Nova Scotia (Canada); Liszewski, Brian [Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario (Canada); McNiven, Andrea [Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Giuliani, Meredith, E-mail: Meredith.Giuliani@rmp.uhn.ca [Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario (Canada)

2017-06-01

Purpose: To develop an entry-to-practice quality and safety competency profile for radiation oncology residency. Methods and Materials: A comprehensive list of potential quality and safety competency items was generated from public and professional resources and interprofessional focus groups. Redundant or out-of-scope items were eliminated through investigator consensus. Remaining items were subjected to an international 2-round modified Delphi process involving experts in radiation oncology, radiation therapy, and medical physics. During Round 1, each item was scored independently on a 9-point Likert scale indicating appropriateness for inclusion in the competency profile. Items indistinctly ranked for inclusion or exclusion were re-evaluated through web conference discussion and reranked in Round 2. Results: An initial 1211 items were compiled from 32 international sources and distilled to 105 unique potential quality and safety competency items. Fifteen of the 50 invited experts participated in round 1: 10 radiation oncologists, 4 radiation therapists, and 1 medical physicist from 13 centers in 5 countries. Round 1 rankings resulted in 80 items included, 1 item excluded, and 24 items indeterminate. Two areas emerged more prominently within the latter group: change management and human factors. Web conference with 5 participants resulted in 9 of these 24 items edited for content or clarity. In Round 2, 12 participants rescored all indeterminate items resulting in 10 items ranked for inclusion. The final 90 enabling competency items were organized into thematic groups consisting of 18 key competencies under headings adapted from Deming's System of Profound Knowledge. Conclusions: This quality and safety competency profile may inform minimum training standards for radiation oncology residency programs.

Profile of drowning victims in a coastal community.

Science.gov (United States)

Nichter, M A; Everett, P B

1989-02-01

Accidental drowning accounts for 15% of all accidental deaths in Pinellas County, Florida, and this study was conducted to better understand the epidemiologic profile of the victim. The medical examiner's records of 230 drownings in Pinellas County from January 1, 1983, through December 31, 1987, were reviewed for demographic and epidemiologic data. Bodies of salt water were the most common drowning site (47%), followed by swimming pools (22%), lakes (11%), baths (7%), and canals (6%). The drowning incidence for males was more than three times that for females. Drowning was endemic among boys less than five years of age (30/100,000/year). Fifty-nine percent of young adult victims had detectable postmortem blood alcohol levels. Drowning rates were highest among children less than five years and adults more than 80 years. Epidemiologic profiles of populations at risk and contributing factors are described and public safety measures are suggested.

Holes in the US nuclear safety net

International Nuclear Information System (INIS)

Utroska, D.

1987-01-01

Contrary to popular perception, the NRC has neither the authority nor the resources to comprehensively regulate the authority nor the resources to comprehensively regulate the nuclear power industry: it cannot check and monitor every nuclear plant in detail to assure reasonable reactor safety. This is widely understood within the power industry. After the Three Mile Island accident, the nuclear industry formed a group called the Institute of Nuclear Power Operations (INPO), based in Atlanta, Georgia. Its self-proclaimed mandate is to pick up the safety initiative where NRC regulations and reviews leave off; to make sure that each nuclear plant in the United States goes beyond compliance with minimum regulations and achieves excellence in safe and efficient performance. INPO's 1986 budget was $44 million, paid to the institute by electricity ratepayers via the nuclear utilities. Among other things, the money funds INPO's development of nuclear plant operating criteria and pays for plant inspections to determine if the standards are being met. INPO has deliberately maintained a low profile. INPO does not become involved in public or media activities on behalf of the industry or in the role of promoting the nuclear power option, the organization's formal institutional plan declares. A key aspect of INPO's public noninvolvement is keeping to itself and its members the results of its nuclear plant safety evaluations. Although consumers fund INPO activities and have a stake in nuclear plant safety, the press and the public are denied access to INPO safety investigation reports. 8 references

Post-licensure safety surveillance for human papillomavirus-16/18-AS04-adjuvanted vaccine: more than 4 years of experience.

Science.gov (United States)

Angelo, Maria-Genalin; Zima, Julia; Tavares Da Silva, Fernanda; Baril, Laurence; Arellano, Felix

2014-05-01

To summarise post-licensure safety surveillance over more than 4 years of routine use of the human papillomavirus-16/18-AS04-adjuvanted vaccine (HPV-16/18 vaccine: Cervarix®, GlaxoSmithKline, Belgium). We describe global post-licensure passive surveillance data based on routine pharmacovigilance from 18 May 2007 until 17 November 2011 and enhanced surveillance implemented during the 2-year national immunisation programme in the UK (school years 2008-2010). Spontaneous reports from countries worldwide showed a similar pattern for the most frequently reported adverse events after HPV-16/18 vaccination. No patterns or trends were observed for potential immune-mediated diseases after vaccination. Observed incidences of Bell's palsy and confirmed Guillain-Barré syndrome were within the expected range in the general population. Outcomes of pregnancy in women who were inadvertently exposed to HPV-16/18 vaccine during pregnancy, were in line with published reports for similar populations. Enhanced surveillance of adverse events in the UK triggered a review of cases of anaphylaxis, angioedema and syncope reports, leading to an update to the prescribing information. Collaborative partnerships between industry and national regulatory agencies facilitated rapid notification and transfer of safety information, allowing for rapid responses in the event of a safety signal of adverse event of concern. More than 4 years of post-licensure experience may provide confidence to providers and the public about the safety profile of HPV-16/18 vaccine in routine use. The safety profile appears to be consistent with pre-licensure data reporting that HPV-16/18 vaccine has an acceptable benefit-risk profile in adolescent girls and women. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.

ST-elevation acute coronary syndromes in the Platelet Inhibition and Patient Outcomes (PLATO) trial

DEFF Research Database (Denmark)

Armstrong, Paul W; Siha, Hany; Fu, Yuling

2012-01-01

Ticagrelor, when compared with clopidogrel, reduced the 12-month risk of vascular death/myocardial infarction and stroke in patients with ST-elevation acute coronary syndromes intended to undergo primary percutaneous coronary intervention in the PLATelet inhibition and patient Outcomes (PLATO...

GOLIMUMAB — A NEW TNF α-BLOCKER. THE REVIEW OF THE EFFICACY AND SAFETY EVALUATION RESULTS

Directory of Open Access Journals (Sweden)

R. V. Denisova

2012-01-01

Full Text Available The article represents the results of efficacy and safety evaluation of the human monoclonal antibodies — golimumab, according to the data of international multicenter randomized double-blind placebo-controlled trials, including patients with active stage of rheumatoid arthritis. It was shown, that golimumab was reliably more effective than placebo both when administered hypodermic and intravenous. The safety profile of golimumab is comparable to that of the other tumor necrosis factor alpha blockers. The review also contains information on the 3d phase of golimumab efficacy and safety research in patients with juvenile idiopathic arthritis.

Safety of licensed vaccines in HIV-infected persons: a systematic review protocol

Science.gov (United States)

2014-01-01

Background Safety of vaccines remains a cornerstone of building public trust on the use of these cost-effective and life-saving public health interventions. In some settings, particularly Sub-Saharan Africa, there is a high prevalence of HIV infection and a high burden of vaccine-preventable diseases. There is evidence suggesting that the immunity induced by some commonly used vaccines is not durable in HIV-infected persons, and therefore, repeated vaccination may be considered to ensure optimal vaccine-induced immunity in this population. However, some vaccines, particularly the live vaccines, may be unsafe in HIV-infected persons. There is lack of evidence on the safety profile of commonly used vaccines among HIV-infected persons. We are therefore conducting a systematic review to assess the safety profile of routine vaccines administered to HIV-infected persons. Methods/Design We will select studies conducted in any setting where licensed and effective vaccines were administered to HIV-infected persons. We will search for eligible studies in PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, Africa-Wide, PDQ-Evidence and CINAHL as well as reference lists of relevant publications. We will screen search outputs, select studies and extract data in duplicate, resolving discrepancies by discussion and consensus. Discussion Globally, immunisation is a major public health strategy to mitigate morbidity and mortality caused by various infectious disease-causing agents. In general, there are efforts to increase vaccination coverage worldwide, and for these efforts to be successful, safety of the vaccines is paramount, even among people living with HIV, who in some situations may require repeated vaccination. Results from this systematic review will be discussed in the context of the safety of routine vaccines among HIV-infected persons. From the safety perspective, we will also discuss whether repeat vaccination strategies may be

Nuclear safety culture and nuclear safety supervision

International Nuclear Information System (INIS)

Chai Jianshe

2013-01-01

In this paper, the author reviews systematically and summarizes up the development process and stage characteristics of nuclear safety culture, analysis the connotation and characteristics of nuclear safety culture, sums up the achievements of our country's nuclear safety supervision, dissects the challenges and problems of nuclear safety supervision. This thesis focused on the relationship between nuclear safety culture and nuclear safety supervision, they are essential differences, but there is a close relationship. Nuclear safety supervision needs to introduce some concepts of nuclear safety culture, lays emphasis on humanistic care and improves its level and efficiency. Nuclear safety supervision authorities must strengthen nuclear safety culture training, conduct the development of nuclear safety culture, make sure that nuclear safety culture can play significant roles. (author)

Analysis of National Major Work Safety Accidents in China, 2003-2012.

Science.gov (United States)

Ye, Yunfeng; Zhang, Siheng; Rao, Jiaming; Wang, Haiqing; Li, Yang; Wang, Shengyong; Dong, Xiaomei

2016-01-01

This study provides a national profile of major work safety accidents in China, which cause more than 10 fatalities per accident, intended to provide scientific basis for prevention measures and strategies to reduce major work safety accidents and deaths. Data from 2003-2012 Census of major work safety accidents were collected from State Administration of Work Safety System (SAWS). Published literature and statistical yearbook were also included to implement information. We analyzed the frequency of accidents and deaths, trend, geographic distribution and injury types. Additionally, we discussed the severity and urgency of emergency rescue by types of accidents. A total of 877 major work safety accidents were reported, resulting in 16,795 deaths and 9,183 injuries. The numbers of accidents and deaths, mortality rate and incidence of major accidents have declined in recent years. The mortality rate and incidence was 0.71 and 1.20 per 10(6) populations in 2012, respectively. Transportation and mining contributed to the highest number of major accidents and deaths. Major aviation and railway accidents caused more casualties per incident, while collapse, machinery, electrical shock accidents and tailing dam accidents were the most severe situation that resulted in bigger proportion of death. Ten years' major work safety accident data indicate that the frequency of accidents and number of eaths was declined and several safety concerns persist in some segments.

Immunogenicity of biologically-derived therapeutics: assessment and interpretation of nonclinical safety studies.

Science.gov (United States)

Ponce, Rafael; Abad, Leslie; Amaravadi, Lakshmi; Gelzleichter, Thomas; Gore, Elizabeth; Green, James; Gupta, Shalini; Herzyk, Danuta; Hurst, Christopher; Ivens, Inge A; Kawabata, Thomas; Maier, Curtis; Mounho, Barbara; Rup, Bonita; Shankar, Gopi; Smith, Holly; Thomas, Peter; Wierda, Dan

2009-07-01

An evaluation of potential antibody formation to biologic therapeutics during the course of nonclinical safety studies and its impact on the toxicity profile is expected under current regulatory guidance and is accepted standard practice. However, approaches for incorporating this information in the interpretation of nonclinical safety studies are not clearly established. Described here are the immunological basis of anti-drug antibody formation to biopharmaceuticals (immunogenicity) in laboratory animals, and approaches for generating and interpreting immunogenicity data from nonclinical safety studies of biotechnology-derived therapeutics to support their progression to clinical evaluation. We subscribe that immunogenicity testing strategies should be adapted to the specific needs of each therapeutic development program, and data generated from such analyses should be integrated with available clinical and anatomic pathology, pharmacokinetic, and pharmacodynamic data to properly interpret nonclinical studies.

Safety balance: Analysis of safety systems

International Nuclear Information System (INIS)

Delage, M.; Giroux, C.

1990-12-01

Safety analysis, and particularly analysis of exploitation of NPPs is constantly affected by EDF and by the safety authorities and their methodologies. Periodic safety reports ensure that important issues are not missed on daily basis, that incidents are identified and that relevant actions are undertaken. French safety analysis method consists of three principal steps. First type of safety balance is analyzed at the normal start-up phase for each unit including the final safety report. This enables analysis of behaviour of units ten years after their licensing. Second type is periodic operational safety analysis performed during a few years. Finally, the third step consists of safety analysis of the oldest units with the aim to improve the safety standards. The three steps of safety analysis are described in this presentation in detail with the aim to present the objectives and principles. Examples of most recent exercises are included in order to illustrate the importance of such analyses

Study of neurontin: titrate to effect, profile of safety (STEPS) trial: a narrative account of a gabapentin seeding trial.

Science.gov (United States)

Krumholz, Samuel D; Egilman, David S; Ross, Joseph S

2011-06-27

Seeding trials, clinical studies conducted by pharmaceutical companies for marketing purposes, have rarely been described in detail. We examined all documents relating to the clinical trial Study of Neurontin: Titrate to Effect, Profile of Safety (STEPS) produced during the Neurontin marketing, sales practices, and product liability litigation, including company internal and external correspondence, reports, and presentations, as well as depositions elicited in legal proceedings of Harden Manufacturing vs Pfizer and Franklin vs Warner-Lambert, most which were created between 1990 and 2009. Using a systematic search strategy, we identified and reviewed all documents related to the STEPS trial in order to identify key themes related to the trial's conduct and determine the extent of marketing involvement in its planning and implementation. Documents demonstrated that STEPS was a seeding trial posing as a legitimate scientific study. Documents consistently described the trial itself, not trial results, to be a marketing tactic in the company's marketing plans. Documents demonstrated that at least 2 external sources questioned the validity of the study before execution, and that data quality during the study was often compromised. Furthermore, documents described company analyses examining the impact of participating as a STEPS investigator on rates and dosages of gabapentin prescribing, finding a positive association. None of these findings were reported in 2 published articles. The STEPS trial was a seeding trial, used to promote gabapentin and increase prescribing among investigators, and marketing was extensively involved in its planning and implementation.

Safety evaluation of cosmetics in the EU. Reality and challenges for the toxicologist.

Science.gov (United States)

Pauwels, Marleen; Rogiers, Vera

2004-06-15

Council Directive 76/768/EEC, its seven amendments and 30 adaptations to technical progress form the basis of the cosmetic EU legislation today. There are actually four key principles for safety in the cosmetic legislation. (i) The full responsibility for the safety of cosmetics for human health is placed on the manufacturer, first importer in the EU or marketer. (ii) The safety evaluation of finished products is based on safety of individual ingredients, more specifically on their chemical structure, toxicological profile and their level of exposure. (iii) A compilation of information on each cosmetic product (dossier) must be kept readily available for inspection by the competent authorities of the Member State concerned. This information source, usually called a technical information file (TIF) or product information file/requirements (PIF(R)), contains, as the most important part, the safety assessment of the product undersigned by a competent safety assessor. (iv) The use of validated replacement alternative methods instead of animal testing forms the 4th key principle for safety of cosmetic products on the EU market. The 7th amendment imposes strict deadlines for the abolition of animal in vivo studies on cosmetic ingredients. These legal requirements induce a number of important challenges for the cosmetic industry and more specifically for the toxicologist involved as safety assessor.

A Systematic Review of the Safety of Lisdexamfetamine Dimesylate

OpenAIRE

Coghill, David R.; Caballero, Beatriz; Sorooshian, Shaw; Civil, Richard

2014-01-01

Background Here we review the safety and tolerability profile of lisdexamfetamine dimesylate (LDX), the first long-acting prodrug stimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD). Methods A PubMed search was conducted for English-language articles published up to 16 September 2013 using the following search terms: (lisdexamfetamine OR lisdexamphetamine OR SPD489 OR Vyvanse OR Venvanse OR NRP104 NOT review [publication type]). Results In short-term, parallel-group...

Patient safety in otolaryngology: a descriptive review.

Science.gov (United States)

Danino, Julian; Muzaffar, Jameel; Metcalfe, Chris; Coulson, Chris

2017-03-01

Human evaluation and judgement may include errors that can have disastrous results. Within medicine and healthcare there has been slow progress towards major changes in safety. Healthcare lags behind other specialised industries, such as aviation and nuclear power, where there have been significant improvements in overall safety, especially in reducing risk of errors. Following several high profile cases in the USA during the 1990s, a report titled "To Err Is Human: Building a Safer Health System" was published. The report extrapolated that in the USA approximately 50,000 to 100,000 patients may die each year as a result of medical errors. Traditionally otolaryngology has always been regarded as a "safe specialty". A study in the USA in 2004 inferred that there may be 2600 cases of major morbidity and 165 deaths within the specialty. MEDLINE via PubMed interface was searched for English language articles published between 2000 and 2012. Each combined two or three of the keywords noted earlier. Limitations are related to several generic topics within patient safety in otolaryngology. Other areas covered have been current relevant topics due to recent interest or new advances in technology. There has been a heightened awareness within the healthcare community of patient safety; it has become a major priority. Focus has shifted from apportioning blame to prevention of the errors and implementation of patient safety mechanisms in healthcare delivery. Type of Errors can be divided into errors due to action and errors due to knowledge or planning. In healthcare there are several factors that may influence adverse events and patient safety. Although technology may improve patient safety, it also introduces new sources of error. The ability to work with people allows for the increase in safety netting. Team working has been shown to have a beneficial effect on patient safety. Any field of work involving human decision-making will always have a risk of error. Within

Antiplatelet therapy in the primary prevention of cardiovascular disease in patients with chronic obstructive pulmonary disease: protocol of a randomised controlled proof-of-concept trial (APPLE COPD-ICON 2).

Science.gov (United States)

Kunadian, Vijay; Chan, Danny; Ali, Hani; Wilkinson, Nina; Howe, Nicola; McColl, Elaine; Thornton, Jared; von Wilamowitz-Moellendorff, Alexander; Holstein, Eva-Maria; Burns, Graham; Fisher, Andrew; Stocken, Deborah; De Soyza, Anthony

2018-05-26

The antiplatelet therapy in the primary prevention of cardiovascular disease in patients with chronic obstructive pulmonary disease (APPLE COPD-ICON2) trial is a prospective 2×2 factorial, double-blinded proof-of-concept randomised controlled trial targeting patients with chronic obstructive pulmonary disease (COPD) at high risk of cardiovascular disease. The primary goal of this trial is to investigate if treatment with antiplatelet therapy will produce the required response in platelet function measured using the Multiplate test in patients with COPD. Patients with COPD are screened for eligibility using inclusion and exclusion criteria. Eligible patients are randomised and allocated into one of four groups to receive aspirin plus placebo, ticagrelor plus placebo, aspirin plus ticagrelor or placebo only. Markers of systemic inflammation, platelet reactivity, arterial stiffness, carotid intima-media thickness (CIMT), lung function and quality of life questionnaires are assessed. The primary outcome consists of inhibition (binary response) of aspirin and ADP-induced platelet function at 6 months. Secondary outcomes include changes in inflammatory markers, CIMT, non-invasive measures of vascular stiffness, quality of life using questionnaires (EuroQol-five dimensions-five levels of perceived problems (EQ5D-5L), St. George's COPD questionnaire) and to record occurrence of repeat hospitalisation, angina, myocardial infarction or death from baseline to 6 months. Safety outcomes will be rates of major and minor bleeding, forced expiratory volume in 1 s, forced vital capacity and Medical Research Council dyspnoea scale. The study was approved by the North East-Tyne and Wear South Research Ethics Committee (15/NE/0155). Findings of the study will be presented in scientific sessions and published in peer-reviewed journals. ISRCTN43245574; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights

Forschungszentrum Rossendorf, Institute of Safety Research. Annual report 2003

Energy Technology Data Exchange (ETDEWEB)

NONE

2004-07-01

The work of the institute is directed to the assessment and enhancement of the safety of technical plants and to the increase of the efficiency and environmental sustainability of those facilities. Subjects of investigation are equally nuclear plants and installations of process industries. To achieve the goals mentioned, the institute is mainly engaged in the scientific fields of thermal fluid dynamics including magneto-hydrodynamics (MHD) and materials sciences. In 2003, the ISR worked on the following main scientific projects. Sub-programme: Plant and Rector Safety. Project: accident analysis of nuclear reactors, safety of materials and components, particle and radiation transport, safety and efficiency of chemical processes. Sub-programme: Thermal Fluid Dynamics. Project: magneto-hydrodynamics, thermal fluid dynamics of multiphase systems. Considerable progress could also be achieved in the CFD simulation of two-phase flows. New approaches for the forces acting on steam bubbles in a water flow could be developed and implemented into the CFX code in close cooperation with the CFX developer ANSYS/CFX. The qualified models allow to simulate the evolution of bubble size specific radial void distribution profiles along the flow path. These theoretical studies and the related experiments at the Rossendorf TOPFLOW test facility represent an important part of the German CFD network that aims at the improvement of thermal hydraulic calculation methods in reactor safety. (orig.)

Forschungszentrum Rossendorf, Institute of Safety Research. Annual report 2003

International Nuclear Information System (INIS)

2004-01-01

The work of the institute is directed to the assessment and enhancement of the safety of technical plants and to the increase of the efficiency and environmental sustainability of those facilities. Subjects of investigation are equally nuclear plants and installations of process industries. To achieve the goals mentioned, the institute is mainly engaged in the scientific fields of thermal fluid dynamics including magneto-hydrodynamics (MHD) and materials sciences. In 2003, the ISR worked on the following main scientific projects. Sub-programme: Plant and Rector Safety. Project: accident analysis of nuclear reactors, safety of materials and components, particle and radiation transport, safety and efficiency of chemical processes. Sub-programme: Thermal Fluid Dynamics. Project: magneto-hydrodynamics, thermal fluid dynamics of multiphase systems. Considerable progress could also be achieved in the CFD simulation of two-phase flows. New approaches for the forces acting on steam bubbles in a water flow could be developed and implemented into the CFX code in close cooperation with the CFX developer ANSYS/CFX. The qualified models allow to simulate the evolution of bubble size specific radial void distribution profiles along the flow path. These theoretical studies and the related experiments at the Rossendorf TOPFLOW test facility represent an important part of the German CFD network that aims at the improvement of thermal hydraulic calculation methods in reactor safety. (orig.)

Off-axis current drive and real-time control of current profile in JT-60U

International Nuclear Information System (INIS)

Suzuki, T.; Ide, S.; Oikawa, T.; Fujita, T.; Ishikawa, M.; Seki, M.; Matsunaga, G.; Hatae, T.; Naito, O.; Hamamatsu, K.; Sueoka, M.; Hosoyama, H.; Nakazato, M.

