Population pharmacokinetic analysis of clopidogrel in healthy Jordanian subjects with emphasis optimal sampling strategy.

Science.gov (United States)

Yousef, A M; Melhem, M; Xue, B; Arafat, T; Reynolds, D K; Van Wart, S A

2013-05-01

Clopidogrel is metabolized primarily into an inactive carboxyl metabolite (clopidogrel-IM) or to a lesser extent an active thiol metabolite. A population pharmacokinetic (PK) model was developed using NONMEM(®) to describe the time course of clopidogrel-IM in plasma and to design a sparse-sampling strategy to predict clopidogrel-IM exposures for use in characterizing anti-platelet activity. Serial blood samples from 76 healthy Jordanian subjects administered a single 75 mg oral dose of clopidogrel were collected and assayed for clopidogrel-IM using reverse phase high performance liquid chromatography. A two-compartment (2-CMT) PK model with first-order absorption and elimination plus an absorption lag-time was evaluated, as well as a variation of this model designed to mimic enterohepatic recycling (EHC). Optimal PK sampling strategies (OSS) were determined using WinPOPT based upon collection of 3-12 post-dose samples. A two-compartment model with EHC provided the best fit and reduced bias in C(max) (median prediction error (PE%) of 9.58% versus 12.2%) relative to the basic two-compartment model, AUC(0-24) was similar for both models (median PE% = 1.39%). The OSS for fitting the two-compartment model with EHC required the collection of seven samples (0.25, 1, 2, 4, 5, 6 and 12 h). Reasonably unbiased and precise exposures were obtained when re-fitting this model to a reduced dataset considering only these sampling times. A two-compartment model considering EHC best characterized the time course of clopidogrel-IM in plasma. Use of the suggested OSS will allow for the collection of fewer PK samples when assessing clopidogrel-IM exposures. Copyright © 2013 John Wiley & Sons, Ltd.

The effect of high-dose dronabinol (oral THC) maintenance on cannabis self-administration.

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Schlienz, Nicolas J; Lee, Dustin C; Stitzer, Maxine L; Vandrey, Ryan

2018-06-01

There is a clear need for advancing the treatment of cannabis use disorders. Prior research has demonstrated that dronabinol (oral THC) can dose-dependently suppress cannabis withdrawal and reduce the acute effects of smoked cannabis. The present study was conducted to evaluate whether high-dose dronabinol could reduce cannabis self-administration among daily users. Non-treatment seeking daily cannabis users (N = 13) completed a residential within-subjects crossover study and were administered placebo, low-dose dronabinol (120 mg/day; 40 mg tid), or high-dose dronabinol (180-240 mg/day; 60-80 mg tid) for 12 consecutive days (order counterbalanced). During each 12-day dronabinol maintenance phase, participants were allowed to self-administer smoked cannabis containing <1% THC (placebo) or 5.7% THC (active) under forced-choice (drug vs. money) or progressive ratio conditions. Participants self-administered significantly more active cannabis compared with placebo in all conditions. When active cannabis was available, self-administration was significantly reduced during periods of dronabinol maintenance compared with placebo maintenance. There was no difference in self-administration between the low- and high-dose dronabinol conditions. Chronic dronabinol dosing can reduce cannabis self-administration in daily cannabis users and suppress withdrawal symptoms. Cannabinoid agonist medications should continue to be explored for therapeutic utility in the treatment of cannabis use disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

Study design and rationale of a comparison of prasugrel and clopidogrel in medically managed patients with unstable angina/non-ST-segment elevation myocardial infarction: the TaRgeted platelet Inhibition to cLarify the Optimal strateGy to medicallY manage Acute Coronary Syndromes (TRILOGY ACS

DEFF Research Database (Denmark)

Chin, Chee Tang; Roe, Matthew T; Fox, Keith A A

2010-01-01

Practice guidelines recommend dual antiplatelet therapy with aspirin and clopidogrel for patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) regardless of in-hospital management strategy. Prasugrel-a thienopyridine adenosine diphosphate receptor antagonist that provides...... higher and less variable levels of platelet inhibition than clopidogrel-has demonstrated benefit when used to treat ACS patients undergoing percutaneous coronary intervention. However, the optimal approach to antiplatelet therapy for high-risk, medically managed NSTE ACS patients remains uncertain...... revascularization procedures for their index event. Patients will be randomly allocated to prasugrel + aspirin versus clopidogrel + aspirin for a median duration of 18 months. A reduction in the maintenance dose of prasugrel for elderly patients (age >or=75 years) and those with body weight or=75 years). TRILOGY...

Safety of low-dose aspirin in endovascular treatment for intracranial atherosclerotic stenosis.

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Ning Ma

Full Text Available OBJECTIVES: To evaluate the safety of low-dose aspirin plus clopidogrel versus high-dose aspirin plus clopidogrel in prevention of vascular risk within 90 days of duration of dual antiplatelet therapy in patients treated with intracranial endovascular treatment. METHODS: From January 2012 to December 2013, this prospective and observational study enrolled 370 patients with symptomatic intracranial atherosclerotic stenosis of ≥70% with poor collateral undergoing intracranial endovascular treatment. Antiplatelet therapy consists of aspirin, at a low-dose of 100 mg or high-dose of 300 mg daily; clopidogrel, at a dose of 75 mg daily for 5 days before endovascular treatment. The dual antiplatelet therapy continued for 90 days after intervention. The study endpoints include acute thrombosis, subacute thrombosis, stroke or death within 90 days after intervention. RESULTS: Two hundred and seventy three patients received low-dose aspirin plus clopidogrel and 97 patients received high-dose aspirin plus clopidogrel before intracranial endovascular treatment. Within 90 days after intervention, there were 4 patients (1.5% with acute thrombosis, 5 patients (1.8% with subacute thrombosis, 17 patients (6.2% with stroke, and 2 death (0.7% in low-dose aspirin group, compared with no patient (0% with acute thrombosis, 2 patient (2.1% with subacute thrombosis, 6 patients (6.2% with stroke, and 2 death (2.1% in high-dose aspirin group, and there were no significant difference in all study endpoints between two groups. CONCLUSION: Low-dose aspirin plus clopidogrel is comparative in safety with high-dose aspirin plus clopidogrel within 90 days of duration of dual antiplatelet therapy in patients treated with intracranial endovascular treatment.

Effects of clopidogrel on the pharmacokinetics of sibutramine and its active metabolites.

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Bae, Jung-Woo; Jang, Choon-Gon; Lee, Seok-Young

2011-12-01

Sibutramine is metabolized by the enzymes CYP2B6 and CYP2C19 into 2 active metabolites, M1 (mono-desmethyl sibutramine) and M2 (di-desmethyl sibutramine). Clopidogrel is a mechanism-based inhibitor of CYP2B6 and CYP2C19. In this study, 13 extensive metabolizers of CYP2B6 and CYP2C19 were evaluated to clarify whether clopidogrel inhibits the formation of the active metabolites of sibutramine. In the control phase, each subject received a 15-mg oral dose of sibutramine. After a washout period of 2 weeks, in the clopidogrel phase, the subjects received 300 mg of clopidogrel on the first day and then 75-mg once daily for 6 days. One hour after the last dosing of clopidogrel, all subjects received 15-mg of sibutramine. Compared with the control phase, the mean sibutramine and M1 plasma concentrations were higher after clopidogrel treatment. Clopidogrel significantly increased the half-life (242% of control phase) and area under the plasma concentration-time curve from 0 to infinity (AUC(inf)) (227% of control phase) of sibutramine and decreased the apparent oral clearance (31% of control phase) of sibutramine. Pharmacokinetic analysis showed significant increases in the AUC(inf) (162% of control phase) of M1. The CYP2B6 and CYP2C19 inhibitor clopidogrel significantly inhibited the formations of M1 from sibutramine and M2 from sibutramine by 37% and 64%, respectively. Therefore, CYP2B6 and CYP2C19 are in vivo catalysts for the formation of the 2 active metabolites of sibutramine.

Genetics Home Reference: clopidogrel resistance

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... Facebook Twitter Home Health Conditions Clopidogrel resistance Clopidogrel resistance Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Clopidogrel resistance is a condition in which the drug clopidogrel ...

Comparative bioavailability of two oral formulations of clopidogrel: Determination of clopidogrel and its carboxylic acid metabolite (SR26334 under fasting and fed conditions in healthy subjects

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Brvar Nina

2014-03-01

Full Text Available Two randomized, single dose, 2-period, 2-sequence crossover studies were conducted to evaluate the comparative bioavailability of two clopidogrel formulations under fasting and fed conditions. Assessment of bioequivalence was based upon measurement of plasma concentrations of the parent drug, clopidogrel, and its major (inactive metabolite, clopidogrel carboxylic acid, using improved methanol-free extraction. Bioequivalence of Krka’s formulation to the innovator’s formulation was demonstrated under both fasting and fed conditions on 205 volunteers. Confidence intervals for AUC0-t, AUC0-inf and Cmax of clopidogrel and its main metabolite were well within the acceptance range of 80.00 to 125.00 %. Food substantially increased the bioavailability of clopidogrel from both formulations, while no effect of food on the extent and rate of exposure to the metabolite was observed. The effect of food was comparable between the two formulations, as indicated by the same direction and rank of food impact on the bioavailability of both formulations.

Clopidogrel Resistance: Current Issues

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NS Neki

2016-05-01

Full Text Available Antiplatelet agents are mainly used in the prevention and management of atherothrombotic complications. Dual antiplatelet therapy, combining aspirin and clopidogrel, is the standard care for patients having acute coronary syndromes or undergoing percutaneous coronary intervention according to the current ACC/AHA and ESC guidelines. But in spite of administration of dual antiplatelet therapy, some patients develop recurrent cardiovascular ischemic events especially stent thrombosis which is a serious clinical problem. Antiplatelet response to clopidogrel varies widely among patients based on ex vivo platelet function measurements. Clopidogrel is an effective inhibitor of platelet activation and aggregation due to its selective and irreversible blockade of the P2Y12 receptor. Patients who display little attenuation of platelet reactivity with clopidogrel therapy are labeled as low or nonresponders or clopidogrel resistant. The mechanism of clopidogrel resistance remains incompletely defined but there are certain clinical, cellular and genetic factors including polymorphisms responsible for therapeutic failure. Currently there is no standardized or widely accepted definition of clopidogrel resistance. The future may soon be realised in the routine measurement of platelet activity in the same way that blood pressure, cholesterol and blood sugar are followed to help guide the therapy, thus improving the care for millions of people. This review focuses on the methods used to identify patients with clopidogrel resistance, the underlying mechanisms, metabolism, clinical significance and current therapeutic strategies to overcome clopidogrel resistance. J Enam Med Col 2016; 6(1: 38-46

A prospective randomized trial of aspirin-clopidogrel combination therapy and dose-adjusted warfarin on indices of thrombogenesis and platelet activation in atrial fibrillation.

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Kamath, Sridhar; Blann, Andrew D; Chin, Bernard S P; Lip, Gregory Y H

2002-08-07

This study was designed to investigate whether or not combination aspirin-clopidogrel therapy would reduce markers of thrombogenesis and platelet activation in atrial fibrillation (AF), in a manner similar to warfarin. Dose-adjusted warfarin is beneficial as thromboprophylaxis in AF, but potentially serious side effects and regular monitoring leave room for alternative therapies. METHODS; We randomized 70 patients with nonvalvular AF who were not on any antithrombotic therapy to either dose-adjusted warfarin (international normalized ratio 2 to 3) (Group I) or combination therapy with aspirin 75 mg and clopidogrel 75 mg (Group II). Plasma indices of thrombogenesis (fibrin D-dimer, prothrombin fragment 1+2) and platelet activation (beta-thromboglobulin [TG] and soluble P-selectin) were quantified, along with platelet aggregation responses to standard agonists, at baseline (pretreatment) and at six weeks posttreatment. RESULTS; Pretreatment levels of fibrin D-dimer (p = 0.001), beta-TG (p = 0.01) and soluble P-selectin (p = 0.03) were raised in patients with AF, whereas plasma prothrombin fragment 1+2 levels and platelet aggregation were not significantly different compared with controls. Dose-adjusted warfarin reduced plasma levels of fibrin D-dimer, prothrombin fragment 1+2 and beta-thromboglobulin levels at six weeks (all p failed to reduce plasma indices of thrombogenesis and platelet activation in AF, although some aspects of ex vivo platelet aggregation were altered. Anticoagulation with warfarin may be superior to combination aspirin-clopidogrel therapy as thromboprophylaxis in AF.

The Effect of Combined Aspirin and Clopidogrel Treatment on Cancer Incidence.

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Leader, Avi; Zelikson-Saporta, Ravit; Pereg, David; Spectre, Galia; Rozovski, Uri; Raanani, Pia; Hermoni, Doron; Lishner, Michael

2017-07-01

Multiple studies have shown an association between aspirin treatment and a reduction in newly diagnosed cancer. Conversely, there are conflicting clinical and laboratory data on the effect of combined clopidogrel and aspirin therapy on cancer incidence, including analyses suggesting an increased cancer risk. No large-scale cohort study has been performed to address this issue in a heterogeneous real-world scenario. We investigated the effect of clopidogrel and aspirin on cancer incidence compared with aspirin alone and no antiplatelet therapy. A population-based historical cohort study of subjects aged ≥50 years covered by Clalit Health Services, an Israeli health maintenance organization, was performed. Patients treated with the newer antiplatelet drugs, prasugrel or ticagrelor, which, like clopidogrel, inhibit adenosine diphosphate receptors, and those with prior cancer were excluded. Prescription records of antiplatelet medication were retrieved. The cohort included 183,912 subjects diagnosed with 21,974 cancer cases based upon the International Classification of Diseases, Ninth Revision. Dual aspirin and clopidogrel was prescribed in 9.6%, while 49% received aspirin alone and 41% used neither. Compared with nonusers, there was a lower risk of cancer in subjects exposed to aspirin with (hazard ratio [HR] 0.46; 95% confidence interval [CI], 0.44-0.49) or without clopidogrel (HR 0.54; 95% CI, 0.52-0.56), on long-term follow-up. Combined treatment was associated with a lower cancer risk than the aspirin-only group (HR 0.92; 95% CI, 0.86-0.97). Dual clopidogrel and aspirin treatment is safe regarding the cancer risk. This study generates the hypothesis that clopidogrel may reduce cancer incidence. Copyright © 2017 Elsevier Inc. All rights reserved.

Use of clopidogrel in the reduction of myocardial damage during percutaneous coronary intervention

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Arijit Dasgupta

2009-03-01

Full Text Available Arijit Dasgupta, Debabrata MukherjeeGill Heart Institute, University of Kentucky, Lexington, KY, USAAbstract: It is estimated that approximately a quarter of patients undergoing coronary intervention may have significant post-procedural creatinine (CK/creatinine kinase myocardial band (CK-MB elevations and approximately half may have post-procedural troponin elevations. Current data suggest that periprocedural infarction is associated with short-, intermediate-, and long-term adverse outcomes, most notably mortality. This review examines the role of clopidogrel in decreasing periprocedural myonecrosis following percutaneous coronary intervention (PCI. Clopidogrel is an important pharmacologic agent used to reduce myocardial infarction post-coronary intervention as assessed directly by the evaluation of cardiac biomarkers and indirectly by the evaluation of short-term ischemic events. The optimal dose of clopidogrel is considered to be at least 300 mg given 6 to 15 hours prior to PCI but there is considerable evidence to suggest that a loading dose of 600 mg given 2 to 6 hours prior to PCI may be more efficacious in limiting post-coronary intervention events. The benefit obtained from clopidogrel appears independent of and incremental to that of other antiplatelet and antithrombotic agents used during and after coronary intervention.Keywords: percutaneous coronary intervention, myonecrosis, clopidogrel, antiplatelet agents, myocardial infarction 

ALARA review of the maintenance and repair jobs of repetitive high radiation dose at Kori Unit 3 and 4

International Nuclear Information System (INIS)

Cho, Y.H.; Moon, J.H.; Kang, C.S.; Lee, J.S.; Lee, D.H.

2003-01-01

The policy of maintaining occupational radiation dose (ORD) as low as reasonably achievable (ALARA) requires the effective reduction of ORD in the phases of design as well as operation of nuclear power plants. It has been identified that a predominant portion of ORD arises during maintenance and repair operations at nuclear power plants. The cost-effective reduction of ORD cannot be achieved without a comprehensive analysis of accumulated ORD data of existing nuclear power plants. To identify the jobs of repetitive high ORD, the ORD data of Kori Units 3 and 4 over 10-year period from 1986 to 1995 were compiled into the PC-based ORD database program. As the radiation job classification structure, 26 main jobs are considered, most of which are further subdivided into detailed jobs. According to the order of the collective dose values for 26 main jobs, 10 jobs of high collective dose are identified. As an ALARA review, then, top 10 jobs of high collective dose are statistically analyzed with regard to 1) dose rate, 2) crew number and 3) job frequency that are the factors determining the collective dose for the radiation job of interest. Through the ALARA review, main reasons causing to high collective dose values are identified as follows. The high collective dose of RCP maintenance job is mainly due to the large crew number and the high job frequency. The characteristics of refueling job are similar to those of RCP maintenance job. However, the high collective doses of SG-related jobs such as S/G nozzle dam job, S/G man-way job and S/G tube maintenance job are mainly due to high radiation dose rate. (author)

Safety and Efficacy of Acute Clopidogrel Load in Patients with Moderate and Severe Ischemic Strokes

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Amir Shaban

2016-01-01

Full Text Available Objective. To study the safety and efficacy of a clopidogrel loading dose in patients with moderate and severe acute ischemic strokes. Background. The safety of clopidogrel loading has been extensively investigated in patients with minor strokes and transient ischemic attacks. Methods. Acute ischemic stroke patients presenting consecutively to our center from 07/01/08 to 07/31/13 were screened. Clopidogrel loading was defined as at least 300 mg dose (with or without aspirin given within 6 hours of admission. We compared outcomes in patients with baseline NIHSS > 3 with and without clopidogrel loading. Results. Inclusion criteria were met for 1011 patients (43.6% females, 69.1% black, median age 63. Patients with clopidogrel loading had lower baseline NIHSS than patients who were not loaded (8 versus 9, p=0.005. The two groups had similar risk for hemorrhagic transformation (p=0.918 and symptomatic hemorrhage (p=0.599. Patients who were loaded had a lower rate of neurological worsening (38.9% versus 48.3%, p=0.031 and less in-hospital mortality (4.3% versus 13.4%, p=0.001 compared to those who were not loaded. The likelihood of having a poor functional outcome did not differ between the two groups after adjusting for NIHSS on admission (OR = 0.71, 95% CI 0.4633–1.0906, p=0.118. Conclusion. Clopidogrel loading dose was not associated with increased risk for hemorrhagic transformation or symptomatic intracranial hemorrhage in our retrospective study and was associated with reduced rates of neuroworsening following moderate and severe stroke.

Effect of cytochrome P450 2C19 polymorphism on adverse cardiovascular events after drug-eluting stent implantation in a large Hakka population with acute coronary syndrome receiving clopidogrel in southern China.

Science.gov (United States)

Zhong, Zhixiong; Hou, Jingyuan; Zhang, Qifeng; Li, Bin; Li, Cunren; Liu, Zhidong; Yang, Min; Zhong, Wei; He, Xuebo; Wu, Hesen; Zhong, Miaocai; Zhao, Pingsen

2018-04-01

The objective of this study is to evaluate the effects of cytochrome P450 2C19 (CYP2C19) polymorphism on adverse cardiovascular events (MACE) in Hakka patients with acute coronary syndrome (ACS) receiving clopidogrel who had undergone coronary drug-eluting stent placement after percutaneous coronary intervention (PCI) in southern China. Genotyping of CYP2C19 and MACE of 934 ACS patients with PCI on clopidogrel maintenance therapy were analyzed. Patients who carried loss-of-function CYP2C19 were treated with a 150-mg maintenance dose of clopidogrel or 90 mg of ticagrelor antiplatelet therapy, and patients who were non-carriers received clopidogrel therapy daily at a maintenance dose of 75 mg and the patients were followed-up for at least 12 months. The primary efficacy endpoint was a composite of cardiovascular death, myocardial infarction, and target vessel revascularization and stroke. The allelic frequency of CYP2C19*2 and CYP2C19*3 of Hakka patients in the current study was 31.64 and 5.19%, respectively. The CYP2C19 wild-type homozygotes (*1/*1) were the most predominant among the patients (40.36%), followed by the CYP2C19*2 heterozygotes (*1/*2) (40.26%). The distribution of CYP2C19 phenotypes was divided into extensive metabolizers (EM; 40.36%), intermediate metabolizers (IM; 45.61%), and poor metabolizers (PM; 14.03%). Based on the genotype-guided antiplatelet therapy, there was no significant association between the carrier status and the clinical outcome at 1, 6, and 12 months. In addition, no significant difference in the rates of bleeding was found among the three groups. After logistic regression analysis, hypertension was the only independent predictor of cardiovascular events (relative risk, 1.501; 95% CI, 1.011 to 2.229; P = 0.044). Our results shed new light on the important benefit of testing CYP2C19 polymorphisms before prescribing clopidogrel in patients treated with drug-eluting stent implantation after PCI. The testing may help to

Effect of Co-Administration of Rivaroxaban and Clopidogrel on Bleeding Time, Pharmacodynamics and Pharmacokinetics: A Phase I Study

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Michael Becka

2012-02-01

Full Text Available Dual antiplatelet therapy with acetylsalicylic acid and a thienopyridine, such as clopidogrel, is effective for the secondary prevention of cardiovascular events in patients with acute coronary syndrome, but there is still a substantial residual risk of recurrence. Although anticoagulant therapy with a vitamin K antagonist (e.g. warfarin in conjunction with antiplatelet therapy has been shown to reduce the risk of cardiovascular events, the rates of bleeding were increased with these combination therapies; hence, triple therapy with warfarin is currently only recommended in patients at low risk of bleeding. In addition, there are other limitations associated with vitamin K antagonist therapy, including the need for routine coagulation monitoring and dose adjustment to maintain the treatment within the therapeutic range. Rivaroxaban is an oral, direct Factor Xa inhibitor; in clinical practice, it is likely that rivaroxaban will be given to patients who also receive antiplatelet therapy, such as clopidogrel. This randomized, non-blinded, three-way crossover study investigated the effect of rivaroxaban on bleeding time when co­administered with clopidogrel. In addition, the influence of clopidogrel on the safety, tolerability, pharmacodynamics and pharmacokinetics of rivaroxaban was investigated. Of 27 healthy male subjects who received a single 300 mg dose of clopidogrel, 14 were identified as clopidogrel responders and were then randomized to the following three treatments: (A two doses of clopidogrel on two consecutive days (300 mg on day 1; 75 mg on day 2; (B one dose of rivaroxaban (15 mg; or (C a combination of treatments A and B (rivaroxaban given on day 2. All treatments were well tolerated. Bleeding time with co­administration of rivaroxaban and clopidogrel was significantly prolonged in four subjects, compared with either drug alone: combination treatment increased the overall least squares-means to 3.77 times baseline (90% confidence

Clopidogrel plus long-term aspirin after femoro-popliteal stenting. The CLAFS project: 1- and 2-year results

Energy Technology Data Exchange (ETDEWEB)

Strecker, Ernst-Peter K.; Boos, Irene B.L.; Goettmann, Dieter; Vetter, Sylvia [Department of Imaging, Interventional Radiology, and Nuclear Medicine, Diakonissen Hospital, Diakonissenstrasse 28, 76199, Karlsruhe (Germany)

2004-02-01

The aim of this study was to determine the patency rate after femoro-popliteal stenting followed by oral clopidogrel plus long-term aspirin. In a prospective trial, 31 patients with a total of 33 femoro-popliteal artery lesions (21 stenoses, 12 occlusions; 24 femoral, 9 popliteal) were treated with flexible tantalum stents after unsuccessful percutaneous transluminal angioplasty (PTA) preceded by local fibrinolysis in 5 of 12 patients with total occlusion. Post-interventionally, oral aspirin 100 mg was started simultaneously for the long term and was combined with an oral loading dose of 300 mg clopidogrel, followed by 75 mg clopidogrel daily for 28 days. Patients were followed for at least 12 months (maximum 34 months) by clinical examination, Doppler pressure measurement, color and duplex sonography, and angiography in case of suspicion of restenosis. In a retrospective analysis, the results were compared with those of historical groups of patients having received aspirin only (41 patients) or a long-term high-dose low molecular weight heparin (LMWH)+aspirin treatment (42 patients). Three small puncture aneurysms were treated successfully by conservative means and were categorized as minor bleeding complication. Cumulative primary patency rate (PPR) was 76{+-}7.5% (1 year), and 70{+-}9.6% (2 years) in the clopidogrel+aspirin group, thus being tendentiously better than in the aspirin-only group showing 75{+-}4.6% (1 year), and 50{+-}8.1% (2 years). Long-term high-dose LMWH+aspirin treatment showed 87{+-}5.8% (1 year), and 72{+-}9.1% (2 years), thus being superior to the other treatment regimes, with a statistically significant difference (p<0.05) between the LMWH+aspirin and the aspirin group. Clopidogrel plus aspirin is a safe medication regimen and may be effective in the prevention of early stent thrombosis. Mid- and long-term patency rate seems to be intermediate as compared with other therapeutic regimens. The LMWH+aspirin seems to be superior compared with

Clopidogrel plus long-term aspirin after femoro-popliteal stenting. The CLAFS project: 1- and 2-year results

International Nuclear Information System (INIS)

Strecker, Ernst-Peter K.; Boos, Irene B.L.; Goettmann, Dieter; Vetter, Sylvia

2004-01-01

The aim of this study was to determine the patency rate after femoro-popliteal stenting followed by oral clopidogrel plus long-term aspirin. In a prospective trial, 31 patients with a total of 33 femoro-popliteal artery lesions (21 stenoses, 12 occlusions; 24 femoral, 9 popliteal) were treated with flexible tantalum stents after unsuccessful percutaneous transluminal angioplasty (PTA) preceded by local fibrinolysis in 5 of 12 patients with total occlusion. Post-interventionally, oral aspirin 100 mg was started simultaneously for the long term and was combined with an oral loading dose of 300 mg clopidogrel, followed by 75 mg clopidogrel daily for 28 days. Patients were followed for at least 12 months (maximum 34 months) by clinical examination, Doppler pressure measurement, color and duplex sonography, and angiography in case of suspicion of restenosis. In a retrospective analysis, the results were compared with those of historical groups of patients having received aspirin only (41 patients) or a long-term high-dose low molecular weight heparin (LMWH)+aspirin treatment (42 patients). Three small puncture aneurysms were treated successfully by conservative means and were categorized as minor bleeding complication. Cumulative primary patency rate (PPR) was 76±7.5% (1 year), and 70±9.6% (2 years) in the clopidogrel+aspirin group, thus being tendentiously better than in the aspirin-only group showing 75±4.6% (1 year), and 50±8.1% (2 years). Long-term high-dose LMWH+aspirin treatment showed 87±5.8% (1 year), and 72±9.1% (2 years), thus being superior to the other treatment regimes, with a statistically significant difference (p<0.05) between the LMWH+aspirin and the aspirin group. Clopidogrel plus aspirin is a safe medication regimen and may be effective in the prevention of early stent thrombosis. Mid- and long-term patency rate seems to be intermediate as compared with other therapeutic regimens. The LMWH+aspirin seems to be superior compared with CLAFS

Clopidogrel and proton pump inhibitors--where do we stand in 2012?

LENUS (Irish Health Repository)

Drepper, Michael D

2012-05-14

Clopidogrel in association with aspirine is considered state of the art of medical treatment for acute coronary syndrome by reducing the risk of new ischemic events. Concomitant treatment with proton pump inhibitors in order to prevent gastrointestinal side effects is recommended by clinical guidelines. Clopidogrel needs metabolic activation predominantly by the hepatic cytochrome P450 isoenzyme Cytochrome 2C19 (CYP2C19) and proton pump inhibitors (PPIs) are extensively metabolized by the CYP2C19 isoenzyme as well. Several pharmacodynamic studies investigating a potential clopidogrel-PPI interaction found a significant decrease of the clopidogrel platelet antiaggregation effect for omeprazole, but not for pantoprazole. Initial clinical cohort studies in 2009 reported an increased risk for adverse cardiovascular events, when under clopidogrel and PPI treatment at the same time. These observations led the United States Food and Drug Administration and the European Medecines Agency to discourage the combination of clopidogrel and PPI (especially omeprazole) in the same year. In contrast, more recent retrospective cohort studies including propensity score matching and the only existing randomized trial have not shown any difference concerning adverse cardiovascular events when concomitantly on clopidogrel and PPI or only on clopidogrel. Three meta-analyses report an inverse correlation between clopidogrel-PPI interaction and study quality, with high and moderate quality studies not reporting any association, rising concern about unmeasured confounders biasing the low quality studies. Thus, no definite evidence exists for an effect on mortality. Because PPI induced risk reduction clearly overweighs the possible adverse cardiovascular risk in patients with high risk of gastrointestinal bleeding, combination of clopidogrel with the less CYP2C19 inhibiting pantoprazole should be recommended.

Exposure control during high maintenance jobs

International Nuclear Information System (INIS)

Hinson, C.S.; Wigginton, J.E.

1991-01-01

Occupational radiation doses at US light-water-cooled reactors (LWRs) have been decreasing every year since 1983. In 1989, the LWR average dose per reactor reached its lowest point since 1973. Historically, maintenance-related activities have accounted for between 70 and 75% of the total occupational doses at US LWRs, and most of this maintenance-related dose is accrued during plant outages. This paper will focus on high dose maintenance jobs such as steam generator replacement, recirculation pipe replacement/crack repair, induction heating stress improvement, and steam generator tube plugging/sleeving and will discuss how the doses associated with these jobs have declined over the past several years through the implementation of various ALARA techniques

Pharmacokinetic drug interactions with clopidogrel: updated review and risk management in combination therapy

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Wang ZY

2015-03-01

Full Text Available Zhi-Yu Wang,1 Meng Chen,1 Ling-Ling Zhu,2 Lu-Shan Yu,3 Su Zeng,3 Mei-Xiang Xiang,4 Quan Zhou1 1Department of Pharmacy, 2VIP Care Ward, Division of Nursing, the Second Affiliated Hospital, School of Medicine, 3Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, 4Department of Cardiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China Background: Coprescribing of clopidogrel and other drugs is common. Available reviews have addressed the drug–drug interactions (DDIs when clopidogrel is as an object drug, or focused on combination use of clopidogrel and a special class of drugs. Clinicians may still be ignorant of those DDIs when clopidogrel is a precipitant drug, the factors determining the degree of DDIs, and corresponding risk management.Methods: A literature search was performed using PubMed, MEDLINE, Web of Science, and the Cochrane Library to analyze the pharmacokinetic DDIs of clopidogrel and new P2Y12 receptor inhibitors.Results: Clopidogrel affects the pharmacokinetics of cerivastatin, repaglinide, ferulic acid, sibutramine, efavirenz, and omeprazole. Low efficacy of clopidogrel is anticipated in the presence of omeprazole, esomeprazole, morphine, grapefruit juice, scutellarin, fluoxetine, azole antifungals, calcium channel blockers, sulfonylureas, and ritonavir. Augmented antiplatelet effects are anticipated when clopidogrel is coprescribed with aspirin, curcumin, cyclosporin, St John’s wort, rifampicin, and angiotensin-converting enzyme inhibitors. The factors determining the degree of DDIs with clopidogrel include genetic status (eg, cytochrome P540 [CYP]2B6*6, CYP2C19 polymorphism, CYP3A5*3, CYP3A4*1G, and CYP1A2-163C>A, species differences, and dose strength. The DDI risk does not exhibit a class effect, eg, the effects of clopidogrel on cerivastatin versus other statins, the effects of proton pump

Inhibition of platelet aggregation by AZD6140, a reversible oral P2Y12 receptor antagonist, compared with clopidogrel in patients with acute coronary syndromes

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Storey, Robert F; Husted, Steen; Harrington, Robert A

2007-01-01

OBJECTIVES: In a substudy of DISPERSE (Dose confIrmation Study assessing anti-Platelet Effects of AZD6140 vs. clopidogRel in non-ST-segment Elevation myocardial infarction)-2, we compared the antiplatelet effects of AZD6140 and clopidogrel and assessed the effects of AZD6140 in clopidogrel...

Concomitant nitrates enhance clopidogrel response during dual anti-platelet therapy.

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Lee, Dong Hyun; Kim, Moo Hyun; Guo, Long Zhe; De Jin, Cai; Cho, Young Rak; Park, Kyungil; Park, Jong Sung; Park, Tae-Ho; Serebruany, Victor

2016-01-15

Despite advances in modern anti-platelet strategies, clopidogrel still remains the cornerstone of dual anti-platelet therapy (DAPT) in patients undergoing percutaneous coronary interventions (PCI). There is some inconclusive evidence that response after clopidogrel may be impacted by concomitant medications, potentially affecting clinical outcomes. Sustained released nitrates (SRN) are commonly used together with clopidogrel in post-PCI setting for mild vasodilatation and nitric oxide-induced platelet inhibition. We prospectively enrolled 458 patients (64.5 ± 9.6 years old, and 73.4% males) following PCI undergoing DAPT with clopidogrel and aspirin. Platelet reactivity was assessed by the VerifyNow™ P2Y12 assay at the maintenance outpatient setting. Concomitant SRN (n=266) significantly (p=0.008) enhanced platelet inhibition after DAPT (251.6 ± 80.9PRU) when compared (232.1 ± 73.5PRU) to the SRN-free (n=192) patients. Multivariate logistic regression analysis with the cut-off value of 253 PRU for defining heightened platelet reactivity confirmed independent correlation of more potent platelet inhibition during DAPT and use of SRN (Relative risk=1.675; Odds ratio [1.059-2.648]; p=0.027). In contrast, statins, calcium-channel blockers, beta blockers, angiotensin receptor blockers, ACE-inhibitors, diuretics, and anti-diabetic agents did not significantly impact platelet inhibition following DAPT. The synergic ability of SRN to enhance response during DAPT may have important clinical implications with regard to better cardiovascular protection, but extra bleeding risks, requiring further confirmation in a large randomized study. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Comparison of effect of locally available brands of clopidogrel on platelet aggregation in patients with coronary disease

International Nuclear Information System (INIS)

Khan, S.B.; Hameedullah; Noor, L.; Awan, Z.A.; Din, S.U.; Muhammad Hafeezullah, M.

2010-01-01

Background: Anticoagulant effect of clopidogrel is of utmost importance in coronary artery disease, especially in prevention of coronary stent thrombosis. Recently, many new local brands of clopidogrel have been launched, with unknown efficacy. This study was conducted with the aim to compare two locally prepared clopidogrel brands, in terms of the effect of a loading dose of 600 mg on inhibition of platelet aggregation in patients with coronary artery disease. Methods: This was a double blind randomised study. Sample population consisting of 35 patients, were admitted at Lady Reading Hospital, Peshawar, for the management of coronary artery disease. Baseline platelet aggregation of all these patients was measured. These patients were divided in two groups randomly. Group-A consisting of 18 patients was given brand 'A' clopidogrel 600 mg, while Group-B consisting of 17 patients was give brand 'B' of clopidogrel 600 mg. The platelet aggregation of both groups was then measured at baseline, and at 2, 4, and 6 hours after taking the loading dose of 600 mg. Results: Platelet aggregation time at baseline in Group-A was 2.61+- 2.28 sec. and in Group-B it was 2.24 +- 1.52 sec. (p=0.57). After 2 hours of clopidogrel administration in Group-A the platelet aggregation time was 1.44 +- 1.58 sec. and in Group-B it was 1.53 +- 1.107 sec. (p=0.85). Platelet aggregation time after 4 hours in Group-A was 0.28 +- 0.57 sec. and in Group-B 1.06 +- 1.03 sec. (p=0.009), and after 6 hours it was 0.00 +- 0.00 sec. in Group-A and in Group-B it was 0.59 +- 0.71 sec. (p=0.001). Conclusion: The two brands of clopidogrel had a significant difference in their effect on inhibition of platelet aggregation. Different brands of clopidogrel may not be equally effective. (author)

Clopidogrel discontinuation and platelet reactivity following coronary stenting

LENUS (Irish Health Repository)

2011-01-01

Summary. Aims: Antiplatelet therapy with aspirin and clopidogrel is recommended for 1 year after drug-eluting stent (DES) implantation or myocardial infarction. However, the discontinuation of antiplatelet therapy has become an important issue as recent studies have suggested a clustering of ischemic events within 90 days of clopidogrel withdrawal. The objective of this investigation was to explore the hypothesis that there is a transient ‘rebound’ increase in platelet reactivity within 3 months of clopidogrel discontinuation. Methods and Results: In this prospective study, platelet function was assessed in patients taking aspirin and clopidogrel for at least 1 year following DES implantation. Platelet aggregation was measured using a modification of light transmission aggregometry in response to multiple concentrations of adenosine diphosphate (ADP), epinephrine, arachidonic acid, thrombin receptor activating peptide and collagen. Clopidogrel was stopped and platelet function was reassessed 1 week, 1 month and 3 months later. Thirty-two patients on dual antiplatelet therapy were recruited. Discontinuation of clopidogrel increased platelet aggregation to all agonists, except arachidonic acid. Platelet aggregation in response to ADP (2.5, 5, 10, and 20 μm) and epinephrine (5 and 20 μm) was significantly increased at 1 month compared with 3 months following clopidogrel withdrawal. Thus, a transient period of increased platelet reactivity to both ADP and epinephrine was observed 1 month after clopidogrel discontinuation. Conclusions: This study demonstrates a transient increase in platelet reactivity 1 month after clopidogrel withdrawal. This phenomenon may, in part, explain the known clustering of thrombotic events observed after clopidogrel discontinuation. This observation requires confirmation in larger populations.

Safety of carotid endarterectomy in patients concurrently on clopidogrel.

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Fleming, Mark D; Stone, William M; Scott, Paul; Chapital, Alyssa B; Fowl, Richard J; Money, Samuel R

2009-01-01

Clopidogrel (Plavix) usage is increasing, primarily for the management of patients with cerebrovascular symptoms and for those receiving drug-eluting coronary artery stents. A significant percentage of these patients will require carotid endarterectomy (CEA) while they are receiving clopidogrel. Recent data have demonstrated an increased incidence of coronary stent thrombosis when clopidogrel is discontinued. The objective of this study was to determine if CEA could be performed safely while patients are continued on clopidogrel therapy. A retrospective cohort design was employed to review consecutive patients who underwent CEA over a 24-month period ending March 2007. Patients were divided into two groups based on the perioperative use of clopidogrel. Preoperative demographics and postoperative results were compared between the two groups and statistically analyzed. Of the 100 patients who underwent CEA, 19 were taking clopidogrel within 5 days of surgery. This comprised the study group. The control group consisted of the 81 patients who did not receive clopidogrel. Heparin anticoagulation was routinely utilized prior to clamping in both groups. Demographics were similar between the groups. There were no statistical differences in morbidity or mortality between the control group and the clopidogrel group. Combined stroke/death rates were equivalent between the two groups (1.2% control vs. 0% clopidogrel). One hematoma developed in the control group, which did not require operative intervention. In this series, our results suggest that patients concurrently on clopidogrel can safely undergo CEA without increased risk of hematoma or neurological complications. In view of recent data demonstrating adverse outcomes in patients discontinuing clopidogrel, this study is useful in optimally managing this group of patients.

THERAPEUTIC EQUIVALENCE OF ORIGINAL CLOPIDOGREL (PLAVIX AND ITS GENERIC (EGITROMB. RESULTS OF COMPARATIVE RANDOMIZED CROSS-OVER BLIND STUDY

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V. V. Yakusevich

2011-01-01

Full Text Available Aim. To study therapeutic equivalence (efficacy, safety and tolerability of original clopidogrel (Plavix and its generic (Egitromb in patients of high cardiovascular risk. Material and methods. Thirty one patients with coronary heart disease and indications for clopidogrel therapy were involved into the randomized cross-over blind study. Half of the patients received original clopidogrel (75 mg daily during the first 2 weeks and then they received generic clopidogrel in the same dose during next 2 weeks. Another half of the patients received the drugs in reverse order. Antiplatelet activity of Plavix and Egitromb was estimated by effects on ADP-induced platelet aggregation initially and after 2 weeks of treatment with each drug. Study blinding was provided by the following approach: doctors of cardiology clinic performed clinical monitoring and drug distribution; coded blood samples for platelet aggregation assessment were studied in independent laboratory of thrombosis; statistical data analysis was performed by biostatistics expert in other research center. Results. 2-week therapy with each drug led to a significant decrease of ADP-induced platelet aggregation which remained low after switching from original drug to generic and vice versa. Aggregation dynamics did not depend on the first administered drug. There were no significant differences between aggregation changes as a result of treatment with original or generic drug. No one adverse event was observed in association with both drugs therapy. Conclusion. Generic drug Egitromb (Egis, Hungary and original clopidogrel Plavix (Sanofi-Aventis, France have equivalent antiplatelet effect.

A Novel Multiplex HRM Assay to Detect Clopidogrel Resistance.

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Zhang, Lichen; Ma, Xiaowei; You, Guoling; Zhang, Xiaoqing; Fu, Qihua

2017-11-22

Clopidogrel is an antiplatelet medicine used to prevent blood clots in patients who have had a heart attack, stroke, or other symptoms. Variability in the clinical response to clopidogrel treatment has been attributed to genetic factors. In particular, five SNPs of rs4244285, rs4986893, rs12248560, rs662 and rs1045642 have been associated with resistance to clopidogrel therapy in Chinese population. This work involves the development of a multiplex high-resolution melting (HRM) assay to genotype all five of these loci in 2 tubes. Amplicons corresponding to distinct SNPs in a common tube were designed with the aid of uMelt prediction software to have different melting temperatures Tm by addition of a GC-rich tail to the 5' end of the certain primers. Two kinds of commercial methods, Digital Fluorescence Molecular Hybridization (DFMH) and Sanger sequencing, were used as a control. Three hundred sixteen DFMH pretested samples from consecutive acute coronary syndrome patients were used for a blinded study of multiplex HRM. The sensitivity of HRM was 100% and the specificity was 99.93% reflecting detection of variants other than the known resistance SNPs. Multiplex HRM is an effective closed-tube, highly accurate, fast, and inexpensive method for genotyping the 5 clopidogrel resistance associated SNPs.

Early clinical outcomes as a function of use of newer oral P2Y inhibitors versus clopidogrel in the EUROMAX trial

DEFF Research Database (Denmark)

Huber, Kurt; Ducrocq, Gregory; Hamm, Christian W

2017-01-01

prehospital bivalirudin with heparin with optional glycoprotein IIb/IIIa inhibitor treatment in patients with ST-segment elevation myocardial infarction triaged to pPCI. Choice of P2Y12 inhibitor was at the investigator's discretion. In a prespecified analysis, we compared event rates with clopidogrel....... Logistic regression was used to adjust for differences in baseline characteristics. Results: Prasugrel or ticagrelor was given as the loading P2Y12 inhibitor in 49% of 2198 patients and as a maintenance therapy in 59%. No differences were observed in rates of acute stent thrombosis for clopidogrel versus...

Influence of Genotype on Warfarin Maintenance Dose Predictions Produced Using a Bayesian Dose Individualization Tool.

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Saffian, Shamin M; Duffull, Stephen B; Roberts, Rebecca L; Tait, Robert C; Black, Leanne; Lund, Kirstin A; Thomson, Alison H; Wright, Daniel F B

2016-12-01

A previously established Bayesian dosing tool for warfarin was found to produce biased maintenance dose predictions. In this study, we aimed (1) to determine whether the biased warfarin dose predictions previously observed could be replicated in a new cohort of patients from 2 different clinical settings, (2) to explore the influence of CYP2C9 and VKORC1 genotype on predictive performance of the Bayesian dosing tool, and (3) to determine whether the previous population used to develop the kinetic-pharmacodynamic model underpinning the Bayesian dosing tool was sufficiently different from the test (posterior) population to account for the biased dose predictions. The warfarin maintenance doses for 140 patients were predicted using the dosing tool and compared with the observed maintenance dose. The impact of genotype was assessed by predicting maintenance doses with prior parameter values known to be altered by genetic variability (eg, EC50 for VKORC1 genotype). The prior population was evaluated by fitting the published kinetic-pharmacodynamic model, which underpins the Bayesian tool, to the observed data using NONMEM and comparing the model parameter estimates with published values. The Bayesian tool produced positively biased dose predictions in the new cohort of patients (mean prediction error [95% confidence interval]; 0.32 mg/d [0.14-0.5]). The bias was only observed in patients requiring ≥7 mg/d. The direction and magnitude of the observed bias was not influenced by genotype. The prior model provided a good fit to our data, which suggests that the bias was not caused by different prior and posterior populations. Maintenance doses for patients requiring ≥7 mg/d were overpredicted. The bias was not due to the influence of genotype nor was it related to differences between the prior and posterior populations. There is a need for a more mechanistic model that captures warfarin dose-response relationship at higher warfarin doses.

Aspirin and clopidogrel resistance: methodological challenges and opportunities

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Armen Yuri Gasparyan

2010-03-01

Full Text Available Armen Yuri GasparyanClinical Research Unit, Russell’s Hall Hospital, Dudley Group of Hospitals NHS Foundation Trust, West Midlands, UKAbstract: Antiplatelet drug resistance is one of the urgent issues in current cardiovascular medicine. Many platelet function tests have been used to define responsiveness of patients with cardiovascular disease to aspirin and clopidogrel. In most studies, cut-off values of platelet function tests for defining responsiveness to antiplatelets were chosen arbitrarily. Different tests provided wide-ranging figures of the prevalence of aspirin and clopidogrel resistance, suggesting poor correlation between currently available platelet function tests. Measurement of platelet size seems to be a promising approach for monitoring antiplatelet drug therapy. This commentary highlights some limitations of studies on aspirin and clopidogrel resistance in patients undergoing coronary interventions.Keywords: aspirin, clopidogrel, resistance, cardiovascular disease, platelet function tests

Is clopidogrel superior to aspirin in secondary prevention of vascular disease?

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Algra Ale

2000-11-01

Full Text Available Abstract The cornerstone in clinical evidence of the relative efficacy of thienopyridines (clopidogrel, ticlopidine versus aspirin in the secondary prevention of vascular disease is the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events trial. This trial showed a modest benefit in the reduction of vascular events by clopidogrel. The results differed according to qualifying disorder: myocardial infarction, -3.7%; ischaemic stroke, +7.3%; and peripheral arterial disease, +23.8% (P = 0.042. Similar results were found for ticlopidine after brain ischaemia. The safety of clopidogrel appears to be similar to that of aspirin and better than that of ticlopidine. However, the recent report of thrombotic thrombocytopenic purpura in association with clopidogrel causes concern.