2008-01-01

Aiming at optimization of current profile in high-β plasmas for higher confinement and stability, a real-time control system of the minimum of the safety factor (q min ) using the off-axis current drive has been developed. The off-axis current drive can raise the safety factor in the centre and help to avoid instability that limits the performance of the plasma. The system controls the injection power of lower-hybrid waves, and hence its off-axis driven current in order to control q min . The real-time control of q min is demonstrated in a high-β plasma, where q min follows the temporally changing reference q min,ref from 1.3 to 1.7. Applying the control to another high-β discharge (β N = 1.7, β p = 1.5) with m/n = 2/1 neo-classical tearing mode (NTM), q min was raised above 2 and the NTM was suppressed. The stored energy increased by 16% with the NTM suppressed, since the resonant rational surface was eliminated. For the future use for current profile control, current density profile for off-axis neutral beam current drive (NBCD) is for the first time measured, using the motional Stark effect diagnostic. Spatially localized NBCD profile was clearly observed at the normalized minor radius ρ of about 0.6-0.8. The location was also confirmed by multi-chordal neutron emission profile measurement. The total amount of the measured beam driven current was consistent with the theoretical calculation using the ACCOME code. The CD location in the calculation was inward shifted than the measurement

Core radial power profile effect on system and core cooling behavior during reflood phase of PWR-LOCA with CCTF data

International Nuclear Information System (INIS)

Akimoto, Hajime; Iguchi, Tadashi; Murao, Yoshio

1985-01-01

In the reactor safety assessment during reflood phase of a PWR-LOCA, it is assumed implicitly that the core thermal hydraulic behavior is evaluated by the one-dimensional model with an average power rod. In order to assess the applicability of the one-dimensional treatment, integral tests were performed with various core radial power profiles using the Cylindrical Core Test Facility (CCTF) whose core includes about 2,000 heater rods. The CCTF results confirm that the core radial power profile has weak effect on the thermal hydraulic behavior in the primary system except core. It is also confirmed that the core differential pressure in the axial direction is predicted by the one-dimensional core model with an average power rod even in the case with a steep radial power profile in the core. Even though the core heat transfer coefficient is dependent on the core radial power profile, it is found that the error of the peak clad surface temperature calculation is less than 15 K using the one-dimensional model in the CCTF tests. The CCTF results support the one-dimensional treatment assumed in the reactor safety assessment. (author)

Profiling of high-frequency accident locations by use of association rules

OpenAIRE

GEURTS, Karolien; WETS, Geert; BRIJS, Tom; VANHOOF, Koen

2003-01-01

In Belgium, traffic safety is one of the government's highest priorities. The identification and profiling of black spots and black zones (geographical locations with high concentrations of traffic accidents) in terms of accident-related data and location characteristics must provide new insights into the complexity and causes of road accidents, which, in turn, provide valuable input for governmental actions. Association rules were used to identify accident-related circumstances that frequent...

An open, randomized, parallel-group study to compare the efficacy and safety profile of inhaled human insulin (exubera) with meformin as adjunctive therapy in patients with type 2 diabetes poorly controlled on a sulfonylurea: response to mikhail and cope

DEFF Research Database (Denmark)

Barnett, Anthony H.; Dreyer, Manfred; Lange, Peter

2006-01-01

OBJECTIVE: To compare the efficacy and safety profile of adding inhaled human insulin (INH; Exubera) or metformin to sulfonylurea monotherapy in patients with poorly controlled type 2 diabetes. RESEARCH DESIGN AND METHODS: We performed an open-label, parallel, 24-week, multicenter trial. At week -1......: In patients with type 2 diabetes poorly controlled on a sulfonylurea (A1C >9.5%), the addition of premeal INH significantly improves glycemic control compared with adjunctive metformin and is well tolerated....

Real-time control of the current density and pressure profiles in Jet

International Nuclear Information System (INIS)

Mazon, D.; Moreau, D.; Litaudon, X.; Joffrin, E.; Laborde, L.; Zabeo, L.; Crisanti, F.; Riva, M.; Felton, R.; Murari, A.; Tala, T.

2003-01-01

In order to ultimately control internal transport barriers during advanced operation scenarios, new algorithms using a truncated singular value decomposition of a linearized model operator have been implemented in the JET real-time controller, with the potentiality of retaining the distributed nature of plasma parameter profiles. First experiments using the simplest, lumped-parameter, version of this technique have been dedicated to the feedback control of the current density profile in a negative shear plasma using three heating and current drive actuators, namely neutral beam injection (NBI), ion cyclotron resonant frequency heating (ICRH) and lower hybrid current drive (LHCD). Successful control of the safety factor profile has been achieved on the time scale of the current redistribution time, first during an extended preheat phase with only LHCD as actuator and, then, in quasi steady-state conditions during the main heating phase of a discharge, using the three heating and current drive actuators

Evolution of the electron temperature profile of ohmically heated plasmas in TFTR

International Nuclear Information System (INIS)

Taylor, G.; Efthimion, P.C.; Arunasalam, V.

1985-08-01

Blackbody electron cyclotron emission was used to ascertain and study the evolution and behavior of the electron temperature profile in ohmically heated plasmas in the Tokamak Fusion Test Reactor (TFTR). The emission was measured with absolutely calibrated millimeter wavelength radiometers. The temperature profile normalized to the central temperature and minor radius is observed to broaden substantially with decreasing limiter safety factor q/sub a/, and is insensitive to the plasma minor radius. Sawtooth activity was seen in the core of most TFTR discharges and appeared to be associated with a flattening of the electron temperature profile within the plasma core where q less than or equal to 1. Two types of sawtooth behavior were identified in large TFTR plasmas (minor radius, a less than or equal to 0.8 m) : a typically 35 to 40 msec period ''normal'' sawtooth, and a ''compound'' sawtooth with 70 to 80 msec period

Airbag 2000: 5th international symposium on sophisticated car occupant safety systems

Energy Technology Data Exchange (ETDEWEB)

Ziegahn, K F [ed.

2000-07-01

Modern concepts for the protection of passengers in vehicles provide the optimal degree of safety. The most well known and technically mature system is the airbag, which uses chemical gas generators, for which the dependability and service life demands are significant. All features of the system must be directly appropriate to the profile of the passenger. (AKF)

Safety margins in deterministic safety analysis

International Nuclear Information System (INIS)

Viktorov, A.

2011-01-01

The concept of safety margins has acquired certain prominence in the attempts to demonstrate quantitatively the level of the nuclear power plant safety by means of deterministic analysis, especially when considering impacts from plant ageing and discovery issues. A number of international or industry publications exist that discuss various applications and interpretations of safety margins. The objective of this presentation is to bring together and examine in some detail, from the regulatory point of view, the safety margins that relate to deterministic safety analysis. In this paper, definitions of various safety margins are presented and discussed along with the regulatory expectations for them. Interrelationships of analysis input and output parameters with corresponding limits are explored. It is shown that the overall safety margin is composed of several components each having different origins and potential uses; in particular, margins associated with analysis output parameters are contrasted with margins linked to the analysis input. While these are separate, it is possible to influence output margins through the analysis input, and analysis method. Preserving safety margins is tantamount to maintaining safety. At the same time, efficiency of operation requires optimization of safety margins taking into account various technical and regulatory considerations. For this, basic definitions and rules for safety margins must be first established. (author)

Development of the safety evaluation system in the respects of organizational factors and workers' consciousness. Pt. 1. Study of validities of functions for necessary evaluation and results obtained

International Nuclear Information System (INIS)

Takano, Kenichi; Tsuge, Tadafumi; Hasegawa, Naoko; Hirose, Ayako; Sasou, Kunihide

2002-01-01

CRIEPI decided to develop the safety evaluation system to investigate the safety level of the industrial sites due to questionnaires of organizational climate, safety managements, and workers' safety consciousness to workers. This report describes the questionnaire survey to apply to the domestic nuclear power plant for using obtained results as a fundamental data in order to construct the safety evaluation system. This system will be used for promoting safety culture in organizations of nuclear power plants. The questionnaire survey was conducted to 14 nuclear power stations for understanding the present status relating to safety issues. This questionnaire involves 122 items classified into following three categories: (1) safety awareness and behavior of plant personnel; (2) safety management; (3) organizational climate, based on the model considering contributing factor groups to safety culture. Obtained results were analyzed by statistical method to prepare functions of evaluation. Additionally, by applying a multivariate analysis, it was possible to extract several crucial factors influencing safety performance and to find a comprehensive safety indicator representing total organizational safety level. Significant relations were identified between accident rates (both labor accidents and facility failures) and above comprehensive safety indicator. Next, 122 questionnaire items were classified into 20 major safety factors to grasp the safety profiles of each site. This profile is considered as indicating the features of each site and also indicating the direction of progress for improvement of safety situation in the site. These findings can be reflected in developing the safety evaluation system, by confirming the validity of the evaluation method and giving specific functions. (author)

Ecological Design of Cooperative Human-Machine Interfaces for Safety of Intelligent Transport Systems

Directory of Open Access Journals (Sweden)

Orekhov Aleksandr

2016-01-01

Full Text Available The paper describes research results in the domain of cooperative intelligent transport systems. The requirements for human-machine interface considering safety issue of for intelligent transport systems (ITSare analyzed. Profiling of the requirements to cooperative human-machine interface (CHMI for such systems including requirements to usability and safety is based on a set of standards for ITSs. An approach and design technique of cooperative human-machine interface for ITSs are suggested. The architecture of cloud-based CHMI for intelligent transport systems has been developed. The prototype of software system CHMI4ITSis described.

A Test Suite for Safety-Critical Java using JML

DEFF Research Database (Denmark)

Ravn, Anders Peter; Søndergaard, Hans

2013-01-01

Development techniques are presented for a test suite for the draft specification of the Java profile for Safety-Critical Systems. Distinguishing features are: specification of conformance constraints in the Java Modeling Language, encoding of infrastructure concepts without implementation bias......, and corresponding specifications of implicitly stated behavioral and real-time properties. The test programs are auto-generated from the specification, while concrete values for test parameters are selected manually. The suite is open source and publicly accessible....

System safety education focused on flight safety

Science.gov (United States)

Holt, E.

1971-01-01

The measures necessary for achieving higher levels of system safety are analyzed with an eye toward maintaining the combat capability of the Air Force. Several education courses were provided for personnel involved in safety management. Data include: (1) Flight Safety Officer Course, (2) Advanced Safety Program Management, (3) Fundamentals of System Safety, and (4) Quantitative Methods of Safety Analysis.

Labor unions and safety climate: perceived union safety values and retail employee safety outcomes.

Science.gov (United States)

Sinclair, Robert R; Martin, James E; Sears, Lindsay E

2010-09-01

Although trade unions have long been recognized as a critical advocate for employee safety and health, safety climate research has not paid much attention to the role unions play in workplace safety. We proposed a multiple constituency model of workplace safety which focused on three central safety stakeholders: top management, ones' immediate supervisor, and the labor union. Safety climate research focuses on management and supervisors as key stakeholders, but has not considered whether employee perceptions about the priority their union places on safety contributes contribute to safety outcomes. We addressed this gap in the literature by investigating unionized retail employee (N=535) perceptions about the extent to which their top management, immediate supervisors, and union valued safety. Confirmatory factor analyses demonstrated that perceived union safety values could be distinguished from measures of safety training, workplace hazards, top management safety values, and supervisor values. Structural equation analyses indicated that union safety values influenced safety outcomes through its association with higher safety motivation, showing a similar effect as that of supervisor safety values. These findings highlight the need for further attention to union-focused measures related to workplace safety as well as further study of retail employees in general. We discuss the practical implications of our findings and identify several directions for future safety research. 2009 Elsevier Ltd. All rights reserved.

An update on safety and immunogenicity of vaccines containing emulsion-based adjuvants.

Science.gov (United States)

Fox, Christopher B; Haensler, Jean

2013-07-01

With the exception of alum, emulsion-based vaccine adjuvants have been administered to far more people than any other adjuvant, especially since the 2009 H1N1 influenza pandemic. The number of clinical safety and immunogenicity evaluations of vaccines containing emulsion adjuvants has correspondingly mushroomed. In this review, the authors introduce emulsion adjuvant composition and history before detailing the most recent findings from clinical and postmarketing data regarding the effects of emulsion adjuvants on vaccine immunogenicity and safety, with emphasis on the most widely distributed emulsion adjuvants, MF59® and AS03. The authors also present a summary of other emulsion adjuvants in clinical development and indicate promising avenues for future emulsion-based adjuvant development. Overall, emulsion adjuvants have demonstrated potent adjuvant activity across a number of disease indications along with acceptable safety profiles.

Safety Culture Enhancement Project. Final Report. A Field Study on Approaches to Enhancement of Safety Culture

Energy Technology Data Exchange (ETDEWEB)

Lowe, Andrew; Hayward, Brent (Dedale Asia Pacific, Albert Park VIC 3206 (Australia))

2006-08-15

results of the Safety Culture Perceptions Questionnaire conducted with site managers to access their opinions about the adequacy of the local safety culture; - a framework of safety-related competencies for managers, representing desirable actions for leading and promoting a positive safety culture; - results of an evaluation survey completed by participants at the conclusion of the Management Workshops to assess the utility of this activity. Section 4 of the report, Recommendations for Future Action, highlights nine proposed activities that could be undertaken to build on the outcomes from this project, to support the enhancement of safety culture within the Swedish nuclear industry in the longer term. Specifically, these recommendations propose actions to: 1. Introduce formal processes to ensure the ongoing development of safety related competencies amongst industry managers. 2. Strengthen the resources, contribution, value and profile of Man Technology Organisation (MTO) expertise within nuclear industry sites, in order to promote a better understanding of human performance issues, enhance error management and accident prevention capabilities. 3. Identify ways to embed existing positive safety culture attributes, in an environment of considerable workforce changes resulting from increasing use of contractors and (expected) retirements amongst an ageing industry employee population. 4. Standardise and improve aspects of incident and accident investigation processes and analysis methodologies currently used, to improve information sharing and optimise learning. 5. Implement harmonised MTO / human factors awareness training programs at appropriate levels for all nuclear industry personnel. 6. Formalise the application of applied teamwork training (as per the principles of Crew Resource Management training in aviation) for NPP Control Room Operators, Maintenance workers and other employees working in safety-critical teams. 7. Increase the use of simulation training to

Linking Safety Analysis to Safety Requirements

DEFF Research Database (Denmark)

Hansen, Kirsten Mark

Software for safety critical systems must deal with the hazards identified by safety analysistechniques: Fault trees, event trees,and cause consequence diagrams can be interpreted as safety requirements and used in the design activity. We propose that the safety analysis and the system design use...

Safety of Research Reactors. Safety Requirements

International Nuclear Information System (INIS)

2010-01-01

The main objective of this Safety Requirements publication is to provide a basis for safety and a basis for safety assessment for all stages in the lifetime of a research reactor. Another objective is to establish requirements on aspects relating to regulatory control, the management of safety, site evaluation, design, operation and decommissioning. Technical and administrative requirements for the safety of research reactors are established in accordance with these objectives. This Safety Requirements publication is intended for use by organizations engaged in the site evaluation, design, manufacturing, construction, operation and decommissioning of research reactors as well as by regulatory bodies

Cardiovascular and heart failure safety profile of vildagliptin: a meta-analysis of 17 000 patients.

Science.gov (United States)

McInnes, G; Evans, M; Del Prato, S; Stumvoll, M; Schweizer, A; Lukashevich, V; Shao, Q; Kothny, W

2015-11-01

To report the cardiovascular (CV) safety profile and heart failure (HF) risk of vildagliptin from a large pool of studies, including trials in high-risk patients with type 2 diabetes mellitus (T2DM), such as those with congestive HF and/or moderate/severe renal impairment. We conducted a retrospective meta-analysis of prospectively adjudicated CV events. Patient-level data were pooled from 40 double-blind, randomized controlled phase III and IV vildagliptin studies. The primary endpoint was occurrence of major adverse CV events (MACEs; myocardial infarction, stroke and CV death). Assessments of the individual MACE components and HF events (requiring hospitalization or new onset) were secondary endpoints. The risk ratio (RR) of vildagliptin (50 mg once- and twice-daily combined) versus comparators (placebo and all non-vildagliptin treatments) was calculated using the Mantel-Haenszel (M-H) method. Of the 17 446 patients, 9599 received vildagliptin (9251.4 subject-years of exposure) and 7847 received comparators (7317.0 subject-years of exposure). The mean age of the patients was 57 years, body mass index 30.5 kg/m(2) (nearly 50% obese), glycated haemoglobin concentration 8.1% and T2DM duration 5.5 years. A MACE occurred in 83 (0.86%) vildagliptin-treated patients and 85 (1.20%) comparator-treated patients, with an M-H RR of 0.82 [95% confidence interval (CI) 0.61-1.11]. Similar RRs were observed for the individual events. Confirmed HF events were reported in 41 (0.43%) vildagliptin-treated patients and 32 (0.45%) comparator-treated patients, with an M-H RR 1.08 (95% CI 0.68-1.70). This large meta-analysis indicates that vildagliptin is not associated with an increased risk of adjudicated MACEs relative to comparators. Moreover, this analysis did not find a significant increased risk of HF in vildagliptin-treated patients. © 2015 John Wiley & Sons Ltd.

Analysis of National Major Work Safety Accidents in China, 2003–2012

Science.gov (United States)

YE, Yunfeng; ZHANG, Siheng; RAO, Jiaming; WANG, Haiqing; LI, Yang; WANG, Shengyong; DONG, Xiaomei

2016-01-01

Background: This study provides a national profile of major work safety accidents in China, which cause more than 10 fatalities per accident, intended to provide scientific basis for prevention measures and strategies to reduce major work safety accidents and deaths. Methods: Data from 2003–2012 Census of major work safety accidents were collected from State Administration of Work Safety System (SAWS). Published literature and statistical yearbook were also included to implement information. We analyzed the frequency of accidents and deaths, trend, geographic distribution and injury types. Additionally, we discussed the severity and urgency of emergency rescue by types of accidents. Results: A total of 877 major work safety accidents were reported, resulting in 16,795 deaths and 9,183 injuries. The numbers of accidents and deaths, mortality rate and incidence of major accidents have declined in recent years. The mortality rate and incidence was 0.71 and 1.20 per 106 populations in 2012, respectively. Transportation and mining contributed to the highest number of major accidents and deaths. Major aviation and railway accidents caused more casualties per incident, while collapse, machinery, electrical shock accidents and tailing dam accidents were the most severe situation that resulted in bigger proportion of death. Conclusion: Ten years’ major work safety accident data indicate that the frequency of accidents and number of eaths was declined and several safety concerns persist in some segments. PMID:27057515

Role of newly formed platelets in thrombus formation in rat after clopidogrel treatment

DEFF Research Database (Denmark)

Kuijpers, Marijke J E; Megens, Remco T A; Nikookhesal, Elham

2011-01-01

Platelet P2Y₁₂ receptors play an important role in arterial thrombosis by stimulating thrombus growth. Both irreversibly (clopidogrel) and reversibly binding (ticagrelor, AZD6140) P2Y₁₂ antagonists are clinically used for restricted periods, but possible differences in platelet function recovery ...

Flupyradifurone: a brief profile of a new butenolide insecticide

Science.gov (United States)

Nauen, Ralf; Jeschke, Peter; Velten, Robert; Beck, Michael E; Ebbinghaus-Kintscher, Ulrich; Thielert, Wolfgang; Wölfel, Katharina; Haas, Matthias; Kunz, Klaus; Raupach, Georg

2015-01-01

BACKGROUND The development and commercialisation of new chemical classes of insecticides for efficient crop protection measures against destructive invertebrate pests is of utmost importance to overcome resistance issues and to secure sustainable crop yields. Flupyradifurone introduced here is the first representative of the novel butenolide class of insecticides active against various sucking pests and showing an excellent safety profile. RESULTS The discovery of flupyradifurone was inspired by the butenolide scaffold in naturally occurring stemofoline. Flupyradifurone acts reversibly as an agonist on insect nicotinic acetylcholine receptors but is structurally different from known agonists, as shown by chemical similarity analysis. It shows a fast action on a broad range of sucking pests, as demonstrated in laboratory bioassays, and exhibits excellent field efficacy on a number of crops with different application methods, including foliar, soil, seed treatment and drip irrigation. It is readily taken up by plants and translocated in the xylem, as demonstrated by phosphor imaging analysis. Flupyradifurone is active on resistant pests, including cotton whiteflies, and is not metabolised by recombinantly expressed CYP6CM1, a cytochrome P450 conferring metabolic resistance to neonicotinoids and pymetrozine. CONCLUSION The novel butenolide insecticide flupyradifurone shows unique properties and will become a new tool for integrated pest management around the globe, as demonstrated by its insecticidal, ecotoxicological and safety profile. © 2014 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. PMID:25351824

Sources of Safety Data and Statistical Strategies for Design and Analysis: Postmarket Surveillance.

Science.gov (United States)

Izem, Rima; Sanchez-Kam, Matilde; Ma, Haijun; Zink, Richard; Zhao, Yueqin

2018-03-01

Safety data are continuously evaluated throughout the life cycle of a medical product to accurately assess and characterize the risks associated with the product. The knowledge about a medical product's safety profile continually evolves as safety data accumulate. This paper discusses data sources and analysis considerations for safety signal detection after a medical product is approved for marketing. This manuscript is the second in a series of papers from the American Statistical Association Biopharmaceutical Section Safety Working Group. We share our recommendations for the statistical and graphical methodologies necessary to appropriately analyze, report, and interpret safety outcomes, and we discuss the advantages and disadvantages of safety data obtained from passive postmarketing surveillance systems compared to other sources. Signal detection has traditionally relied on spontaneous reporting databases that have been available worldwide for decades. However, current regulatory guidelines and ease of reporting have increased the size of these databases exponentially over the last few years. With such large databases, data-mining tools using disproportionality analysis and helpful graphics are often used to detect potential signals. Although the data sources have many limitations, analyses of these data have been successful at identifying safety signals postmarketing. Experience analyzing these dynamic data is useful in understanding the potential and limitations of analyses with new data sources such as social media, claims, or electronic medical records data.

Pre-clinical efficacy and safety of experimental vaccines based on non-replicating vaccinia vectors against yellow fever.

Directory of Open Access Journals (Sweden)

Birgit Schäfer

Full Text Available BACKGROUND: Currently existing yellow fever (YF vaccines are based on the live attenuated yellow fever virus 17D strain (YFV-17D. Although, a good safety profile was historically attributed to the 17D vaccine, serious adverse events have been reported, making the development of a safer, more modern vaccine desirable. METHODOLOGY/PRINCIPAL FINDINGS: A gene encoding the precursor of the membrane and envelope (prME protein of the YFV-17D strain was inserted into the non-replicating modified vaccinia virus Ankara and into the D4R-defective vaccinia virus. Candidate vaccines based on the recombinant vaccinia viruses were assessed for immunogenicity and protection in a mouse model and compared to the commercial YFV-17D vaccine. The recombinant live vaccines induced γ-interferon-secreting CD4- and functionally active CD8-T cells, and conferred full protection against lethal challenge already after a single low immunization dose of 10(5 TCID(50. Surprisingly, pre-existing immunity against wild-type vaccinia virus did not negatively influence protection. Unlike the classical 17D vaccine, the vaccinia virus-based vaccines did not cause mortality following intracerebral administration in mice, demonstrating better safety profiles. CONCLUSIONS/SIGNIFICANCE: The non-replicating recombinant YF candidate live vaccines induced a broad immune response after single dose administration, were effective even in the presence of a pre-existing immunity against vaccinia virus and demonstrated an excellent safety profile in mice.

Pre-Clinical Efficacy and Safety of Experimental Vaccines Based on Non-Replicating Vaccinia Vectors against Yellow Fever

Science.gov (United States)

Schäfer, Birgit; Holzer, Georg W.; Joachimsthaler, Alexandra; Coulibaly, Sogue; Schwendinger, Michael; Crowe, Brian A.; Kreil, Thomas R.; Barrett, P. Noel; Falkner, Falko G.

2011-01-01

Background Currently existing yellow fever (YF) vaccines are based on the live attenuated yellow fever virus 17D strain (YFV-17D). Although, a good safety profile was historically attributed to the 17D vaccine, serious adverse events have been reported, making the development of a safer, more modern vaccine desirable. Methodology/Principal Findings A gene encoding the precursor of the membrane and envelope (prME) protein of the YFV-17D strain was inserted into the non-replicating modified vaccinia virus Ankara and into the D4R-defective vaccinia virus. Candidate vaccines based on the recombinant vaccinia viruses were assessed for immunogenicity and protection in a mouse model and compared to the commercial YFV-17D vaccine. The recombinant live vaccines induced γ-interferon-secreting CD4- and functionally active CD8-T cells, and conferred full protection against lethal challenge already after a single low immunization dose of 105 TCID50. Surprisingly, pre-existing immunity against wild-type vaccinia virus did not negatively influence protection. Unlike the classical 17D vaccine, the vaccinia virus-based vaccines did not cause mortality following intracerebral administration in mice, demonstrating better safety profiles. Conclusions/Significance The non-replicating recombinant YF candidate live vaccines induced a broad immune response after single dose administration, were effective even in the presence of a pre-existing immunity against vaccinia virus and demonstrated an excellent safety profile in mice. PMID:21931732

Elucidation of xenobiotic metabolism pathways in human skin and human skin models by proteomic profiling.

Directory of Open Access Journals (Sweden)

Sven van Eijl

Full Text Available BACKGROUND: Human skin has the capacity to metabolise foreign chemicals (xenobiotics, but knowledge of the various enzymes involved is incomplete. A broad-based unbiased proteomics approach was used to describe the profile of xenobiotic metabolising enzymes present in human skin and hence indicate principal routes of metabolism of xenobiotic compounds. Several in vitro models of human skin have been developed for the purpose of safety assessment of chemicals. The suitability of these epidermal models for studies involving biotransformation was assessed by comparing their profiles of xenobiotic metabolising enzymes with those of human skin. METHODOLOGY/PRINCIPAL FINDINGS: Label-free proteomic analysis of whole human skin (10 donors was applied and analysed using custom-built PROTSIFT software. The results showed the presence of enzymes with a capacity for the metabolism of alcohols through dehydrogenation, aldehydes through dehydrogenation and oxidation, amines through oxidation, carbonyls through reduction, epoxides and carboxylesters through hydrolysis and, of many compounds, by conjugation to glutathione. Whereas protein levels of these enzymes in skin were mostly just 4-10 fold lower than those in liver and sufficient to support metabolism, the levels of cytochrome P450 enzymes were at least 300-fold lower indicating they play no significant role. Four epidermal models of human skin had profiles very similar to one another and these overlapped substantially with that of whole skin. CONCLUSIONS/SIGNIFICANCE: The proteomics profiling approach was successful in producing a comprehensive analysis of the biotransformation characteristics of whole human skin and various in vitro skin models. The results show that skin contains a range of defined enzymes capable of metabolising different classes of chemicals. The degree of similarity of the profiles of the in vitro models indicates their suitability for epidermal toxicity testing. Overall, these

C-Band Airport Surface Communications System Engineering-Initial High-Level Safety Risk Assessment and Mitigation

Science.gov (United States)

Zelkin, Natalie; Henriksen, Stephen

2011-01-01

This document is being provided as part of ITT's NASA Glenn Research Center Aerospace Communication Systems Technical Support (ACSTS) contract: "New ATM Requirements--Future Communications, C-Band and L-Band Communications Standard Development." ITT has completed a safety hazard analysis providing a preliminary safety assessment for the proposed C-band (5091- to 5150-MHz) airport surface communication system. The assessment was performed following the guidelines outlined in the Federal Aviation Administration Safety Risk Management Guidance for System Acquisitions document. The safety analysis did not identify any hazards with an unacceptable risk, though a number of hazards with a medium risk were documented. This effort represents an initial high-level safety hazard analysis and notes the triggers for risk reassessment. A detailed safety hazards analysis is recommended as a follow-on activity to assess particular components of the C-band communication system after the profile is finalized and system rollout timing is determined. A security risk assessment has been performed by NASA as a parallel activity. While safety analysis is concerned with a prevention of accidental errors and failures, the security threat analysis focuses on deliberate attacks. Both processes identify the events that affect operation of the system; and from a safety perspective the security threats may present safety risks.

Efficacy and safety of fixed-ratio combination of insulin degludec and liraglutide (IDegLira) for the treatment of type 2 diabetes

DEFF Research Database (Denmark)

Vedtofte, Louise; Knop, Filip K; Vilsbøll, Tina

2017-01-01

to tackle the progressive nature of T2D. Areas covered: The efficacy and safety profile of IDegLira - a once-daily, fixed-ratio combination of insulin degludec and liraglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), for the treatment of T2D - has been extensively evaluated. IDegLira's phase 3......INTRODUCTION: Type 2 diabetes (T2D) is a progressive disease with increasing prevalence in most countries. The majority of patients with T2D have inadequate glycaemic control, which increases the risk of diabetic complications later in life. New therapies with improved safety profiles are required...... addition and titration of the individual agents in the management of T2D....

Human health safety evaluation of cosmetics in the EU: A legally imposed challenge to science

International Nuclear Information System (INIS)

Pauwels, M.; Rogiers, V.

2010-01-01

As stated in the European legislation, cosmetic products present on the European market must be safe for the consumer. Safety evaluation of the products is carried out by a qualified safety assessor who needs to consider potential exposure scenarios next to the physicochemical and toxicological profiles of all composing ingredients. Whereas, until recently, the tools to determine the toxicological profile of cosmetic ingredients mainly consisted of animal experiments, they have now been narrowed down substantially by the legally imposed animal testing ban on cosmetic ingredients, taken up in the Cosmetic Products Directive (76/768/EEC). This Directive, however, is not a stand-alone piece of European legislation, since as well directly as indirectly it is influenced by a complex web of related legislations. Vertical legislations deal with different categories of chemicals, including dangerous substances, biocides, plant protection products, food additives, medicinal products, and of course also cosmetics. Horizontal legislative texts, on the contrary, cover more general fields such as protection of experimental animals, consumer product safety, misleading of consumers, specific provisions for aerosols, and others. Experience has learnt that having a general overview of these related legislations is necessary to understand their impact on the cosmetic world in general terms and on cosmetic safety evaluation in particular. This goes for a variety of concerned parties, including national and European regulators/agencies, contract laboratories, raw material suppliers, cosmetic companies, research and educational centers. They all deal with a number of aspects important for the quality and toxicity of cosmetics and their ingredients. This review summarises the most relevant points of the legislative texts of different types of product categories and emphasises their impact on the safety evaluation of cosmetics.

Human health safety evaluation of cosmetics in the EU: a legally imposed challenge to science.

Science.gov (United States)

Pauwels, M; Rogiers, V

2010-03-01

As stated in the European legislation, cosmetic products present on the European market must be safe for the consumer. Safety evaluation of the products is carried out by a qualified safety assessor who needs to consider potential exposure scenarios next to the physicochemical and toxicological profiles of all composing ingredients. Whereas, until recently, the tools to determine the toxicological profile of cosmetic ingredients mainly consisted of animal experiments, they have now been narrowed down substantially by the legally imposed animal testing ban on cosmetic ingredients, taken up in the Cosmetic Products Directive (76/768/EEC). This Directive, however, is not a stand-alone piece of European legislation, since as well directly as indirectly it is influenced by a complex web of related legislations. Vertical legislations deal with different categories of chemicals, including dangerous substances, biocides, plant protection products, food additives, medicinal products, and of course also cosmetics. Horizontal legislative texts, on the contrary, cover more general fields such as protection of experimental animals, consumer product safety, misleading of consumers, specific provisions for aerosols, and others. Experience has learnt that having a general overview of these related legislations is necessary to understand their impact on the cosmetic world in general terms and on cosmetic safety evaluation in particular. This goes for a variety of concerned parties, including national and European regulators/agencies, contract laboratories, raw material suppliers, cosmetic companies, research and educational centers. They all deal with a number of aspects important for the quality and toxicity of cosmetics and their ingredients. This review summarises the most relevant points of the legislative texts of different types of product categories and emphasises their impact on the safety evaluation of cosmetics.

Systematic drug safety evaluation based on public genomic expression (Connectivity Map) data: Myocardial and infectious adverse reactions as application cases

International Nuclear Information System (INIS)

Wang, Kejian; Weng, Zuquan; Sun, Liya; Sun, Jiazhi; Zhou, Shu-Feng; He, Lin

2015-01-01

Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure–activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. In the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. - Highlights: • Drugs causing common toxicity lead to similar in vitro gene expression changes. • We built a model to predict drug toxicity with drug-specific expression profiles. • Drugs with FDA black box warnings were effectively identified by our model. • In vitro assay can detect severe toxicity in the early stage of drug development

Systematic drug safety evaluation based on public genomic expression (Connectivity Map) data: Myocardial and infectious adverse reactions as application cases

Energy Technology Data Exchange (ETDEWEB)

Wang, Kejian, E-mail: kejian.wang.bio@gmail.com [Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai (China); Weng, Zuquan [Japan National Institute of Occupational Safety and Health, Kawasaki (Japan); Sun, Liya [Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai (China); Sun, Jiazhi; Zhou, Shu-Feng [Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL (United States); He, Lin, E-mail: helin@Bio-X.com [Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai (China)

2015-02-13

Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure–activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. In the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. - Highlights: • Drugs causing common toxicity lead to similar in vitro gene expression changes. • We built a model to predict drug toxicity with drug-specific expression profiles. • Drugs with FDA black box warnings were effectively identified by our model. • In vitro assay can detect severe toxicity in the early stage of drug development.

From Safety Critical Java Programs to Timed Process Models

DEFF Research Database (Denmark)

Thomsen, Bent; Luckow, Kasper Søe; Thomsen, Lone Leth

2015-01-01

frameworks, we have in recent years pursued an agenda of translating hard-real-time embedded safety critical programs written in the Safety Critical Java Profile [33] into networks of timed automata [4] and subjecting those to automated analysis using the UPPAAL model checker [10]. Several tools have been...... built and the tools have been used to analyse a number of systems for properties such as worst case execution time, schedulability and energy optimization [12–14,19,34,36,38]. In this paper we will elaborate on the theoretical underpinning of the translation from Java programs to timed automata models...... and briefly summarize some of the results based on this translation. Furthermore, we discuss future work, especially relations to the work in [16,24] as Java recently has adopted first class higher order functions in the form of lambda abstractions....

Patient safety in organizational culture as perceived by leaderships of hospital institutions with different types of administration

Directory of Open Access Journals (Sweden)

Natasha Dejigov Monteiro da Silva

2016-06-01

Full Text Available Abstract OBJECTIVE To identify the perceptions of leaderships toward patient safety culture dimensions in the routine of hospitals with different administrative profiles: government, social and private organizations, and make correlations among participating institutions regarding dimensions of patient safety culture used. METHOD A quantitative cross-sectional study that used the Self Assessment Questionnaire 30 translated into Portuguese. The data were processed by analysis of variance (ANOVA in addition to descriptive statistics, with statistical significance set at p-value ≤ 0.05. RESULTS According to the participants' perceptions, the significant dimensions of patient safety culture were 'patient safety climate' and 'organizational learning', with 81% explanatory power. Mean scores showed that among private organizations, higher values were attributed to statements; however, the correlation between dimensions was stronger among government hospitals. CONCLUSION Different hospital organizations present distinct values for each dimension of patient safety culture and their investigation enables professionals to identify which dimensions need to be introduced or improved to increase patient safety.

An open-label extension study to evaluate the safety of ropinirole prolonged release in Chinese patients with advanced Parkinson's disease.

Science.gov (United States)

Zhang, Zhenxin; Wang, Jian; Zhang, Xiaoying; Chen, Shengdi; Wang, Zhenfu; Zhang, Baorong; Liu, Chunfeng; Qu, Qiumin; Cheng, Yan; Zhu, Rongxuan; Li, Jie; Hu, Jingqiu; Cai, Meng

2015-04-01

This open-label extension (OLE) study evaluated the safety profile of ropinirole prolonged release (PR) administered for 24 weeks as adjunctive to levodopa in Chinese patients with advanced Parkinson's disease (PD). This was a 24 week, flexible-dose, OLE study in Chinese patients with advanced PD who received 24 week treatment with ropinirole PR in the preceding double-blind (DB), phase III study (NCT01154166) and had no break in receiving study treatment while switching from the DB study to the OLE study. In the OLE study, patients received ropinirole PR once daily, starting with 2 mg/d and increasing up to 8 mg/d at week 4 (2 mg increment/week); if tolerable, the dose could be further increased in 4 mg increments up to 24 mg/d according to clinical judgment. There were no efficacy assessments. Safety assessments included monitoring adverse events (AEs), neurological examination, Gambling Symptom Assessment Scale questionnaire, liver chemistry, and laboratory tests. Of the 295 enrolled patients, 282 completed the study. The most common reason for withdrawal was AEs (n = 9, 3.1%). The mean duration to ropinirole PR treatment was 173.1 days and an overall median daily dose of ropinirole was 8 mg (range: 2-24 mg). Overall, 114 (38.6%) patients experienced on-treatment AEs; the most frequent reported AEs ( ≥ 2%) were dyskinesia (6.1%), dizziness (4.1%), nausea (3.4%), hallucinations (3.4%), somnolence (2.7%) and decreased weight (2.4%). Sixty-eight patients (23.1%) experienced treatment-related AEs. Six patients experienced serious AEs (SAEs), of which hallucination was determined to be a treatment-related SAE. There were no other significant safety findings. No new safety signals for ropinirole were identified. The safety profile of ropinirole was consistent with the preceding DB study and also with the established safety profile for ropinirole. Results support the long-term use of ropinirole PR as an adjunctive to levodopa in Chinese patients

Simultaneous real-time control of the current and pressure profiles in JET: experiments and modelling

Energy Technology Data Exchange (ETDEWEB)

Mazon, D.; Laborde, L.; Litaudon, X.; Moreau, D.; Zabeo, L.; Joffrin, E. [Association Euratom-CEA Cadarache (DSM/DRFC), 13 - Saint-Paul-lez-Durance (France). Dept. de Recherches sur la Fusion Controlee; Murari, A. [Consorzio RFX Association Euratom-ENEA, Padova (Italy); Ariola, M.; Albanese, R.; Tommasi, G. de; Pironti, A. [Association Euratom-ENEA, CREATE, Napoly (Italy); Moreau, D. [EFDA-JET CSU, Culham Science Centre, Abingdon, OX (United Kingdom); Tala, T. [Euratom-Tekes Association, VTT Processes (Finland); Crisanti, F.; Pericoli-Ridolfini, V.; Tuccillo, A. [Association Euratom-ENEA, C.R. Frascati (Italy); Baar, M. de; Vries, P. de [Euratom-FOM Association, TEC Cluster, Nieuwegein (Netherlands); De la Luna, E. [Euratom-Ciemat Association (Spain); Felton, R.; Corrigan, G. [Euratom-UKAEA Association, Culham Science Centre, Abingdon (United Kingdom)

2004-07-01

Real-time control of the plasma profiles (current density, pressure and flow) is one of the major issues for sustaining internal transport barriers (ITB) in a high performance plasma, with a large bootstrap current fraction. We have recently investigated the experimental and numerical aspects of the simultaneous control of the current and pressure profiles in JET ITB discharges. The current density and the electron temperature were successfully controlled via the safety factor profile (or via its inverse the tau-profile) and the {rho}{sup *}{sub Te} profile respectively. The results of these new studies are presented. With only a limited number of actuators, the technique aims at minimizing an integral square error signal which combines the 2 profiles, rather than attempting to control plasma parameters at some given radii with great precision. The resulting fuzziness of the control scheme allows the plasma to relax towards a physically accessible non-linear state which may not be accurately known in advance, but is close enough to the requested one to provide the required plasma performance. Closed loop experiments have allow to reach different target q and {rho}{sup *}{sub Te} profiles, and to some degree, to displace the region of maximum electron temperature gradient. The control has also shown some robustness in front of rapid transients.

Cocoa content influences chocolate molecular profile investigated by MALDI-TOF mass spectrometry.

Science.gov (United States)

Bonatto, Cínthia C; Silva, Luciano P

2015-06-01

Chocolate authentication is a key aspect of quality control and safety. Matrix-assisted laser desorption ionization time-of flight (MALDI-TOF) mass spectrometry (MS) has been demonstrated to be useful for molecular profiling of cells, tissues, and even food. The present study evaluated if MALDI-TOF MS analysis on low molecular mass profile may classify chocolate samples according to the cocoa content. The molecular profiles of seven processed commercial chocolate samples were compared by using MALDI-TOF MS. Some ions detected exclusively in chocolate samples corresponded to the metabolites of cocoa or other constituents. This method showed the presence of three distinct clusters according to confectionery and sensorial features of the chocolates and was used to establish a mass spectra database. Also, novel chocolate samples were evaluated in order to check the validity of the method and to challenge the database created with the mass spectra of the primary samples. Thus, the method was shown to be reliable for clustering unknown samples into the main chocolate categories. Simple sample preparation of the MALDI-TOF MS approach described will allow the surveillance and monitoring of constituents during the molecular profiling of chocolates. © 2014 Society of Chemical Industry.

An update on the safety of nutraceuticals and effects on lipid parameters.

Science.gov (United States)

Cicero, Arrigo F G; Colletti, Alessandro

2018-03-01

Cardiovascular diseases (CVDs) are the leading cause of mortality and disability in developed countries, whereas a large portion of patients in primary prevention have uncontrolled level of CVD risk factors. Dietary supplementation with bioactive natural compounds with demonstrated lipid-lowering effects is currently supported by the international guidelines for CVD prevention and some international expert panels. Areas covered: This review provides insights on issues concerning the tolerability and safety of the most commonly used nutraceuticals with demonstrated lipid-lowering effect in humans. They will be then divided into three main categories according to their mechanism of action (cholesterol synthesis inhibitors, intestinal cholesterol absorption inhibitors, and LDL-C excretion stimulants) and their pharmacological profile will be discussed. Expert opinion: A growing body of preclinical, epidemiological and clinical evidence has defined the tolerability and safety profile of the most commonly used lipid-lowering nutraceuticals. In the most part of cases, the side effects are mild and reversible. However, detailed knowledge of specific health risks and pharmacological interactions for each individual compound is needed for the management of frail patients, such as children, elderly, patients with liver or renal failure, and patients consuming numerous drugs.

Human factors in safety assessment. Safety culture assessment

International Nuclear Information System (INIS)

Zhang Li; Deng Zhiliang; Wang Yiqun; Huang Weigang

1996-01-01

This paper analyses the present conditions and problems in enterprises safety assessment, and introduces the characteristics and effects of safety culture. The authors think that safety culture must be used as a 'soul' to form the pattern of modern safety management. Furthermore, they propose that the human safety and synthetic safety management assessment in a system should be changed into safety culture assessment. Finally, the assessment indicators are discussed

Finite element analysis in defining the optimal shape and safety factor of retentive clasp arms of removable partial denture

Directory of Open Access Journals (Sweden)

Šćepanović Miodrag

2013-01-01

Full Text Available Bacground/Aim. Retentive force of removable partial denture (RPD directly depends on elastic force of stretched retentive clasp arms (RCAs. During deflection RCA must have even stress distribution. Safety factor is the concept which can be applied in estimating durability and functionality of RCAs. This study was based on analyzing properties of clasps designed by conventional clasp wax profiles and defining the optimal shapes of RCAs for stress distribution and safety factor aspects. Methods. Computer-aided-design (CAD models of RCAs with simulated properties of materials used for fabrication of RPD cobalt-chromium-molybdenum (CoCrMo alloy, commercially pure titanium (CPTi and polyacetale were analyzed. Results. The research showed that geometrics of Rapidflex profiles from the BIOS concept are defined for designing and modeling RCAs from CoCrMo alloys. I-Bar and Bonihard clasps made from CPTi might have the same design as Co- CrMo clasp only by safety factor aspect, but it is obvious that CPTi are much more flexible, so their shape must be more massive. Polyacetale clasps should not be fabricated by BIOS concept for CoCrMo alloy. A proof for that is the low value of safety factor. Conclusion. The BIOS concept should be used only for RCAs made of CoCrMo alloy and different wax profiles should be used for fabricating clasps of other investigated materials. The contribution of this study may be the improvement of present systems for defining the clasps shapes made from CoCrMo alloys. The more significant application is possibility of creating new concepts in defining shapes of RCA made from CPTi and polyacetale.

Safety Culture Enhancement Project. Final Report. A Field Study on Approaches to Enhancement of Safety Culture

International Nuclear Information System (INIS)

Lowe, Andrew; Hayward, Brent

2006-08-01

Safety Culture Perceptions Questionnaire conducted with site managers to access their opinions about the adequacy of the local safety culture; - a framework of safety-related competencies for managers, representing desirable actions for leading and promoting a positive safety culture; - results of an evaluation survey completed by participants at the conclusion of the Management Workshops to assess the utility of this activity. Section 4 of the report, Recommendations for Future Action, highlights nine proposed activities that could be undertaken to build on the outcomes from this project, to support the enhancement of safety culture within the Swedish nuclear industry in the longer term. Specifically, these recommendations propose actions to: 1. Introduce formal processes to ensure the ongoing development of safety related competencies amongst industry managers. 2. Strengthen the resources, contribution, value and profile of Man Technology Organisation (MTO) expertise within nuclear industry sites, in order to promote a better understanding of human performance issues, enhance error management and accident prevention capabilities. 3. Identify ways to embed existing positive safety culture attributes, in an environment of considerable workforce changes resulting from increasing use of contractors and (expected) retirements amongst an ageing industry employee population. 4. Standardise and improve aspects of incident and accident investigation processes and analysis methodologies currently used, to improve information sharing and optimise learning. 5. Implement harmonised MTO / human factors awareness training programs at appropriate levels for all nuclear industry personnel. 6. Formalise the application of applied teamwork training (as per the principles of Crew Resource Management training in aviation) for NPP Control Room Operators, Maintenance workers and other employees working in safety-critical teams. 7. Increase the use of simulation training to enhance non

Fundamental safety principles. Safety fundamentals

International Nuclear Information System (INIS)

2007-01-01

This publication states the fundamental safety objective and ten associated safety principles, and briefly describes their intent and purpose. The fundamental safety objective - to protect people and the environment from harmful effects of ionizing radiation - applies to all circumstances that give rise to radiation risks. The safety principles are applicable, as relevant, throughout the entire lifetime of all facilities and activities - existing and new - utilized for peaceful purposes, and to protective actions to reduce existing radiation risks. They provide the basis for requirements and measures for the protection of people and the environment against radiation risks and for the safety of facilities and activities that give rise to radiation risks, including, in particular, nuclear installations and uses of radiation and radioactive sources, the transport of radioactive material and the management of radioactive waste

Fundamental safety principles. Safety fundamentals

International Nuclear Information System (INIS)

2006-01-01

This publication states the fundamental safety objective and ten associated safety principles, and briefly describes their intent and purpose. The fundamental safety objective - to protect people and the environment from harmful effects of ionizing radiation - applies to all circumstances that give rise to radiation risks. The safety principles are applicable, as relevant, throughout the entire lifetime of all facilities and activities - existing and new - utilized for peaceful purposes, and to protective actions to reduce existing radiation risks. They provide the basis for requirements and measures for the protection of people and the environment against radiation risks and for the safety of facilities and activities that give rise to radiation risks, including, in particular, nuclear installations and uses of radiation and radioactive sources, the transport of radioactive material and the management of radioactive waste

Mathematical modeling of efficacy and safety for anticancer drugs clinical development.

Science.gov (United States)

Lavezzi, Silvia Maria; Borella, Elisa; Carrara, Letizia; De Nicolao, Giuseppe; Magni, Paolo; Poggesi, Italo

2018-01-01

Drug attrition in oncology clinical development is higher than in other therapeutic areas. In this context, pharmacometric modeling represents a useful tool to explore drug efficacy in earlier phases of clinical development, anticipating overall survival using quantitative model-based metrics. Furthermore, modeling approaches can be used to characterize earlier the safety and tolerability profile of drug candidates, and, thus, the risk-benefit ratio and the therapeutic index, supporting the design of optimal treatment regimens and accelerating the whole process of clinical drug development. Areas covered: Herein, the most relevant mathematical models used in clinical anticancer drug development during the last decade are described. Less recent models were considered in the review if they represent a standard for the analysis of certain types of efficacy or safety measures. Expert opinion: Several mathematical models have been proposed to predict overall survival from earlier endpoints and validate their surrogacy in demonstrating drug efficacy in place of overall survival. An increasing number of mathematical models have also been developed to describe the safety findings. Modeling has been extensively used in anticancer drug development to individualize dosing strategies based on patient characteristics, and design optimal dosing regimens balancing efficacy and safety.

Management of safety, safety culture and self assessment

International Nuclear Information System (INIS)

Carnino, A.