Does "smoker's paradox" exist in clopidogrel-treated Turkish patients with acute coronary syndrome.

Science.gov (United States)

Edem, Efe; Kirdök, Ali Hikmet; Kınay, Ahmet Ozan; Tekin, Ümit İlker; Taş, Sedat; Alpaslan, Erkan; Pabuccu, Mustafa Türker; Akdeniz, Bahri

2016-01-01

Previously conducted studies revealed that smoking enhanced the efficacy of clopidogrel by increasing formation of the active metabolite (AM) from the prodrug through induction of the cytochrome CYP1A2. The expression of cytochrome enzymes depends on genotype and no data exists in literature conducted in Turkish patients comparing the clopidogrel responsiveness between active smokers and non-active smokers treated with clopidogrel. In this study, our aim was to investigate the clopidogrel responsiveness in clopidogrel-treated Turkish acute coronary syndrome (ACS) patients according to their smoking status. We retrospectively enrolled 258 patients who were hospitalized due to ACS. Clinical variables of the patients, especially smoking status were recorded. Clopidogrel resistance was evaluated by using adenosine diphosphate (ADP) induced platelet aggregometry. Clopidogrel resistance was detected as a change in maximal aggregation ≤20% from baseline. A total of 139 patients were active smokers while 12 were former smokers. 107 patients did not have a history of smoking. Ten of the smokers were hyporesponsive to clopidogrel, whereas 36 of non-smokers were hyporesponsive to clopidogrel (p value >612.5 predicted the clopidogrel resistance with a sensitivity of 60% (OR: 100.65, %95 CI = 19.996-506.615 p paradox" probably exists in Turkish ACS patients.

Clopidogrel is not associated with major bleeding complications during peripheral arterial surgery.

Science.gov (United States)

Stone, David H; Goodney, Philip P; Schanzer, Andres; Nolan, Brian W; Adams, Julie E; Powell, Richard J; Walsh, Daniel B; Cronenwett, Jack L

2011-09-01

Persistent variation in practice surrounds preoperative clopidogrel management at the time of vascular surgery. While some surgeons preferentially discontinue clopidogrel citing a perceived risk of perioperative bleeding, others will proceed with surgery in patients taking clopidogrel for an appropriate indication. The purpose of this study was to determine whether preoperative clopidogrel use was associated with significant bleeding complications during peripheral arterial surgery. We reviewed a prospective regional vascular surgery registry recorded by 66 surgeons from 15 centers in New England from 2003 to 2009. Preoperative clopidogrel use within 48 hours of surgery was analyzed among patients undergoing carotid endarterectomy (CEA), lower extremity bypass (LEB), endovascular abdominal aortic aneurysm repair (EVAR), and open abdominal aortic aneurysm repair (oAAA). Ruptured AAAs were excluded. Endpoints included postoperative bleeding requiring reoperation, as well as the incidence and volume of blood transfusion. Statistical analysis was performed using analysis of variance, Fisher exact, χ(2), and Wilcoxon rank-sum tests. Over the study interval, a total of 10,406 patients underwent surgery, including 5264 CEA, 2883 LEB, 1125 EVAR, and 1134 oAAA repair. Antiplatelet use among all patients varied, with 19% (n = 2010) taking no antiplatelet agents, 69% (n = 7132) taking aspirin (ASA) alone, 2.2% (n = 229) taking clopidogrel alone, and 9.7% (n = 1017) taking both ASA and clopidogrel. Clopidogrel alone or as dual antiplatelet therapy was most frequently used prior to CEA and least frequently prior to oAAA group (CEA 16.1%, LEB 9.0%, EVAR 6.5%, oAAA 5%). Reoperation for bleeding was not significantly different among patients based on antiplatelet regimen (none 1.5%, ASA 1.3%, clopidogrel 0.9%, ASA/clopidogrel 1.5%, P = .74). When analyzed by operation type, no difference in reoperation for bleeding was seen across antiplatelet regimens. There was also no

Effects of ticagrelor versus clopidogrel on platelet function in fibrinolytic-treated STEMI patients undergoing early PCI.

Science.gov (United States)

Dehghani, Payam; Lavoie, Andrea; Lavi, Shahar; Crawford, Jennifer J; Harenberg, Sebastian; Zimmermann, Rodney H; Booker, Jeff; Kelly, Sheila; Cantor, Warren J; Mehta, Shamir R; Bagai, Akshay; Goodman, Shaun G; Cheema, Asim N

2017-10-01

Patients undergoing PCI early after fibrinolytic therapy are at high risk for both thrombotic and bleeding complications. We sought to assess the pharmacodynamic effects of ticagrelor versus clopidogrel in the fibrinolytic-treated STEMI patients undergoing early PCI. Patients undergoing PCI within 24 hours of tenecteplase (TNK), aspirin, and clopidogrel for STEMI were randomized to receive additional clopidogrel 300 mg followed by 75 mg daily or ticagrelor 180 mg followed by 90 mg twice daily. The platelet reactivity units (PRU) were measured with the VerifyNow Assay before study drug administration (baseline) at 4 and 24 hours post-PCI. The primary end point was PRU ≤208 at 4 hours. A total of 140 patients (74 in ticagrelor and 66 in clopidogrel group) were enrolled. The mean PRU values at baseline were similar for the 2 groups (257.8±52.9 vs 259.5±56.7, P=.85, respectively). Post-PCI, patients on ticagrelor, compared to those on clopidogrel, had significantly lower PRU at 4 hours (78.7±88 vs 193.6±86.5, respectively, PPCI frequently had PRU >208. In this high-risk population, ticagrelor provides more prompt and potent platelet inhibition compared with clopidogrel (Funded by Astra Zeneca; NCT01930591, https://clinicaltrials.gov/ct2/show/NCT01930591). Copyright © 2017 Elsevier Inc. All rights reserved.

Association of platelet responsiveness with clopidogrel metabolism: role of compliance in the assessment of "resistance".

Science.gov (United States)

Serebruany, Victor; Cherala, Ganesh; Williams, Craig; Surigin, Serge; Booze, Christopher; Kuliczkowski, Wiktor; Atar, Dan

2009-12-01

Noncompliance is probably the major cause of clopidogrel "resistance." However, noncompliance is difficult to prove without confirming that the drug has been administered. Therefore, detection of plasma clopidogrel and/or metabolite(s) as the reliable objective method to confirm compliance is important. We sought to correlate the inhibition of platelet aggregation (IPA) with plasma levels of unchanged clopidogrel (UC), active thiol metabolite (ATM), and inactive carboxyl metabolite (ICM) in a large cohort of patients with coronary artery disease and ischemic stroke treated with clopidogrel. We conducted secondary post-hoc analyses of IPA and plasma UC, ATM, and ICM in a dataset consisting of presumably compliant patients with coronary disease (n = 422) and post-stroke (n = 209). Overall noncompliance rate was 22% (n = 138), while such risks were significantly higher in stroke survivors (n = 79, or 38%) when compared to patients with coronary disease (14%; n = 59; P = .001). Only ICM (19,154 +/- 7,228 ng/ml) was suitable for detecting compliance, while UC (15.2 +/- 9.4 ng/ml), and ATM (8.1 +/- 3.7 ng/ml) in most cases are barely detectable, and diminish over time in the stored samples. The best correlation with IPA (r2 = 0.847) was observed for active metabolite, followed by unchanged clopidogrel (r2 = 0.602), and finally inactive metabolite (r2 = 0.529). The predictive value for noncompliance was also high for inactive metabolite (c-statistic = 0.911). Therapy with clopidogrel is associated with double-digit underestimated risks for noncompliance, especially in stroke survivors, supporting the hypothesis that lack of IPA, and clopidogrel "resistance" are attributed to hidden noncompliance. Plasma ICM, but not UC, or ATM is a useful marker to monitor compliance to clopidogrel in registries and clinical trials.

Mortality in primary angioplasty patients starting antiplatelet therapy with prehospital prasugrel or clopidogrel

DEFF Research Database (Denmark)

Goldstein, Patrick; Grieco, Niccolò; Ince, Hüseyin

2016-01-01

hospitalization, we report here the 1-year follow-up data, including cardiovascular (CV) mortality. METHODS AND RESULTS: MULTIPRAC is a multinational, prospective registry of patients with ST-elevation myocardial infarction (STEMI) from 25 hospitals in nine countries, all of which had an established practice...... of prehospital start of dual antiplatelet therapy in place. The key outcome was CV death at 1 year. Among 2,036 patients followed-up through 1 year, 49 died (2.4%), 10 during the initial hospitalization and 39 within 1 year after hospital discharge. The primary analysis was based on the P2Y12-inhibitor, used...... from prehospital loading dose through hospital discharge. Prasugrel (n=824) was more commonly used than clopidogrel (n=425). The observed 1-year rates for CV death were 0.5% with prasugrel and 2.6% with clopidogrel. After adjustment for differences in baseline characteristics, treatment with prasugrel...

ANTI-INFLAMMATORY EFFECT OF CLOPIDOGREL IN ATHEROSCLEROSIS

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L. I. Buriachkovskaia

2011-01-01

Full Text Available Aim. To analyze the literary and own data about clopidogrel influence on platelets during inflammation and to reveal particularities of its usage in ischemic heart disease (IHD patients with active inflammation. Material and methods. The platelet morphology and a number of leukocyte-platelet aggregates (LTA were investigated with scanning electron microscopy in 110 patients with stable angina pectoris of I-III functional class and 18 healthy volunteers. Spontaneous and ADP-induced platelet aggregation were assessed with laser aggregatometre manufactured by LLC “BIOLA”. Mean platelet volume (MPV was estimated with the hematological analyzer . All investigations were performed in IHD patients before and after 2 months of clopidogrel treatment 75 mg a day. Results. IHD patients demonstrated appearance of LTA and big reticular platelets in the blood, increase in MPV and spontaneous aggregation. ADP-induced platelet aggregation was rarely increased probably due to acetylsalicylic acid therapy in all IHD patients. These platelet activity changes are connected with increased risk of thrombotic events and correlated with inflammation markers levels. After 2 months of clopidogrel treatment LTA number reduced in 4 times and big reticular platelets number decreased in 2.5 times as well as MPV and spontaneous aggregation achieved the normal ranges. Conclusion. Clopidogrel has not only antithrombotic effect but also can diminish platelets morphological and functional changes connected with inflammation.

P2Y12 Receptor Antagonist, Clopidogrel, Does Not Contribute to Risk of Osteoporotic Fractures in Stroke Patients

DEFF Research Database (Denmark)

Jørgensen, Niklas R; Schwarz, Peter; Iversen, Helle K

2017-01-01

Background: Stroke is a leading cause of mortality and morbidity. It is associated with excessive bone loss and risk of fracture in stroke patients is high. The P2Y12R antagonist and platelet inhibitor, clopidogrel, is widely used for secondary prevention after a stroke. However, recent studies...... have shown that clopidogrel has negative effects on bone and that long-term clopidogrel use is associated with increased fracture risk. The purpose of the current study was therefore to investigate the association of clopidogrel treatment with risk of fractures in stroke and TIA patients.......Methods:The study was a cohort study including all subjects who were prescribed clopidogrel between 1996 and 2008 in Denmark (n= 77,503). Age- and gender matched controls (n= 232,510) were randomly selected from the background population. The study end-points were occurrence of stroke or TIA and occurrence...

Effect of scutellarin on the metabolism and pharmacokinetics of clopidogrel in rats.

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Chen, Xinmeng; Jin, Jing; Chen, Yaobin; Peng, Lingling; Zhong, Guoping; Li, Jiali; Bi, Huichang; Cai, Yefeng; Huang, Min

2015-01-01

Erigeron breviscapus (Vant.) Hand-Mazz, a traditional Chinese medicine, is often co-prescribed with clopidogrel for the treatment of ischemic vascular diseases. Scutellarin is the representative bioactive flavonoid isolated from this herb. The aim of this study was to explore the effect of scutellarin on the metabolism and pharmacokinetics of clopidogrel. The in vitro studies using rat liver microsomes showed that scutellarin significantly inhibited the metabolism of clopidogrel. The IC50 value was 2.1 µM. Ten male rats were employed to investigate the effect of scutellarin on the pharmacokinetics of clopidogrel in vivo. After pretreatment with scutellarin, there were significant increases in the AUC0-∞ (from 0.9 ± 0.4 to 1.7 ± 0.6 ng/ml h; p <0.05) and Cmax (from 0.4 ± 0.1 to 0.9 ± 0.1 ng/ml; p <0.05) of clopidogrel. The pharmacokinetic data for clopidogrel active metabolite showed significant decreases in AUC0-∞ (18.2 ± 5.6 to 11.4 ± 3.7 ng/ml h; p <0.05) and Cmax (from 8.2 ± 1.2 to 4.3 ± 0.3 ng/ml; p <0.05) after pretreatment with scutellarin. Collectively, the metabolism and pharmacokinetics of clopidogrel were significantly affected by scutellarin. This study indicated that potential herb-drug interaction between scutellarin and clopidogrel should be taken into consideration in clinical use. Copyright © 2014 John Wiley & Sons, Ltd.

New in vitro effects of clopidogrel on platelets in hyperlipidemic and healthy subjects

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Derya Özsavcı

2010-06-01

Full Text Available Objective: We aimed to detect novel in vitro effects of clopidogrel on platelets by assessment of the following parameters: malondialdehyde, glutathione, nitrite, aggregation response, and expressions of P-selectin, fibrinogen, apolipoprotein A1, apolipoprotein B, and phosphatidylserine.Materials and Methods: Platelets were obtained from healthy (n: 9 and hyperlipidemic (n: 9 volunteers. Expressions of P-selectin, fibrinogen, apolipoproteins A1/B and phosphatidylserine with and without clopidogrel were assayed by flow cytometry. Malondialdehyde, glutathione, aggregation and nitrite levels were also assayed. Results: Without clopidogrel, the baseline values of platelet aggregation, malondialdehyde, and expressions of P-selectin, fibrinogen and phosphatidylserine were significantly higher, whereas nitrite and expression of apolipoproteins A1/B were significantly lower in hyperlipidemics than in the healthy group. In both groups, clopidogrel significantly reduced aggregation and expression of fibrinogen, but it elevated nitrite levels. Clopidogrel significantly decreased P-selectin and phosphatidylserine expression and malondialdehyde but increased expressions of apolipoproteins A1/B only in hyperlipidemics. Conclusion: It seems that clopidogrel has some new in vitro antiplatelet effects. The present study is a basic in vitro study to suggest new insights into the effects of clopidogrel on platelet functions.

Clinical determinants of clopidogrel responsiveness in a heterogeneous cohort of Puerto Rican Hispanics.

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Hernandez-Suarez, Dagmar F; Scott, Stuart A; Tomey, Matthew I; Melin, Kyle; Lopez-Candales, Angel; Buckley, Charlotte E; Duconge, Jorge

2017-09-01

Clopidogrel is by far the most prescribed platelet adenosine diphosphate (ADP) antagonist in Puerto Rico despite the advent of newer agents (prasugrel and ticagrelor). Given the paucity of data on clopidogrel responsiveness in Hispanics, we sought to determine the association between clinical characteristics and platelet reactivity in Puerto Rican patients on clopidogrel therapy. A total of 100 Puerto Rican patients on clopidogrel therapy were enrolled and allocated into two groups: Group I, without high on-treatment platelet reactivity (HTPR); and Group II, with HTPR. Platelet function was measured ex vivo using the VerifyNow® P2Y12 assay. The cohort was comprised of Hispanic patients with coronary artery disease (57%), peripheral artery disease (32%), carotid artery stenosis (7%), cerebral artery aneurysm (2%), and stroke (2%). Mean platelet reactivity was 200 ± 61 P2Y12 reaction units (PRUs) (range: 8-324), and 35% of patients had HTPR (PRUs ⩾ 230). Multivariable logistic regression analysis determined that diabetes mellitus (DM) [odds ratio (OR) = 3.27; 95% confidence interval (CI): 1.20-8.96], use of proton-pump inhibitors (PPIs) (OR = 3.60; 95% CI: 1.09-11.82), and calcium channel blockers (CCBs) (OR = 3.10; 95% CI: 1.09-8.83) were independent predictors of HTPR ( p Puerto Rican Hispanic patients on clopidogrel, 35% had HTPR. Furthermore, DM, PPIs and CCBs predicted HTPR. Clinical outcome data are needed to identify appropriate PRU thresholds for risk prediction in the Puerto Rican population.

[Clinical applications of dosing algorithm in the predication of warfarin maintenance dose].

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Huang, Sheng-wen; Xiang, Dao-kang; An, Bang-quan; Li, Gui-fang; Huang, Ling; Wu, Hai-li

2011-12-27

To evaluate the feasibility of clinical application for genetic based dosing algorithm in the predication of warfarin maintenance dose in Chinese population. The clinical data were collected and blood samples harvested from a total of 126 patients undergoing heart valve replacement. The genotypes of VKORC1 and CYP2C9 were determined by melting curve analysis after PCR. They were divided randomly into the study and control groups. In the study group, the first three doses of warfarin were prescribed according to the predicted warfarin maintenance dose while warfarin was initiated at 2.5 mg/d in the control group. The warfarin doses were adjusted according to the measured international normalized ratio (INR) values. And all subjects were followed for 50 days after an initiation of warfarin therapy. At the end of a 50-day follow-up period, the proportions of the patients on a stable dose were 82.4% (42/51) and 62.5% (30/48) for the study and control groups respectively. The mean durations of reaching a stable dose of warfarin were (27.5 ± 1.8) and (34.7 ± 1.8) days and the median durations were (24.0 ± 1.7) and (33.0 ± 4.5) days in the study and control groups respectively. Significant differences existed in the durations of reaching a stable dose between the two groups (P = 0.012). Compared with the control group, the hazard ratio (HR) for the duration of reaching a stable dose was 1.786 in the study group (95%CI 1.088 - 2.875, P = 0.026). The predicted dosing algorithm incorporating genetic and non-genetic factors may shorten the duration of achieving efficiently a stable dose of warfarin. And the present study validates the feasibility of its clinical application.

Effects of VKORC1 Genetic Polymorphisms on Warfarin Maintenance Dose Requirement in a Chinese Han Population

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Yan, Xiaojuan; Yang, Feng; Zhou, Hanyun; Zhang, Hongshen; Liu, Jianfei; Ma, Kezhong; Li, Yi; Zhu, Jun; Ding, Jianqiang

2015-01-01

Background VKORC1 is reported to be capable of treating several diseases with thrombotic risk, such as cardiac valve replacement. Some single-nucleotide polymorphisms (SNPs) in VKORC1 are documented to be associated with clinical differences in warfarin maintenance dose. This study explored the correlations of VKORC1–1639 G/A, 1173 C/T and 497 T/G genetic polymorphisms with warfarin maintenance dose requirement in patients undergoing cardiac valve replacement. Material/Methods A total of 298 patients undergoing cardiac valve replacement were recruited. During follow-up, clinical data were recorded. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was applied to detect VKORC1–1639 G/A, 1173 C/T and 497 T/G polymorphisms, and genotypes were analyzed. Results Correlations between warfarin maintenance dose and baseline characteristics revealed statistical significances of age, gender and operation methods with warfarin maintenance dose (all PWarfarin maintenance dose in VKORC1–1639 G/A AG + GG carriers was obviously higher than in AA carriers (Pwarfarin maintenance dose was apparently higher in patients with CT genotype (Pwarfarin maintenance dose (all Pwarfarin maintenance dose in patients undergoing cardiac valve replacement; meanwhile, gender, operation method and method for heart valve replacement might also be correlate with warfarin maintenance dose. PMID:26583785

Predictors of premature clopidogrel discontinuation within 30 days of successful coronary artery stenting

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Çayan Cakir

2018-01-01

Full Text Available Objective: We aimed to determine the prevalence, predictors, and mortality rate of premature clopidogrel discontinuation within 30 days of successful coronary stenting. Methods: All consecutive patients who underwent successful coronary stent implantation at our hospital between December 2006 and December 2007 were prospectively included in this study. Patients were interviewed by telephone 30 days after stent implantation. Premature clopidogrel discontinuation was defined as follows: patients who did not continue clopidogrel after discharge were defined as “never used” and patients who received clopidogrel for <20 days or interrupted therapy for at least 5 successive days within the first 30 days were defined as “partially used.” Results: Follow-up data were available for 381 patients and 58 (15.2% patients reported premature clopidogrel discontinuation. No mortality and only 1 (0.3% stent thrombosis occurred in adherent patients, whereas there were 2 (3.4% mortalities and 6 (10.3% stent thrombosis in the patients who prematurely discontinued clopidogrel. Those who discontinued clopidogrel therapy were older (P = 0.02, more likely to be female (P = 0.02, single (P = 0.03, of lower economic (P < 0.05 and educational status (P < 0.01, more likely to have chronic disease (P = 0.04, less likely to have undergone previous stenting (P = 0.01, and were more likely to be receiving a larger number of drugs (P < 0.05. In multivariate analysis, low- or intermediate-economic status, no history of previous stent implantation, and total number of prescribed drugs using were factors independently associated with premature clopidogrel discontinuation. Conclusion: This study demonstrates several predictors of premature clopidogrel discontinuation. This data may help clinicians pay particular attention to these patients in an attempt to improve the outcomes of coronary stenting.

Association of clopidogrel treatment with risk of mortality and cardiovascular events following myocardial infarction in patients with and without diabetes

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Andersson, Charlotte; Lyngbæk, Stig; Nguyen, Cu Dinh

2012-01-01

Pharmacodynamic studies have shown that persistently high platelet reactivity is common in patients with diabetes in spite of clopidogrel treatment. Clinical trials have not convincingly demonstrated that clopidogrel benefits patients with diabetes as much patients without diabetes....

Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular disease

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Squizzato, Alessandro; Keller, Tymen; Romualdi, Erica; Middeldorp, Saskia

2011-01-01

Aspirin is the prophylactic antiplatelet drug of choice for people with cardiovascular disease. Adding a second antiplatelet drug to aspirin may produce additional benefit for those at high risk and those with established cardiovascular disease. To quantify the benefit and harm of adding clopidogrel

Pharmacogenetic association study on clopidogrel response in Puerto Rican Hispanics with cardiovascular disease: a novel characterization of a Caribbean population

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Hernandez-Suarez DF

2018-06-01

Full Text Available Dagmar F Hernandez-Suarez,1 Mariana R Botton,2 Stuart A Scott,2 Matthew I Tomey,3 Mario J Garcia,4 Jose Wiley,4 Pedro A Villablanca,5 Kyle Melin,6 Angel Lopez-Candales,7 Jessicca Y Renta,8 Jorge Duconge9 1Cardiovascular Medicine Division, Department of Medicine, University of Puerto Rico School of Medicine, San Juan, PR, USA; 2Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 3Cardiovascular Medicine Division, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 4Division of Cardiovascular Diseases, Department of Medicine, Montefiore Medical Center/Albert Einstein College of Medicine New York, NY, USA; 5Division of Cardiology, Department of Medicine, New York University Langone Medical Center, New York, NY, USA; 6Department of Pharmacy Practice, University of Puerto Rico Medical Sciences Campus, San Juan, PR, USA; 7Cardiovascular Medicine Division, Department of Medicine, University of Puerto Rico School of Medicine, San Juan, PR, USA; 8Department of Biochemistry, University of Puerto Rico Medical Sciences Campus, San Juan, PR, USA; 9Pharmaceutical Sciences Department, University of Puerto Rico Medical Sciences Campus, San Juan, PR, USA Introduction: High on-treatment platelet reactivity (HTPR to clopidogrel imparts an increased risk for ischemic events in adults with coronary artery disease. Platelet reactivity varies with ethnicity and is influenced by both clinical and genetic variables; however, no clopidogrel pharmacogenetic studies with Puerto Rican patients have been reported. Therefore, we sought to identify clinical and genetic determinants of on-treatment platelet reactivity in a cohort of Puerto Rican patients with cardiovascular disease. Methods: We performed a retrospective study of 111 patients on 75 mg/day maintenance dose of clopidogrel. Patients were allocated into 2 groups: Group I, without HTPR; and Group II, with HTPR. Platelet function was

Efficacy and Safety of a Colistin Loading Dose, High-Dose Maintenance Regimen in Critically Ill Patients With Multidrug-Resistant Gram-Negative Pneumonia.

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Elefritz, Jessica L; Bauer, Karri A; Jones, Christian; Mangino, Julie E; Porter, Kyle; Murphy, Claire V

2017-09-01

Emergence of multidrug-resistant (MDR) gram-negative (GN) pathogens and lack of novel antibiotics have increased the use of colistin, despite unknown optimal dosing. This study aimed to evaluate the safety and efficacy of a colistin loading dose, high-dose (LDHD) maintenance regimen in patients with MDR-GN pneumonia. A retrospective cohort analysis was performed comparing critically ill patients with MDR-GN pneumonia pre- and postimplementation of a colistin LDHD guideline with a primary outcome of clinical cure. Safety was assessed using incidence of acute kidney injury (AKI) based on RIFLE (risk, injury, failure, loss, end-stage renal disease) criteria. Seventy-two patients met the inclusion criteria (42 preimplementation and 30 postimplementation). Clinical cure was achieved in 23 (55%) patients in the preimplementation group and 20 (67%) patients in the postimplementation group ( P = .31). AKI occurred in 50% of the patients during the preimplementation period and 58% during the postimplementation period ( P = .59) with no difference in initiation rates of renal replacement therapy. The increased clinical cure rate after implementation of the colistin LDHD guideline did not reach statistical significance. The LDHD guideline, however, was not associated with an increased incidence of AKI, despite higher intravenous colistin doses. Opportunity exists to optimize colistin dosage while balancing toxicity, but larger studies are warranted.

Safety, tolerability, and initial efficacy of AZD6140, the first reversible oral adenosine diphosphate receptor antagonist, compared with clopidogrel, in patients with non-ST-segment elevation acute coronary syndrome: primary results of the DISPERSE-2 trial

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Cannon, Christopher P; Husted, Steen; Harrington, Robert A

2007-01-01

, or clopidogrel 300-mg loading dose plus 75 mg once daily for up to 12 weeks. RESULTS: The primary end point, the Kaplan-Meier rate of major or minor bleeding through 4 weeks, was 8.1% in the clopidogrel group, 9.8% in the AZD6140 90-mg group, and 8.0% in the AZD6140 180-mg group (p = 0.43 and p = 0.......96, respectively, vs. clopidogrel); the major bleeding rates were 6.9%, 7.1%, and 5.1%, respectively (p = 0.91 and p = 0.35, respectively, vs. clopidogrel). Although not statistically significant, favorable trends were seen in the Kaplan-Meier rates of myocardial infarction (MI) over the entire study period (MI: 5...

Pharmacogenetics of clopidogrel: comparison between a standard and a rapid genetic testing.

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Saracini, Claudia; Vestrini, Anna; Galora, Silvia; Armillis, Alessandra; Abbate, Rosanna; Giusti, Betti

2012-06-01

CYP2C19 variant alleles are independent predictors of clopidogrel response variability and occurrence of major adverse cardiovascular events in high-risk vascular patients on clopidogrel therapy. Increasing evidence suggests a combination of platelet function testing with CYP2C19 genetic testing may be more effective in identifying high-risk individuals for alternative antiplatelet therapeutic strategies. A crucial point in evaluating the use of these polymorphisms in clinical practice, besides test accuracy, is the cost of the genetic test and rapid availability of the results. One hundred acute coronary syndrome patients were genotyped for CYP2C19*2,*3,*4,*5, and *17 polymorphisms with two platforms: Verigene(®) and the TaqMan(®) system. Genotyping results obtained by the classical TaqMan approach and the rapid Verigene approach showed a 100% concordance for all the five polymorphisms investigated. The Verigene system had shorter turnaround time with respect to TaqMan. The cost of reagents for TaqMan genotyping was lower than that for the Verigene system, but the effective manual staff involvement and the relative cost resulted in higher cost for TaqMan than for Verigene. The Verigene system demonstrated good performance in terms of turnaround time and cost for the evaluation of the clopidogrel poor metabolizer status, giving genetic information in suitable time (206 min) for a therapeutic strategy decision.

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

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

2017-08-01

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

Perioperative clopidogrel is associated with increased bleeding and blood transfusion at the time of lower extremity bypass.

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Jones, Douglas W; Schermerhorn, Marc L; Brooke, Benjamin S; Conrad, Mark F; Goodney, Philip P; Wyers, Mark C; Stone, David H

2017-06-01

Controversy persists surrounding the perceived bleeding risk associated with perioperative clopidogrel use in patients undergoing lower extremity bypass (LEB). The purpose of this study was to examine the LEB bleeding risk and clinical sequelae associated with clopidogrel. All LEBs in the Vascular Quality Initiative (VQI) from 2008 to 2014 were studied. The exposure was perioperative clopidogrel. Primary outcomes were blood transfusion, estimated blood loss ≥500 mL, and reoperation for bleeding. Secondary outcomes included mean operative time, major cardiac events, respiratory complications, infectious complications, and in-hospital mortality. Univariate and multivariable analyses were used to analyze patients on the basis of clopidogrel use and its association with outcomes. Nonparametric test for trend and Mantel-Haenszel methods were used to analyze association of clopidogrel use with blood transfusion and secondary outcomes. Among the LEB cohort (N = 9179), 28% (n = 2544) were taking clopidogrel and 72% (n = 6635) were not. Patients taking clopidogrel were more likely to have coronary disease, prior coronary intervention, abnormal findings on stress test, and aspirin use (P blood transfusion (38% vs 24%; P blood loss ≥500 mL (21% vs 12%; P blood transfusion (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.5-2.1; P 2-unit blood transfusion (OR, 2.0; 95% CI, 1.7-2.5; P blood transfusion amount revealed no remaining effect of clopidogrel on major cardiac events (OR, 1.1; P = .4) or respiratory complications (OR, 1.0; P = .8). Perioperative clopidogrel use in LEB surgery is associated with increased blood loss and blood transfusion. Associated clinical sequelae include increased cardiac and pulmonary complications. Accordingly, surgeons should consider discontinuation of perioperative clopidogrel when it is clinically appropriate unless it is strongly indicated at the time of LEB. Copyright © 2017 Society for Vascular Surgery. Published by

A pharmacogenetics-based warfarin maintenance dosing algorithm from Northern Chinese patients.

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Jinxing Chen

Full Text Available Inconsistent associations with warfarin dose were observed in genetic variants except VKORC1 haplotype and CYP2C9*3 in Chinese people, and few studies on warfarin dose algorithm was performed in a large Chinese Han population lived in Northern China. Of 787 consenting patients with heart-valve replacements who were receiving long-term warfarin maintenance therapy, 20 related Single nucleotide polymorphisms were genotyped. Only VKORC1 and CYP2C9 SNPs were observed to be significantly associated with warfarin dose. In the derivation cohort (n = 551, warfarin dose variability was influenced, in decreasing order, by VKORC1 rs7294 (27.3%, CYP2C9*3(7.0%, body surface area(4.2%, age(2.7%, target INR(1.4%, CYP4F2 rs2108622 (0.7%, amiodarone use(0.6%, diabetes mellitus(0.6%, and digoxin use(0.5%, which account for 45.1% of the warfarin dose variability. In the validation cohort (n = 236, the actual maintenance dose was significantly correlated with predicted dose (r = 0.609, P<0.001. Our algorithm could improve the personalized management of warfarin use in Northern Chinese patients.

A Pharmacogenetics-Based Warfarin Maintenance Dosing Algorithm from Northern Chinese Patients

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Luo, Fang; Wang, Jin'e; Shi, Yi; Tan, Yu; Chen, Qianlong; Zhang, Yu; Hui, Rutai; Wang, Yibo

2014-01-01

Inconsistent associations with warfarin dose were observed in genetic variants except VKORC1 haplotype and CYP2C9*3 in Chinese people, and few studies on warfarin dose algorithm was performed in a large Chinese Han population lived in Northern China. Of 787 consenting patients with heart-valve replacements who were receiving long-term warfarin maintenance therapy, 20 related Single nucleotide polymorphisms were genotyped. Only VKORC1 and CYP2C9 SNPs were observed to be significantly associated with warfarin dose. In the derivation cohort (n = 551), warfarin dose variability was influenced, in decreasing order, by VKORC1 rs7294 (27.3%), CYP2C9*3(7.0%), body surface area(4.2%), age(2.7%), target INR(1.4%), CYP4F2 rs2108622 (0.7%), amiodarone use(0.6%), diabetes mellitus(0.6%), and digoxin use(0.5%), which account for 45.1% of the warfarin dose variability. In the validation cohort (n = 236), the actual maintenance dose was significantly correlated with predicted dose (r = 0.609, Pwarfarin use in Northern Chinese patients. PMID:25126975

High-dose buprenorphine: perioperative precautions and management strategies.

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Roberts, D M; Meyer-Witting, M

2005-02-01

Buprenorphine has been in clinical use in anaesthesia for several decades. Recently, the high-dose sublingual formulation (Subutex, Reckitt Benckiser, Slough, U.K.) has been increasingly used as maintenance therapy in opioid dependence, as an alternative to methadone and other pharmacological therapies. Buprenorphine has unique pharmacological properties making it well suited for use as a maintenance therapy in opioid dependence. However, these same properties may cause difficulty in the perioperative management of pain. Buprenorphine is a partial opioid agonist, attenuating the effects of supplemental illicit or therapeutic opioid agonists. As a result of its high receptor affinity, supplemental opioids do not readily displace buprenorphine from the opioid receptor in standard doses. High-dose buprenorphine has an extended duration of action that prolongs both of these effects. The perioperative management of patients stabilized on high-dose buprenorphine and undergoing surgery requires consideration of the likely analgesic requirements. Where possible the buprenorphine should be continued. Pain management should focus on maximizing non-opioid analgesia, local anaesthesia and non-pharmacological techniques. Where pain may not be adequately relieved by these methods, the addition of a full opioid agonist such as fentanyl or morphine at appropriate doses should be considered, accompanied by close monitoring in a high dependency unit. In situations where this regimen is unlikely to be effective, preoperative conversion to morphine or methadone may be an option. Where available, liaison with a hospital-based alcohol and drug service should always be considered.

Effects of clopidogrel and clarithromycin on the disposition of sibutramine and its active metabolites M1 and M2 in relation to CYP2B6*6 polymorphism.

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Pan, Wei; Bae, Soo-Kyung; Shim, Eon-Jeong; Park, Sung-Eun; Lee, Sang-Seop; Park, Soo-Jin; Yeo, Chang-Woo; Zhou, Hong-Hao; Shon, Ji-Hong; Shin, Jae-Gook

2013-02-01

Plasma concentrations of sibutramine and its two active metabolites after single oral dose of sibutramine were determined in Korean healthy male subjects with different CYP2B6 genotypes (CYP2B6*1/*1, *1/*6 and *6/*6), either alone or after four-day pretreatment with clopidogrel or clarithromycin. The pretreatment with clopidogrel and clarithromycin raised the mean area under the concentration-time curve (AUC) of sibutramine by 163% and 255%, respectively. Co-administration of clarithromycin, combined with CYP2B6*6/*6 genotype, led to highest concentration of sibutramine. The molar sum AUC (M1 + M2) was raised by 35% in the clopidogrel phase but not significantly affected by clarithromycin or CYP2B6 genotype. The CYP2B6*6/*6 subjects in the clopidogrel phase showed the highest molar AUC (M1 + M2) among three genotype groups throughout the three phases. The exposure of sibutramine and its metabolites seemed to be associated with the CYP2B6 genotype. The treatment of clopidogrel significantly altered the disposition of active metabolites as well as sibutramine, but clarithromycin only affects the disposition of sibutramine. These results suggest that the perturbation of CYP2B6 activity may contribute to the inter-individual variation of sibutramine drug responses although the clinical relevance is remained to be established.

A review of a priori regression models for warfarin maintenance dose prediction.

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Ben Francis

Full Text Available A number of a priori warfarin dosing algorithms, derived using linear regression methods, have been proposed. Although these dosing algorithms may have been validated using patients derived from the same centre, rarely have they been validated using a patient cohort recruited from another centre. In order to undertake external validation, two cohorts were utilised. One cohort formed by patients from a prospective trial and the second formed by patients in the control arm of the EU-PACT trial. Of these, 641 patients were identified as having attained stable dosing and formed the dataset used for validation. Predicted maintenance doses from six criterion fulfilling regression models were then compared to individual patient stable warfarin dose. Predictive ability was assessed with reference to several statistics including the R-square and mean absolute error. The six regression models explained different amounts of variability in the stable maintenance warfarin dose requirements of the patients in the two validation cohorts; adjusted R-squared values ranged from 24.2% to 68.6%. An overview of the summary statistics demonstrated that no one dosing algorithm could be considered optimal. The larger validation cohort from the prospective trial produced more consistent statistics across the six dosing algorithms. The study found that all the regression models performed worse in the validation cohort when compared to the derivation cohort. Further, there was little difference between regression models that contained pharmacogenetic coefficients and algorithms containing just non-pharmacogenetic coefficients. The inconsistency of results between the validation cohorts suggests that unaccounted population specific factors cause variability in dosing algorithm performance. Better methods for dosing that take into account inter- and intra-individual variability, at the initiation and maintenance phases of warfarin treatment, are needed.

A review of a priori regression models for warfarin maintenance dose prediction.

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Francis, Ben; Lane, Steven; Pirmohamed, Munir; Jorgensen, Andrea

2014-01-01

A number of a priori warfarin dosing algorithms, derived using linear regression methods, have been proposed. Although these dosing algorithms may have been validated using patients derived from the same centre, rarely have they been validated using a patient cohort recruited from another centre. In order to undertake external validation, two cohorts were utilised. One cohort formed by patients from a prospective trial and the second formed by patients in the control arm of the EU-PACT trial. Of these, 641 patients were identified as having attained stable dosing and formed the dataset used for validation. Predicted maintenance doses from six criterion fulfilling regression models were then compared to individual patient stable warfarin dose. Predictive ability was assessed with reference to several statistics including the R-square and mean absolute error. The six regression models explained different amounts of variability in the stable maintenance warfarin dose requirements of the patients in the two validation cohorts; adjusted R-squared values ranged from 24.2% to 68.6%. An overview of the summary statistics demonstrated that no one dosing algorithm could be considered optimal. The larger validation cohort from the prospective trial produced more consistent statistics across the six dosing algorithms. The study found that all the regression models performed worse in the validation cohort when compared to the derivation cohort. Further, there was little difference between regression models that contained pharmacogenetic coefficients and algorithms containing just non-pharmacogenetic coefficients. The inconsistency of results between the validation cohorts suggests that unaccounted population specific factors cause variability in dosing algorithm performance. Better methods for dosing that take into account inter- and intra-individual variability, at the initiation and maintenance phases of warfarin treatment, are needed.

Platelet function testing to predict hyporesponsiveness to clopidogrel in patients with chest pain seen in the emergency department

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Sharma RK

2013-05-01

Full Text Available Rakesh K Sharma,1 Stephen W Erickson,1 Rohit Sharma,2 Donald J Voelker,1 Hanumanth K Reddy,1 Harvinder Dod,2 James D Marsh1 1Division of Cardiovascular Medicine, University of Arkansas for Medical Sciences, Little Rock, 2Medical Center of South Arkansas, El Dorado, AR, USA Background: A dual antiplatelet regimen has been shown to reduce the risk of major adverse cardiovascular events after percutaneous coronary intervention. However, there is little information available on inhibition of platelet aggregation in patients with a prior coronary stent presenting with chest pain. This study evaluated the prevalence of hyporesponsiveness to clopidogrel and factors associated with this in patients presenting to our emergency department with chest pain who had previously undergone coronary stent placement and were prescribed dual antiplatelet therapy. Methods: Responsiveness to clopidogrel was evaluated in a cohort of 533 consecutive stented patients presenting to the emergency department with chest pain. P2Y12 reaction units (PRU and percent P2Y12 inhibition with clopidogrel were measured in all patients. Of 533 patients, 221 (41.6% had PRU ≥ 230. A multivariate logistic regression model was used to determine the relationship between hyporesponsiveness to clopidogrel (defined as PRU ≥ 230 and several potential risk factors, ie, gender, age, race, type 1 or type 2 diabetes, hypertension, smoking, chronic renal failure, and obesity. Results: There was a greater risk of hyporesponsiveness in African Americans than in non-African American patients (adjusted odds ratio [OR] = 2.165, in patients with type 2 diabetes than in those without (adjusted OR = 2.109, and in women than in men (adjusted OR = 1.813, as well as a greater risk of hyporesponsiveness with increasing age (adjusted OR = 1.167 per decade. Conclusion: There was a high prevalence of hyporesponsiveness to clopidogrel in patients presenting with chest pain and a prior coronary stent. Non

Effect of addition of clopidogrel to aspirin on subdural hematoma: meta-analysis of randomized clinical trials.

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Bakheet, Majid F; Pearce, Lesly A; Hart, Robert G

2015-06-01

Clopidogrel combined with aspirin is routinely prescribed after coronary artery stenting, in patients with acute coronary syndromes, and recently to prevent stroke in patients with acute minor ischemic stroke and TIA. Subdural hematomas are an important complication of antithrombotic treatment, but the risk associated with clopidogrel plus aspirin has not been previously defined. To quantify the risk of subdural hematoma associated with dual antiplatelet therapy with clopidogrel plus aspirin. Randomized clinical trials comparing clopidogrel plus aspirin with aspirin alone were identified by searching the Cochrane Central Register of Controlled Trials from 1990 to 2014, and restricted to those with more than 7 days of treatment. Two reviewers independently extracted data about subdural hematomas. Of 24 randomized trials testing clopidogrel added to aspirin, results for subdural hematoma were available for 11 trials, of which eight did not identify any subdural hematomas. The three trials reporting subdural hematomas were double-blind and included patients with recent lacunar stroke, acute coronary syndromes or atrial fibrillation with a total of 23,136 patients (mean age 66 years) and reported 39 subdural hematomas during a mean follow-up 2.1 years per patient. Clopidogrel plus aspirin was associated with a significantly increased risk of subdural hematoma compared with aspirin alone (risk ratio 2.0, 95% CI 1.0, 3.8; P = 0.04; fixed effects model; I2 for heterogeneity of 0%, P = 0.51). The average absolute incidence of subdural hematoma averaged 1.1 (95% CI 0.7,1.6) per 1000 patient - years among those assigned clopidogrel plus aspirin in 11 randomized trials. The absolute rate of subdural hematoma during dual antiplatelet therapy is low, averaging 1.1 per 1000 patient-years. Chronic treatment with clopidogrel plus aspirin significantly increases the risk of subdural hematoma compared with aspirin alone. © 2014 World Stroke Organization.

Effects of Clopidogrel Therapy on Oxidative Stress, Inflammation, Vascular Function and Progenitor Cells in Stable Coronary Artery Disease

Science.gov (United States)

Ramadan, Ronnie; Dhawan, Saurabh S.; Syed, Hamid; Pohlel, F. Khan; Binongo, Jose Nilo G.; Ghazzal, Ziyad B.; Quyyumi, Arshed A.

2014-01-01

Background Traditional cardiovascular risk factors lead to endothelial injury and activation of leucocytes and platelets that initiate and propagate atherosclerosis. We proposed that clopidogrel therapy in patients with stable CAD imparts a pleiotropic effect that extends beyond anti-platelet aggregation to other athero-protective processes. Methods Forty-one subjects were randomized in a double-blind, placebo-controlled crossover study to either clopidogrel 75 mg daily or placebo for 6-weeks, and then transitioned immediately to the other treatment for an additional 6 weeks. We assessed 1) endothelial function as flow-mediated dilation of the brachial artery, 2) arterial stiffness and central augmentation index using applanation tonometry, 3) vascular function as fingertip reactive hyperemia index, 4) inflammation by measuring plasma CD40 ligand and serum high-sensitivity c-reactive protein levels, 5) oxidative stress by measuring plasma aminothiols, and 6) circulating progenitor cells, at baseline and at the end of each 6-week treatment period. Results Clopidogrel therapy resulted in a significant reduction in soluble CD40 ligand (p=0.03), a pro-thrombotic and pro-inflammatory molecule derived mainly from activated platelets. However, clopidogrel therapy had no effect on endothelial function, arterial stiffness, inflammatory and oxidative stress markers, or progenitor cells. Conclusions Our findings suggest a solitary anti-platelet effect of clopidogrel therapy in patients with stable CAD, with no effect on other sub-clinical markers of cardiovascular disease risk. PMID:24336012

Acinetobacter Prosthetic Joint Infection Treated with Debridement and High-Dose Tigecycline.

Science.gov (United States)

Vila, Andrea; Pagella, Hugo; Amadio, Claudio; Leiva, Alejandro

2016-12-01

Prosthesis retention is not recommended for multidrug-resistant Acinetobacter prosthetic joint infection due to its high failure rate. Nevertheless, replacing the prosthesis implies high morbidity and prolonged hospitalization. Although tigecycline is not approved for the treatment of prosthetic joint infection due to multidrug resistant Acinetobacter baumannii, its appropriate use may preclude prosthesis exchange. Since the area under the curve divided by the minimum inhibitory concentration is the best pharmacodynamic predictor of its efficacy, we used tigecycline at high dose, in order to optimize its efficacy and achieve implant retention in 3 patients who refused prosthesis exchange. All patients with prosthetic joint infections treated at our Institution are prospectively registered in a database. Three patients with early prosthetic joint infection of total hip arthroplasty due to multidrug resistant A. baumannii were treated with debridement, antibiotics and implant retention, using a high maintenance dose of tigecycline (100 mg every 12 hours). The cases were retrospectively reviewed. All patients signed informed consent for receiving off-label use of tigecycline. Tigecycline was well tolerated, allowing its administration at high maintenance dose for a median of 40 days (range 30-60). Two patients were then switched to minocycline at standard doses for a median of 3.3 months in order to complete treatment. Currently, none of the patients showed relapse. Increasing the dose of tigecycline could be considered as a means to better attain pharmacodynamic targets in patients with severe or difficult-to-treat infections. Tigecycline at high maintenance dose might be useful when retention of the implant is attempted for treatment for prosthetic joint infections due to multidrug resistant Acinetobacter. Although this approach might be promising, off-label use of tigecycline should be interpreted cautiously until prospective data are available. Tigecycline is

Post Hoc Analyses of Randomized Clinical Trial for the Effect of Clopidogrel Added to Aspirin on Kidney Function.