2000-01-01

Safety management is the term used for the measures required to ensure that an acceptable level of safety is maintained throughout the life of an installation, including decommissioning. The safety culture concept and its implementation are described in part one of the paper. The principles of safety are now quite well known and are implemented worldwide. It leads to a situation where harmonization is being achieved as indicated by the entry into force of the Convention on Nuclear Safety. To go beyond the present nuclear safety levels, management of safety and safety culture will be the means for achieving progress. Recent events which took place in major nuclear power countries have shown the importance of the management and the consequences on safety. At the same time, electricity deregulation is coming and will impact on safety through reductions in staffing and in operation and maintenance cost at nuclear installations. Management of safety as well as its control and monitoring by the safety authorities become a key to the future of nuclear energy.(author)

Assessing the general safety and tolerability of vildagliptin: value of pooled analyses from a large safety database versus evaluation of individual studies

Science.gov (United States)

Schweizer, Anja; Dejager, Sylvie; Foley, James E; Kothny, Wolfgang

2011-01-01

Aim: Analyzing safety aspects of a drug from individual studies can lead to difficult-to-interpret results. The aim of this paper is therefore to assess the general safety and tolerability, including incidences of the most common adverse events (AEs), of vildagliptin based on a large pooled database of Phase II and III clinical trials. Methods: Safety data were pooled from 38 studies of ≥12 to ≥104 weeks’ duration. AE profiles of vildagliptin (50 mg bid; N = 6116) were evaluated relative to a pool of comparators (placebo and active comparators; N = 6210). Absolute incidence rates were calculated for all AEs, serious AEs (SAEs), discontinuations due to AEs, and deaths. Results: Overall AEs, SAEs, discontinuations due to AEs, and deaths were all reported with a similar frequency in patients receiving vildagliptin (69.1%, 8.9%, 5.7%, and 0.4%, respectively) and patients receiving comparators (69.0%, 9.0%, 6.4%, and 0.4%, respectively), whereas drug-related AEs were seen with a lower frequency in vildagliptin-treated patients (15.7% vs 21.7% with comparators). The incidences of the most commonly reported specific AEs were also similar between vildagliptin and comparators, except for increased incidences of hypoglycemia, tremor, and hyperhidrosis in the comparator group related to the use of sulfonylureas. Conclusions: The present pooled analysis shows that vildagliptin was overall well tolerated in clinical trials of up to >2 years in duration. The data further emphasize the value of a pooled analysis from a large safety database versus assessing safety and tolerability from individual studies. PMID:21415917

The safety of phosphodiesterase type 5 inhibitors for erectile dysfunction.

Science.gov (United States)

Ventimiglia, Eugenio; Capogrosso, Paolo; Montorsi, Francesco; Salonia, Andrea

2016-01-01

Phosphodiesterase type 5 inhibitors (PDE5Is) are the leading drugs for the treatment of erectile dysfunction (ED), being recommended as a first line treatment by both the European and US urological guidelines. PDE5Is are highly effective as compared to placebo, well tolerated and have a very low, though not negligible, rate of severe treatment-related adverse events. This paper reviews the safety profile of currently available PDE5Is, comparing them in a broad spectrum ED population and outlining a number of real-life aspects of importance in the real-life everyday clinical setting. Guidelines unanimously agree in considering PDE5Is as first line treatments for ED when well-tolerated and not contraindicated. Despite the fact that no high-grade evidence comparing the efficacy and the safety for PDE5Is is currently available, published data seem to suggest that there are no major differences in their safety profiles. Moreover, although oral PDE5Is were shown to cause more AEs than placebo, they were generally mild and well tolerated.

Behavioral integrity for safety, priority of safety, psychological safety, and patient safety : a team-level study

NARCIS (Netherlands)

Leroy, H.; Dierynck, B.; Anseel, F.; Simons, T.; Halbesleben, J.R.; McCaughey, D.; Savage, G.T.; Sels, L.

2012-01-01

This article clarifies how leader behavioral integrity for safety helps solve follower's double bind between adhering to safety protocols and speaking up about mistakes against protocols. Path modeling of survey data in 54 nursing teams showed that head nurse behavioral integrity for safety

Immunogenicity, safety and reactogenicity of a booster dose of the 10-valent pneumococcal Nontypeable H. influenzae Protein D conjugate vaccine coadministered with DTPa-IPV-Hib in Dutch children

NARCIS (Netherlands)

Van Den Bergh, Menno R.; Spijkerman, Judith; François, Nancy; Swinnen, Kristien; Borys, Dorota; Schuerman, Lode; Veenhoven, Reinier H.; Sanders, Elisabeth A M

2016-01-01

Background: Immune responses and safety profiles may be affected when vaccines are coadministered. We evaluated the immunogenicity, safety and reactogenicity of a booster dose of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate (PHiD-CV; Synflorix GSK Vaccines) and

Playground Safety

Science.gov (United States)

... Prevention Fall Prevention Playground Safety Poisoning Prevention Road Traffic Safety Sports Safety Get Email Updates To receive ... at the Consumer Product Safety Commission’s Playground Safety website . References U.S. Consumer Product Safety Commission. Injuries and ...

Sun safety knowledge and practice in UK postal delivery workers.

Science.gov (United States)

Houdmont, J; Davis, S; Griffiths, A

2016-06-01

Postal delivery workers spend a large proportion of their work time outdoors, placing them at increased risk of skin cancer. To date, no studies have examined occupational sun safety knowledge and practice within this group in the UK. To describe the occupational sun safety knowledge and practice of UK postal delivery workers and to investigate the association of demographic, personal and occupational factors with knowledge and practice in order to identify potential strategies for improving sun safety in this occupational group. Postal delivery workers completed a questionnaire that collected data on occupational sun safety knowledge and practice in addition to demographic, personal and workplace characteristics. One-way analysis of variances were applied to assess differences in knowledge and practice by these characteristics. A total of 1153 postal delivery workers completed the questionnaire, a 60% response rate. Thirty-three per cent reported receiving sun safety training within the previous 12 months. The majority of respondents reported correct knowledge on three of the six domains and good practice on four of the six behavioural domains. However, only one-fifth of respondents reported wearing sunglasses and ensuring a plentiful intake of water. Knowledge and practice differed significantly according to demographic, personal and workplace characteristics. There is a need to raise the profile of occupational skin cancer in this occupational group and to increase the priority given to occupational sun safety policies alongside targeted and tailored interventions, the effect of which can be evaluated. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine.

Non-clinical models: validation, study design and statistical consideration in safety pharmacology.

Science.gov (United States)

Pugsley, M K; Towart, R; Authier, S; Gallacher, D J; Curtis, M J

2010-01-01

The current issue of the Journal of Pharmacological and Toxicological Methods (JPTM) focuses exclusively on safety pharmacology methods. This is the 7th year the Journal has published on this topic. Methods and models that specifically relate to methods relating to the assessment of the safety profile of a new chemical entity (NCE) prior to first in human (FIH) studies are described. Since the Journal started publishing on this topic there has been a major effort by safety pharmacologists, toxicologists and regulatory scientists within Industry (both large and small Pharma as well as Biotechnology companies) and also from Contract Research Organizations (CRO) to publish the surgical details of the non-clinical methods utilized but also provide important details related to standard and non-standard (or integrated) study models and designs. These details from core battery and secondary (or ancillary) drug safety assessment methods used in drug development programs have been the focus of these special issues and have been an attempt to provide validation of methods. Similarly, the safety pharmacology issues of the Journal provide the most relevant forum for scientists to present novel and modified methods with direct applicability to determination of drug safety-directly to the safety pharmacology scientific community. The content of the manuscripts in this issue includes the introduction of additional important surgical methods, novel data capture and data analysis methods, improved study design and effects of positive control compounds with known activity in the model. Copyright 2010 Elsevier Inc. All rights reserved.

More safety by improving the safety culture

International Nuclear Information System (INIS)

Laaksonen, J.

1993-01-01

In its meeting in 1986, after Chernobyl accident, the INSAG group concluded, that the most important reason for the accident was lack of safety culture. Later the group realized that the safety culture, if it is well enough, can be used as a powerful tool to assess and develop practices affecting safety in any country. A comprehensive view on the various aspects of safety culture was presented in the INSAG-4 report published in 1991. Finland was among the first nations include the concept of safety culture in its regulations. This article describes the roles of government and the regulatory body in creating a national safety culture. How safety culture is seen in the operation of a nuclear power plant is also discussed. (orig.)

Trust in the pharmaceutical sector : Analysis of drug safety controversies by means of drug life cycles

NARCIS (Netherlands)

Hernández, J.F.

2015-01-01

Before obtaining a marketing approval, the efficacy and safety profile of drugs is studied in specific populations and under well-controlled circumstances. After marketing approval, the drug is made available and used in ‘real world conditions’, which are known to deviate from the trial setting.

Early Performance and Safety of the Micra Transcatheter Pacemaker in Pigs.

Science.gov (United States)

Bonner, Matthew; Eggen, Michael; Haddad, Tarek; Sheldon, Todd; Williams, Eric

2015-11-01

The Micra® Transcatheter Pacing System (TPS; Medtronic Inc., Minneapolis, MN, USA) is a miniaturized single-chamber pacemaker system that is delivered via catheter through the femoral vein. In this study, the electrical performance was compared between the TPS and a traditional leaded pacemaker. In addition, the safety profile of the two systems was compared by thorough monitoring for a number of adverse events. The TPS was implanted in the right ventricular apex of 10 Yucatan mini pigs and a Medtronic single-lead pacemaker (SLP) was implanted in the right ventricular apex of another 10 pigs and connected to a traditional pacemaker. The electrical performance of all devices was monitored for 12 weeks. The safety profile of each system was characterized using x-ray, computed tomography, ultrasound, blood work, and necropsy to monitor for a variety of adverse events. At implant the mean pacing thresholds were 0.58 ± 0.17 V @0.24 ms and 0.75 ± 0.29 V @0.21 ms for the TPS and the SLP respectively. After 12 weeks, mean thresholds were 0.94 ± 0.46 V and 1.85 ± 0.75 V (P pacemaker system. © 2015 Medtronic PLC. Pacing and Clinical Electrophysiology published by Wiley Periodicals, Inc.

Dependence of the DIII-D beta limit on the current profile

Energy Technology Data Exchange (ETDEWEB)

Strait, E.J.; Chu, M.S.; Ferron, J.R.; Lao, L.L.; Osborne, T.H.; Taylor, T.S.; Turnbull, A.D. (General Atomics, San Diego, CA (United States)); Lazarus, E.A. (Oak Ridge National Lab., TN (United States))

1991-01-01

The maximum beta values achieved in DIII-D are not fully described by the simple scaling law [beta][sub max][proportional to]I/aB. There is, in addition, a dependence on the form of the current profile as parameterized by the safety factor q and internal inductance l[sub i]. The maximum experimentally achieved value of normalized beta [beta][sub N] = [beta]/(I/aB) varies from 3.5 at low safety factor q (q[sub 95]<3) to 5 at higher values of q. At low q, discharges are terminated by disruptions at high [beta][sub N] and at both the low and high l[sub i] boundaries of the stable range. These disruptions are attributed to external and global kink modes. At higher q, such disruptions are much less frequent, and beta is limited by slowly growing resistive modes, fishbones, and possibly by ballooning modes. At each value of q, the maximum beta tends to increase with internal inductance l[sub i]. A numerical study of kink mode stability has shown a similar trend for optimized pressure profiles. These observations have suggested a new scaling law for the operational beta limit: [beta][sub max]=4l[sub i](I/aB), which fits the DIII-D data well. (author) 13 refs., 4 figs.

SAFETY

CERN Multimedia

Niels Dupont

2013-01-01

CERN Safety rules and Radiation Protection at CMS The CERN Safety rules are defined by the Occupational Health & Safety and Environmental Protection Unit (HSE Unit), CERN’s institutional authority and central Safety organ attached to the Director General. In particular the Radiation Protection group (DGS-RP1) ensures that personnel on the CERN sites and the public are protected from potentially harmful effects of ionising radiation linked to CERN activities. The RP Group fulfils its mandate in collaboration with the CERN departments owning or operating sources of ionising radiation and having the responsibility for Radiation Safety of these sources. The specific responsibilities concerning "Radiation Safety" and "Radiation Protection" are delegated as follows: Radiation Safety is the responsibility of every CERN Department owning radiation sources or using radiation sources put at its disposition. These Departments are in charge of implementing the requi...

A firm size and safety performance profile of the U.S. motor carrier industry : [executive summary].

Science.gov (United States)

2015-11-01

Motor carrier crashes continue to present a societal and public policy : problem. Large commercial truck crashes are a topic of serious concern : in Iowa. Statistics illustrate the need to make further progress on the : safety performance of motor ca...

Reactor protection system software test-case selection based on input-profile considering concurrent events and uncertainties

International Nuclear Information System (INIS)

Khalaquzzaman, M.; Lee, Seung Jun; Cho, Jaehyun; Jung, Wondea

2016-01-01

Recently, the input-profile-based testing for safety critical software has been proposed for determining the number of test cases and quantifying the failure probability of the software. Input-profile of a reactor protection system (RPS) software is the input which causes activation of the system for emergency shutdown of a reactor. This paper presents a method to determine the input-profile of a RPS software which considers concurrent events/transients. A deviation of a process parameter value begins through an event and increases owing to the concurrent multi-events depending on the correlation of process parameters and severity of incidents. A case of reactor trip caused by feedwater loss and main steam line break is simulated and analyzed to determine the RPS software input-profile and estimate the number of test cases. The different sizes of the main steam line breaks (e.g., small, medium, large break) with total loss of feedwater supply are considered in constructing the input-profile. The uncertainties of the simulation related to the input-profile-based software testing are also included. Our study is expected to provide an option to determine test cases and quantification of RPS software failure probability. (author)

1-D profiling using highly dispersive guided waves

Science.gov (United States)

Volker, Arno; van Zon, Tim

2014-02-01

Corrosion is one of the industries major issues regarding the integrity of assets. Currently, inspections are conducted at regular intervals to ensure a sufficient integrity level of these assets. Cost reduction while maintaining a high level of reliability and safety of installations is a major challenge. There are many situations where the actual defect location is not accessible, e.g., a pipe support or a partially buried pipe. Guided wave tomography has been developed to reconstruct the wall thickness of steel pipes. In case of bottom of the line corrosion, i.e., a single corrosion pit, a simpler approach may be followed. Data is collected in a pitch-catch configuration at the 12 o'clock position using highly dispersive guided waves. After dispersion correction the data collapses to a short pulse, any residual dispersion indicates wall loss. The phase spectrum is used to invert for the wall thickness profile in the circumferential direction, assuming a Gaussian defect profile. The approach is evaluated on numerically simulated and on measured data. The method is intended for rapid, semi-quantitative screening of pipes.

1-D profiling using highly dispersive guided waves

International Nuclear Information System (INIS)

Volker, Arno; Zon, Tim van

2014-01-01

Corrosion is one of the industries major issues regarding the integrity of assets. Currently, inspections are conducted at regular intervals to ensure a sufficient integrity level of these assets. Cost reduction while maintaining a high level of reliability and safety of installations is a major challenge. There are many situations where the actual defect location is not accessible, e.g., a pipe support or a partially buried pipe. Guided wave tomography has been developed to reconstruct the wall thickness of steel pipes. In case of bottom of the line corrosion, i.e., a single corrosion pit, a simpler approach may be followed. Data is collected in a pitch-catch configuration at the 12 o'clock position using highly dispersive guided waves. After dispersion correction the data collapses to a short pulse, any residual dispersion indicates wall loss. The phase spectrum is used to invert for the wall thickness profile in the circumferential direction, assuming a Gaussian defect profile. The approach is evaluated on numerically simulated and on measured data. The method is intended for rapid, semi-quantitative screening of pipes

Assessing the general safety and tolerability of vildagliptin: value of pooled analyses from a large safety database versus evaluation of individual studies

Directory of Open Access Journals (Sweden)

Schweizer A

2011-02-01

Full Text Available Anja Schweizer1, Sylvie Dejager2, James E Foley3, Wolfgang Kothny31Novartis Pharma AG, Basel, Switzerland; 2Novartis Pharma SAS, Rueil-Malmaison, France; 3Novartis Pharmaceuticals Corporation, East Hanover, NJ, USAAim: Analyzing safety aspects of a drug from individual studies can lead to difficult-to-interpret results. The aim of this paper is therefore to assess the general safety and tolerability, including incidences of the most common adverse events (AEs, of vildagliptin based on a large pooled database of Phase II and III clinical trials.Methods: Safety data were pooled from 38 studies of ≥12 to ≥104 weeks' duration. AE profiles of vildagliptin (50 mg bid; N = 6116 were evaluated relative to a pool of comparators (placebo and active comparators; N = 6210. Absolute incidence rates were calculated for all AEs, serious AEs (SAEs, discontinuations due to AEs, and deaths.Results: Overall AEs, SAEs, discontinuations due to AEs, and deaths were all reported with a similar frequency in patients receiving vildagliptin (69.1%, 8.9%, 5.7%, and 0.4%, respectively and patients receiving comparators (69.0%, 9.0%, 6.4%, and 0.4%, respectively, whereas drug-related AEs were seen with a lower frequency in vildagliptin-treated patients (15.7% vs 21.7% with comparators. The incidences of the most commonly reported specific AEs were also similar between vildagliptin and comparators, except for increased incidences of hypoglycemia, tremor, and hyperhidrosis in the comparator group related to the use of sulfonylureas.Conclusions: The present pooled analysis shows that vildagliptin was overall well tolerated in clinical trials of up to >2 years in duration. The data further emphasize the value of a pooled analysis from a large safety database versus assessing safety and tolerability from individual studies.Keywords: type 2 diabetes, dipeptidyl peptidase-4, edema, safety, vildagliptin

Safety of nuclear power plants: Design. Safety requirements

International Nuclear Information System (INIS)

2000-01-01

The present publication supersedes the Code on the Safety of Nuclear Power Plants: Design (Safety Series No. 50-C-D (Rev. 1), issued in 1988). It takes account of developments relating to the safety of nuclear power plants since the Code on Design was last revised. These developments include the issuing of the Safety Fundamentals publication, The Safety of Nuclear Installations, and the present revision of various safety standards and other publications relating to safety. Requirements for nuclear safety are intended to ensure adequate protection of site personnel, the public and the environment from the effects of ionizing radiation arising from nuclear power plants. It is recognized that technology and scientific knowledge advance, and nuclear safety and what is considered adequate protection are not static entities. Safety requirements change with these developments and this publication reflects the present consensus. This Safety Requirements publication takes account of the developments in safety requirements by, for example, including the consideration of severe accidents in the design process. Other topics that have been given more detailed attention include management of safety, design management, plant ageing and wearing out effects, computer based safety systems, external and internal hazards, human factors, feedback of operational experience, and safety assessment and verification. This publication establishes safety requirements that define the elements necessary to ensure nuclear safety. These requirements are applicable to safety functions and the associated structures, systems and components, as well as to procedures important to safety in nuclear power plants. It is expected that this publication will be used primarily for land based stationary nuclear power plants with water cooled reactors designed for electricity generation or for other heat production applications (such as district heating or desalination). It is recognized that in the case of

Safety of nuclear power plants: Design. Safety requirements

International Nuclear Information System (INIS)

2004-01-01

The present publication supersedes the Code on the Safety of Nuclear Power Plants: Design (Safety Series No. 50-C-D (Rev. 1), issued in 1988). It takes account of developments relating to the safety of nuclear power plants since the Code on Design was last revised. These developments include the issuing of the Safety Fundamentals publication, The Safety of Nuclear Installations, and the present revision of various safety standards and other publications relating to safety. Requirements for nuclear safety are intended to ensure adequate protection of site personnel, the public and the environment from the effects of ionizing radiation arising from nuclear power plants. It is recognized that technology and scientific knowledge advance, and nuclear safety and what is considered adequate protection are not static entities. Safety requirements change with these developments and this publication reflects the present consensus. This Safety Requirements publication takes account of the developments in safety requirements by, for example, including the consideration of severe accidents in the design process. Other topics that have been given more detailed attention include management of safety, design management, plant ageing and wearing out effects, computer based safety systems, external and internal hazards, human factors, feedback of operational experience, and safety assessment and verification. This publication establishes safety requirements that define the elements necessary to ensure nuclear safety. These requirements are applicable to safety functions and the associated structures, systems and components, as well as to procedures important to safety in nuclear power plants. It is expected that this publication will be used primarily for land based stationary nuclear power plants with water cooled reactors designed for electricity generation or for other heat production applications (such as district heating or desalination). It is recognized that in the case of

Performance of food safety management systems in poultry meat preparation processing plants in relation to Campylobacter spp. contamination.

Science.gov (United States)

Sampers, Imca; Jacxsens, Liesbeth; Luning, Pieternel A; Marcelis, Willem J; Dumoulin, Ann; Uyttendaele, Mieke

2010-08-01

A diagnostic instrument comprising a combined assessment of core control and assurance activities and a microbial assessment instrument were used to measure the performance of current food safety management systems (FSMSs) of two poultry meat preparation companies. The high risk status of the company's contextual factors, i.e., starting from raw materials (poultry carcasses) with possible high numbers and prevalence of pathogens such as Campylobacter spp., requires advanced core control and assurance activities in the FSMS to guarantee food safety. The level of the core FSMS activities differed between the companies, and this difference was reflected in overall microbial quality (mesophilic aerobic count), presence of hygiene indicators (Enterobacteriaceae, Staphylococcus aureus, and Escherichia coli), and contamination with pathogens such as Salmonella, Listeria monocytogenes, and Campylobacter spp. The food safety output expressed as a microbial safety profile was related to the variability in the prevalence and contamination levels of Campylobacter spp. in poultry meat preparations found in a Belgian nationwide study. Although a poultry meat processing company could have an advanced FSMS in place and a good microbial profile (i.e., lower prevalence of pathogens, lower microbial numbers, and less variability in microbial contamination), these positive factors might not guarantee pathogen-free products. Contamination could be attributed to the inability to apply effective interventions to reduce or eliminate pathogens in the production chain of (raw) poultry meat preparations.

Implementation of the safety culture for HANARO safety management

Energy Technology Data Exchange (ETDEWEB)

Wu, Jong Sup; Han, Gee Yang; Kim, Ik Soo [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2008-11-15

Safety is the fundamental principal upon which a management system is based. The IAEA INSAG(International Nuclear Safety Group) states the general aims of a safety management system. One of which is to foster and support a strong safety culture through the development and reinforcement of good safety attitudes and behavior in individuals and teams, so as to allow them to carry out their tasks safety. The safety culture activities have been implemented and the importance of a safety management in nuclear activities for a reactor application and utilization has also been emphasized for more than 10 years in HANARO which is a 30 MW multi purpose research reactor that achieved its first criticality in February 1995. The safety culture activities and implementation have been conducted continuously to enhance its safe operation such as the seminars and lectures related to safety matters, participation in international workshops and the development of safety culture indicators, a survey on the attitude of HANARO staff toward the safety culture indicators, a survey on the attitude of HANARO staff toward the safety culture, the development of operational safety performance indicators (SPIs), the preparation of a safety text book and the development of an e Learning program for a safety education purpose.

Implementation of the safety culture for HANARO safety management

International Nuclear Information System (INIS)

Wu, Jong Sup; Han, Gee Yang; Kim, Ik Soo

2008-01-01

Safety is the fundamental principal upon which a management system is based. The IAEA INSAG(International Nuclear Safety Group) states the general aims of a safety management system. One of which is to foster and support a strong safety culture through the development and reinforcement of good safety attitudes and behavior in individuals and teams, so as to allow them to carry out their tasks safety. The safety culture activities have been implemented and the importance of a safety management in nuclear activities for a reactor application and utilization has also been emphasized for more than 10 years in HANARO which is a 30 MW multi purpose research reactor that achieved its first criticality in February 1995. The safety culture activities and implementation have been conducted continuously to enhance its safe operation such as the seminars and lectures related to safety matters, participation in international workshops and the development of safety culture indicators, a survey on the attitude of HANARO staff toward the safety culture indicators, a survey on the attitude of HANARO staff toward the safety culture, the development of operational safety performance indicators (SPIs), the preparation of a safety text book and the development of an e Learning program for a safety education purpose

Implementation of the safety culture for HANARO Safety Management

International Nuclear Information System (INIS)

Wu, Jongsup; Han, Geeyang; Kim, Iksoo

2008-01-01

Safety is the fundamental principal upon which the management system is based. The IAEA INSAG(International Nuclear Safety Group) states the general aims of the safety management system. One of which is to foster and support a strong safety culture through the development and reinforcement of good safety attitudes and behavior in individuals and teams so as to allow them to carry out their tasks safety. The safety culture activities have been implemented and the importance of safety management in nuclear activities for a reactor application and utilization has also been emphasized more than 10 years in HANARO which is a 30 MW multi-purpose research reactor and achieved its first criticality in February 1995. The safety culture activities and implementations have been conducted continuously to enhance its safe operation like the seminars and lectures related to safety matters, participation in international workshops, the development of safety culture indicators, the survey on the attitude of safety culture, the development of operational safety performance indicators (SPIs), the preparation of a safety text book and the development of an e-Learning program for safety education. (author)

Nuclear safety

International Nuclear Information System (INIS)

Tarride, Bruno

2015-10-01

The author proposes an overview of methods and concepts used in the nuclear industry, at the design level as well as at the exploitation level, to ensure an acceptable safety level, notably in the case of nuclear reactors. He first addresses the general objectives of nuclear safety and the notion of acceptable risk: definition and organisation of nuclear safety (relationships between safety authorities and operators), notion of acceptable risk, deterministic safety approach and main safety principles (safety functions and confinement barriers, concept of defence in depth). Then, the author addresses the safety approach at the design level: studies of operational situations, studies of internal and external aggressions, safety report, design principles for important-for-safety systems (failure criterion, redundancy, failure prevention, safety classification). The next part addresses safety during exploitation and general exploitation rules: definition of the operation domain and of its limits, periodic controls and tests, management in case of incidents, accidents or aggressions

Formal Safety versus Real Safety: Quantitative and Qualitative Approaches to Safety Culture – Evidence from Estonia

Directory of Open Access Journals (Sweden)

Järvis Marina

2016-10-01

Full Text Available This paper examines differences between formal safety and real safety in Estonian small and medium-sized enterprises. The results reveal key issues in safety culture assessment. Statistical analysis of safety culture questionnaires showed many organisations with an outstanding safety culture and positive safety attitudes. However, qualitative data indicated some important safety weaknesses and aspects that should be included in the process of evaluation of safety culture in organisations.

Preclinical safety profile of trastuzumab emtansine (T-DM1): Mechanism of action of its cytotoxic component retained with improved tolerability

Energy Technology Data Exchange (ETDEWEB)

Poon, Kirsten Achilles, E-mail: achilles.kirsten@gene.com [Genentech, Inc., South San Francisco, CA (United States); Flagella, Kelly; Beyer, Joseph [Genentech, Inc., South San Francisco, CA (United States); Tibbitts, Jay [UCB, Brussels (Belgium); Kaur, Surinder; Saad, Ola; Yi, Joo-Hee; Girish, Sandhya; Dybdal, Noel; Reynolds, Theresa [Genentech, Inc., South San Francisco, CA (United States)

2013-12-01

Trastuzumab emtansine (T-DM1) is the first antibody-drug conjugate (ADC) approved for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. The therapeutic premise of ADCs is based on the hypothesis that targeted delivery of potent cytotoxic drugs to tumors will provide better tolerability and efficacy compared with non-targeted delivery, where poor tolerability can limit efficacious doses. Here, we present results from preclinical studies characterizing the toxicity profile of T-DM1, including limited assessment of unconjugated DM1. T-DM1 binds primate ErbB2 and human HER2 but not the rodent homolog c-neu. Therefore, antigen-dependent and non-antigen-dependent toxicity was evaluated in monkeys and rats, respectively, in both single- and repeat-dose studies; toxicity of DM1 was assessed in rats only. T-DM1 was well tolerated at doses up to 40 mg/kg (∼ 4400 μg DM1/m{sup 2}) and 30 mg/kg (∼ 6000 μg DM1/m{sup 2}) in rats and monkeys, respectively. In contrast, DM1 was only tolerated up to 0.2 mg/kg (1600 μg DM1/m{sup 2}). This suggests that at least two-fold higher doses of the cytotoxic agent are tolerated in T-DM1, supporting the premise of ADCs to improve the therapeutic index. In addition, T-DM1 and DM1 safety profiles were similar and consistent with the mechanism of action of DM1 (i.e., microtubule disruption). Findings included hepatic, bone marrow/hematologic (primarily platelet), lymphoid organ, and neuronal toxicities, and increased numbers of cells of epithelial and phagocytic origin in metaphase arrest. These adverse effects did not worsen with chronic dosing in monkeys and are consistent with those reported in T-DM1-treated patients to date. - Highlights: • T-DM1 was well tolerated in preclinical studies in rats and cynomolgus monkeys. • T-DM1 is associated with bone marrow/hematologic, hepatic, and neuronal toxicities. • T-DM1 toxicities are related to DM1 mechanisms of action and pharmacologic

The Concepts of Risk, Safety, and Security: Applications in Everyday Language.

Science.gov (United States)

Boholm, Max; Möller, Niklas; Hansson, Sven Ove

2016-02-01

The concepts of risk, safety, and security have received substantial academic interest. Several assumptions exist about their nature and relation. Besides academic use, the words risk, safety, and security are frequent in ordinary language, for example, in media reporting. In this article, we analyze the concepts of risk, safety, and security, and their relation, based on empirical observation of their actual everyday use. The "behavioral profiles" of the nouns risk, safety, and security and the adjectives risky, safe, and secure are coded and compared regarding lexical and grammatical contexts. The main findings are: (1) the three nouns risk, safety, and security, and the two adjectives safe and secure, have widespread use in different senses, which will make any attempt to define them in a single unified manner extremely difficult; (2) the relationship between the central risk terms is complex and only partially confirms the distinctions commonly made between the terms in specialized terminology; (3) whereas most attempts to define risk in specialized terminology have taken the term to have a quantitative meaning, nonquantitative meanings dominate in everyday language, and numerical meanings are rare; and (4) the three adjectives safe, secure, and risky are frequently used in comparative form. This speaks against interpretations that would take them as absolute, all-or-nothing concepts. © 2015 Society for Risk Analysis.

Systematic drug safety evaluation based on public genomic expression (Connectivity Map) data: myocardial and infectious adverse reactions as application cases.

Science.gov (United States)

Wang, Kejian; Weng, Zuquan; Sun, Liya; Sun, Jiazhi; Zhou, Shu-Feng; He, Lin

2015-02-13

Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure-activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. In the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. Copyright © 2015 Elsevier Inc. All rights reserved.

Defining safety culture and the nexus between safety goals and safety culture. 1. An Investigation Study on Practical Points of Safety Management

International Nuclear Information System (INIS)

Hasegawa, Naoko; Takano, Kenichi; Hirose, Ayako

2001-01-01

In a report after the Chernobyl accident, the International Atomic Energy Agency indicated the definition and the importance of safety culture and the ideal organizational state where safety culture pervades. However, the report did not mention practical approaches to enhance safety culture. In Japan, although there had been investigations that clarified the consciousness of employees and the organizational climate in the nuclear power and railway industries, organizational factors that clarified the level of organization safety and practical methods that spread safety culture in an organization had not been studied. The Central Research Institute of the Electric Power Industry conducted surveys of organizational culture for the construction, chemical, and manufacturing industries. The aim of our study was to clarify the organizational factors that influence safety in an organization expressed in employee safety consciousness, commitment to safety activities, rate of accidents, etc. If these areas were clarified, the level of organization safety might be evaluated, and practical ways could be suggested to enhance the safety culture. Consequently, a series of investigations was conducted to clarify relationships among organizational climate, employee consciousness, safety management and activities, and rate of accidents. The questionnaire surveys were conducted in 1998-1999. The subjects were (a) managers of the safety management sections in the head offices of the construction, chemical, and manufacturing industries; (b) responsible persons in factories of the chemical and manufacturing industries; and (c) general workers in factories of the chemical and manufacturing industries. The number of collected data was (a) managers in the head office: 48 from the construction industry and 58 from the chemical and manufacturing industries, (b) responsible persons in factories: 567, and (c) general workers: from 29 factories. Items in the questionnaires were selected from

Priming patient safety: A middle-range theory of safety goal priming via safety culture communication.

Science.gov (United States)

Groves, Patricia S; Bunch, Jacinda L

2018-05-18

The aim of this paper is discussion of a new middle-range theory of patient safety goal priming via safety culture communication. Bedside nurses are key to safe care, but there is little theory about how organizations can influence nursing behavior through safety culture to improve patient safety outcomes. We theorize patient safety goal priming via safety culture communication may support organizations in this endeavor. According to this theory, hospital safety culture communication activates a previously held patient safety goal and increases the perceived value of actions nurses can take to achieve that goal. Nurses subsequently prioritize and are motivated to perform tasks and risk assessment related to achieving patient safety. These efforts continue until nurses mitigate or ameliorate identified risks and hazards during the patient care encounter. Critically, this process requires nurses to have a previously held safety goal associated with a repertoire of appropriate actions. This theory suggests undergraduate educators should foster an outcomes focus emphasizing the connections between nursing interventions and safety outcomes, hospitals should strategically structure patient safety primes into communicative activities, and organizations should support professional development including new skills and the latest evidence supporting nursing practice for patient safety. © 2018 John Wiley & Sons Ltd.

Highway Safety Program Manual: Volume 3: Motorcycle Safety.

Science.gov (United States)

National Highway Traffic Safety Administration (DOT), Washington, DC.

Volume 3 of the 19-volume Highway Safety Program Manual (which provides guidance to State and local governments on preferred highway safety practices) concentrates on aspects of motorcycle safety. The purpose and specific objectives of a State motorcycle safety program are outlined. Federal authority in the highway safety area and general policies…

Safety of fenbendazole in Chinese ring-necked pheasants (Phasianus colchicus).

Science.gov (United States)

Griffith, R; Yaeger, M; Hostetter, S; Tell, L A; Wetzlich, S; Vickroy, T; Lillie, B; MacFarlane, W; Laudenslager, T; Whitley, E; Dzikamunhenga, R; Larson, W

2014-03-01

Ring-necked pheasants raised on propagation farms can be severely parasitized with Syngamus trachea (gapeworm) and other parasitic worms. Fenbendazole is a highly effective benzimidazole-class anthelmintic that is not currently approved for game bird species in the United States. The objective of this work was to provide target animal safety data to support a label claim for fenbendazole in pheasants at 100 parts per million (ppm) in the feed for 7 consecutive days. Demonstration of safety in young pheasants and a separate demonstration of reproductive safety in adult birds were required. In the young bird study, 160 Chinese ring-necked pheasants (Phasianus colchicus, 80 males and 80 females) were fed a commercial game bird starter ration containing no antibiotics, growth promoters, or coccidiostats until day 0 of the study (approximately 21 days of age). On day 0 the birds were placed on their respective study diets containing fenbendazole at 0, 100, 300, and 500 ppm for 21 days (three times the normal treatment duration). Clinical observations were recorded twice daily. Feed consumption, feed conversion rate, and body weights were determined for each pen. Three birds from each pen were randomly selected for necropsy, histopathology, and clinical pathology. Birds were carefully examined for feathering abnormalities immediately following euthanasia. The remaining birds in each pen were submitted for drug concentration analysis so that concentrations (for low vs. high treatment levels) could be correlated with clinical observations, clinical pathology, and histologic findings. There no morbidities or mortalities after study day--1. There were no statistically significant treatment-related differences in feed consumption, feed conversion rates, body weights, serum biochemistry profiles, hematologic profiles, gross necropsy findings, histopathologic examination, and feathering. Allowable liver and muscle concentrations of fenbendazole sulfone in turkeys are 6 and 2

Safety of nuclear power plants: Operation. Safety requirements

International Nuclear Information System (INIS)

2004-01-01

The safety of a nuclear power plant is ensured by means of its proper siting, design, construction and commissioning, followed by the proper management and operation of the plant. In a later phase, proper decommissioning is required. This Safety Requirements publication supersedes the Code on the Safety of Nuclear Power Plants: Operation, which was issued in 1988 as Safety Series No. 50-C-O (Rev. 1). The purpose of this revision was: to restructure Safety Series No. 50-C-O (Rev. 1) in the light of the basic objectives, concepts and principles in the Safety Fundamentals publication The Safety of Nuclear Installations. To be consistent with the requirements of the International Basic Safety Standards for Protection against Ionizing Radiation and for the Safety of Radiation Sources. And to reflect current practice and new concepts and technical developments. Guidance on fulfillment of these Safety Requirements may be found in the appropriate Safety Guides relating to plant operation. The objective of this publication is to establish the requirements which, in the light of experience and the present state of technology, must be satisfied to ensure the safe operation of nuclear power plants. These requirements are governed by the basic objectives, concepts and principles that are presented in the Safety Fundamentals publication The Safety of Nuclear Installations. This publication deals with matters specific to the safe operation of land based stationary thermal neutron nuclear power plants, and also covers their commissioning and subsequent decommissioning

Safety of nuclear power plants: Operation. Safety requirements

International Nuclear Information System (INIS)

2003-01-01

The safety of a nuclear power plant is ensured by means of its proper siting, design, construction and commissioning, followed by the proper management and operation of the plant. In a later phase, proper decommissioning is required. This Safety Requirements publication supersedes the Code on the Safety of Nuclear Power Plants: Operation, which was issued in 1988 as Safety Series No. 50-C-O (Rev. 1). The purpose of this revision was: to restructure Safety Series No. 50-C-O (Rev. 1) in the light of the basic objectives, concepts and principles in the Safety Fundamentals publication The Safety of Nuclear Installations. To be consistent with the requirements of the International Basic Safety Standards for Protection against Ionizing Radiation and for the Safety of Radiation Sources. And to reflect current practice and new concepts and technical developments. Guidance on fulfillment of these Safety Requirements may be found in the appropriate Safety Guides relating to plant operation. The objective of this publication is to establish the requirements which, in the light of experience and the present state of technology, must be satisfied to ensure the safe operation of nuclear power plants. These requirements are governed by the basic objectives, concepts and principles that are presented in the Safety Fundamentals publication The Safety of Nuclear Installations. This publication deals with matters specific to the safe operation of land based stationary thermal neutron nuclear power plants, and also covers their commissioning and subsequent decommissioning

Safety of nuclear power plants: Operation. Safety requirements

International Nuclear Information System (INIS)

2000-01-01

The safety of a nuclear power plant is ensured by means of its proper siting, design, construction and commissioning, followed by the proper management and operation of the plant. In a later phase, proper decommissioning is required. This Safety Requirements publication supersedes the Code on the Safety of Nuclear Power Plants: Operation, which was issued in 1988 as Safety Series No. 50-C-O (Rev. 1). The purpose of this revision was: to restructure Safety Series No. 50-C-O (Rev. 1) in the light of the basic objectives, concepts and principles in the Safety Fundamentals publication The Safety of Nuclear Installations; to be consistent with the requirements of the International Basic Safety Standards for Protection against Ionizing Radiation and for the Safety of Radiation Sources; and to reflect current practice and new concepts and technical developments. Guidance on fulfillment of these Safety Requirements may be found in the appropriate Safety Guides relating to plant operation. The objective of this publication is to establish the requirements which, in the light of experience and the present state of technology, must be satisfied to ensure the safe operation of nuclear power plants. These requirements are governed by the basic objectives, concepts and principles that are presented in the Safety Fundamentals publication The Safety of Nuclear Installations. This publication deals with matters specific to the safe operation of land based stationary thermal neutron nuclear power plants, and also covers their commissioning and subsequent decommissioning

Implementation of the safety culture for HANARO safety management

Energy Technology Data Exchange (ETDEWEB)

Wu, Jongsup; Han, Geeyang; Kim, Iksoo [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2008-11-15

Safety is the fundamental principal upon which a management system is based. The IAEA INSAG (International Nuclear Safety Group) states the general aims of a safety management system. One of which is to foster and support a strong safety culture through the development and reinforcement of good safety attitudes and behavior in individuals and teams, so as to allow them to carry out their tasks safely. The safety culture activities have been implemented and the importance of a safety management in nuclear activities for a reactor application and utilization has also been emphasized for more than 10 years in HANARO which is a 30MW multi-purpose research reactor that achieved its first criticality in February 1995. The safety culture activities and implementations have been conducted continuously to enhance its safe operation such as the seminars and lectures related to safety matters, participation in international workshops and the development of safety culture indicators, a survey on the attitude of HANARO staff toward the safety culture, the development of operational safety performance indicators (SPIs), the preparation of a safety text book and the development of a e-learning program for a safety education purpose.

Implementation of the safety culture for HANARO safety management

International Nuclear Information System (INIS)

Wu, Jongsup; Han, Geeyang; Kim, Iksoo

2008-01-01

Safety is the fundamental principal upon which a management system is based. The IAEA INSAG (International Nuclear Safety Group) states the general aims of a safety management system. One of which is to foster and support a strong safety culture through the development and reinforcement of good safety attitudes and behavior in individuals and teams, so as to allow them to carry out their tasks safely. The safety culture activities have been implemented and the importance of a safety management in nuclear activities for a reactor application and utilization has also been emphasized for more than 10 years in HANARO which is a 30MW multi-purpose research reactor that achieved its first criticality in February 1995. The safety culture activities and implementations have been conducted continuously to enhance its safe operation such as the seminars and lectures related to safety matters, participation in international workshops and the development of safety culture indicators, a survey on the attitude of HANARO staff toward the safety culture, the development of operational safety performance indicators (SPIs), the preparation of a safety text book and the development of a e-learning program for a safety education purpose

Sources of Safety Data and Statistical Strategies for Design and Analysis: Transforming Data Into Evidence.

Science.gov (United States)

Ma, Haijun; Russek-Cohen, Estelle; Izem, Rima; Marchenko, Olga V; Jiang, Qi

2018-03-01

Safety evaluation is a key aspect of medical product development. It is a continual and iterative process requiring thorough thinking, and dedicated time and resources. In this article, we discuss how safety data are transformed into evidence to establish and refine the safety profile of a medical product, and how the focus of safety evaluation, data sources, and statistical methods change throughout a medical product's life cycle. Some challenges and statistical strategies for medical product safety evaluation are discussed. Examples of safety issues identified in different periods, that is, premarketing and postmarketing, are discussed to illustrate how different sources are used in the safety signal identification and the iterative process of safety assessment. The examples highlighted range from commonly used pediatric vaccine given to healthy children to medical products primarily used to treat a medical condition in adults. These case studies illustrate that different products may require different approaches, and once a signal is discovered, it could impact future safety assessments. Many challenges still remain in this area despite advances in methodologies, infrastructure, public awareness, international harmonization, and regulatory enforcement. Innovations in safety assessment methodologies are pressing in order to make the medical product development process more efficient and effective, and the assessment of medical product marketing approval more streamlined and structured. Health care payers, providers, and patients may have different perspectives when weighing in on clinical, financial and personal needs when therapies are being evaluated.

Safety profiles of anti-VEGF drugs: bevacizumab, ranibizumab, aflibercept and ziv-aflibercept on human retinal pigment epithelium cells in culture

Science.gov (United States)

Malik, Deepika; Tarek, Mohamed; Caceres del Carpio, Javier; Ramirez, Claudio; Boyer, David; Kenney, M Cristina; Kuppermann, Baruch D

2014-01-01

Purpose To compare the safety profiles of antivascular endothelial growth factor (VEGF) drugs ranibizumab, bevacizumab, aflibercept and ziv-aflibercept on retinal pigment epithelium cells in culture. Methods Human retinal pigment epithelium cells (ARPE-19) were exposed for 24 h to four anti-VEGF drugs at 1/2×, 1×, 2× and 10× clinical concentrations. Cell viability and mitochondrial membrane potential assay were performed to evaluate early apoptotic changes and rate of overall cell death. Results Cell viability decreased at 10× concentrations in bevacizumab (82.38%, p=0.0001), aflibercept (82.68%, p=0.0002) and ziv-aflibercept (77.25%, p<0.0001), but not at lower concentrations. However, no changes were seen in cell viability in ranibizumab-treated cells at all concentrations including 10×. Mitochondrial membrane potential was slightly decreased in 10× ranibizumab-treated cells (89.61%, p=0.0006) and 2× and 10× aflibercept-treated cells (88.76%, 81.46%; p<0.01, respectively). A larger reduction in mitochondrial membrane potential was seen at 1×, 2× and 10× concentrations of bevacizumab (86.53%, 74.38%, 66.67%; p<0.01) and ziv-aflibercept (73.50%, 64.83% and 49.65% p<0.01) suggestive of early apoptosis at lower doses, including the clinical doses. Conclusions At clinical doses, neither ranibizumab nor aflibercept produced evidence of mitochondrial toxicity or cell death. However, bevacizumab and ziv-aflibercept showed mild mitochondrial toxicity at clinically relevant doses. PMID:24836865

The impact of masculinity on safety oversights, safety priority and safety violations in two male-dominated occupations

DEFF Research Database (Denmark)

Nielsen, Kent; Hansen, Claus D.; Bloksgaard, Lotte

2015-01-01

Background Although men have a higher risk of occupational injuries than women the role of masculinity for organizational safety outcomes has only rarely been the object of research. Aim The current study investigated the association between masculinity and safety oversights, safety priority......-related context factors (safety leadership, commitment of the safety representative, and safety involvement) and three safety-related outcome factors (safety violations, safety oversights and safety priority) were administered twice 12 months apart to Danish ambulance workers (n = 1157) and slaughterhouse workers...

Launching the dialogue: Safety and innovation as partners for success in advanced manufacturing.

Science.gov (United States)

Geraci, C L; Tinkle, S S; Brenner, S A; Hodson, L L; Pomeroy-Carter, C A; Neu-Baker, N

2018-06-01

Emerging and novel technologies, materials, and information integrated into increasingly automated and networked manufacturing processes or into traditional manufacturing settings are enhancing the efficiency and productivity of manufacturing. Globally, there is a move toward a new era in manufacturing that is characterized by: (1) the ability to create and deliver more complex designs of products; (2) the creation and use of materials with new properties that meet a design need; (3) the employment of new technologies, such as additive and digital techniques that improve on conventional manufacturing processes; and (4) a compression of the time from initial design concept to the creation of a final product. Globally, this movement has many names, but "advanced manufacturing" has become the shorthand for this complex integration of material and technology elements that enable new ways to manufacture existing products, as well as new products emerging from new technologies and new design methods. As the breadth of activities associated with advanced manufacturing suggests, there is no single advanced manufacturing industry. Instead, aspects of advanced manufacturing can be identified across a diverse set of business sectors that use manufacturing technologies, ranging from the semiconductors and electronics to the automotive and pharmaceutical industries. The breadth and diversity of advanced manufacturing may change the occupational and environmental risk profile, challenge the basic elements of comprehensive health and safety (material, process, worker, environment, product, and general public health and safety), and provide an opportunity for development and dissemination of occupational and environmental health and safety (OEHS) guidance and best practices. It is unknown how much the risk profile of different elements of OEHS will change, thus requiring an evolution of health and safety practices. These changes may be accomplished most effectively through multi

Questions regarding the safety and duration of immunity following live yellow fever vaccination.

Science.gov (United States)

Amanna, Ian J; Slifka, Mark K

2016-12-01

The World Health Organization (WHO) and other health agencies have concluded that yellow fever booster vaccination is unnecessary since a single dose of vaccine confers lifelong immunity. Areas covered: We reviewed the clinical studies cited by health authorities in their investigation of both the safety profile and duration of immunity for the YFV-17D vaccine and examined the position that booster vaccination is no longer needed. We found that antiviral immunity may be lost in 1-in-3 to 1-in-5 individuals within 5 to 10 years after a single vaccination and that children may be at greater risk for primary vaccine failure. The safety profile of YFV-17D was compared to other licensed vaccines including oral polio vaccine (OPV) and the rotavirus vaccine, RotaShield, which have subsequently been withdrawn from the US and world market, respectively. Expert commentary: Based on these results and recent epidemiological data on vaccine failures (particularly evident at >10 years after vaccination), we believe that current recommendations to no longer administer YFV-17D booster vaccination be carefully re-evaluated, and that further development of safer vaccine approaches should be considered.