Science.gov (United States)

Ikeme, Jesse C; Pergola, Pablo E; Scherzer, Rebecca; Shlipak, Michael G; Benavente, Oscar R; Peralta, Carmen A

2017-07-07

Despite the high burden of CKD, few specific therapies are available that can halt disease progression. In animal models, clopidogrel has emerged as a potential therapy to preserve kidney function. The effect of clopidogrel on kidney function in humans has not been established. The Secondary Prevention of Small Subcortical Strokes Study randomized participants with prior lacunar stroke to treatment with aspirin or aspirin plus clopidogrel. We compared annual eGFR decline and incidence of rapid eGFR decline (≥30% from baseline) using generalized estimating equations and interval-censored proportional hazards regression, respectively. We also stratified our analyses by baseline eGFR, systolic BP target, and time after randomization. At randomization, median age was 62 (interquartile range, 55-71) years old; 36% had a history of diabetes, 90% had hypertension, and the median eGFR was 81 (interquartile range, 65-94) ml/min per 1 m 2 . Persons receiving aspirin plus clopidogrel had an average annual change in kidney function of -1.39 (95% confidence interval, -1.15 to -1.62) ml/min per 1.73 m 2 per year compared with -1.52 (95% confidence interval, -1.30 to -1.74) ml/min per 1.73 m 2 per year among persons receiving aspirin only ( P =0.42). Rapid kidney function decline occurred in 21% of participants receiving clopidogrel plus aspirin compared with 22% of participants receiving aspirin plus placebo (hazard ratio, 0.94; 95% confidence interval, 0.79 to 1.10; P =0.42). Findings did not vary by baseline eGFR, time after randomization, or systolic BP target (all P values for interaction were >0.3). We found no effect of clopidogrel added to aspirin compared with aspirin alone on kidney function decline among persons with prior lacunar stroke. Copyright © 2017 by the American Society of Nephrology.

Effect of Smoking on Pharmacokinetics of Clopidogrel, an ...

African Journals Online (AJOL)

... in patients undergoing PCI. Keywords: Antiplatelet, Clopidogrel, Pharmacokinetics, Smoking, Cigarette ..... regimen of choice to prevent thrombotic complications. [2,16]. ... either the parent drug [19] or the carboxylic acid metabolite as an ...

Clopidogrel, a P2Y12 receptor antagonist, potentiates the inflammatory response in a rat model of peptidoglycan polysaccharide-induced arthritis.

Directory of Open Access Journals (Sweden)

Analia E Garcia

Full Text Available The P2Y12 receptor plays a crucial role in the regulation of platelet activation by several agonists, which is irreversibly antagonized by the active metabolite of clopidogrel, a widely used anti-thrombotic drug. In this study, we investigated whether reduction of platelet reactivity leads to reduced inflammatory responses using a rat model of erosive arthritis. We evaluated the effect of clopidogrel on inflammation in Lewis rats in a peptidoglycan polysaccharide (PG-PS-induced arthritis model with four groups of rats: 1 untreated, 2 clopidogrel-treated, 3 PG-PS-induced, and 4 PG-PS-induced and clopidogrel-treated. There were significant differences between the PG-PS+clopidogrel group when compared to the PG-PS group including: increased joint diameter and clinical manifestations of inflammation, elevated plasma levels of pro-inflammatory cytokines (IL-1 beta, interferon (IFN gamma, and IL-6, an elevated neutrophil blood count and an increased circulating platelet count. Plasma levels of IL-10 were significantly lower in the PG-PS+clopidogrel group compared to the PG-PS group. Plasma levels of platelet factor 4 (PF4 were elevated in both the PG-PS and the PG-PS+clopidogrel groups, however PF4 levels showed no difference upon clopidogrel treatment, suggesting that the pro- inflammatory effect of clopidogrel may be due to its action on cells other than platelets. Histology indicated an increase in leukocyte infiltration at the inflammatory area of the joint, increased pannus formation, blood vessel proliferation, subsynovial fibrosis and cartilage erosion upon treatment with clopidogrel in PG-PS-induced arthritis animals. In summary, animals treated with clopidogrel showed a pro-inflammatory effect in the PG-PS-induced arthritis animal model, which might not be mediated by platelets. Elucidation of the mechanism of clopidogrel-induced cell responses is important to understand the role of the P2Y12 receptor in inflammation.

Clopidogrel, a P2Y12 receptor antagonist, potentiates the inflammatory response in a rat model of peptidoglycan polysaccharide-induced arthritis.

Science.gov (United States)

Garcia, Analia E; Mada, Sripal R; Rico, Mario C; Dela Cadena, Raul A; Kunapuli, Satya P

2011-01-01

The P2Y12 receptor plays a crucial role in the regulation of platelet activation by several agonists, which is irreversibly antagonized by the active metabolite of clopidogrel, a widely used anti-thrombotic drug. In this study, we investigated whether reduction of platelet reactivity leads to reduced inflammatory responses using a rat model of erosive arthritis. We evaluated the effect of clopidogrel on inflammation in Lewis rats in a peptidoglycan polysaccharide (PG-PS)-induced arthritis model with four groups of rats: 1) untreated, 2) clopidogrel-treated, 3) PG-PS-induced, and 4) PG-PS-induced and clopidogrel-treated. There were significant differences between the PG-PS+clopidogrel group when compared to the PG-PS group including: increased joint diameter and clinical manifestations of inflammation, elevated plasma levels of pro-inflammatory cytokines (IL-1 beta, interferon (IFN) gamma, and IL-6), an elevated neutrophil blood count and an increased circulating platelet count. Plasma levels of IL-10 were significantly lower in the PG-PS+clopidogrel group compared to the PG-PS group. Plasma levels of platelet factor 4 (PF4) were elevated in both the PG-PS and the PG-PS+clopidogrel groups, however PF4 levels showed no difference upon clopidogrel treatment, suggesting that the pro- inflammatory effect of clopidogrel may be due to its action on cells other than platelets. Histology indicated an increase in leukocyte infiltration at the inflammatory area of the joint, increased pannus formation, blood vessel proliferation, subsynovial fibrosis and cartilage erosion upon treatment with clopidogrel in PG-PS-induced arthritis animals. In summary, animals treated with clopidogrel showed a pro-inflammatory effect in the PG-PS-induced arthritis animal model, which might not be mediated by platelets. Elucidation of the mechanism of clopidogrel-induced cell responses is important to understand the role of the P2Y12 receptor in inflammation.

Aspirin, but not clopidogrel, reduces collateral conductance in a rabbit model of femoral artery occlusion

NARCIS (Netherlands)

Hoefer, Imo E.; Grundmann, Sebastian; Schirmer, Stephan; van Royen, Niels; Meder, Benjamin; Bode, Christoph; Piek, Jan J.; Buschmann, Ivo R.

2005-01-01

OBJECTIVES The objective of this study was to test the potential of aspirin and clopidogrel to influence collateral artery growth (arteriogenesis). BACKGROUND Aspirin and clopidogrel are antiplatelet agents commonly used in the treatment of ischemic cardiovascular disease. Both inhibit platelet

Clopidogrel plus aspirin versus aspirin alone for preventing cardiovascular events.

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Squizzato, Alessandro; Bellesini, Marta; Takeda, Andrea; Middeldorp, Saskia; Donadini, Marco Paolo

2017-12-14

Aspirin is the prophylactic antiplatelet drug of choice for people with cardiovascular disease. Adding a second antiplatelet drug to aspirin may produce additional benefit for people at high risk and people with established cardiovascular disease. This is an update to a previously published review from 2011. To review the benefit and harm of adding clopidogrel to aspirin therapy for preventing cardiovascular events in people who have coronary disease, ischaemic cerebrovascular disease, peripheral arterial disease, or were at high risk of atherothrombotic disease, but did not have a coronary stent. We updated the searches of CENTRAL (2017, Issue 6), MEDLINE (Ovid, 1946 to 4 July 2017) and Embase (Ovid, 1947 to 3 July 2017) on 4 July 2017. We also searched ClinicalTrials.gov and the WHO ICTRP portal, and handsearched reference lists. We applied no language restrictions. We included all randomised controlled trials comparing over 30 days use of aspirin plus clopidogrel with aspirin plus placebo or aspirin alone in people with coronary disease, ischaemic cerebrovascular disease, peripheral arterial disease, or at high risk of atherothrombotic disease. We excluded studies including only people with coronary drug-eluting stent (DES) or non-DES, or both. We collected data on mortality from cardiovascular causes, all-cause mortality, fatal and non-fatal myocardial infarction, fatal and non-fatal ischaemic stroke, major and minor bleeding. The overall treatment effect was estimated by the pooled risk ratio (RR) with 95% confidence interval (CI), using a fixed-effect model (Mantel-Haenszel); we used a random-effects model in cases of moderate or severe heterogeneity (I 2 ≥ 30%). We assessed the quality of the evidence using the GRADE approach. We used GRADE profiler (GRADE Pro) to import data from Review Manager to create a 'Summary of findings' table. The search identified 13 studies in addition to the two studies in the previous version of our systematic review. Overall

Efficacy of Clopidogrel and Clinical Outcome When Clopidogrel Is Coadministered With Atorvastatin and Lansoprazole

Science.gov (United States)

Zhang, Jian-rong; Wang, Di-qing; Du, Jun; Qu, Guang-su; Du, Jian-lin; Deng, Song-bai; Liu, Ya-jie; Cai, Jin-xi; She, Qiang

2015-01-01

Abstract This prospective, randomized, nonblind, controlled trial evaluated the effects of clopidogrel on platelet function upon coadministration with atorvastatin and lansoprazole. One hundred four adult patients with non-ST-segment elevated acute coronary syndrome (NSTE-ACS) who underwent percutaneous coronary intervention (PCI) with drug-eluting stent implantation were included. All patients were treated with standard dual antiplatelet therapy (DAPT) plus rosuvastatin 10 mg daily after the operation. On the sixth day after PCI, patients were randomly divided into 4 groups, Group A: DAPT + atorvastatin 20 mg daily (a change from rosuvastatin to atorvastatin) + lansoprazole 30 mg daily, Group B: DAPT + atorvastatin 20 mg daily (a change from rosuvastatin to atorvastatin), Group C: DAPT + lansoprazole 30 mg daily (continuing to take rosuvastatin), Group D is the control group. Additional drugs were used according to the situation of patients. Platelet function and concentrations of platelet activation markers (granular membrane protein 140 (P-selectin), thromboxane B2 (TXB2), and human soluble cluster of differentiation 40 ligand (sCD40L)) were assessed before randomization and at 15- and 30-day follow-up visits. All patients were maintained on treatment for 6 months and observed for bleeding and ischemic events. A total of 104 patients were enrolled, 27 patients in group A, 26 patients in Group B/C, 25 patients in Group D separately, and all the patients were analyzed. There were no differences in platelet function and the levels of platelet activation markers (P-selectin, TXB2, and sCD40L) among or within the 4 groups at the 3 time points of interest (P > 0.05). In the subsequent 6 months, no significant bleeding events occurred, and 12 patients experienced ischemic events, these results were also not significantly different among the groups (P > 0.05). In patients diagnosed with NSTE-ACS who have had drug-eluting stent

Analysis of the Interaction between Clopidogrel, Aspirin, and Proton Pump Inhibitors Using the FDA Adverse Event Reporting System Database.

Science.gov (United States)

Suzuki, Yukiya; Suzuki, Honami; Umetsu, Ryogo; Uranishi, Hiroaki; Abe, Junko; Nishibata, Yuri; Sekiya, Yasuaki; Miyamura, Nobuteru; Hara, Hideaki; Tsuchiya, Teruo; Kinosada, Yasutomi; Nakamura, Mitsuhiro

2015-01-01

Clopidogrel is an antiplatelet agent widely used in combination with aspirin to limit the occurrence of cardiovascular (embolic/thrombotic) events. Consensus guidelines recommend proton pump inhibitors (PPIs) as a gastrointestinal (GI) prophylactic measure for all patients receiving dual antiplatelet therapy with clopidogrel and aspirin. The objective of this study was to analyze the effect of the simultaneous use of clopidogrel, aspirin, and PPIs on hemorrhagic and embolic/thrombotic events using the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. Reports of hemorrhagic and embolic/thrombotic events between 2004 and 2013 were analyzed with a reporting odds ratio (ROR) algorithm and logistic regression methods. The Medical Dictionary for Regulatory Activities Preferred Terms was used to identify such events. Regarding hemorrhagic events, the adjusted RORs of the concomitant use of aspirin and clopidogrel and those of PPIs prescribed with aspirin and clopidogrel were 4.40 (95% confidence interval [CI], 4.02-4.81) and 3.40 (95% CI, 2.84-4.06), respectively. For embolic/thrombotic events, the adjusted RORs of the concomitant use of aspirin and clopidogrel and those of PPIs prescribed with aspirin and clopidogrel were 2.37 (95% CI, 2.16-2.59) and 2.38 (95% CI, 2.00-2.84), respectively. Among patients included in the FAERS database, the concurrent use of aspirin and clopidogrel with PPIs reduced the adjusted ROR of GI hemorrhagic events. PPIs had little influence on the adjusted ROR of embolic/thrombotic events. These results support the use of PPIs as a preventive measure against GI hemorrhagic events for patients receiving clopidogrel and aspirin.

Comparative effect of clopidogrel plus aspirin and aspirin monotherapy on hematological parameters using propensity score matching

Directory of Open Access Journals (Sweden)

Hayasaka M

2013-02-01

Full Text Available Masatoshi Hayasaka,1 Yasuo Takahashi,2 Yayoi Nishida,2 Yoshikazu Yoshida,1 Shinji Hidaka,3 Satoshi Asai41Department of Pharmacy, Nihon University Itabashi Hospital, Tokyo, 2Division of Genomic Epidemiology and Clinical Trials, Clinical Trials Research Center, Nihon University School of Medicine, Tokyo, 3Laboratory of Pharmaceutical Regulatory Science, Department of Pharmacy, School of Pharmacy, Nihon University, Chiba, 4Division of Pharmacology, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo, JapanBackground: Clopidogrel and aspirin are antiplatelet agents that are recommended to reduce the risk of recurrent stroke and other cardiovascular events. Dual antiplatelet therapy with clopidogrel and aspirin has been shown to increase the risk of hemorrhage, but the effects of the drugs on laboratory parameters have not been well studied in real-world clinical settings. Therefore, we evaluated and compared the effects of combination therapy with clopidogrel plus aspirin and aspirin monotherapy on laboratory parameters.Methods: We used data from the Nihon University School of Medicine Clinical Data Warehouse obtained between November 2004 and May 2011 to identify cohorts of new users (n = 130 of clopidogrel (75 mg/day plus aspirin (100 mg/day and a propensity score matched sample of new users (n = 130 of aspirin alone (100 mg/day. We used a multivariate regression model to compare serum levels of creatinine, aspartate aminotransferase, and alanine aminotransferase, as well as hematological parameters including hemoglobin level, hematocrit, and white blood cell, red blood cell, and platelet counts up to 2 months after the start of administration of the study drugs.Results: There were no significant differences for any characteristics and baseline laboratory parameters between users of clopidogrel plus aspirin and users of aspirin alone. Reductions in white blood cell and red blood cell counts, hemoglobin levels, and

The Clopidogrel-PPI Interaction

DEFF Research Database (Denmark)

Juel, Jacob; Pareek, Manan; Jensen, Svend Eggert

2014-01-01

the potential for PPIs, especially omeprazole, to decrease the efficacy of clopidogrel, and both the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) have issued warnings regarding the concomitant use of these medications. A review of the literature revealed that the pharmacodynamic...... studies support an interaction, whereas the clinical evidence, which is mainly based on nonrandomized, observational studies and secondary analyses of randomized trials, is conflicting. We conclude that PPIs should be prescribed together with DAPT for patients in whom they are recommended according...

Assessment of analytical techniques for characterization of crystalline clopidogrel forms in patent applications

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Luiz Marcelo Lira

2014-04-01

Full Text Available The aim of this study was to evaluate two important aspects of patent applications of crystalline forms of drugs: (i the physicochemical characterization of the crystalline forms; and (ii the procedure for preparing crystals of the blockbuster drug clopidogrel. To this end, searches were conducted using online patent databases. The results showed that: (i the majority of patent applications for clopidogrel crystalline forms failed to comply with proposed Brazilian Patent Office guidelines. This was primarily due to insufficient number of analytical techniques evaluating the crystalline phase. In addition, some patent applications lacked assessment of chemical/crystallography purity; (ii use of more than two analytical techniques is important; and (iii the crystallization procedure for clopidogrel bisulfate form II were irreproducible based on the procedure given in the patent application.

An evaluation of high-dose jobs for ALARA improvement

International Nuclear Information System (INIS)

Mun, J. H.; Kim, H. S.

1997-01-01

It is well known that about 70 percent of occupational dose have incurred from maintenance jobs at outage period. To reduce occupational dose, first, the high-dose jobs at the outage period should be identified and evaluated. For this, the database program is used, which contains the ORE data of reference plants, Kori Units 3 and 4. As a result, it is found that the jobs related to steam generator are the highest dose jobs in terms of collective ORE dose. From the analysis of the job procedures of those jobs, the ALARA improvements are also derived

Costs and consequences of direct-to-consumer advertising for clopidogrel in Medicaid.

Science.gov (United States)

Law, Michael R; Soumerai, Stephen B; Adams, Alyce S; Majumdar, Sumit R

2009-11-23

Direct-to-consumer advertising (DTCA) is assumed to be a major driver of rising pharmaceutical costs. Yet, research on how it affects costs is limited. Therefore, we studied clopidogrel, a commonly used and heavily marketed antiplatelet agent, which was first sold in 1998 and first direct-to-consumer advertised in 2001. We examined pharmacy data from 27 Medicaid programs from 1999 through 2005. We used interrupted time series analysis to analyze changes in the number of units dispensed, cost per unit dispensed, and total pharmacy expenditures after DTCA initiation. In 1999 and 2000, there was no DTCA for clopidogrel; from 2001 through 2005, DTCA spending exceeded $350 million. Direct-to-consumer advertising did not change the preexisting trend in the number of clopidogrel units dispensed per 1000 enrollees (P = .10). However, there was a sudden and sustained increase in cost per unit of $0.40 after DTCA initiation (95% confidence interval, $0.31-$0.49; P consumer advertising was not associated with an increase in clopidogrel use over and above preexisting trends. However, Medicaid pharmacy expenditures increased substantially after the initiation of DTCA because of a concomitant increase in the cost per unit. If drug price increases after DTCA initiation are common, there are important implications for payers and for policy makers in the United States and elsewhere.

Eight-year follow-up of the Clopidogrel After Surgery for Coronary Artery Disease (CASCADE) trial.

Science.gov (United States)

Hage, Ali; Voisine, Pierre; Erthal, Fernanda; Larose, Éric; Glineur, David; Chow, Benjamin; Tremblay, Hugo; Fortier, Jacqueline; Ko, Gifferd; Une, Dai; Farkouh, Michael; Mesana, Thierry G; LeMay, Michel; Kulik, Alexander; Ruel, Marc

2018-01-01

In this 8 years' follow-up study, we evaluated the long-term outcomes of the addition of clopidogrel to aspirin during the first year after coronary artery bypass grafting, versus aspirin plus placebo, with respect to survival, major adverse cardiac, or major cerebrovascular events, including revascularization, functional status, graft patency, and native coronary artery disease progression. In the initial Clopidogrel After Surgery for Coronary Artery Disease trial, 113 patients were randomized to receive either daily clopidogrel (n = 56) or placebo (n = 57), in addition to aspirin, in a double-blind fashion for 1 year after coronary artery bypass grafting. All patients were re-evaluated to collect long-term clinical data. Surviving patients with a glomerular filtration rate > 30 mL/min were asked to undergo a coronary computed tomography angiogram to evaluate the late saphenous vein graft patency and native coronary artery disease progression. At a median follow-up of 7.6 years, survival rate was 85.5% ± 3.8% (P = .23 between the 2 groups). A trend toward enhanced freedom from all-cause death or major adverse cardiac or cerebrovascular events, including revascularization, was observed in the aspirin-clopidogrel group (P = .11). No difference in functional status or freedom from angina was observed between the 2 groups (P > .57). The long-term patency of saphenous vein graft was 89.11% in the aspirin-clopidogrel group versus 91.23% in the aspirin-placebo group (P = .79). A lower incidence of moderate to severe native disease progression was observed in the aspirin-clopidogrel group versus the aspirin-placebo group (7 out of 122 vs 13 out of 78 coronary segments that showed progression, respectively [odds ratio, 0.3 ± 0.2; 95% confidence interval, 0.1-0.8; P = .02]). At 8 years' follow-up, the addition of clopidogrel to aspirin during the first year after coronary artery bypass grafting exhibited a lower incidence of moderate to severe

Policy objective of generic medicines from the investment perspective: The case of clopidogrel.

Science.gov (United States)

Elek, Péter; Harsányi, András; Zelei, Tamás; Csetneki, Kata; Kaló, Zoltán

2017-05-01

The objective of generic drug policies in most countries is defined from a disinvestment perspective: reduction in expenditures without compromising health outcomes. However, in countries with restricted access of patients to original patented drugs, the objective of generic drug policies can also be defined from an investment perspective: health gain by improved patient access without need for additional health budget. This study examines the investment aspect of generic medicines by analyzing clopidogrel utilization in European countries between 2004 and 2014 using multilevel panel data models. We find that clopidogrel consumption was strongly affected by affordability constraints before the generic entry around 2009, but this effect decayed by 2014. After controlling for other variables, utilization had a substantially larger trend increase in lower-income European countries than in the higher-income ones. Generic entry increased clopidogrel consumption only in lower- and average-income countries but not in the highest-income ones. An earlier generic entry was associated with a larger effect. The case of clopidogrel indicates that the entrance of generics may increase patient access to effective medicines, most notably in lower-income countries, thereby reducing inequalities between European patients. Policymakers should also consider this investment aspect of generic medicines when designing pharmaceutical policies. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Attenuated expression of the tight junction proteins is involved in clopidogrel-induced gastric injury through p38 MAPK activation

International Nuclear Information System (INIS)

Wu, Hai-Lu; Gao, Xin; Jiang, Zong-Dan; Duan, Zhao-Tao; Wang, Shu-Kui; He, Bang-Shun; Zhang, Zhen-Yu; Xie, Hong-Guang

2013-01-01

Highlights: ► Clopidogrel suppressed GES-1 cell viability in a concentration- and time-dependent manner. ► Clopidogrel significantly increased dextran permeability, reduced occludin and ZO-1 expression, and induced cell apoptosis. ► Clopidogrel activated p38 MAPK signaling pathway. ► Activation of p38 activity was involved in clopidogrel-induced increase in gastric epithelial cells permeability and disruption of TJ. -- Abstract: Bleeding complications and delayed healing of gastric ulcer associated with use of clopidogrel is a common clinical concern; however, the underlying mechanisms remain to be determined. This study aimed to clarify whether clopidogrel could cause the damage of the human gastric epithelial cells and to further elucidate the mechanisms involved. After human gastric epithelial cell line GES-1 had been treated with clopidogrel (0.5–2.5 mM), the cell proliferation was examined by MTT assay, apoptosis was measured with DAPI staining and flow cytometry analysis, and the barrier function of the tight junctions (TJ) was evaluated by permeability measurement and transmission electron microscopy. Moreover, expression of the TJ proteins occludin and ZO-1 and the phosphorylation of the mitogen-activated protein kinases (MAPK) p38, ERK, and JNK were examined by western blot. In addition, three MAPK inhibitors specific to p38, ERK and JNK were used, respectively, to verify the signaling pathways responsible for regulating the expression of the TJ proteins being tested. Results showed that clopidogrel significantly increased dextran permeability, induced apoptosis, suppressed GES-1 cell viability, and reduced the expression of the TJ proteins (occludin and ZO-1), acting through p38 MAPK phosphorylation. Furthermore, these observed effects were partially abolished by SB-203580 (a p38 MAPK inhibitor), rather than by either U-0126 (an ERK inhibitor) or SP-600125 (a JNK inhibitor), suggesting that clopidogrel-induced disruption in the gastric

Effect of Clopidogrel on Platelet CD Markers in Normal Individuals and in Patients with Untreated Type 2 Diabetes Mellitus

International Nuclear Information System (INIS)

Saboor, M.; Moinuddin, M.; Ilyas, S.