Questions regarding the safety and duration of immunity following live yellow fever vaccination

Science.gov (United States)

Amanna, Ian J.; Slifka, Mark K.

2016-01-01

Introduction The World Health Organization (WHO) and other health agencies have concluded that yellow fever booster vaccination is unnecessary since a single dose of vaccine confers lifelong immunity. Areas Covered We reviewed the clinical studies cited by health authorities in their investigation of both the safety profile and duration of immunity for the YFV-17D vaccine and examined the position that booster vaccination is no longer needed. We found that antiviral immunity may be lost in 1-in-3 to 1-in-5 individuals within 5 to 10 years after a single vaccination and that children may be at greater risk for primary vaccine failure. The safety profile of YFV-17D was compared to other licensed vaccines including oral polio vaccine (OPV) and the rotavirus vaccine, RotaShield, which have subsequently been withdrawn from the US and world market, respectively. Expert Commentary Based on these results and recent epidemiological data on vaccine failures (particularly evident at >10 years after vaccination), we believe that current recommendations to no longer administer YFV-17D booster vaccination be carefully re-evaluated, and that further development of safer vaccine approaches should be considered. PMID:27267203

Safety-critical Java for low-end embedded platforms

DEFF Research Database (Denmark)

Søndergaard, Hans; Korsholm, Stephan E.; Ravn, Anders Peter

2012-01-01

We present an implementation of the Safety-Critical Java profile (SCJ), targeted for low-end embedded platforms with as little as 16 kB RAM and 256 kB flash. The distinctive features of the implementation are a combination of a lean Java virtual machine (HVM), with a bare metal kernel implementing...... hardware objects, first level interrupt handlers, and native variables, and an infrastructure written in Java which is minimized through program specialization. The HVM allows the implementation to be easily ported to embedded platforms which have a C compiler as part of the development environment...

Leadership and Management for Safety. General Safety Requirements

International Nuclear Information System (INIS)

2016-01-01

This Safety Requirements publication establishes requirements that support Principle 3 of the Fundamental Safety Principles in relation to establishing, sustaining and continuously improving leadership and management for safety and an integrated management system. It emphasizes that leadership for safety, management for safety, an effective management system and a systemic approach (i.e. an approach in which interactions between technical, human and organizational factors are duly considered) are all essential to the specification and application of adequate safety measures and to the fostering of a strong safety culture. Leadership and an effective management system will integrate safety, health, environmental, security, quality, human-and-organizational factor, societal and economic elements. The management system will ensure the fostering of a strong safety culture, regular assessment of performance and the application of lessons from experience. The publication is intended for use by regulatory bodies, operating organizations (registrants and licensees) and other organizations concerned with facilities and activities that give rise to radiation risks

Does Employee Safety Matter for Patients Too? Employee Safety Climate and Patient Safety Culture in Health Care.

Science.gov (United States)

Mohr, David C; Eaton, Jennifer Lipkowitz; McPhaul, Kathleen M; Hodgson, Michael J

2015-04-22

We examined relationships between employee safety climate and patient safety culture. Because employee safety may be a precondition for the development of patient safety, we hypothesized that employee safety culture would be strongly and positively related to patient safety culture. An employee safety climate survey was administered in 2010 and assessed employees' views and experiences of safety for employees. The patient safety survey administered in 2011 assessed the safety culture for patients. We performed Pearson correlations and multiple regression analysis to examine the relationships between a composite measure of employee safety with subdimensions of patient safety culture. The regression models controlled for size, geographic characteristics, and teaching affiliation. Analyses were conducted at the group level using data from 132 medical centers. Higher employee safety climate composite scores were positively associated with all 9 patient safety culture measures examined. Standardized multivariate regression coefficients ranged from 0.44 to 0.64. Medical facilities where staff have more positive perceptions of health care workplace safety climate tended to have more positive assessments of patient safety culture. This suggests that patient safety culture and employee safety climate could be mutually reinforcing, such that investments and improvements in one domain positively impacts the other. Further research is needed to better understand the nexus between health care employee and patient safety to generalize and act upon findings.

Country Nuclear Power Profiles - 2012 Edition

International Nuclear Information System (INIS)

2012-08-01

The Country Nuclear Power Profiles compile background information on the status and development of nuclear power programmes in Member States. The CNPP's main objectives are to consolidate information about the nuclear power infrastructures in participating countries, and to present factors related to the effective planning, decision making and implementation of nuclear power programmes that together lead to safe and economical operations of nuclear power plants. The CNPP summarizes organizational and industrial aspects of nuclear power programs and provides information about the relevant legislative, regulatory, and international framework in each country. Its descriptive and statistical overview of the overall economic, energy, and electricity situation in each country and its nuclear power framework is intended to serve as an integrated source of key background information about nuclear power programs in the world. Topics such as reactor safety, nuclear fuel cycle, radioactive waste management and research programmes are for the most part not discussed in detail. Statistical data about nuclear plant operations, population, energy and electricity use are drawn from the PRIS, EEDB, World Development Indicators (WDI) of the World Bank and the national contributions. This publication is updated and the scope of coverage expanded annually. This is the 2012 edition, issued on CD-ROM and Web pages. It contains updated country information for 51 countries. The CNPP is updated based on information voluntarily provided by participating IAEA Member States. Participants include the 29 countries that have operating nuclear power plants, as well as 22 countries with past or planned nuclear power. Each of the 51 profiles in this publication is self-standing, and contains information officially provided by the respective national authorities. For the 2012 edition, 20 countries provided updated or new profiles. These are Argentina, Armenia, Bangladesh, Chile, Germany, Ghana

Safety and efficacy of tiotropium Respimat versus HandiHaler in patients naive to treatment with inhaled anticholinergics

DEFF Research Database (Denmark)

Wise, Robert; Calverley, Peter Ma; Dahl, Ronald

2015-01-01

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) who were naive to anticholinergics before the TIOtropium Safety and Performance In Respimat (TIOSPIR) trial may reflect patients seen in practice, in particular in primary care. In addition, investigating safety...... in these patients avoids the potential bias in patients who previously received anticholinergics and may be tolerant of their effects. AIMS: The aim of this study was to evaluate whether patients naive to anticholinergic therapy who were treated with tiotropium Respimat 2.5 or 5 μg had different safety and efficacy...... the Respimat and HandiHaler groups. Rates of exacerbations in the subgroup of patients with moderate disease were similar across the Respimat and HandiHaler groups. CONCLUSIONS: Tiotropium Respimat and HandiHaler have similar safety and efficacy profiles in patients who are naive to anticholinergic therapy....

Meta-Analysis on Randomized Controlled Trials of Vaccines with QS-21 or ISCOMATRIX Adjuvant : Safety and Tolerability

NARCIS (Netherlands)

Bigaeva, Emilia; Doorn, Eva van; Liu, Heng; Hak, Eelko

2016-01-01

BACKGROUND AND OBJECTIVES: QS-21 shows in vitro hemolytic effect and causes side effects in vivo. New saponin adjuvant formulations with better toxicity profiles are needed. This study aims to evaluate the safety and tolerability of QS-21 and the improved saponin adjuvants (ISCOM, ISCOMATRIX and

Software Safety Risk in Legacy Safety-Critical Computer Systems

Science.gov (United States)

Hill, Janice L.; Baggs, Rhoda

2007-01-01

Safety Standards contain technical and process-oriented safety requirements. Technical requirements are those such as "must work" and "must not work" functions in the system. Process-Oriented requirements are software engineering and safety management process requirements. Address the system perspective and some cover just software in the system > NASA-STD-8719.13B Software Safety Standard is the current standard of interest. NASA programs/projects will have their own set of safety requirements derived from the standard. Safety Cases: a) Documented demonstration that a system complies with the specified safety requirements. b) Evidence is gathered on the integrity of the system and put forward as an argued case. [Gardener (ed.)] c) Problems occur when trying to meet safety standards, and thus make retrospective safety cases, in legacy safety-critical computer systems.

Safety assessment and verification for nuclear power plants. Safety guide

International Nuclear Information System (INIS)

2001-01-01

This publication supports the Safety Requirements on the Safety of Nuclear Power Plants: Design. This Safety Guide was prepared on the basis of a systematic review of all the relevant publications including the Safety Fundamentals, Safety of Nuclear Power Plants: Design, current and ongoing revisions of other Safety Guides, INSAG reports and other publications that have addressed the safety of nuclear power plants. This Safety Guide also provides guidance for Contracting Parties to the Convention on Nuclear Safety in meeting their obligations under Article 14 on Assessment and Verification of Safety. The Safety Requirements publication entitled Safety of Nuclear Power Plants: Design states that a comprehensive safety assessment and an independent verification of the safety assessment shall be carried out before the design is submitted to the regulatory body. This publication provides guidance on how this requirement should be met. This Safety Guide provides recommendations to designers for carrying out a safety assessment during the initial design process and design modifications, as well as to the operating organization in carrying out independent verification of the safety assessment of new nuclear power plants with a new or already existing design. The recommendations for performing a safety assessment are suitable also as guidance for the safety review of an existing plant. The objective of reviewing existing plants against current standards and practices is to determine whether there are any deviations which would have an impact on plant safety. The methods and the recommendations of this Safety Guide can also be used by regulatory bodies for the conduct of the regulatory review and assessment. Although most recommendations of this Safety Guide are general and applicable to all types of nuclear reactors, some specific recommendations and examples apply mostly to water cooled reactors. Terms such as 'safety assessment', 'safety analysis' and 'independent

Passive Shielding Effect on Space Profile of Magnetic Field Emissions for Wireless Power Transfer to Vehicles

DEFF Research Database (Denmark)

Batra, Tushar; Schaltz, Erik

2015-01-01

Magnetic fields emitted by wireless power transfer systems are of high importance with respect to human safety and health. Aluminum and ferrite are used in the system to reduce the fields and are termed as passive shielding. In this paper, the influence of these materials on the space profile has...... fields for wireless power transfer for vehicle applications....

Reactor safety research and safety technology. Pt. 2

International Nuclear Information System (INIS)

Theenhaus, R.; Wolters, J.

1987-01-01

The state of HTR safety research work reached permits a comprehensive and reliable answer to be given to questions which have been raised by the reactor accident at Chernobyl, regarding HTR safety. Together with the probability safety analyses, the way to a safety concept suitable for an HTR is cleared; instructions are given for design optimisation with regard to safety technique and economy. The consequences of a graphite fire, the neutron physics design and the consequenes of the lack of a safety containment are briefly described. (DG) [de

Radiation safety actuality in Republic of Moldova

International Nuclear Information System (INIS)

Kuharuk, E.S.

2011-01-01

Radioecological monitoring issues and radiation safety are actual in the Republic of Moldova. Japan events show us the possibility of natural disasters. Republic of Moldova is surrounded by 8 NPPs, the closest being at the distance of 160 km. Moldovas territory is in seismic zone where underground earthquake shocks reaches 7 points or more. Thatis why radiation safety and radioecological monitoring is actual in our republic. Traces of Chernobyl were left in Moldovas soils. The fallouts of radio nuclides formed on the soil surfaces in the Republic of Moldova following the Chernobyl Nuclear Power Station Accident have been continuously affected by attacks of both natural and technicaly generated agents since the time of fallout. During the past decade a shift in emphasis has taken place regarding the need for more complete and accurate information on reservoir sedimentation. Classical sedimentation surveys involve repeated field measurement and, therefore, this is probably the most costly and time consuming method. The application of radio nuclides, particularly Cs 137, for water erosion and sedimentation studies in Republic of Moldova has not been attempted so far. This paper presents the results obtained on reservoir sedimentation rates in an area subjected to wide range in land degradation dy sheet-rill erosion. The profil characteristics support the assumption that in most undisturbed sites there is a sharp decline in Cs 137 activity with increasing dept. Such an asymmetrical distribution of the Cs 137 would suggest a standard pattern in the form of a cantilever. If the validity of this assamption is accepted it is possible to define two major types of Cs 137 cantilever distribution: shallow and deep buried cantilever. The main criterion in classifying these pattents lies generally in the shape of Cs 137 depth profile and particularly in burial magnitude of Cs 137 peak derived from Chernobyl. Hills area has been impacted by greatest sendimentation. This regional

Safety climate and safety behaviors in the construction industry: The importance of co-workers commitment to safety.

Science.gov (United States)

Schwatka, Natalie V; Rosecrance, John C

2016-06-16

There is growing empirical evidence that as safety climate improves work site safety practice improve. Safety climate is often measured by asking workers about their perceptions of management commitment to safety. However, it is less common to include perceptions of their co-workers commitment to safety. While the involvement of management in safety is essential, working with co-workers who value and prioritize safety may be just as important. To evaluate a concept of safety climate that focuses on top management, supervisors and co-workers commitment to safety, which is relatively new and untested in the United States construction industry. Survey data was collected from a cohort of 300 unionized construction workers in the United States. The significance of direct and indirect (mediation) effects among safety climate and safety behavior factors were evaluated via structural equation modeling. Results indicated that safety climate was associated with safety behaviors on the job. More specifically, perceptions of co-workers commitment to safety was a mediator between both management commitment to safety climate factors and safety behaviors. These results support workplace health and safety interventions that build and sustain safety climate and a commitment to safety amongst work teams.

Safety

International Nuclear Information System (INIS)

1998-01-01

A brief account of activities carried out by the Nuclear power plants Jaslovske Bohunice in 1997 is presented. These activities are reported under the headings: (1) Nuclear safety; (2) Industrial and health safety; (3) Radiation safety; and Fire protection

Safety Justification and Safety Case for Safety-critical Software in Digital Reactor Protection System

International Nuclear Information System (INIS)

Kwon, Kee-Choon; Lee, Jang-Soo; Jee, Eunkyoung

2016-01-01

Nuclear safety-critical software is under strict regulatory requirements and these regulatory requirements are essential for ensuring the safety of nuclear power plants. The verification & validation (V and V) and hazard analysis of the safety-critical software are required to follow regulatory requirements through the entire software life cycle. In order to obtain a license from the regulatory body through the development and validation of safety-critical software, it is essential to meet the standards which are required by the regulatory body throughout the software development process. Generally, large amounts of documents, which demonstrate safety justification including standard compliance, V and V, hazard analysis, and vulnerability assessment activities, are submitted to the regulatory body during the licensing process. It is not easy to accurately read and evaluate the whole documentation for the development activities, implementation technology, and validation activities. The safety case methodology has been kwon a promising approach to evaluate the level and depth of the development and validation results. A safety case is a structured argument, supported by a body of evidence that provides a compelling, comprehensible, and valid case that a system is safe for a given application in a given operating environment. It is suggested to evaluate the level and depth of the results of development and validation by applying safety case methodology to achieve software safety demonstration. A lot of documents provided as evidence are connected to claim that corresponds to the topic for safety demonstration. We demonstrated a case study in which more systematic safety demonstration for the target system software is performed via safety case construction than simply listing the documents

Safety Justification and Safety Case for Safety-critical Software in Digital Reactor Protection System

Energy Technology Data Exchange (ETDEWEB)

Kwon, Kee-Choon; Lee, Jang-Soo [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Jee, Eunkyoung [KAIST, Daejeon (Korea, Republic of)

2016-10-15

Nuclear safety-critical software is under strict regulatory requirements and these regulatory requirements are essential for ensuring the safety of nuclear power plants. The verification & validation (V and V) and hazard analysis of the safety-critical software are required to follow regulatory requirements through the entire software life cycle. In order to obtain a license from the regulatory body through the development and validation of safety-critical software, it is essential to meet the standards which are required by the regulatory body throughout the software development process. Generally, large amounts of documents, which demonstrate safety justification including standard compliance, V and V, hazard analysis, and vulnerability assessment activities, are submitted to the regulatory body during the licensing process. It is not easy to accurately read and evaluate the whole documentation for the development activities, implementation technology, and validation activities. The safety case methodology has been kwon a promising approach to evaluate the level and depth of the development and validation results. A safety case is a structured argument, supported by a body of evidence that provides a compelling, comprehensible, and valid case that a system is safe for a given application in a given operating environment. It is suggested to evaluate the level and depth of the results of development and validation by applying safety case methodology to achieve software safety demonstration. A lot of documents provided as evidence are connected to claim that corresponds to the topic for safety demonstration. We demonstrated a case study in which more systematic safety demonstration for the target system software is performed via safety case construction than simply listing the documents.

New Safety rules

CERN Multimedia

Safety Commission

2008-01-01

The revision of CERN Safety rules is in progress and the following new Safety rules have been issued on 15-04-2008: Safety Procedure SP-R1 Establishing, Updating and Publishing CERN Safety rules: http://cern.ch/safety-rules/SP-R1.htm; Safety Regulation SR-S Smoking at CERN: http://cern.ch/safety-rules/SR-S.htm; Safety Regulation SR-M Mechanical Equipment: http://cern.ch/safety-rules/SR-M.htm; General Safety Instruction GSI-M1 Standard Lifting Equipment: http://cern.ch/safety-rules/GSI-M1.htm; General Safety Instruction GSI-M2 Standard Pressure Equipment: http://cern.ch/safety-rules/GSI-M2.htm; General Safety Instruction GSI-M3 Special Mechanical Equipment: http://cern.ch/safety-rules/GSI-M3.htm. These documents apply to all persons under the Director General’s authority. All Safety rules are available at the web page: http://www.cern.ch/safety-rules The Safety Commission

The role of probabilistic safety assessment and probabilistic safety criteria in nuclear power plant safety

International Nuclear Information System (INIS)

1992-01-01

The purpose of this Safety Report is to provide guidelines on the role of probabilistic safety assessment (PSA) and a range of associated reference points, collectively referred to as probabilistic safety criteria (PSC), in nuclear safety. The application of this Safety Report and the supporting Safety Practice publication should help to ensure that PSA methodology is used appropriately to assess and enhance the safety of nuclear power plants. The guidelines are intended for use by nuclear power plant designers, operators and regulators. While these guidelines have been prepared with nuclear power plants in mind, the principles involved have wide application to other nuclear and non-nuclear facilities. In Section 2 of this Safety Report guidelines are established on the role PSA can play as part of an overall safety assurance programme. Section 3 summarizes guidelines for the conduct of PSAs, and in Section 4 a PSC framework is recommended and guidance is provided for the establishment of PSC values

Safety of Nuclear Power Plants: Design. Specific Safety Requirements

International Nuclear Information System (INIS)

2012-01-01

On the basis of the principles included in the Fundamental Safety Principles, IAEA Safety Standards Series No. SF-1, this Safety Requirements publication establishes requirements applicable to the design of nuclear power plants. It covers the design phase and provides input for the safe operation of the power plant. It elaborates on the safety objective, safety principles and concepts that provide the basis for deriving the safety requirements that must be met for the design of a nuclear power plant. Contents: 1. Introduction; 2. Applying the safety principles and concepts; 3. Management of safety in design; 4. Principal technical requirements; 5. General plant design; 6. Design of specific plant systems.

Discussion on the safety classification of nuclear safety mechanical equipment

International Nuclear Information System (INIS)

Shen Wei

2010-01-01

The purpose and definition of the equipment safety classification in nuclear plant are introduced. The differences of several safety classification criterions are compared, and the object of safety classification is determined. According to the regulation, the definition and category of the safety functions are represented. The safety classification method, safety classification process, safety class interface, and the requirement for the safety class mechanical equipment are explored. At last, the relation of the safety classification between the mechanical and electrical equipment is presented, and the relation of the safety classification between mechanical equipment and system is also presented. (author)

Traceability of Software Safety Requirements in Legacy Safety Critical Systems

Science.gov (United States)

Hill, Janice L.

2007-01-01

How can traceability of software safety requirements be created for legacy safety critical systems? Requirements in safety standards are imposed most times during contract negotiations. On the other hand, there are instances where safety standards are levied on legacy safety critical systems, some of which may be considered for reuse for new applications. Safety standards often specify that software development documentation include process-oriented and technical safety requirements, and also require that system and software safety analyses are performed supporting technical safety requirements implementation. So what can be done if the requisite documents for establishing and maintaining safety requirements traceability are not available?

Safety design

International Nuclear Information System (INIS)

Kunitomi, Kazuhiko; Shiozawa, Shusaku

2004-01-01

JAERI established the safety design philosophy of the HTTR based on that of current reactors such as LWR in Japan, considering inherent safety features of the HTTR. The strategy of defense in depth was implemented so that the safety engineering functions such as control of reactivity, removal of residual heat and confinement of fission products shall be well performed to ensure safety. However, unlike the LWR, the inherent design features of the high-temperature gas-cooled reactor (HTGR) enables the HTTR meet stringent regulatory criteria without much dependence on active safety systems. On the other hand, the safety in an accident typical to the HTGR such as the depressurization accident initiated by a primary pipe rupture shall be ensured. The safety design philosophy of the HTTR considers these unique features appropriately and is expected to be the basis for future Japanese HTGRs. This paper describes the safety design philosophy and safety evaluation procedure of the HTTR especially focusing on unique considerations to the HTTR. Also, experiences obtained from an HTTR safety review and R and D needs for establishing the safety philosophy for the future HTGRs are reported

A Microbial Assessment Scheme to measure microbial performance of Food Safety Management Systems.

Science.gov (United States)

Jacxsens, L; Kussaga, J; Luning, P A; Van der Spiegel, M; Devlieghere, F; Uyttendaele, M

2009-08-31

A Food Safety Management System (FSMS) implemented in a food processing industry is based on Good Hygienic Practices (GHP), Hazard Analysis Critical Control Point (HACCP) principles and should address both food safety control and assurance activities in order to guarantee food safety. One of the most emerging challenges is to assess the performance of a present FSMS. The objective of this work is to explain the development of a Microbial Assessment Scheme (MAS) as a tool for a systematic analysis of microbial counts in order to assess the current microbial performance of an implemented FSMS. It is assumed that low numbers of microorganisms and small variations in microbial counts indicate an effective FSMS. The MAS is a procedure that defines the identification of critical sampling locations, the selection of microbiological parameters, the assessment of sampling frequency, the selection of sampling method and method of analysis, and finally data processing and interpretation. Based on the MAS assessment, microbial safety level profiles can be derived, indicating which microorganisms and to what extent they contribute to food safety for a specific food processing company. The MAS concept is illustrated with a case study in the pork processing industry, where ready-to-eat meat products are produced (cured, cooked ham and cured, dried bacon).

JAK Inhibitors: Treatment Efficacy and Safety Profile in Patients with Psoriasis

Directory of Open Access Journals (Sweden)

Leeyen Hsu

2014-01-01

Full Text Available Janus kinase (JAK pathways are key mediators in the immunopathogenesis of psoriasis. Psoriasis treatment has evolved with the advent of targeted therapies, which inhibit specific components of the psoriasis proinflammatory cascade. JAK inhibitors have been studied in early phase trials for psoriasis patients, and the data are promising for these agents as potential treatment options. Tofacitinib, an oral or topically administered JAK1 and JAK3 inhibitor, and ruxolitinib, a topical JAK1 and JAK2 inhibitor, have been most extensively studied in psoriasis, and both improved clinical symptoms of psoriasis. Additional JAK1 or JAK3 inhibitors are being studied in clinical trials. In phase III trials for rheumatoid arthritis, tofacitinib was efficacious in patients with inadequate responses to tumor necrosis factor inhibitors, methotrexate monotherapy, or disease-modifying antirheumatic drugs. The results of phase III trials are pending for these therapies in psoriasis, and these agents may represent important alternatives for patients with inadequate responses to currently available agents. Further investigations with long-term clinical trials are necessary to verify their utility in psoriasis treatment and assess their safety in this patient population.

Safety KPIs - Monitoring of safety performance

Directory of Open Access Journals (Sweden)

Andrej Lališ

2014-09-01

Full Text Available This paper aims to provide brief overview of aviation safety development focusing on modern trends represented by implementation of Safety Key Performance Indicators. Even though aviation is perceived as safe means of transport, it is still struggling with its complexity given by long-term growth and robustness which it has reached today. Thus nowadays safety issues are much more complex and harder to handle than ever before. We are more and more concerned about organizational factors and control mechanisms which have potential to further increase level of aviation safety. Within this paper we will not only introduce the concept of Key Performance Indicators in area of aviation safety as an efficient control mechanism, but also analyse available legislation and documentation. Finally we will propose complex set of indicators which could be applied to Czech Air Navigation Service Provider.