2015-01-01

The objective of this study was to evaluate the effect of clopidogrel response in patients with untreated type 2 diabetes mellitus as compared with normal individuals. One hundred and seven subjects i.e. 32 normal and 75 patients with untreated type 2 diabetes mellitus were enrolled in this study. In the first step, normal subjects as well as diabetic patients were selected and tested for various laboratory parameters and platelets flow cytometry. In the second step, an antiplatelet drug (clopidogrel) was administered for 10 days to each individual enrolled in the study. After 10 days blood samples were collected for platelets flow cytometry. CD41 and CD61 did not show any change after the administration of clopidogrel in resting and activated platelets. CD63 and CD62p positivity was increased in normal and in diabetic patients' platelets after activation with ADP before clopidogrel. It was decreased in normal resting and ADP stimulated platelets after clopidogrel treatment. CD63 and CD62p positivity in resting and ADP stimulated patients platelets was also decreased after clopidogrel treatment. The change was, however, not as marked as in normal subjects. (author)

Platelet reactivity in the early and late phases of acute coronary syndromes according to cytochrome P450 2C19 phenotypes.

Science.gov (United States)

Nagashima, Zenko; Tsukahara, Kengo; Morita, Satoshi; Endo, Tsutomu; Sugano, Teruyasu; Hibi, Kiyoshi; Himeno, Hideo; Fukui, Kazuki; Umemura, Satoshi; Kimura, Kazuo

2013-09-01

It remains unknown whether the time course of the antiplatelet effects of clopidogrel differs according to cytochrome P450 (CYP) 2C19 phenotype in Japanese patients with acute coronary syndromes (ACS). Platelet reactivity was serially assessed by VerifyNow-P2Y12 assay (Accumetrics, San Diego, CA, USA). Results were expressed as P2Y12-reaction-units (PRU) in 177 patients with ACS who underwent stent implantation and received aspirin plus a 300-mg loading dose of clopidogrel followed by 75 mg/day. High on-clopidogrel treatment platelet reactivity (HTPR) was defined as PRU>235. On the basis of the CYP2C19*2 and *3 alleles, 46 patients (26.0%) were classified as extensive metabolizers (EM), 103 (58.2%) as intermediate metabolizers (IM), and 28 (15.8%) as poor metabolizers (PM). At fashion (168±99 vs. 213±77 vs. 278±69, pJapanese patients with ACS carried CYP2C19 variant alleles. The majority of IM and PM had increased platelet reactivity during the early phase of ACS. Although HTPR was frequently observed even 14-28 days after standard maintenance doses of clopidogrel in PM, the incidence of adverse outcomes did not differ, irrespective of CYP2C19 genotype. Copyright © 2013 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Application of estimating effective dose from external radiation using two dosimeters during maintenance periods at KNPPS

International Nuclear Information System (INIS)

Kim, Hee Geun; Kong, Tae Young

2008-01-01

The application of a two-dosimeter and its algorithm and a test of its use in an inhomogeneous high radiation field are described. The goal was to develop an improved method for estimating the effective dose during maintenance periods at Korean nuclear power plants (NPPs). The use of the method in domestic and international NPPs including USA, Canada and Japan was also investigated. The algorithms used by the Canadian Ontario Power Generation (OPG) and American ANSI HPS N13.41, Lakshmanan, NCRP, EPRI and Texas A and M University were extensively analyzed as two-dosimeter algorithms. The possibility of their application to NPPs was evaluated using data for each algorithm from two-dosimeter results for an inhomogeneous high radiation field during maintenance periods at Korean NPPs. (author)

Platelet reactivity in response to loading dose of atorvastatin or rosuvastatin in patients with stable coronary disease before percutaneous coronary intervention: The STATIPLAT randomized study.

Science.gov (United States)

Godino, Cosmo; Pavon, Anna Giulia; Mangieri, Antonio; Salerno, Anna; Cera, Michela; Monello, Alberto; Chieffo, Alaide; Magni, Valeria; Cappelletti, Alberto; Margonato, Alberto; Colombo, Antonio

2017-08-01

The acute effects of statin loading dose (LD) on platelet reactivity in patients with chronic stable angina (CSA) are not completely clear. We hypothesized that LDs of atorvastatin and rosuvastatin have different pharmacodynamic acute effects on platelet aggregability in CSA patients with baseline normal platelet reactivity while on dual antiplatelet therapy (DAPT). From September 2011 to February 2014, all consecutive CSA patients on chronic DAPT (aspirin and clopidogrel) were evaluated before elective percutaneous coronary intervention (PCI). An initial assessment of platelet reactivity in response to thrombin receptor agonist, ADP, and ASP (respectively, indicative of the response to clopidogrel and aspirin) was performed with impedance aggregometry. Patients with high platelet reactivity to ADP test (area under the curve >47) were excluded. The remaining patients were randomized into 3 treatment groups: Group A, atorvastatin LD 80 mg; Group B, rosuvastatin LD 40 mg; and Group C, no statin LD (control group). A second assessment of platelet reactivity was performed ≥12 hours after statin LD. 682 patients were screened and 145 were randomized into the 3 groups. At baseline and after statin LD, no significant difference was found in platelet reactivity in response to 3 different agonists between the 3 groups. Subgroup analysis showed that platelet reactivity to ADP test was significantly lower in patients chronically treated with low-dose statins (n = 94) compared with statin-naïve patients (n = 51; 15.32 ± 1.50 vs 18.59 ± 1.30; P = 0.007). Loading dose of atorvastatin (80 mg) or rosuvastatin (40 mg) did not induce significant variation in platelet reactivity in CSA patients with baseline reduced platelet reactivity as in chronic DAPT. Our data confirm that chronic concomitant treatment with low-dose statins and clopidogrel resulted in significantly lower platelet reactivity compared with clopidogrel alone. © 2017 Wiley Periodicals, Inc.

The paradox of clopidogrel use in patients with acute coronary syndromes and diabetes: insight from the Diabetes and Acute Coronary Syndrome Registry.

Science.gov (United States)

Ferlini, Marco; Musumeci, Giuseppe; Grieco, Niccolò; Rossini, Roberta; De Servi, Stefano; Mafrici, Antonio; Sponzilli, Carlo; Demarchi, Andrea; Assanelli, Emilio M; Camisasca, Paola; Chizzola, Giuliano; Corrada, Elena; Farina, Andrea; Pedrinazzi, Claudio; Lettieri, Corrado; Oltrona Visconti, Luigi

2018-06-01

Patients with diabetes mellitus (DM) and acute coronary syndromes have a greater level of platelet aggregation and a poor response to oral antiplatelet drugs. Clopidogrel is still widely used in clinical practice, despite the current evidence favoring ticagrelor and prasugrel. The aim of this study was to investigate the determinants of clopidogrel use in the population of the multicenter prospective 'Acute Coronary Syndrome and Diabetes Registry' carried out during a 9-week period between March and May 2015 at 29 Hospitals. A total of 559 consecutive acute coronary syndrome patients [mean age: 68.7±11.3 years, 50% ST-elevation myocardial infarction (STEMI)], with 'known DM' (56%) or 'hyperglycemia' at admission, were included in the registry; 460 (85%) patients received a myocardial revascularization. At hospital discharge, dual antiplatelet therapy was prescribed to 88% of the patients (clopidogrel ticagrelor and prasugrel to 39, 38, and 23%, respectively). Differences in P2Y12 inhibitor administration were recorded on the basis of history of diabetes, age, and clinical presentation (unstable angina/non-STEMI vs. non-STEMI). On univariate analysis, age older than 75 years or more, known DM, peripheral artery disease, previous myocardial infarction, previous revascularization, complete revascularization, previous cerebrovascular event, creatinine clearance, unstable angina/non-STEMI at presentation, Global Registry of Acute Coronary Events Score, EuroSCORE, CRUSADE Bleeding Score, and oral anticoagulant therapy were significantly associated with clopidogrel choice at discharge. On multivariate analysis, only oral anticoagulant therapy and the CRUSADE Bleeding Score remained independent predictors of clopidogrel prescription. In the present registry of a high-risk population, clopidogrel was the most used P2Y12 inhibitor at hospital discharge, confirming the 'paradox' to treat sicker patients with the less effective drug. Diabetic status, a marker of higher

Calcium-channel blockers do not alter the clinical efficacy of clopidogrel after myocardial infarction: a nationwide cohort study

DEFF Research Database (Denmark)

Olesen, Jonas B; Gislason, Gunnar H; Charlot, Mette G

2011-01-01

Objectives The purpose of this study was to determine the risk of adverse cardiovascular events associated with concomitant use of clopidogrel and calcium-channel blockers (CCBs) in patients with myocardial infarction (MI). Background CCBs inhibit a variety of cytochrome P-450 enzymes, some...... patients treated and not treated with clopidogrel, with a hazard ratio of 1.15 (95% confidence interval [CI]: 1.07 to 1.24) and 1.05 (95% CI: 1.01 to 1.11), respectively. The increased risk was independent of clopidogrel use; the hazard rate ratio was 1.08 (95% CI: 0.99 to 1.18). Analyses of all additional...... adverse end points and propensity score–matched models provided similar results. Conclusions The clinical efficacy of clopidogrel in patients with a recent MI is not modified by concomitant CCB treatment. This potential drug interaction is unlikely to have clinical significance....

Blødningskomplikationer ved behandling med clopidogrel og acetylsalicylsyre efter akut koronart syndrom

DEFF Research Database (Denmark)

Kjær, Janus; Larsen, Christian Hastrup; Poulsen, Tina Svenstrup

2006-01-01

INTRODUCTION: The Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) study showed that patients with unstable angina pectoris (UAP) and non-ST-elevation myocardial infarction (NSTEMI) benefit from combined therapy with acetylsalicylic acid (ASA) and clopidogrel. However, only...... patients entering clinical randomized trials were studied. We sought to assess whether the risk of bleeding increased after the introduction of the CURE criteria in an unselected population of Danish patients with NSTEMI or UAP. MATERIALS AND METHODS: The CURE criteria were implemented in the Department...

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

Science.gov (United States)

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

2007-06-01

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

Efficacy of Clopidogrel and Clinical Outcome When Clopidogrel Is Coadministered With Atorvastatin and Lansoprazole: A Prospective, Randomized, Controlled Trial.

Science.gov (United States)

Zhang, Jian-rong; Wang, Di-qing; Du, Jun; Qu, Guang-su; Du, Jian-lin; Deng, Song-bai; Liu, Ya-jie; Cai, Jin-xi; She, Qiang

2015-12-01

This prospective, randomized, nonblind, controlled trial evaluated the effects of clopidogrel on platelet function upon coadministration with atorvastatin and lansoprazole. One hundred four adult patients with non-ST-segment elevated acute coronary syndrome (NSTE-ACS) who underwent percutaneous coronary intervention (PCI) with drug-eluting stent implantation were included. All patients were treated with standard dual antiplatelet therapy (DAPT) plus rosuvastatin 10  mg daily after the operation. On the sixth day after PCI, patients were randomly divided into 4 groups, Group A: DAPT + atorvastatin 20  mg daily (a change from rosuvastatin to atorvastatin) + lansoprazole 30  mg daily, Group B: DAPT + atorvastatin 20  mg daily (a change from rosuvastatin to atorvastatin), Group C: DAPT + lansoprazole 30  mg daily (continuing to take rosuvastatin), Group D is the control group. Additional drugs were used according to the situation of patients. Platelet function and concentrations of platelet activation markers (granular membrane protein 140 (P-selectin), thromboxane B2 (TXB2), and human soluble cluster of differentiation 40 ligand (sCD40L)) were assessed before randomization and at 15- and 30-day follow-up visits. All patients were maintained on treatment for 6 months and observed for bleeding and ischemic events. A total of 104 patients were enrolled, 27 patients in group A, 26 patients in Group B/C, 25 patients in Group D separately, and all the patients were analyzed. There were no differences in platelet function and the levels of platelet activation markers (P-selectin, TXB2, and sCD40L) among or within the 4 groups at the 3 time points of interest (P > 0.05). In the subsequent 6 months, no significant bleeding events occurred, and 12 patients experienced ischemic events, these results were also not significantly different among the groups (P > 0.05). In patients diagnosed with NSTE-ACS who have had drug-eluting stent implantation

Clopidogrel-Induced Insulin Autoimmune Syndrome: A Newly Recognized Cause of Hypoglycemia in a Patient Without Diabetes.

Science.gov (United States)

Rajpal, Aman; Kassem, Laure Sayyed; Moscoso-Cordero, Maria; Arafah, Baha M

2017-09-01

Insulin autoimmune syndrome (IAS), defined as hyperinsulinemic hypoglycemia with high titers of anti-insulin antibodies, is frequently reported in Japanese patients but rarely observed in whites. We report in this study on a 79-year-old white male without diabetes who developed IAS following exposure to clopidogrel, a drug not previously known to cause hypoglycemia. The patient presented with recurrent symptomatic hypoglycemia. During one episode, serum glucose was 45 mg/dL, whereas insulin and C-peptide levels were 40,000 mIU/mL and 40 ng/mL, respectively. Additional studies revealed no intake of insulin or its secretagogues, whereas anti-insulin antibody titer was high (59.3 nmol/L). Although total insulin levels were consistently high, free insulin concentrations (polyethylene glycol precipitation) were appropriate for ambient glycemia. The patient was found to have HLA-DRB1*0404, a feature often reported in Japanese patients with IAS. Three weeks prior to symptom onset, he was started on clopidogrel, a drug that does not have a sulfhydryl group, but its active metabolite does. Clopidogrel was switched to a nonsulfhydryl antiplatelet agent, and glucocorticoid therapy was initiated. Shortly thereafter, the frequency of hypoglycemic episodes decreased, and glucocorticoids were tapered over the ensuing 3 months. No hypoglycemic episodes were noted during 6 months of observation after discontinuing glucocorticoids, whereas the total insulin and anti-insulin antibody levels normalized. The data indicate that IAS should be considered in the differential diagnosis of hyperinsulinemic hypoglycemia in seemingly well individuals, even when no drugs known to cause IAS were used. Clinical suspicion of IAS can avoid expensive imaging and unnecessary surgery in affected patients.

Increased mortality associated with low use of clopidogrel in patients with heart failure and acute myocardial infarction not undergoing percutaneous coronary intervention

DEFF Research Database (Denmark)

Bonde, Lisbeth; Sorensen, Rikke; Fosbøl, Emil Loldrup

2010-01-01

with patients not treated with clopidogrel. Similarly, 2 groups without HF were identified. Risks of all-cause death were obtained by the Kaplan-Meier method and Cox regression analyses. RESULTS: We identified 56,944 patients with first-time AMI. In the matched cohort with HF (n = 5,050) and a mean follow......OBJECTIVES: We studied the association of clopidogrel with mortality in acute myocardial infarction (AMI) patients with heart failure (HF) not receiving percutaneous coronary intervention (PCI). BACKGROUND: Use of clopidogrel after AMI is low in patients with HF, despite the fact that clopidogrel...... is associated with absolute mortality reduction in AMI patients. METHODS: All patients hospitalized with first-time AMI (2000 through 2005) and not undergoing PCI within 30 days from discharge were identified in national registers. Patients with HF treated with clopidogrel were matched by propensity score...

Serious clopidogrel associated renal hematoma in a type 2 diabetic patient with primary hyperparathyroidism after extracorporeal shock wave lithotripsy

International Nuclear Information System (INIS)

Bahceci, Mithat; Tuzcu, Alpaslan; Agil, Cuneyt; Akay, Ferruh; Akay, Hatice

2005-01-01

Renal hematoma after extracorporeal shock wave lithotripsy SWL is a rare complication. We report a case of a large renal hematoma following SWL that resulted in nephrectomy in a type 2 diabetic patient with primary hyperparathyroidism using clopidogrel due to coronary heart disease CHD. Although it was claimed that preoperative use of clopidogrel was not associated with increased bleeding, all patients who are scheduled for SWL should be interrogated in terms of using of platelet aggregation inhibitors such as clopidogrel, and these drugs should be interrupted appropriately before undergoing SWL. (author)

Effect of clopidogrel premedication in off-pump cardiac surgery: are we forfeiting the benefits of reduced hemorrhagic sequelae?

Science.gov (United States)

Kapetanakis, Emmanouil I; Medlam, Diego A; Petro, Kathleen R; Haile, Elizabeth; Hill, Peter C; Dullum, Mercedes K C; Bafi, Ammar S; Boyce, Steven W; Corso, Paul J

2006-04-04

Premedication with clopidogrel has reduced thrombotic complications after percutaneous coronary revascularization procedures. However, because of the enhanced and irreversible platelet inhibition by clopidogrel, patients requiring surgical revascularization have a higher risk of bleeding complications and transfusion requirements. A principal benefit of surgical coronary revascularization without cardiopulmonary bypass is its lower hemorrhagic sequelae. The purpose of this study was to evaluate the effect of preoperative clopidogrel administration in the incidence of hemostatic reexploration, blood product transfusion rates, morbidity, and mortality in patients undergoing off-pump coronary artery bypass graft surgery using a large patient sample and a risk-adjusted approach. Two hundred eighty-one patients (17.9%) did and 1291 (82.1%) did not receive clopidogrel before their surgery, for a total of 1572 patients undergoing isolated off-pump coronary artery bypass graft surgery between January 2000 and June 2002. Risk-adjusted logistic regression analyses and a matched pair analyses by propensity scores were used to assess the association between clopidogrel administration and reoperation as a result of bleeding, intraoperative and postoperative blood transfusions received, and the need for multiple transfusions. Hemorrhage-related preoperative risk factors identified in the literature and those found significant in a univariate model were used. The clopidogrel group had a higher likelihood of hemostatic reoperations (odds ratio [OR], 5.1; 95% confidence interval [CI], 2.47 to 10.47; P<0.01) and an increased need in overall packed red blood cell (OR, 2.6; 95% CI, 1.94 to 3.60; P<0.01), multiple unit (OR, 1.6; 95% CI, 1.07 to 2.48; P=0.02), and platelet (OR, 2.5; 95% CI, 1.77 to 3.66; P<0.01) transfusions. Surgical outcomes and operative mortality (1.4% versus 1.4%; P=1.00) were not statistically different. Clopidogrel administration in the cardiology suite increases

Adjustable Maintenance Dosing with Budesonide/Formoterol Reduces Asthma Exacerbations Compared with Traditional Fixed Dosing: A Five-Month Multicentre Canadian Study

Directory of Open Access Journals (Sweden)

J Mark FitzGerlad

2003-01-01

Full Text Available BACKGROUND: Adjustable maintenance dosing with budesonide/formoterol in a single inhaler (Symbicort, AstraZeneca, Lund, Sweden may provide a convenient means of maintaining asthma control with the minimum effective medication level.

Efficacy and Tolerability of High-Dose Escitalopram in Posttraumatic Stress Disorder.

Science.gov (United States)

Qi, Wei; Gevonden, Martin; Shalev, Arieh

2017-02-01

Open-label trials suggest that escitalopram (up to 20 mg/d) is an effective treatment for some, but not all posttraumatic stress disorder (PTSD) patients. Higher doses of escitalopram effectively reduced major depression symptoms in patients who had not responded to regular doses. The current study examines the efficacy, tolerability, and adherence to high-dose escitalopram in PTSD. Forty-five PTSD patients received 12 weeks of gradually increasing doses of escitalopram reaching 40 mg daily at 4 weeks. Among those, 12 participants received regular doses of antidepressants at study onset including escitalopram (n = 7). The Clinician-Administered PTSD Scale (CAPS) evaluated PTSD symptoms severity before treatment, at 3 months (upon treatment termination), and at 6 months (maintenance effect). A 20% reduction in CAPS scores was deemed clinically significant. Adverse events and medication adherence were monitored at each clinical session. Linear mixed-models analysis showed a significant reduction of mean CAPS scores (11.5 ± 18.1 points) at 3 months and maintenance of gains by 6 months (F2,34.56 = 8.15, P = 0.001). Eleven participants (34.3%) showed clinically significant improvement at 3 months. Only 9 participants (20%) left the study. There were no serious adverse events and few mild ones with only 2 adverse events (diarrhea, 11.1%; drowsiness, 11.1%) reported by more than 10% of participants. High doses of escitalopram are tolerable and well adhered to in PTSD. Their beneficial effect at a group level is due to a particularly good response in a subset of patients.Variability in prior pharmacological treatment precludes a definite attribution of the results to high doses of escitalopram.

Identification of dose-reduction techniques for BWR and PWR repetitive high-dose jobs

International Nuclear Information System (INIS)

Dionne, B.J.; Baum, J.W.

1984-01-01

As a result of concern about the apparent increase in collective radiation dose to workers at nuclear power plants, this project will provide information to industry in preplanning for radiation protection during maintenance operations. This study identifies Boiling Water Reactor (BWR) and Pressurized Water Reactor (PWR) repetitive jobs, and respective collective dose trends and dose reduction techniques. 3 references, 2 tables

Evaluación económica del tratamiento con ácido acetilsalicílico más esomeprazol comparado con clopidogrel en la prevención de la hemorragia gastrointestinal Economic evaluation of the treatment of aspirin plus esomeprazole compared to clopidogrel in gastrointestinal bleeding prevention

Directory of Open Access Journals (Sweden)

Carme Piñol

2006-02-01

Full Text Available Objetivo: Evaluar la eficiencia del ácido acetilsalicílico (AAS más esomeprazol frente a clopidogrel en la prevención de la hemorragia gastrointestinal. Métodos: Análisis coste-efectividad (árbol de decisión de 2 ramas: AAS más esomeprazol y clopidogrel respecto a la evitación de casos de hemorragia gastrointestinal en 2 años, y análisis de sensibilidad. Resultados: El coste total del tratamiento con AAS más esomeprazol (2.865 S por paciente libre de hemorragia fue inferior al clopidogrel (2.965 S. El tratamiento con AAS resultó dominante. En todos los análisis de sensibilidad la combinación siguió siendo dominante. Al sustituir esomeprazol 40 mg por omeprazol 40 mg, el coste del tratamiento combinado descendió hasta 1.934S/por episodio evitado. Conclusiones: La asociación de esomeprazol y AAS es más coste-efectiva que clopidogrel en la prevención de la hemorragia gastrointestinal. La combinación con omeprazol resulta aún más coste-efectiva.Objective: To evaluate the use of aspirin plus esomeprazole vs. clopidogrel in the prevention of gastrointestinal bleeding. Methods: We performed a cost-effectiveness analysis (two-branch decision tree: aspirin plus esomeprazole or clopidogrel of prevention of gastrointestinal bleeding over a 2-year period, as well as sensitivity analyses. Results: The total cost of aspirin plus esomeprazole treatment (2,865S/patient free of hemorrhage was lower than that of clopidogrel (2,965S. Aspirin treatment was dominant. The combination continued to be dominant in all sensitivity analyses. When esomeprazole 40 mg was substituted by omeprazole 40 mg, the cost of combination therapy decreased to 1,934 S/prevented hemorrhage. Conclusions: The association of esomeprazole and aspirin is more cost-effective than clopidogrel in preventing gastrointestinal bleeding. Aspirin plus omeprazole was even more cost-effective.

Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke

DEFF Research Database (Denmark)

Sacco, Ralph L; Diener, Hans-Christoph; Yusuf, Salim

2008-01-01

BACKGROUND: Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens--aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel. METHODS: In this double-blind, 2-by-2 factorial trial, we randomly...

Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Denmark: a retrospective analysis of nationwide registry data

DEFF Research Database (Denmark)

Sørensen, Rikke; Hansen, Morten L; Abildstrøm, Steen

2009-01-01

BACKGROUND: Combinations of aspirin, clopidogrel, and vitamin K antagonists are widely used in patients after myocardial infarction. However, data for the safety of combinations are sparse. We examined the risk of hospital admission for bleeding associated with different antithrombotic regimens...... according to the following groups: monotherapy with aspirin, clopidogrel, or vitamin K antagonist; dual therapy with aspirin plus clopidogrel, aspirin plus vitamin K antagonist, or clopidogrel plus vitamin K antagonist; or triple therapy including all three drugs. Risk of hospital admission for bleeding...... was 2.6% for the aspirin group, 4.6% for clopidogrel, 4.3% for vitamin K antagonist, 3.7% for aspirin plus clopidogrel, 5.1% for aspirin plus vitamin K antagonist, 12.3% for clopidogrel plus vitamin K antagonist, and 12.0% for triple therapy. With aspirin as reference, adjusted hazard ratios...

Neurotoxicity and low paclitaxel clearance associated with concomitant clopidogrel therapy in a 60 year old Caucasian woman with ovarian carcinoma

DEFF Research Database (Denmark)

Bergmann, Troels K; Filppula, Anne M; Launiainen, Terhi

2015-01-01

% of the cohort geometric mean (385 L/h; range 176-726). She was hospitalised thrice, developed severe neuropathy and paclitaxel treatment was subsequently discontinued. In vitro, 30 min preincubation with 100 μM clopidogrel acyl-β-D-glucuronide inhibited the depletion rate of 0.5 μM paclitaxel by 51......AIM: The aim of this case report is to describe a novel pharmacokinetic drug-drug interaction between the antiplatelet agent clopidogrel and the antineoplastic agent paclitaxel. METHODS: The patient was identified in a previously described cohort of 93 patients with ovarian carcinoma treated...... with paclitaxel. The effect of clopidogrel acyl-β-D-glucuronide on the metabolism of paclitaxel was assessed in human liver microsomes. The analysis of clopidogrel in plasma and the quantification of paclitaxel and 6α-hydroxypaclitaxel in in vitro samples were performed by liquid chromatography tandem mass...

Development of dose rate estimation system for FBR maintenance

Energy Technology Data Exchange (ETDEWEB)

Iizawa, Katsuyuki [Japan Nuclear Cycle Development Inst., Tsuruga Head Office, International Cooperation and Technology Development Center, Tsuruga, Fukui (Japan); Takeuchi, Jun; Yoshikawa, Satoru [Hitachi Engineering Company, Ltd., Hitachi, Ibaraki (Japan); Urushihara, Hiroshi [Ibaraki Hitachi Information Service Co., Ltd., Omika, Ibaraki (Japan)

2001-09-01

During maintenance activities on the primary sodium cooling system by an FBR Personnel radiation exposure arises mainly from the presence of radioactive corrosion products (CP). A CP behavior analysis code, PSYCHE, and a radiation shielding calculation code, QAD-CG, have been developed and applied to investigate the possible reduction of radiation exposure of workers. In order to make these evaluation methods more accessible to plant engineers, the user interface of the codes has been improved and an integrated system, including visualization of the calculated gamma-ray radiation dose-rate map, has been developed. The system has been verified by evaluating the distribution of the radiation dose-rate within the Monju primary heat transport system cells from the estimated saturated CP deposition and distribution which would be present following about 20 cycles of full power operation. (author)

Development of dose rate estimation system for FBR maintenance

International Nuclear Information System (INIS)

Iizawa, Katsuyuki; Takeuchi, Jun; Yoshikawa, Satoru; Urushihara, Hiroshi

2001-01-01

During maintenance activities on the primary sodium cooling system by an FBR Personnel radiation exposure arises mainly from the presence of radioactive corrosion products (CP). A CP behavior analysis code, PSYCHE, and a radiation shielding calculation code, QAD-CG, have been developed and applied to investigate the possible reduction of radiation exposure of workers. In order to make these evaluation methods more accessible to plant engineers, the user interface of the codes has been improved and an integrated system, including visualization of the calculated gamma-ray radiation dose-rate map, has been developed. The system has been verified by evaluating the distribution of the radiation dose-rate within the Monju primary heat transport system cells from the estimated saturated CP deposition and distribution which would be present following about 20 cycles of full power operation. (author)

Azithromycin maintenance therapy in patients with cystic fibrosis : A dose advice based on a review of pharmacokinetics, efficacy, and side effects

NARCIS (Netherlands)

Wilms, Erik B.; Touw, Daniel J.; Heijerman, Harry G.M.; Van Der Ent, Cornelis K.

Azithromycin maintenance therapy results in improvement of respiratory function in patients with cystic fibrosis (CF). In azithromycin maintenance therapy, several dosing schemes are applied. In this review, we combine current knowledge about azithromycin pharmacokinetics with the dosing schedules

Relation between the Change in Mean Platelet Volume and Clopidogrel Resistance in Patients Undergoing Percutaneous Coronary Intervention.

Science.gov (United States)

Koh, Young-Youp; Kim, Hyung Ho; Choi, Dong-Hyun; Lee, Young-Min; Ki, Young-Jae; Kang, Seong-Ho; Park, Geon; Chung, Joong-Wha; Chang, Kyong-Sig; Hong, Soon-Pyo

2015-01-01

We aimed to determine the association between the change in mean platelet volume (MPV) over time and aspirin/ clopidogrel resistance in patients undergoing percutaneous coronary intervention (PCI). The MPV and platelet function were analysed in 302 patients who underwent PCI. MPV changes were associated with increased aspirin reaction units (ARU, r = 0.114; P = 0.047), increased P2Y12 reaction units (PRU, r = 0.193; P = 0.001), and decreased P2Y12% inhibition (PI%, r = - 0.273; P resistant group (≥235 PRU or ≤15% of PI%) showed a significantly higher positive change in MPV (ΔMPV) values than the clopidogrel responder group (0.53 ± 0.78 vs. 0.13 ± 0.69 fL, P resistant and responder groups were 72.6% and 59.3%, respectively. After adjusting for traditional risk factors, the odds ratio in the clopidogrel resistant group with ΔMPV ≥0.2 fL was 4.10 (95% confidence interval; 1.84-9.17). In conclusion, ΔMPV was associated with PRU and PI%; a positive ΔMPV was an independent predictive marker for clopidogrel resistance after PCI.

Impact of CYP2C19 Metabolizer Status on Patients With ACS Treated With Prasugrel Versus Clopidogrel.

Science.gov (United States)

Doll, Jacob A; Neely, Megan L; Roe, Matthew T; Armstrong, Paul W; White, Harvey D; Prabhakaran, Dorairaj; Winters, Kenneth J; Duvvuru, Suman; Sundseth, Scott S; Jakubowski, Joseph A; Gurbel, Paul A; Bhatt, Deepak L; Ohman, E Magnus; Fox, Keith A A

2016-03-01

Certain alleles of the CYP2C19 gene are associated with higher platelet reactivity and increased ischemic events among patients treated with clopidogrel. However, the relationship of CYP2C19 genotype and outcomes in medically managed patients with acute coronary syndromes (ACS) is not known. This study sought to assess the effect of CYP2C19 genotype on ischemic outcomes in patients with ACS initially managed medically without revascularization who were randomized to either clopidogrel or prasugrel. We classified patients as extensive metabolizers (EM) or reduced metabolizers (RM) based on CYP2C19 genotype and evaluated ischemic outcomes and platelet reactivity. Among 9,326 patients enrolled from 2008 to 2011, 5,736 participated in the genetics cohort; of these, 2,236 had platelet function testing data. There was no association between CYP2C19 metabolizer status (EM vs. RM) and the primary composite endpoint of cardiovascular death, myocardial infarction (MI), or stroke (hazard ratio [HR]: 0.86). EM and RM patients had similar rates of the primary endpoint whether treated with prasugrel (HR: 0.82) or clopidogrel (HR: 0.91; p for interaction = 0.495). After adjusting for clinical and treatment variables, EM patients had a lower risk of MI versus RM patients (HR: 0.80), but risks of other outcomes were similar. RM patients had significantly higher mean P2Y12 reaction units versus EM patients when treated with clopidogrel (39.93), but not with prasugrel (3.87). CYP2C19 metabolizer status is not associated with the composite outcome of cardiovascular death, MI, or stroke in medically managed ACS patients treated with clopidogrel or prasugrel. Our findings do not support routine CYP2C19 genetic testing in this population. (A Comparison of Prasugrel and Clopidogrel in Acute Coronary Syndrome Subjects [TRILOGY ACS]; NCT00699998). Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Clopidogrel in infants with systemic-to-pulmonary-artery shunts

DEFF Research Database (Denmark)

Wessel, David L; Berger, Felix; Li, Jennifer S

2013-01-01

BACKGROUND: Infants with cyanotic congenital heart disease palliated with placement of a systemic-to-pulmonary-artery shunt are at risk for shunt thrombosis and death. We investigated whether the addition of clopidogrel to conventional therapy reduces mortality from any cause and morbidity relate......-related morbidity. (Funded by Sanofi-Aventis and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00396877.)....

Adalimumab Dose Tapering in Psoriasis: Predictive Factors for Maintenance of Complete Clearance.

Science.gov (United States)

Hansel, Katharina; Bianchi, Leonardo; Lanza, Francesco; Bini, Vittorio; Stingeni, Luca

2017-03-10

Psoriasis can be managed successfully with long-term biologics. Real-life clinical practice may require dose tapering as a therapeutic option to reduce the risk of drug-exposure and to increase cost-effectiveness. The responsiveness to extended intervals between adalimumab doses and the possible predictive factors of maintenance of complete clearance were studied in a retrospective 7-year single-centre analysis. Thirty patients who achieved complete clearance with adalimumab underwent dose tapering, progressively extending between-dose intervals (to 21-28 days). Sixty percent of subjects (group A) maintained complete clearance, whereas 40.0% (group B) relapsed and were switched back to the standard dosage to re-achieve complete clearance. Body mass index (BMI) and time to achieve Psoriasis Area Severity Index (PASI-100) with adalimumab standard treatment before dose tapering were significantly lower in group A than in group B (multi-variate Cox regression: p < 0.05, Kaplan-Meier analysis: p < 0.001, respectively). This study suggests that patients with lower BMI and shorter time to achieve PASI-100 with adalimumab standard dose were significantly more likely to be candidates for dose tapering.

Clopidogrel administration prior to coronary artery bypass grafting surgery: the cardiologist's panacea or the surgeon's headache?

Science.gov (United States)

Kapetanakis, Emmanouil I; Medlam, Diego A; Boyce, Steven W; Haile, Elizabeth; Hill, Peter C; Dullum, Mercedes K C; Bafi, Ammar S; Petro, Kathleen R; Corso, Paul J

2005-03-01

Thrombotic complications after percutaneous coronary intervention procedures have decreased in past years mainly due to the use of clopidogrel antiplatelet therapy. However, the risk of bleeding due to enhanced and irreversible platelet inhibition in patients who will require surgical coronary revascularization instead has not been adequately addressed in the literature. The purpose of this study was to evaluate the effect of pre-operative clopidrogel exposure in haemorrhage-related re-exploration rates, peri-operative transfusion requirements, morbidity, and mortality in patients undergoing coronary artery bypass grafting (CABG) surgery. A study population of 2359 patients undergoing isolated CABG between January 2000 and June 2002 was reviewed. Of these, 415 (17.6%) received clopidogrel prior to CABG surgery, and 1944 (82.4%) did not. A risk-adjusted logistic regression analysis was used to assess the association between clopidogrel pre-medication (vs. no) and haemostatic re-operation, intraoperative and post-operative blood transfusion rates, and multiple transfusions received. Haemorrhage-related pre-operative risk factors identified from the literature and those found significant in a univariate model were used. Furthermore, a sub-cohort, matched-pair by propensity scores analysis, was also conducted. The clopidogrel group had a higher likelihood of haemostatic re-operation [OR = 4.9, (95% CI, 2.63-8.97), P < 0.01], an increase in total packed red blood cell transfusions [OR = 2.2, (95% CI, 1.70-2.84), P < 0.01], multiple unit blood transfusions [OR = 1.9, (95% CI, 1.33-2.75), P < 0.01] and platelet transfusions [OR = 2.6, (95% CI, 1.95-3.56), P < 0.01]. Surgical outcomes and operative mortality [OR = 1.5, (95% CI, 0.36-6.51), P = 0.56] were not significantly different. Pre-operative clopidogrel exposure increases the risk of haemostatic re-operation and the requirements for blood and blood product transfusion during, and after, CABG surgery.

Valsartan combined with clopidogrel and/or leflunomide for the treatment of progressive immunoglobulin A nephropathy.

Science.gov (United States)

Cheng, Genyang; Liu, Dongwei; Margetts, Peter; Liu, Limin; Zhao, Zhanzheng; Liu, Zhangsuo; Tang, Lin; Fang, Yudong; Li, Haijian; Guo, Yuanyuan; Chen, Fengmei; Liu, Fengxun

2015-02-01

The current standard treatment for IgA nephropathy relies on steroid and/or immunosuppressive therapy and angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blocker (ARB). This study examines the benefits and safety of combining valsartan with clopidogrel and leflunomide as a treatment for progressive IgA nephropathy. Patients with primary IgA nephropathy, confirmed by renal biopsy, were recruited for this study. Patients were separated into four groups (n = 42 each) after 2 months of run-in period of valsartan treatment. All patients were treated with valsartan alone (Group 1) or valsartan and either clopidogrel (Group 2) or leflunomide (Group 3) or both clopidogrel and leflunomide (Group 4). Each group was followed up for their next 24 months for 24 h urinary protein excretion, serum creatinine and estimated glomerular filtration rate (eGFR) to assess the effect of the treatment. Adverse effects were recorded concurrently to evaluate the safety of the treatment. Of all 168 patients, 107 were males and 61 were females, with an average age of 33.8 ± 8.79 years. Baseline characteristics were comparable among the four groups (P > 0.05) prior to the experimental treatment. There was a significant (P Valsartan combined with Clopidogrel and Leflunomide can reduce the urinary proteins loss and renal function deterioration for IgA nephropathy patients and cause minimal adverse reactions. Our study suggests a new clinical treatment option for IgA nephropathy. © 2014 Asian Pacific Society of Nephrology.

The role of clopidogrel in early and sustained arterial patency after fibrinolysis for ST-segment elevation myocardial infarction: the ECG CLARITY-TIMI 28 Study.

Science.gov (United States)

Scirica, Benjamin M; Sabatine, Marc S; Morrow, David A; Gibson, C Michael; Murphy, Sabina A; Wiviott, Stephen D; Giugliano, Robert P; McCabe, Carolyn H; Cannon, Christopher P; Braunwald, Eugene

2006-07-04

This study was designed to determine the relationship between clopidogrel and early ST-segment resolution (STRes) and the interaction of the two with clinical outcomes after fibrinolysis. ST-segment resolution is an early noninvasive marker of coronary reperfusion. The CLARITY-TIMI 28 (Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction 28) trial randomized 3,491 patients with ST-segment elevation myocardial infarction (STEMI) undergoing fibrinolysis to clopidogrel versus placebo. ST-segment resolution was defined as complete (>70%), partial (30% to 70%), or none (STRes between the clopidogrel and placebo groups at 90 min (38.4% vs. 36.6% at 90 min). When patients were stratified by STRes category, treatment with clopidogrel resulted in greater benefit among those with evidence of early STRes, with greater odds of an open artery at late angiography in patients with partial (odds ratio [OR] 1.4, p = 0.04) or complete (OR 2.0, p STRes, but no improvement in those with no STRes at 90 min (OR 0.89, p = 0.48) (p for interaction = 0.003). Clopidogrel was also associated with a significant reduction in the odds of an in-hospital death or myocardial infarction in patients who achieved partial (OR 0.30, p = 0.003) or complete STRes at 90 min (OR 0.49, p = 0.056), whereas clinical benefit was not apparent in patients who had no STRes (OR 0.98, p = 0.95) (p for interaction = 0.027). By 30 days, the clinical benefit of clopidogrel was predominately seen in patients with complete STRes. Clopidogrel appears to improve late coronary patency and clinical outcomes by preventing reocclusion of open arteries rather than by facilitating early reperfusion.

Haplotype of platelet receptor P2RY12 gene is associated with residual clopidogrel on-treatment platelet reactivity.

Science.gov (United States)

Nie, Xiao-Yan; Li, Jun-Lei; Zhang, Yong; Xu, Yang; Yang, Xue-Li; Fu, Yu; Liang, Guang-Kai; Lu, Yun; Liu, Jian; Shi, Lu-Wen

To investigate a possible association between common variations of the P2RY12 and the residual clopidogrel on-treatment platelet reactivity after adjusting for the influence of CYP2C19 tested by thromboelastography (TEG). One hundred and eighty patients with acute coronary syndrome (ACS) treated with clopidogrel and aspirin were included and platelet function was assessed by TEG. Five selected P2RY12 single nucleotide polymorphisms (SNPs; rs6798347, rs6787801, rs6801273, rs6785930, and rs2046934), which cover the common variations in the P2RY12 gene and its regulatory regions, and three CYP2C19 SNPs ( * 2, * 3, * 17) were genotyped and possible haplotypes were analyzed. The high on-treatment platelet reactivity (HTPR) prevalence defined by a platelet inhibition rate <30% by TEG in adenosine diphosphate (ADP)-channel was 69 (38.33%). Six common haplotypes were inferred from four of the selected P2RY12 SNPs (denoted H 0 to H 5 ) according to the linkage disequilibrium R square (except for rs2046934). Haplotype H 1 showed a significantly lower incidence of HTPR than the reference haplotype (H 0 ) in the total study population while haplotypes H 1 and H 2 showed significantly lower incidences of HTPR than H 0 in the nonsmoker subgroup after adjusting for CYP2C19 effects and demographic characteristics. rs2046934 (T744C) did not show any significant association with HTPR. The combination of common P2RY12 variations including regulatory regions rather than rs2046934 (T744C) that related to pharmacodynamics of clopidogrel in patients with ACS was independently associated with residual on-clopidogrel platelet reactivity. This is apart from the established association of the CYP2C19. This association seemed more important in the subgroup defined by smoking.

The dose effects of short-term dronabinol (oral THC) maintenance in daily cannabis users.

Science.gov (United States)

Vandrey, Ryan; Stitzer, Maxine L; Mintzer, Miriam Z; Huestis, Marilyn A; Murray, Jeannie A; Lee, Dayong

2013-02-01

Prior studies have separately examined the effects of dronabinol (oral THC) on cannabis withdrawal, cognitive performance, and the acute effects of smoked cannabis. A single study examining these clinically relevant domains would benefit the continued evaluation of dronabinol as a potential medication for the treatment of cannabis use disorders. Thirteen daily cannabis smokers completed a within-subject crossover study and received 0, 30, 60 and 120mg dronabinol per day for 5 consecutive days. Vital signs and subjective ratings of cannabis withdrawal, craving and sleep were obtained daily; outcomes under active dose conditions were compared to those obtained under placebo dosing. On the 5th day of medication maintenance, participants completed a comprehensive cognitive performance battery and then smoked five puffs of cannabis for subjective effects evaluation. Each dronabinol maintenance period occurred in a counterbalanced order and was separated by 9 days of ad libitum cannabis use. Dronabinol dose-dependently attenuated cannabis withdrawal and resulted in few adverse side effects or decrements in cognitive performance. Surprisingly, dronabinol did not alter the subjective effects of smoked cannabis, but cannabis-induced increases in heart rate were attenuated by the 60 and 120mg doses. Dronabinol's ability to dose-dependently suppress cannabis withdrawal may be therapeutically beneficial to individuals trying to stop cannabis use. The absence of gross cognitive impairment or side effects in this study supports safety of doses up to 120mg/day. Continued evaluation of dronabinol in targeted clinical studies of cannabis treatment, using an expanded range of doses, is warranted. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Correlation between Colon Transit Time Test Value and Initial Maintenance Dose of Laxative in Children with Chronic Functional Constipation

Science.gov (United States)

Kim, Mock Ryeon; Park, Hye Won; Son, Jae Sung; Lee, Ran

2016-01-01

Purpose To evaluate the correlation between colon transit time (CTT) test value and initial maintenance dose of polyethylene glycol (PEG) 4000 or lactulose. Methods Of 415 children with chronic functional constipation, 190 were enrolled based on exclusion criteria using the CTT test, defecation diary, and clinical chart. The CTT test was performed with prior disimpaction. The laxative dose for maintenance was determined on the basis of the defecation diary and clinical chart. The Shapiro-Wilk test and Pearson's and Spearman's correlations were used for statistical analysis. Results The overall group median value and interquartile range of the CTT test was 43.8 (31.8) hours. The average PEG 4000 dose for maintenance in the overall group was 0.68±0.18 g/kg/d; according to age, the dose was 0.73±0.16 g/kg/d (encopresis, abnormal CTT test subtype) for either laxative. Even in the largest group (overall, n=109, younger than 8 years and on PEG 4000), the correlation was weak (Pearson's correlation coefficient [R]=0.268, p=0.005). Within the abnormal transit group, subgroup (n=73, younger than 8 years and on PEG 4000) correlation was weak (R=0.267, p=0.022). Conclusion CTT test value cannot predict the initial maintenance dose of PEG 4000 or lactulose with linear correlation. PMID:27738600

Myelotoxicity after high-dose methotrexate in childhood acute leukemia is influenced by 6-mercaptopurine dosing but not by intermediate thiopurine methyltransferase activity

DEFF Research Database (Denmark)

Levinsen, Mette; Rosthøj, Susanne; Nygaard, Ulrikka

2015-01-01

Purpose: Through enhancement of 6-mercaptopurine (6MP) bioavailability and inhibition of purine de novo synthesis, high-dose methotrexate (HD-MTX) may increase incorporation into DNA of 6-thioguanine nucleotides, the cytotoxic metabolites of 6MP. Patients with intermediate activity of thiopurine...... methyltransferase (TPMTIA) have higher cytosol 6-thioguanine nucleotide levels. We investigated toxicity following HD-MTX during MTX/6MP maintenance therapy in relation to 6MP and TPMT. Methods: Using linear mixed models, we explored myelo- and hepatotoxicity in relation to 6MP dosage and TPMT phenotype following 1......,749 HD-MTX courses to 411 children with acute lymphoblastic leukemia on maintenance therapy. Results: The degree of myelosuppression following HD-MTX was similar for patients with TPMTIA and patients with high TPMT activity (TPMTHA), when HD-MTX started with same blood counts and 6MP doses. However...