HSE's safety assessment principles for criticality safety

International Nuclear Information System (INIS)

Simister, D N; Finnerty, M D; Warburton, S J; Thomas, E A; Macphail, M R

2008-01-01

The Health and Safety Executive (HSE) published its revised Safety Assessment Principles for Nuclear Facilities (SAPs) in December 2006. The SAPs are primarily intended for use by HSE's inspectors when judging the adequacy of safety cases for nuclear facilities. The revised SAPs relate to all aspects of safety in nuclear facilities including the technical discipline of criticality safety. The purpose of this paper is to set out for the benefit of a wider audience some of the thinking behind the final published words and to provide an insight into the development of UK regulatory guidance. The paper notes that it is HSE's intention that the Safety Assessment Principles should be viewed as a reflection of good practice in the context of interpreting primary legislation such as the requirements under site licence conditions for arrangements for producing an adequate safety case and for producing a suitable and sufficient risk assessment under the Ionising Radiations Regulations 1999 (SI1999/3232 www.opsi.gov.uk/si/si1999/uksi_19993232_en.pdf). (memorandum)

Heel Effect: Dose Mapping And Profiling For Mobile C-Arm Fluoroscopy Unit Toshiba SXT-1000A

International Nuclear Information System (INIS)

Husaini Salleh; Mohd Khalid Matori; Muhammad Jamal Md Isa; Mohd Ramli Arshad; Shahrul Azlan Azizan; Mohd Firdaus Abdul Rahman; Md Khairusalih Md Zin

2014-01-01

Heel Effect is the well known phenomena in x-ray production. It contributes the effect to image formation and as well as scattered radiation. But there is paucity in the study related to heel effect. This study is for mapping and profiling the dose on the surface of water phantom by using mobile C-arm unit Toshiba SXT-1000A. Based on the result the dose profile is increasing up to about 57 % from anode to cathode bound of the irradiated area. This result and information can be used as a guide to manipulate these phenomena for better image quality and radiation safety for this specific and dedicated fluoroscopy unit. (author)

ITER safety

International Nuclear Information System (INIS)

Raeder, J.; Piet, S.; Buende, R.

1991-01-01

As part of the series of publications by the IAEA that summarize the results of the Conceptual Design Activities for the ITER project, this document describes the ITER safety analyses. It contains an assessment of normal operation effluents, accident scenarios, plasma chamber safety, tritium system safety, magnet system safety, external loss of coolant and coolant flow problems, and a waste management assessment, while it describes the implementation of the safety approach for ITER. The document ends with a list of major conclusions, a set of topical remarks on technical safety issues, and recommendations for the Engineering Design Activities, safety considerations for siting ITER, and recommendations with regard to the safety issues for the R and D for ITER. Refs, figs and tabs

Safety culture

International Nuclear Information System (INIS)

Keen, L.J.

2003-01-01

Safety culture has become a topic of increasing interest for industry and regulators as issues are raised on safety problems around the world. The keys to safety culture are organizational effectiveness, effective communications, organizational learning, and a culture that encourages the identification and resolution of safety issues. The necessity of a strong safety culture places an onus on all of us to continually question whether the safety measures already in place are sufficient, and are being applied. (author)

Safety Climate, Perceived Risk, and Involvement in Safety Management

OpenAIRE

Kouabenan , Dongo Rémi; Ngueutsa , Robert ,; Safiétou , Mbaye

2015-01-01

International audience; This article examines the relationship between safety climate, risk perception and involvement in safety management by first-line managers (FLM). Sixty-three FLMs from two French nuclear plants answered a questionnaire measuring perceived workplace safety climate, perceived risk, and involvement in safety management. We hypothesized that a positive perception of safety climate would promote substantial involvement in safety management, and that this effect would be str...

Assessment of the impact of dipped guideways on urban rail transit systems: Ventilation and safety requirements

Science.gov (United States)

1982-01-01

The ventilation and fire safety requirements for subway tunnels with dipped profiles between stations as compared to subway tunnels with level profiles were evaluated. This evaluation is based upon computer simulations of a train fire emergency condition. Each of the tunnel configurations evaluated was developed from characteristics that are representative of modern transit systems. The results of the study indicate that: (1) The level tunnel system required about 10% more station cooling than dipped tunnel systems in order to meet design requirements; and (2) The emergency ventilation requirements are greater with dipped tunnel systems than with level tunnel systems.

Angioedema Spotlight: A Closer Examination of Sacubitril/Valsartan Safety Results.

Science.gov (United States)

Owens, Ryan E; Oliphant, Carrie S

2017-01-01

Incorporation of neprilysin inhibition into heart failure pharmacotherapy regimens has recently been recommended by U.S. guidelines, based on results from the PARADIGM-HF trial comparing sacubitril/valsartan to enalapril. While most of the discussion has focused on efficacy, a closer examination of the safety results, particularly the incidence of angioedema during the run-in and double-blind periods, is also warranted. Although no major safety concerns were identified, an angioedema risk comparable to enalapril was found, primarily in the black population. Therefore, despite combination with an angiotensin receptor blocker, which historically has a lower incidence of angioedema, the addition of neprilysin inhibition yields an angioedema risk profile comparable to angiotensin converting enzyme (ACE) inhibitors. Clinicians should recognize this safety risk when prescribing sacubitril/valsartan and remain vigilant in counseling patients regarding the signs and symptoms of angioedema. As recommended by the guidelines, avoiding sacubitril/valsartan use concurrently or within 36 hours of the last dose of an ACE inhibitor or in patients with a history of angioedema is also crucial to minimize angioedema risk and prevent patient harm. © Copyright 2017 by the American Board of Family Medicine.

10 CFR 70.62 - Safety program and integrated safety analysis.

Science.gov (United States)

2010-01-01

...; (iv) Potential accident sequences caused by process deviations or other events internal to the... have experience in nuclear criticality safety, radiation safety, fire safety, and chemical process... this safety program; namely, process safety information, integrated safety analysis, and management...

A semi-quantitative translational pharmacology analysis to understand the relationship between in vitro ENT1 inhibition and the clinical incidence of dyspnoea and bronchospasm

International Nuclear Information System (INIS)

Rosenbrier Ribeiro, Lyn; Ian Storer, R.

2017-01-01

Adenosine contributes to the pathophysiology of respiratory disease, and adenosine challenge leads to bronchospasm and dyspnoea in patients. The equilibrative nucleoside transporter 1 (ENT1) terminates the action of adenosine by removal from the extracellular environment. Therefore, it is proposed that inhibition of ENT1 in respiratory disease patients leads to increased adenosine concentrations, triggering bronchospasm and dyspnoea. This study aims to assess the translation of in vitro ENT1 inhibition to the clinical incidence of bronchospasm and dyspnoea in respiratory disease, cardiovascular disease and healthy volunteer populations. Four marketed drugs with ENT1 activity were assessed; dipyridamole, ticagrelor, draflazine, cilostazol. For each patient population, the relationship between in vitro ENT1 [ 3 H]-NBTI binding affinity (K i ) and [ 3 H]-adenosine uptake (IC 50 ) to the incidence of: (1) bronchospasm/severe dyspnoea; (2) tolerated dyspnoea and; (3) no adverse effects, was evaluated. A high degree of ENT1 inhibition (≥ 13.3x K i , ≥ 4x IC 50 ) associated with increased incidence of bronchospasm/severe dyspnoea for patients with respiratory disease only, whereas a lower degree of ENT1 inhibition (≥ 0.1x K i , ≥ 0.05x IC 50 ) associated with a tolerable level of dyspnoea in both respiratory and cardiovascular disease patients. ENT1 inhibition had no effect in healthy volunteers. Furthermore, physicochemical properties correlative with ENT1 binding were assessed using a set of 1625 diverse molecules. Binding to ENT1 was relatively promiscuous (22% compounds K i < 1 μM) especially for neutral or basic molecules, and greater incidence tracked with higher lipophilicity (clogP > 5). This study rationalises inclusion of an assessment of ENT1 activity during early safety profiling for programs targeting respiratory disorders. - Highlights: • ENT1 inhibition causes bronchospasm and severe dyspnoea in respiratory patients. • Neutral or basic

Safety Assessment for Research Reactors and Preparation of the Safety Analysis Report. Specific Safety Guide

Energy Technology Data Exchange (ETDEWEB)

NONE

2011-11-15

The IAEA's Statute authorizes the Agency to 'establish or adopt' standards of safety for protection of health and minimization of danger to life and property' - standards that the IAEA must use in its own operations, and which States can apply by means of their regulatory provisions for nuclear and radiation safety. The IAEA does this in consultation with the competent organs of the United Nations and with the specialized agencies concerned. A comprehensive set of high quality standards under regular review is a key element of a stable and sustainable global safety regime, as is the IAEA's assistance in their application. The IAEA commenced its safety standards programme in 1958. The emphasis placed on quality, fitness for purpose and continuous improvement has led to the widespread use of the IAEA standards throughout the world. The Safety Standards Series now includes unified Fundamental Safety Principles, which represent an international consensus on what must constitute a high level of protection and safety. With the strong support of the Commission on Safety Standards, the IAEA is working to promote the global acceptance and use of its standards. Standards are only effective if they are properly applied in practice. The IAEA's safety services encompass design, siting and engineering safety, operational safety, radiation safety, safe transport of radioactive material and safe management of radioactive waste, as well as governmental organization, regulatory matters and safety culture in organizations. These safety services assist Member States in the application of the standards and enable valuable experience and insights to be shared. Regulating safety is a national responsibility, and many States have decided to adopt the IAEA's standards for use in their national regulations. For parties to the various international safety conventions, IAEA standards provide a consistent, reliable means of ensuring the effective fulfilment of obligations under the conventions

Safety Assessment for Research Reactors and Preparation of the Safety Analysis Report. Specific Safety Guide

International Nuclear Information System (INIS)

2011-01-01

The IAEA's Statute authorizes the Agency to 'establish or adopt' standards of safety for protection of health and minimization of danger to life and property' - standards that the IAEA must use in its own operations, and which States can apply by means of their regulatory provisions for nuclear and radiation safety. The IAEA does this in consultation with the competent organs of the United Nations and with the specialized agencies concerned. A comprehensive set of high quality standards under regular review is a key element of a stable and sustainable global safety regime, as is the IAEA's assistance in their application. The IAEA commenced its safety standards programme in 1958. The emphasis placed on quality, fitness for purpose and continuous improvement has led to the widespread use of the IAEA standards throughout the world. The Safety Standards Series now includes unified Fundamental Safety Principles, which represent an international consensus on what must constitute a high level of protection and safety. With the strong support of the Commission on Safety Standards, the IAEA is working to promote the global acceptance and use of its standards. Standards are only effective if they are properly applied in practice. The IAEA's safety services encompass design, siting and engineering safety, operational safety, radiation safety, safe transport of radioactive material and safe management of radioactive waste, as well as governmental organization, regulatory matters and safety culture in organizations. These safety services assist Member States in the application of the standards and enable valuable experience and insights to be shared. Regulating safety is a national responsibility, and many States have decided to adopt the IAEA's standards for use in their national regulations. For parties to the various international safety conventions, IAEA standards provide a consistent, reliable means of ensuring the effective fulfilment of obligations under the conventions

PWR AXIAL BURNUP PROFILE ANALYSIS

International Nuclear Information System (INIS)

J.M. Acaglione

2003-01-01

The purpose of this activity is to develop a representative ''limiting'' axial burnup profile for pressurized water reactors (PWRs), which would encompass the isotopic axial variations caused by different assembly irradiation histories, and produce conservative isotopics with respect to criticality. The effect that the low burnup regions near the ends of spent fuel have on system reactivity is termed the ''end-effect''. This calculation will quantify the end-effects associated with Pressurized Water Reactor (PWR) fuel assemblies emplaced in a hypothetical 21 PWR waste package. The scope of this calculation covers an initial enrichment range of 3.0 through 5.0 wt% U-235 and a burnup range of 10 through 50 GWd/MTU. This activity supports the validation of the process for ensuring conservative generation of spent fuel isotopics with respect to criticality safety applications, and the use of burnup credit for commercial spent nuclear fuel. The intended use of these results will be in the development of PWR waste package loading curves, and applications involving burnup credit. Limitations of this evaluation are that the limiting profiles are only confirmed for use with the B andW 15 x 15 fuel assembly design. However, this assembly design is considered bounding of all other typical commercial PWR fuel assembly designs. This calculation is subject to the Quality Assurance Requirements and Description (QARD) because this activity supports investigations of items or barriers on the Q-list (YMP 2001)

Comparison of the Adverse Event Profile of TheraSphere® with SIR-Spheres® for the Treatment of Unresectable Hepatocellular Carcinoma: A Systematic Review.

Science.gov (United States)

Kallini, Joseph Ralph; Gabr, Ahmed; Thorlund, Kristian; Balijepalli, Chakrapani; Ayres, Dieter; Kanters, Steve; Ebrahim, Shanil; Mills, Edward; Lewandowski, Robert J; Salem, Riad

2017-07-01

To compare the safety profiles of TheraSphere ® (glass) and SIR-Spheres ® (resin) Y90 microspheres for the treatment of hepatocellular carcinoma. A systematic review was conducted using the databases MEDLINE, Embase, and Cochrane Trials Register to identify all relevant studies. Baseline characteristics and adverse events of all grades related to gastrointestinal, hepatobiliary, and respiratory systems were collected along with commonly reported outcomes related to post-embolization syndrome. For all outcomes, data from each study were tabulated for each intervention. Adverse events and patients were summed across studies on TheraSphere ® and SIR-Spheres ® , respectively, and the resulting proportion of patients experiencing an outcome for both interventions was calculated. Thirty-one observational studies were included in the review. In the adverse events of all grades, more patients treated with resin microspheres reported gastric ulcers, hepatic encephalopathy, cholecystitis, hepatic failure, and pleural effusion. Patients treated with resin microspheres also had more hepatobiliary adverse events of grade 3 or higher. In the events related to post-embolization syndrome, glass microspheres exhibited a similar safety profile compared to resin microspheres. Ascites and nausea grade 3 or higher were recorded more frequently with glass microsphere treatment. Based on this review of the published literature, glass microspheres exhibit a safety profile with fewer gastrointestinal and pulmonary adverse events compared to resin microspheres in the treatment of hepatocellular carcinoma.

In question: the scientific value of preclinical safety pharmacology and toxicology studies with cell-based therapies

Directory of Open Access Journals (Sweden)

Christiane Broichhausen

2014-01-01

Full Text Available A new cell-based medicinal product containing human regulatory macrophages, known as Mreg_UKR, has been developed and conforms to expectations of a therapeutic drug. Here, Mreg_UKR was subjected to pharmacokinetic, safety pharmacology, and toxicological testing, which identified no adverse reactions. These results would normally be interpreted as evidence of the probable clinical safety of Mreg_UKR; however, we contend that, owing to their uncertain biological relevance, our data do not fully support this conclusion. This leads us to question whether there is adequate scientific justification for preclinical safety testing of similar novel cell-based medicinal products using animal models. In earlier work, two patients were treated with regulatory macrophages prior to kidney transplantation. In our opinion, the absence of acute or chronic adverse effects in these cases is the most convincing available evidence of the likely safety of Mreg_UKR in future recipients. On this basis, we consider that safety information from previous clinical investigations of related cell products should carry greater weight than preclinical data when evaluating the safety profile of novel cell-based medicinal products. By extension, we argue that omitting extensive preclinical safety studies before conducting small-scale exploratory clinical investigations of novel cell-based medicinal products data may be justifiable in some instances.

Clinical safety assessment of oral higenamine supplementation in healthy, young men.

Science.gov (United States)

Bloomer, R J; Schriefer, J M; Gunnels, T A

2015-10-01

Higenamine, an herbal agent also known as norcoclaurine, is thought to stimulate β-androgenic receptors and possess lipolytic activity. It is currently making its way into the dietary supplement market. To our knowledge, no studies have been conducted to determine the safety profile of oral higenamine when used alone and in conjunction with other commonly used lipolytic agents. Forty-eight men were assigned to ingest either a placebo, higenamine, caffeine, or higenamine + caffeine + yohimbe bark extract daily for a period of 8 weeks. Before and after 4 and 8 weeks of supplementation, the following variables were measured: resting respiratory rate, heart rate, blood pressure, urinalysis, complete blood count, metabolic panel, liver enzyme activity, and lipid panel. No interaction effects were noted for any variable (p > 0.05), with no changes of statistical significance occurring across time for any of the four conditions (p > 0.05). This is the first study to determine the safety profile of oral higenamine intake in human subjects. Our data indicate that 8 weeks of daily higenamine supplementation, either alone or in conjunction with caffeine and yohimbe bark extract, does not result in a statistically significant change in any of the measured outcome variables. Additional studies, inclusive of a larger sample size, are needed to extend these initial findings. © The Author(s) 2015.

IAEA Safety Standards

International Nuclear Information System (INIS)

2016-09-01

The IAEA Safety Standards Series comprises publications of a regulatory nature covering nuclear safety, radiation protection, radioactive waste management, the transport of radioactive material, the safety of nuclear fuel cycle facilities and management systems. These publications are issued under the terms of Article III of the IAEA’s Statute, which authorizes the IAEA to establish “standards of safety for protection of health and minimization of danger to life and property”. Safety standards are categorized into: • Safety Fundamentals, stating the basic objective, concepts and principles of safety; • Safety Requirements, establishing the requirements that must be fulfilled to ensure safety; and • Safety Guides, recommending measures for complying with these requirements for safety. For numbering purposes, the IAEA Safety Standards Series is subdivided into General Safety Requirements and General Safety Guides (GSR and GSG), which are applicable to all types of facilities and activities, and Specific Safety Requirements and Specific Safety Guides (SSR and SSG), which are for application in particular thematic areas. This booklet lists all current IAEA Safety Standards, including those forthcoming

78 FR 53790 - Public Forum-Safety Culture: Enhancing Transportation Safety

Science.gov (United States)

2013-08-30

... NATIONAL TRANSPORTATION SAFETY BOARD Public Forum--Safety Culture: Enhancing Transportation Safety On Tuesday and Wednesday, September 10-11, 2013, the National Transportation Safety Board (NTSB) will convene a forum titled, ``Safety Culture: Enhancing Transportation Safety.'' The forum will begin at 9:00...

New conducted electrical weapons: Electrical safety relative to relevant standards.

Science.gov (United States)

Panescu, Dorin; Nerheim, Max; Kroll, Mark W; Brave, Michael A

2017-07-01

We have previously published about TASER ® conducted electrical weapons (CEW) compliance with international standards. CEWs deliver electrical pulses that can inhibit a person's neuromuscular control or temporarily incapacitate. An eXperimental Rotating-Field (XRF) waveform CEW and the X2 CEW are new 2-shot electrical weapon models designed to target a precise amount of delivered charge per pulse. They both can deploy 1 or 2 dart pairs, delivered by 2 separate cartridges. Additionally, the XRF controls delivery of incapacitating pulses over 4 field vectors, in a rotating sequence. As in our previous study, we were motivated by the need to understand the cardiac safety profile of these new CEWs. The goal of this paper is to analyze the nominal electrical outputs of TASER XRF and X2 CEWs in reference to provisions of all relevant international standards that specify safety requirements for electrical medical devices and electrical fences. Although these standards do not specifically mention CEWs, they are the closest electrical safety standards and hence give very relevant guidance. The outputs of several TASER XRF and X2 CEWs were measured under normal operating conditions. The measurements were compared against manufacturer specifications. CEWs electrical output parameters were reviewed against relevant safety requirements of UL 69, IEC 60335-2-76 Ed 2.1, IEC 60479-1, IEC 60479-2, AS/NZS 60479.1, AS/NZS 60479.2, IEC 60601-1 and BS EN 60601-1. Our study confirmed that the nominal electrical outputs of TASER XRF and X2 CEWs lie within safety bounds specified by relevant standards.

Drug safety data mining with a tree-based scan statistic.

Science.gov (United States)

Kulldorff, Martin; Dashevsky, Inna; Avery, Taliser R; Chan, Arnold K; Davis, Robert L; Graham, David; Platt, Richard; Andrade, Susan E; Boudreau, Denise; Gunter, Margaret J; Herrinton, Lisa J; Pawloski, Pamala A; Raebel, Marsha A; Roblin, Douglas; Brown, Jeffrey S

2013-05-01

In post-marketing drug safety surveillance, data mining can potentially detect rare but serious adverse events. Assessing an entire collection of drug-event pairs is traditionally performed on a predefined level of granularity. It is unknown a priori whether a drug causes a very specific or a set of related adverse events, such as mitral valve disorders, all valve disorders, or different types of heart disease. This methodological paper evaluates the tree-based scan statistic data mining method to enhance drug safety surveillance. We use a three-million-member electronic health records database from the HMO Research Network. Using the tree-based scan statistic, we assess the safety of selected antifungal and diabetes drugs, simultaneously evaluating overlapping diagnosis groups at different granularity levels, adjusting for multiple testing. Expected and observed adverse event counts were adjusted for age, sex, and health plan, producing a log likelihood ratio test statistic. Out of 732 evaluated disease groupings, 24 were statistically significant, divided among 10 non-overlapping disease categories. Five of the 10 signals are known adverse effects, four are likely due to confounding by indication, while one may warrant further investigation. The tree-based scan statistic can be successfully applied as a data mining tool in drug safety surveillance using observational data. The total number of statistical signals was modest and does not imply a causal relationship. Rather, data mining results should be used to generate candidate drug-event pairs for rigorous epidemiological studies to evaluate the individual and comparative safety profiles of drugs. Copyright © 2013 John Wiley & Sons, Ltd.

Experimental validation of a Lyapunov-based controller for the plasma safety factor and plasma pressure in the TCV tokamak

Science.gov (United States)

Mavkov, B.; Witrant, E.; Prieur, C.; Maljaars, E.; Felici, F.; Sauter, O.; the TCV-Team

2018-05-01

In this paper, model-based closed-loop algorithms are derived for distributed control of the inverse of the safety factor profile and the plasma pressure parameter β of the TCV tokamak. The simultaneous control of the two plasma quantities is performed by combining two different control methods. The control design of the plasma safety factor is based on an infinite-dimensional setting using Lyapunov analysis for partial differential equations, while the control of the plasma pressure parameter is designed using control techniques for single-input and single-output systems. The performance and robustness of the proposed controller is analyzed in simulations using the fast plasma transport simulator RAPTOR. The control is then implemented and tested in experiments in TCV L-mode discharges using the RAPTOR model predicted estimates for the q-profile. The distributed control in TCV is performed using one co-current and one counter-current electron cyclotron heating actuation.

Identifying measures to balance the risk profile of the Tihange 2 NPP

International Nuclear Information System (INIS)

D'Eer, A.M.; Monniez, J.J.

2001-01-01

In Belgium, each Nuclear Power Plant is subject to a periodic safety reassessment. In this context, it was found to be desirable to perform a Probabilistic Safety Assessment (PSA) in support of the ten yearly back-fitting process. The Tihange 2 NPP is a 3-loop PWR having a thermal capacity of 2905 MW. Analysis of the plant's risk profile shows that implementing feasible measures for improvement of the shutdown risk, would be beneficial. This is because a configuration leading to significant risk, namely cold pressurization when the residual heat removal system is lost during reduced primary inventory, thus can be avoided. As a result the risk between reactor shutdown and power operation will be balanced. The presentation describes the lessons learnt regarding the Tihange 2 shutdown PSA model and the expected benefits following implementation of one of the proposed measures. (author)

Data Profiling

OpenAIRE

Hladíková, Radka

2010-01-01

Title: Data Profiling Author: Radka Hladíková Department: Department of Software Engineering Supervisor: Ing. Vladimír Kyjonka Supervisor's e-mail address: Abstract: This thesis puts mind on problems with data quality and data profiling. This Work analyses and summarizes problems of data quality, data defects, process of data quality, data quality assessment and data profiling. The main topic is data profiling as a process of researching data available in existing...

Efficacy and Safety of Remifentanil as an Alternative Labor Analgesic

Directory of Open Access Journals (Sweden)

Sandeep Devabhakthuni

2013-01-01

Full Text Available The objective of this review was to evaluate the clinical efficacy and safety of remifentanil in the management of labor pain. Although neuraxial analgesia is the best option during labor, alternative analgesic options are needed for patients with contraindications. Using a systematic literature search, clinical outcomes of remifentanil for labor pain have been summarized. Also, comparisons of remifentanil to other options including meperidine, epidural analgesia, fentanyl, and nitrous oxide are provided. Based on the literature review, remifentanil is associated with high overall maternal satisfaction and favorable side-effect profile. However, due to the low reporting of adverse events, large, randomized controlled trials are needed to evaluate maternal and neonatal safety adequately and determine the optimal dosing needed to provide effective analgesia. While remifentanil is a feasible alternative for patients who cannot or do not want to receive epidural analgesia, administration should be monitored closely for potential adverse effects.

Nuclear safety

International Nuclear Information System (INIS)

1991-02-01

This book reviews the accomplishments, operations, and problems faced by the defense Nuclear Facilities Safety Board. Specifically, it discusses the recommendations that the Safety Board made to improve safety and health conditions at the Department of Energy's defense nuclear facilities, problems the Safety Board has encountered in hiring technical staff, and management problems that could affect the Safety Board's independence and credibility

Sensory characteristics of European, dried, fermented sausages and the correlation to volatile profile

DEFF Research Database (Denmark)

Stahnke, Marie Louise Heller; Sunesen, Lars Oddershede; De Smedt, Anny

1999-01-01

In the European FAIR-project: Control of Bioflavour and Safety in Northern and Mediterranean Fermented Meat Products (FAIR-CT97-3227) four different sausage types were manufactured in five replicates and characterised by sensory and analytical means. The objective of the present study was to char......In the European FAIR-project: Control of Bioflavour and Safety in Northern and Mediterranean Fermented Meat Products (FAIR-CT97-3227) four different sausage types were manufactured in five replicates and characterised by sensory and analytical means. The objective of the present study...... was to characterise the flavour pattern of the FAIR sausages with regards to sensory perceived compounds and volatile/sensory profiles. According to gas chromatography-olfactometry the greatest differences between the Northern and Mediterranean sausages were attributed to coffee/roasted, phenolic and vinegar odours...

Preclinical safety and efficacy of a new recombinant FIX drug product for treatment of hemophilia B.

Science.gov (United States)

Dietrich, Barbara; Schiviz, Alexandra; Hoellriegl, Werner; Horling, Frank; Benamara, Karima; Rottensteiner, Hanspeter; Turecek, Peter L; Schwarz, Hans Peter; Scheiflinger, Friedrich; Muchitsch, Eva-Maria

2013-11-01

Baxter has developed a new recombinant factor IX (rFIX) drug product (BAX326) for treating patients with hemophilia B, or congenital FIX deficiency. An extensive preclinical program evaluated the pharmacokinetics, efficacy, and safety of BAX326 in different species. The efficacy of BAX326 was tested in three mouse models of primary pharmacodynamics: tail-tip bleeding, carotid occlusion, and thrombelastography. The pharmacokinetics was evaluated after a single intravenous bolus injection in mice, rats, and macaques. Toxicity was assessed in rats and macaques, safety pharmacology in rabbits and macaques, and immunogenicity in mice. BAX326 was shown to be efficacious in all three primary pharmacodynamic studies (P ≤ 0.0076). Hemostatic efficacy was dose related and similar for the three lots tested. Pharmacokinetic results showed that rFIX activity and rFIX antigen concentrations declined in a bi-phasic manner, similar to a previously licensed rFIX product. BAX326 was well tolerated in rabbits and macaques at all dose levels; no thrombogenic events and no adverse clinical, respiratory, or cardiovascular effects occurred. BAX326 was also shown to have a similar immunogenicity profile to the comparator rFIX product in mice. These results demonstrate that BAX326 has a favorable preclinical safety and efficacy profile, predictive of a comparable effect to that of the previously licensed rFIX in humans.

Adverse outcomes in maternity care for women with a low risk profile in The Netherlands: a case series analysis

NARCIS (Netherlands)

Martijn, L.; Jacobs, A.; Amelink-Verburg, M.; Wentzel, R.; Buitendijk, S.; Wensing, M.

2013-01-01

BACKGROUND: This study aimed to perform a structural analysis of determinants of risk of critical incidents in care for women with a low risk profile at the start of pregnancy with a view on improving patient safety. METHODS: We included 71 critical incidents in primary midwifery care and subsequent

[Adverse outcomes in maternity care for women with a low risk profile in The Netherlands: a case series analysis

NARCIS (Netherlands)

Martijn, L.M.; Jacobs, A.; Amelink-Verburg, M.P.; Wentzel, R.; Buitendijk, S.E.; Wensing, M.

2014-01-01

BACKGROUND: This study aimed to perform a structural analysis of determinants of risk of critical incidents in care for women with a low risk profile at the start of pregnancy with a view on improving patient safety. METHODS: We included 71 critical incidents in primary midwifery care and subsequent

Auto Safety

Science.gov (United States)

... Safe Videos for Educators Search English Español Auto Safety KidsHealth / For Parents / Auto Safety What's in this ... by teaching some basic rules. Importance of Child Safety Seats Using a child safety seat (car seat) ...

LFR safety approach and main ELFR safety analysis results

International Nuclear Information System (INIS)

Bubelis, E.; Schikorr, M.; Frogheri, M.; Mansani, L.; Bandini, G.; Burgazzi, L.; Mikityuk, K.; Zhang, Y.; Lo Frano, R.; Forgione, N.

2013-01-01

LFR safety approach: → A global safety approach for the LFR reference plant has been assessed and the safety analyses methodology has been developed. → LFR follows the general guidelines of the Generation IV safety concept recommendations. Thus, improved safety and higher reliability are recognized as an essential priority. → The fundamental safety objectives and the Defence-in-Depth (DiD) approach, as described by IAEA Safety Guides, have been preserved. → The recommendations of the Risk and Safety Working Group (RSWG) of GEN-IV IF has been taken into account: • safety is to be “built-in” in the fundamental design rather than “added on”; • full implementation of the Defence-in-Depth principles in a manner that is demonstrably exhaustive, progressive, tolerant, forgiving and well-balanced; • “risk-informed” approach - deterministic approach complemented with a probabilistic one; • adoption of an integrated methodology that can be used to evaluate and document the safety of Gen IV nuclear systems - ISAM. In particular the OPT tool is the fundamental methodology used throughout the design process

Safety campaigns. TIS Launches New Safety Information Campaign

CERN Multimedia

2001-01-01

Need to start a new installation and worried about safety aspects? Or are you newly responsible for safety matters in a CERN building? Perhaps you're simply interested in how to make the working environment safer for yourself and your colleagues. Whatever the case, a new information campaign launched by TIS this week can help. The most visible aspects of the new campaign will be posters distributed around the Laboratory treating a different subject each month. The Web site - http://safety.cern.ch/ - which provides all safety related information. But these are not the only aspects of the new campaign. Members of the TIS/GS group, whose contact details can be found on the safety web site, are available to give information and advice on a one-to-one basis at any time. The campaign's launch has been timed to coincide with European Safety Week, organized by the European Agency for Safety and Health at Work and the subject treated in the first posters is safety inspection. This particular topic only concerns thos...

Development of site profiles for dose reconstruction used in worker compensation claims.

Science.gov (United States)

Kenoyer, Judson L; Scalsky, Edward D; Taulbee, Timothy D

2008-07-01

For the purpose of dose reconstruction, personal dosimeter data and measured intakes through bioassay analysis (i.e., in-vivo and in-vitro measurements) should be used whenever possible and given precedence over area monitoring data, survey data, or source term data. However, this is not always possible. A worker's exposure record may be incomplete or missing, or, based on directives and guidelines at the time, a worker may not have been monitored during his or her time of employment. In an effort to recognize, analyze, and incorporate all possible considerations of potential exposures, the National Institute for Occupational Safety and Health Radiation Dose Reconstruction Program developed "site profiles" for all of the major U.S. Department of Energy sites and Atomic Weapons Employer sites. Site profiles are technical documents that (1) provide a brief, general overview of the site; (2) identify the facilities on site with a brief description of the processes and radionuclides used in these processes; (3) contain detailed information on the historical detection limits for film, thermoluminescent dosimeter, and bioassay measurements that are used by the dose reconstructor to interpret a worker's available monitoring records; and (4) provide important supporting information for the dose reconstructor to use if the monitoring data are inadequate or unavailable. When a complete set of monitoring data for an individual is unavailable, it is the parameters in the site profile that are of the most use to the dose reconstructor. These parameters include facility monitoring data (by radionuclide, mechanism of intake, year of exposure, location within a facility); occupational medical x rays and techniques used; environmental measurements (by area on site, radiation type, energy range); minimum detectable activities of the types and kinds of instruments used to detect the different radionuclides; specific source terms (quantities of material and their molecular form

The safety of pharmacologic treatment for pediatric obesity.

Science.gov (United States)

Chao, Ariana M; Wadden, Thomas A; Berkowitz, Robert I

2018-04-01

Pediatric obesity is a serious public health concern. Five medications have been approved by the Food and Drug Administration (FDA) for chronic weight management in adults with obesity, when used as an adjunct to lifestyle modification. Orlistat is the only FDA-approved medication for pediatric patients aged 12 years and above. Areas covered: This paper summarizes safety and efficacy data from clinical trials of weight loss medications conducted among pediatric samples. Relevant studies were identified through searches in PubMed. Expert opinion: Orlistat, as an adjunct to lifestyle modification, results in modest weight losses and may be beneficial for some pediatric patients with obesity. However, gastrointestinal side effects are common and may limit use. In adults taking orlistat, rare but severe adverse events, including liver and renal events, have been reported. Recent pediatric pharmacokinetic studies of liraglutide have demonstrated similar safety and tolerability profiles as found in adults, with gastrointestinal disorders being the most common adverse events. Clinical trials are needed of liraglutide, as well as other medications for obesity, that systematically evaluate their risks and benefits in pediatric patients.

Chapter No.4. Safety analyses

International Nuclear Information System (INIS)

2002-01-01

In 2001 the activity in the field of safety analyses was focused on verification of the safety analyses reports for NPP V-2 Bohunice and NPP Mochovce concerning the new profiled fuel and probabilistic safety assessment study for NPP Mochovce. The calculation safety analyses were performed and expert reviews for the internal UJD needs were elaborated. An important part of work was performed also in solving of scientific and technical tasks appointed within bilateral projects of co-operation between UJD and its international partnership organisations as well as within international projects ordered and financed by the European Commission. All these activities served as an independent support for UJD in its deterministic and probabilistic safety assessment of nuclear installations. A special attention was paid to a review of probabilistic safety assessment study of level 1 for NPP Mochovce. The probabilistic safety analysis of NPP related to the full power operation was elaborated in the study and a contribution of the technical and operational improvements to the risk decreasing was quantified. A core damage frequency of the reactor was calculated and the dominant initiating events and accident sequences with the major contribution to the risk were determined. The target of the review was to determine the acceptance of the sources of input information, assumptions, models, data, analyses and obtained results, so that the probabilistic model could give a real picture of the NPP. The review of the study was performed in co-operation of UJD with the IAEA (IPSART mission) as well as with other external organisations, which were not involved in the elaboration of the reviewed document and probabilistic model of NPP. The review was made in accordance with the IAEA guidelines and methodical documents of UJD and US NRC. In the field of calculation safety analyses the UJD activity was focused on the analysis of an operational event, analyses of the selected accident scenarios

The association between EMS workplace safety culture and safety outcomes.

Science.gov (United States)

Weaver, Matthew D; Wang, Henry E; Fairbanks, Rollin J; Patterson, Daniel

2012-01-01

Prior studies have highlighted wide variation in emergency medical services (EMS) workplace safety culture across agencies. To determine the association between EMS workplace safety culture scores and patient or provider safety outcomes. We administered a cross-sectional survey to EMS workers affiliated with a convenience sample of agencies. We recruited these agencies from a national EMS management organization. We used the EMS Safety Attitudes Questionnaire (EMS-SAQ) to measure workplace safety culture and the EMS Safety Inventory (EMS-SI), a tool developed to capture self-reported safety outcomes from EMS workers. The EMS-SAQ provides reliable and valid measures of six domains: safety climate, teamwork climate, perceptions of management, working conditions, stress recognition, and job satisfaction. A panel of medical directors, emergency medical technicians and paramedics, and occupational epidemiologists developed the EMS-SI to measure self-reported injury, medical errors and adverse events, and safety-compromising behaviors. We used hierarchical linear models to evaluate the association between EMS-SAQ scores and EMS-SI safety outcome measures. Sixteen percent of all respondents reported experiencing an injury in the past three months, four of every 10 respondents reported an error or adverse event (AE), and 89% reported safety-compromising behaviors. Respondents reporting injury scored lower on five of the six domains of safety culture. Respondents reporting an error or AE scored lower for four of the six domains, while respondents reporting safety-compromising behavior had lower safety culture scores for five of the six domains. Individual EMS worker perceptions of workplace safety culture are associated with composite measures of patient and provider safety outcomes. This study is preliminary evidence of the association between safety culture and patient or provider safety outcomes.

Transformational and passive leadership as cross-level moderators of the relationships between safety knowledge, safety motivation, and safety participation.

Science.gov (United States)

Jiang, Lixin; Probst, Tahira M

2016-06-01

While safety knowledge and safety motivation are well-established predictors of safety participation, less is known about the impact of leadership styles on these relationships. The purpose of the current study was to examine whether the positive relationships between safety knowledge and motivation and safety participation are contingent on transformational and passive forms of safety leadership. Using multilevel modeling with a sample of 171 employees nested in 40 workgroups, we found that transformational safety leadership strengthened the safety knowledge-participation relationship, whereas passive leadership weakened the safety motivation-participation relationship. Under low transformational leadership, safety motivation was not related to safety participation; under high passive leadership, safety knowledge was not related to safety participation. These results are discussed in light of organizational efforts to increase safety-related citizenship behaviors. Copyright © 2016 Elsevier Ltd and National Safety Council. All rights reserved.

Selecting of key safety parameters in reactor nuclear safety supervision

International Nuclear Information System (INIS)

He Fan; Yu Hong

2014-01-01

The safety parameters indicate the operational states and safety of research reactor are the basis of nuclear safety supervision institution to carry out effective supervision to nuclear facilities. In this paper, the selecting of key safety parameters presented by the research reactor operating unit to National Nuclear Safety Administration that can express the research reactor operational states and safety when operational occurrence or nuclear accident happens, and the interrelationship between them are discussed. Analysis shows that, the key parameters to nuclear safety supervision of research reactor including design limits, operational limits and conditions, safety system settings, safety limits, acceptable limits and emergency action level etc. (authors)

Light vehicle crash avoidance needs and countermeasure profiles for safety applications based on vehicle-to-vehicle communications

Science.gov (United States)

2013-04-30

This report discusses light-vehicle crash countermeasure profiles and functions for five target pre-crash scenario groups based on vehicle-to-vehicle (V2V) communications. Target pre-crash scenario groups include rear-end, lane change, opposite direc...

The orthodontist's profile in Minas Gerais

Directory of Open Access Journals (Sweden)

Luiz Fernando Eto

2012-06-01

Full Text Available OBJECTIVE: Due of the growing number of orthodontists and courses in Orthodontics, interest has grown in having a profile of these practitioners in Minas Gerais state (Brazil, showing how do they work in order to promote excellence in orthodontics, showing the most used techniques, the changes in the target public, and other views that impact on the future of the specialty and professional groups. METHODS: Questionnaires were sent to all orthodontists registered with the Regional Council of Dentistry of Minas Gerais (Conselho Regional de Odontologia de Minas Gerais, CRO-MG until March 30, 2005, consisting of 722 professionals. Questionnaires were sent back by 241 (33% professionals. CONCLUSIONS: This study clarified some relevant aspects about the profile of orthodontists in Minas Gerais regarding their individuality, training and the techniques used. The patient base was composed mainly of teenagers (33.75% and young adults (27.45%, with referral predominantly by the patients themselves (46.79%. Among the most important facts, we can mention the lack of use of some individual protection equipment, with only 37.76% using all the features of biological safety. Final exams have been requested less frequently than initial records, and findings from the literature review is even more frightening, considering the importance of these records. Looking at the future of the profession, optimistic orthodontists did not exceed half (45% of participants.

Long-Term Safety of Drug-Eluting and Bare-Metal Stents

DEFF Research Database (Denmark)

Palmerini, Tullio; Benedetto, Umberto; Biondi-Zoccai, Giuseppe

2015-01-01

BACKGROUND: Previous meta-analyses have investigated the relative safety and efficacy profiles of different types of drug-eluting stents (DES) and bare-metal stents (BMS); however, most prior trials in these meta-analyses reported follow-up to only 1 year, and as such, the relative long-term safety....... RESULTS: Fifty-one trials that included a total of 52,158 randomized patients with follow-up duration ≥3 years were analyzed. At a median follow-up of 3.8 years, cobalt-chromium everolimus-eluting stents (EES) were associated with lower rates of mortality, definite stent thrombosis (ST), and myocardial...... infarction than BMS, paclitaxel-eluting stents (PES), and sirolimus-eluting stents (SES) and less ST than BES. Phosphorylcholine-based zotarolimus-eluting stents had lower rates of definite ST than SES and lower rates of myocardial infarction than BMS and PES. The late rates of target...

Perceived organizational support for safety and employee safety voice: the mediating role of coworker support for safety.

Science.gov (United States)

Tucker, Sean; Chmiel, Nik; Turner, Nick; Hershcovis, M Sandy; Stride, Chris B

2008-10-01

In the present study, we modeled 2 sources of safety support (perceived organizational support for safety and perceived coworker support for safety) as predictors of employee safety voice, that is, speaking out in an attempt to change unsafe working conditions. Drawing on social exchange and social impact theories, we hypothesized and tested a mediated model predicting employee safety voice using a cross-sectional survey of urban bus drivers (n = 213) in the United Kingdom. Hierarchical regression analysis showed that perceived coworker support for safety fully mediated the relationship between perceived organizational support for safety and employee safety voice. This study adds to the employee voice literature by evaluating the important role that coworkers can play in encouraging others to speak out about safety issues. Implications for research and practice related to change-oriented safety communication are discussed.

Safety of Research Reactors. Specific Safety Requirements (French Edition)

International Nuclear Information System (INIS)

2017-01-01

This Safety Requirements publication establishes requirements for all main areas of safety for research reactors, with particular emphasis on requirements for design and operation. It explains the safety objectives and concepts that form the basis for safety and safety assessment for all stages in the lifetime of a research reactor. Technical and administrative requirements for the safety of new research reactors are established in accordance with these objectives and concepts, and they are to be applied to the extent practicable for existing research reactors. The safety requirements established in this publication for the management of safety and regulatory supervision apply to site evaluation, design, manufacturing, construction, commissioning, operation (including utilization and modification), and planning for decommissioning of research reactors (including critical assemblies and subcritical assemblies). The publication is intended for use by regulatory bodies and other organizations with responsibilities in these areas and in safety analysis, verification and review, and the provision of technical support.

Relationships among Safety Climate, Safety Behavior, and Safety Outcomes for Ethnic Minority Construction Workers

Directory of Open Access Journals (Sweden)

Sainan Lyu

2018-03-01

Full Text Available In many countries, it is common practice to attract and employ ethnic minority (EM or migrant workers in the construction industry. This primarily occurs in order to alleviate the labor shortage caused by an aging workforce with a lack of new entrants. Statistics show that EM construction workers are more likely to have occupational fatal and nonfatal injuries than their local counterparts; however, the mechanism underlying accidents and injuries in this vulnerable population has been rarely examined. This study aims to investigate relationships among safety climate, safety behavior, and safety outcomes for EM construction workers. To this end, a theoretical research model was developed based on a comprehensive review of the current literature. In total, 289 valid questionnaires were collected face-to-face from 223 Nepalese construction workers and 56 Pakistani construction workers working on 15 construction sites in Hong Kong. Structural equation modelling was employed to validate the constructs and test the hypothesized model. Results show that there were significant positive relationships between safety climate and safety behaviors, and significant negative relationships between safety behaviors and safety outcomes for EM construction workers. This research contributes to the literature regarding EM workers by providing empirical evidence of the mechanisms by which safety climate affects safety behaviors and outcomes. It also provides insights in order to help the key stakeholders formulate safety strategies for EM workers in many areas where numerous EM workers are employed, such as in the U.S., the UK, Australia, Singapore, Malaysia, and the Middle East.

Relationships among Safety Climate, Safety Behavior, and Safety Outcomes for Ethnic Minority Construction Workers.

Science.gov (United States)

Lyu, Sainan; Hon, Carol K H; Chan, Albert P C; Wong, Francis K W; Javed, Arshad Ali

2018-03-09

In many countries, it is common practice to attract and employ ethnic minority (EM) or migrant workers in the construction industry. This primarily occurs in order to alleviate the labor shortage caused by an aging workforce with a lack of new entrants. Statistics show that EM construction workers are more likely to have occupational fatal and nonfatal injuries than their local counterparts; however, the mechanism underlying accidents and injuries in this vulnerable population has been rarely examined. This study aims to investigate relationships among safety climate, safety behavior, and safety outcomes for EM construction workers. To this end, a theoretical research model was developed based on a comprehensive review of the current literature. In total, 289 valid questionnaires were collected face-to-face from 223 Nepalese construction workers and 56 Pakistani construction workers working on 15 construction sites in Hong Kong. Structural equation modelling was employed to validate the constructs and test the hypothesized model. Results show that there were significant positive relationships between safety climate and safety behaviors, and significant negative relationships between safety behaviors and safety outcomes for EM construction workers. This research contributes to the literature regarding EM workers by providing empirical evidence of the mechanisms by which safety climate affects safety behaviors and outcomes. It also provides insights in order to help the key stakeholders formulate safety strategies for EM workers in many areas where numerous EM workers are employed, such as in the U.S., the UK, Australia, Singapore, Malaysia, and the Middle East.

Lurasidone for schizophrenia: a review of the efficacy and safety profile for this newly approved second-generation antipsychotic.

Science.gov (United States)

Citrome, L

2011-02-01

To describe the efficacy and safety of lurasidone for the treatment of schizophrenia. The pivotal registration trials were accessed by querying the literature databases PubMed, EMBASE, ISI Web of Knowledge, as well as http://www.fda.gov and http://www.clinicaltrials.gov for the search term 'lurasidone'. Product labelling provided additional information. All available clinical reports of studies were identified. Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the available study reports, abstracts and posters. Additional safety outcomes subject to NNH analysis were obtained from product labelling. Lurasidone is a second-generation antipsychotic approved for the treatment of schizophrenia at a recommended starting dose of 40 mg/day administered once daily with food (≥350 calories). The maximum recommended dose is 80 mg/day. Regulatory approval was based primarily on a clinical trial programme that included four 6-week randomised clinical trials demonstrating efficacy vs. placebo in acute patients with schizophrenia. One additional Phase II clinical trial was considered a failed study because neither lurasidone nor the active control, haloperidol, separated from placebo on the primary outcome measure. One additional Phase III study was completed after the new drug application was submitted to the US Food and Drug Administration. Efficacy outcomes appear consistently in favour of lurasidone 80 mg/day vs. placebo on multiple measures of psychopathology, however, at least two studies also demonstrated efficacy for the doses of 40 and 120 mg/day. NNT vs. placebo was 3-6 for response as defined by ≥20% reduction in psychopathological rating scale total scores from baseline, depending on the study and the dose. Response as defined by a ≥30% improvement yielded NNTs ranging from 7 to 13. The most common adverse events in the clinical trials were

SURVEYS OF ORGANIZATIONAL CULTURE AND SAFETY CULTURE IN NUCLEAR POWER