A Cost-Effectiveness Analysis of Clopidogrel for Patients with Non-ST-Segment Elevation Acute Coronary Syndrome in China.

Science.gov (United States)

Cui, Ming; Tu, Chen Chen; Chen, Er Zhen; Wang, Xiao Li; Tan, Seng Chuen; Chen, Can

2016-09-01

There are a number of economic evaluation studies of clopidogrel for patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) published from the perspective of multiple countries in recent years. However, relevant research is quite limited in China. We aimed to estimate the long-term cost effectiveness for up to 1-year treatment with clopidogrel plus acetylsalicylic acid (ASA) versus ASA alone for NSTEACS from the public payer perspective in China. This analysis used a Markov model to simulate a cohort of patients for quality-adjusted life years (QALYs) gained and incremental cost for lifetime horizon. Based on the primary event rates, adherence rate, and mortality derived from the CURE trial, hazard functions obtained from published literature were used to extrapolate the overall survival to lifetime horizon. Resource utilization, hospitalization, medication costs, and utility values were estimated from official reports, published literature, and analysis of the patient-level insurance data in China. To assess the impact of parameters' uncertainty on cost-effectiveness results, one-way sensitivity analyses were undertaken for key parameters, and probabilistic sensitivity analysis (PSA) was conducted using the Monte Carlo simulation. The therapy of clopidogrel plus ASA is a cost-effective option in comparison with ASA alone for the treatment of NSTEACS in China, leading to 0.0548 life years (LYs) and 0.0518 QALYs gained per patient. From the public payer perspective in China, clopidogrel plus ASA is associated with an incremental cost of 43,340 China Yuan (CNY) per QALY gained and 41,030 CNY per LY gained (discounting at 3.5% per year). PSA results demonstrated that 88% of simulations were lower than the cost-effectiveness threshold of 150,721 CYN per QALY gained. Based on the one-way sensitivity analysis, results are most sensitive to price of clopidogrel, but remain well below this threshold. This analysis suggests that treatment with

Effects of continuous administration of clopidogrel before off-pump coronary artery bypass grafting in patients with acute coronary syndrome. A propensity score analysis

International Nuclear Information System (INIS)

Song, Suk-Won; Youn, Young-Nam; Yi, Gijong; Lee, Sak; Yoo, Kyung-Jong

2008-01-01

Clopidogrel has become standard treatment after urgent percutaneous coronary revascularization. Due to its enhanced and irreversible platelet inhibition, patients undergoing urgent surgical revascularization have a higher risk of bleeding complications and transfusions. Therefore, the effect of preoperative continuous administration of clopidogrel on the incidence of hemorrhagic complications in patients undergoing off-pump coronary artery bypass surgery with acute coronary syndrome was evaluated. From March 2004 to September 2006, 172 patients with acute coronary syndrome underwent isolated off-pump coronary artery bypass surgery; 70 (40.7%) and 102 (59.3%) of these patients did or did not take clopidogrel before surgery respectively. Seventy patients in each group were matched using propensity scores and associations between preoperative continuous administration of clopidogrel and postoperative bleeding, hemostatic reoperation, blood products received, the need for multiple transfusions and early graft patency by coronary computed tomography were assessed. Univariate analysis showed the continuous clopidogrel group had similar levels of postoperative bleeding for 24 h (601.4±312.6 ml vs 637.2±452.4 ml, p=0.616) and rates of reexploration (1.4% vs 1.4%), perioperative blood transfusion (33.3% vs 34.3%, p>0.05) and platelet transfusion (2.9% vs 7.1%, p=0.44) compared with the non-continuous group. Preoperative continuous administration of clopidogrel did not increase the risk of hemorrhagic complications in patients with acute coronary syndrome undergoing isolated off-pump coronary artery bypass surgery. These findings indicate that surgery after clopidogrel treatment in patients with acute coronary syndrome should not be delayed until platelet function returns to normal because they may have a higher risk of recurrent myocardial ischemic events. (author)

Two Different Maintenance Strategies in the Hospital Environment: Preventive Maintenance for Older Technology Devices and Predictive Maintenance for Newer High-Tech Devices.

Science.gov (United States)

Sezdi, Mana

2016-01-01

A maintenance program generated through the consideration of characteristics and failures of medical equipment is an important component of technology management. However, older technology devices and newer high-tech devices cannot be efficiently managed using the same strategies because of their different characteristics. This study aimed to generate a maintenance program comprising two different strategies to increase the efficiency of device management: preventive maintenance for older technology devices and predictive maintenance for newer high-tech devices. For preventive maintenance development, 589 older technology devices were subjected to performance verification and safety testing (PVST). For predictive maintenance development, the manufacturers' recommendations were used for 134 high-tech devices. These strategies were evaluated in terms of device reliability. This study recommends the use of two different maintenance strategies for old and new devices at hospitals in developing countries. Thus, older technology devices that applied only corrective maintenance will be included in maintenance like high-tech devices.

Collection of radiation resistant characteristics reports for instruments and materials in high dose rate environment

International Nuclear Information System (INIS)

Kusano, Joichi

2008-03-01

This document presents the collected official reports of radiation irradiation study for the candidate materials to be used in high dose rate environment as J-PARC facility. The effect of radiation damage by loss-beam or secondary particle beam of the accelerators influences the performance and the reliability of various instruments. The knowledge on the radiation resistivity of the materials is important to estimate the life of the equipments, the maintenance interval and dose evaluation for the personnel at the maintenance period. The radiation damage consists with mechanical property, electrical property and gas-evolution property. (author)

Ticlopidine-, clopidogrel-, and prasugrel-associated thrombotic thrombocytopenic purpura: a 20-year review from the Southern Network on Adverse Reactions (SONAR).

Science.gov (United States)

Jacob, Sony; Dunn, Brianne L; Qureshi, Zaina P; Bandarenko, Nicholas; Kwaan, Hau C; Pandey, Dilip K; McKoy, June M; Barnato, Sara E; Winters, Jeffrey L; Cursio, John F; Weiss, Ivy; Raife, Thomas J; Carey, Patricia M; Sarode, Ravindra; Kiss, Joseph E; Danielson, Constance; Ortel, Thomas L; Clark, William F; Rock, Gail; Matsumoto, Masanori; Fujimura, Yoshihiro; Zheng, X Long; Chen, Hao; Chen, Fei; Armstrong, John M; Raisch, Dennis W; Bennett, Charles L

2012-11-01

Thienopyridine-derivatives (ticlopidine, clopidogrel, and prasugrel) are the primary antiplatelet agents. Thrombotic thrombocytopenic purpura (TTP) is a rare drug-associated syndrome, with the thienopyridines being the most common drugs implicated in this syndrome. We reviewed 20 years of information on clinical, epidemiologic, and laboratory findings for thienopyridine-associated TTP. Four, 11, and 11 cases of thienopyridine-associated TTP were reported in the first year of marketing of ticlopidine (1989), clopidogrel (1998), and prasugrel (2010), respectively. As of 2011, the FDA received reports of 97 ticlopidine-, 197 clopidogrel-, and 14 prasugrel-associated TTP cases. Severe deficiency of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) was present in 80% and antibodies to 100% of these TTP patients on ticlopidine, 0% of the patients with clopidogrel-associated TTP (p < 0.05), and an unknown percentage of patients with prasugrel-associated TTP. TTP is associated with use of each of the three thienopyridines, although the mechanistic pathways may differ. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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...

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.

Dose reduction at nuclear power plants

International Nuclear Information System (INIS)

Baum, J.W.; Dionne, B.J.

1983-01-01

The collective dose equivalent at nuclear power plants increased from 1250 rem in 1969 to nearly 54,000 rem in 1980. This rise is attributable primarily to an increase in nuclear generated power from 1289 MW-y to 29,155 MW-y; and secondly, to increased average plant age. However, considerable variation in exposure occurs from plant to plant depending on plant type, refueling, maintenance, etc. In order to understand the factors influencing these differences, an investigation was initiated to study dose-reduction techniques and effectiveness of as low as reasonably achievable (ALARA) planning at light water plants. Objectives are to: identify high-dose maintenance tasks and related dose-reduction techniques; investigate utilization of high-reliability, low-maintenance equipment; recommend improved radioactive waste handling equipment and procedures; examine incentives for dose reduction; and compile an ALARA handbook

Clopidogrel in a combined therapy with anticancer drugs-effect on tumor growth, metastasis, and treatment toxicity: Studies in animal models.

Directory of Open Access Journals (Sweden)

Agnieszka Denslow

Full Text Available Clopidogrel, a thienopyridine derivative with antiplatelet activity, is widely prescribed for patients with cardiovascular diseases. In addition to antiplatelet activity, antiplatelet agents possess anticancer and antimetastatic properties. Contrary to this, results of some studies have suggested that the use of clopidogrel and other thienopyridines accelerates the progression of breast, colorectal, and prostate cancer. Therefore, in this study, we aimed to evaluate the efficacy of clopidogrel and various anticancer agents as a combined treatment using mouse models of breast, colorectal, and prostate cancer. Metastatic dissemination, selected parameters of platelet morphology and biochemistry, as well as angiogenesis were assessed. In addition, body weight, blood morphology, and biochemistry were evaluated to test toxicity of the studied compounds. According to the results, clopidogrel increased antitumor and/or antimetastatic activity of chemotherapeutics such as 5-fluorouracil, cyclophosphamide, and mitoxantrone, whereas it decreased the anticancer activity of doxorubicin, cisplatin, and tamoxifen. The mechanisms of such divergent activities may be based on the modulation of tumor vasculature via factors, such as transforming growth factor β1 released from platelets. Moreover, clopidogrel increased the toxicity of docetaxel and protected against mitoxantrone-induced toxicity, which may be due to the modulation of hepatic enzymes and protection of the vasculature, respectively. These results demonstrate that antiplatelet agents can be useful but also dangerous in anticancer treatment and therefore use of thienopyridines in patients undergoing chemotherapy should be carefully evaluated.

Formulation and evaluation of orally disintegrating clopidogrel tablets

Directory of Open Access Journals (Sweden)

Gamal Mohamed Mahrous

Full Text Available ABSTRACT Recent advances in drug delivery systems have aimed to achieve better patient compliance. One of these advances is the formulation of orally disintegrating tablets (ODTs that dissolve instantaneously, releasing drugs within a few seconds without the need of water. The main objective of this paper was to prepare and develop ODTs of clopidogrel. The ODTs were prepared by direct compression. The effect of three superdisintegrants, namely crospovidone, croscarmellose sodium, and sodium starch glycolate, using three different disintegration times on the dissolution rate was investigated. The prepared tablets were evaluated for hardness, friability, disintegration time and in vitro drug release. Furthermore, the interaction of clopidogrel with the formulation excipients was studied using differential scanning calorimetry (DSC. DSC studies revealed that there were no interactions between the drug and the excipients used. All tablets had hardness values in the range 4.0-5.2 kp and friability lower than 1%. The weight and drug content uniformity of all formulations was within official limits according to BP. In vitro drug release studies of the ODTs showed that more than 90% of the drug was released within ten minutes. A palatability test in human volunteers showed acceptable taste and mouth feel. Thus, the obtained results conclusively demonstrated successful rapid disintegration of the formulated tablets and acceptable palatability.

Methadone dose increase and abstinence reinforcement for treatment of continued heroin use during methadone maintenance.

Science.gov (United States)

Preston, K L; Umbricht, A; Epstein, D H

2000-04-01

Although methadone maintenance is an effective therapy for heroin dependence, some patients continue to use heroin and may benefit from therapeutic modifications. This study evaluated a behavioral intervention, a pharmacological intervention, and a combination of both interventions. Throughout the study all patients received daily methadone hydrochloride maintenance (initially 50 mg/d orally) and weekly counseling. Following baseline treatment patients who continued to use heroin were randomly assigned to 1 of 4 interventions: (1) contingent vouchers for opiate-negative urine specimens (n = 29 patients); (2) methadone hydrochloride dose increase to 70 mg/d (n = 31 patients); (3) combined contingent vouchers and methadone dose increase (n = 32 patients); and (4) neither intervention (comparison standard; n = 28 patients). Methadone dose increases were double blind. Vouchers had monetary value and were exchangeable for goods and services. Groups not receiving contingent vouchers received matching vouchers independent of urine test results. Primary outcome measure was opiate-negative urine specimens (thrice weekly urinalysis). Contingent vouchers and a methadone dose increase each significantly increased the percentage of opiate-negative urine specimens during intervention. Contingent vouchers, with or without a methadone dose increase, increased the duration of sustained abstinence as assessed by urine screenings. Methadone dose increase, with or without contingent vouchers, reduced self-reported frequency of use and self-reported craving. In patients enrolled in a methadone-maintainence program who continued to use heroin, abstinence reinforcement and a methadone dose increase were each effective in reducing use. When combined, they did not dramatically enhance each other's effects on any 1 outcome measure, but they did seem to have complementary benefits.

Dose-related difference in progression rates of cytomegalovirus retinopathy during foscarnet maintenance therapy. AIDS Clinical Trials Group Protocol 915 Team.

Science.gov (United States)

Holland, G N; Levinson, R D; Jacobson, M A

1995-05-01

A previous dose-ranging study of foscarnet maintenance therapy for cytomegalovirus retinopathy showed a positive relationship between dose and survival but could not confirm a relationship between dose and time to first progression. This retrospective analysis of data from that study was undertaken to determine whether there was a relationship between dose and progression rates, which reflects the amount of retina destroyed when progression occurs. Patients were randomly given one of two foscarnet maintenance therapy doses (90 mg/kg of body weight/day [FOS-90 group] or 120 mg/kg of body weight/day [FOS-120 group] after induction therapy. Using baseline and follow-up photographs and pre-established definitions and methodology in a masked analysis, posterior progression rates and foveal proximity rates for individual lesions, selected by prospectively defined criteria, were calculated in each patient. Rates were compared between groups. The following median rates were greater for the FOS-90 group (N = 8) than for the FOS-120 group (N = 10): greatest maximum rate at which lesions enlarged in a posterior direction (43.5 vs 12.5 microns/day; P = .002); posterior progression rate for lesions closest to the fovea (42.8 vs 5.5 microns/day; P = .010); and maximum foveal proximity rate for either eye (32.3 vs 3.4 microns/day; P = .031). Patients receiving higher doses of foscarnet have slower rates of progression and therefore less retinal tissue damage during maintenance therapy. A foscarnet maintenance therapy dose of 120 mg/kg of body weight/day instead of 90 mg/kg of body weight/day may help to preserve vision in patients with cytomegalovirus retinopathy.

Latin American Clinical Epidemiology Network Series - Paper 8: Ticagrelor was cost-effective vs. clopidogrel in acute coronary syndrome in Chile.

Science.gov (United States)

De la Puente, Catherine; Vallejos, Carlos; Bustos, Luis; Zaror, Carlos; Velasquez, Monica; Lanas, Fernando

2017-06-01

To evaluate the incremental cost-effectiveness ratio (ICER) of the use of ticagrelor as a substitute for clopidogrel for secondary prevention of acute coronary syndrome in Chile. Cost-effectiveness analysis based on a Markov model: Safety and effectiveness data of ticagrelor were obtained from a systematic review of the literature. Costs are expressed in Chilean pesos (CLP) as of 2013. The evaluation was conducted from the payer standpoint. A probabilistic sensitivity analysis comprising discount rates and national cost variability was done. A budget impact analysis estimated for 2015 was conducted to calculate the total cost for both treatments. The ICER with a discount rate of 6% for ticagrelor vs. clopidogrel was CLP 4,893,126 per quality-adjusted life-year (QALY) gained (=9,689 US$). In the budget impact analysis for the baseline scenario, considering 100% of treatment, coverage, and adherence, ticagrelor represented an additional cost of CLP 5,233,854,272, for 979 QALYs gained compared with clopidogrel. Ticagrelor is cost-effective in comparison with clopidogrel for the secondary prevention of acute coronary syndrome. These findings are similar to those reported in other international cost-effectiveness studies. Copyright © 2016 Elsevier Inc. All rights reserved.

A randomized, 2-period, crossover design study to assess the effects of dexlansoprazole, lansoprazole, esomeprazole, and omeprazole on the steady-state pharmacokinetics and pharmacodynamics of clopidogrel in healthy volunteers.

Science.gov (United States)

Frelinger, Andrew L; Lee, Ronald D; Mulford, Darcy J; Wu, Jingtao; Nudurupati, Sai; Nigam, Anu; Brooks, Julie K; Bhatt, Deepak L; Michelson, Alan D

2012-04-03

The aim of this study was to assess the effects of different proton pump inhibitors (PPIs) on the steady-state pharmacokinetics and pharmacodynamics of clopidogrel. Metabolism of clopidogrel requires cytochrome P450s (CYPs), including CYP2C19. However, PPIs may inhibit CYP2C19, potentially reducing the effectiveness of clopidogrel. A randomized, open-label, 2-period, crossover study of healthy subjects (n = 160, age 18 to 55 years, homozygous for CYP2C19 extensive metabolizer genotype, confined, standardized diet) was conducted. Clopidogrel 75 mg with or without a PPI (dexlansoprazole 60 mg, lansoprazole 30 mg, esomeprazole 40 mg, or, as a positive control to maximize potential interaction and demonstrate assay sensitivity, omeprazole 80 mg) was given daily for 9 days. Pharmacokinetics and pharmacodynamics were assessed on days 9 and 10. Pharmacodynamic end-points were vasodilator-stimulated phosphoprotein P2Y(12) platelet reactivity index, maximal platelet aggregation to 5 and 20 μmol/l adenosine diphosphate, and VerifyNow P2Y12 platelet response units. Pharmacokinetic and pharmacodynamic responses with omeprazole demonstrated assay sensitivity. The area under the curve for clopidogrel active metabolite decreased significantly with esomeprazole but not with dexlansoprazole or lansoprazole. Similarly, esomeprazole but not dexlansoprazole or lansoprazole significantly reduced the effect of clopidogrel on vasodilator-stimulated phosphoprotein platelet reactivity index. All PPIs decreased the peak plasma concentration of clopidogrel active metabolite (omeprazole > esomeprazole > lansoprazole > dexlansoprazole) and showed a corresponding order of potency for effects on maximal platelet aggregation and platelet response units. Generation of clopidogrel active metabolite and inhibition of platelet function were reduced less by the coadministration of dexlansoprazole or lansoprazole with clopidogrel than by the coadministration of esomeprazole or omeprazole. These

Ticagrelor versus clopidogrel in real-world patients with ST elevation myocardial infarction: 1-year results by propensity score analysis

OpenAIRE

Vercellino, Matteo; S?nchez, Federico Ariel; Boasi, Valentina; Perri, Dino; Tacchi, Chiara; Secco, Gioel Gabrio; Cattunar, Stefano; Pistis, Gianfranco; Mascelli, Giovanni

2017-01-01

Background European guidelines recommend the use of ticagrelor versus clopidogrel in patients with ST elevation myocardial infarction (STEMI). This recommendation is based on inconclusive results and subanalyses from clinical trials. Few data are available on the effects of ticagrelor in a real-world population. Methods To compare the effects of ticagrelor and clopidogrel in a real-world STEMI population, we conducted a pre-post case-control study examining all patients with STEMI included in...

Budesonide/formoterol maintenance plus reliever therapy

DEFF Research Database (Denmark)

Bisgaard, Hans; Le Roux, Pascal; Bjåmer, Ditlef

2006-01-01

on ICS investigated whether a novel regimen using budesonide/formoterol for maintenance and reliever therapy (Symbicort maintenance and relief therapy [SMART]) [Symbicort; AstraZeneca R&D, Lund, Sweden] could reduce exacerbations. METHODS: Patients received SMART (budesonide/formoterol 80/4.5 microg qd...... maintenance plus additional inhalations for symptom relief), budesonide/formoterol 80/4.5 microg qd for maintenance (fixed combination), or higher-dose budesonide 320 microg qd (fixed-dose budesonide). Blinded as-needed medication (terbutaline 0.4 microg) was provided in both fixed-dose groups. RESULTS: SMART...... prolonged the time to first exacerbation vs fixed-dose budesonide (p = 0.02) and fixed-dose combination (p SMART vs fixed-dose budesonide and fixed-dose combination (0.08/patient vs 0.28/patient and 0.40/patient...

Development of high-immersive simulation system for designing maintenance strategy and its application to CLEAR-I

International Nuclear Information System (INIS)

Yang, Zihui; He, Tao; Shang, Leiming; Long, Pengcheng; Hu, Liqin

2015-01-01

Highlights: • A system was self-developed to simulate and verify the maintenance strategy. • Large-scale 3D radiation scene can be rapidly built and rendered in real-time. • A high efficiency simulation way was provided by tracking 6-DOF body motion. • It has been applied to CLEAR-I and proved maintenance strategy was feasible. - Abstract: The maintenance strategy is imperative and important to be considered in the design process of advanced nuclear reactor as early as possible. The design and validation of the maintenance strategy are key challenges which remain to be resolved due to the complex mechanical structure, the expensive physical mockup, and the potential risk of radiation hazards. In this paper, a high-immersive interactive simulation system has been developed to simulate and verify maintenance strategy by using virtual reality. Main features include: (1) rapid modeling and real-time rendering of the large-scale three-dimensional radiation scene, (2) real-time interactive roaming by tracking the 6-DOF body motion, (3) the interactive disassembly simulation of the mechanism structure were controlled by the hand gestures. The system can provide designers with an intuitive experience environment, an efficient and flexible interactive way as well as the whole process simulation of maintenance strategy. It has been applied to simulate and verify the maintenance strategy of the spallation target proton beam window for China LEAd-based research Reactor (CLEAR-I). The simulation result proved the maintenance strategy of proton beam window was reasonable and feasible. The system was useful to verify maintenance strategy, optimize maintenance operation, reduce intervention time and exposure dose of workers. It provided a high efficiency and low cost way for simulating maintenance strategy to meet the requirements of ALARA rules and can be extended to other nuclear facilities

Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial

NARCIS (Netherlands)

Dewilde, Willem J. M.; Oirbans, Tom; Verheugt, Freek W. A.; Kelder, Johannes C.; de Smet, Bart J. G. L.; Herrman, Jean-Paul; Adriaenssens, Tom; Vrolix, Mathias; Heestermans, Antonius A. C. M.; Vis, Marije M.; Tijsen, Jan G. P.; van 't Hof, Arnoud W.; ten Berg, Jurriën M.; Schölzel, B. E.; van den Branden, B. J.; Plokker, H. W. M.; Bosschaert, M. A.; Slagboom, T.; Vos, J.; Brueren, B. R. G.; Breet, N. J.; Sheikjoesoef, K.; Aarnoudse, W.; Rasoul, S.; van Mieghem, C.; Vandendriessche, T.; Cornelis, K.

2013-01-01

If percutaneous coronary intervention (PCI) is required in patients taking oral anticoagulants, antiplatelet therapy with aspirin and clopidogrel is indicated, but such triple therapy increases the risk of serious bleeding. We investigated the safety and efficacy of clopidogrel alone compared with

Prediction of warfarin maintenance dose in Han Chinese patients using a mechanistic model based on genetic and non-genetic factors.

Science.gov (United States)

Lu, Yuan; Yang, Jinbo; Zhang, Haiyan; Yang, Jin

2013-07-01

Many attempts have been made to predict the warfarin maintenance dose in patients beginning warfarin therapy using a descriptive model based on multiple linear regression. Here we report the first attempt to develop a comprehensive mechanistic model integrating in vitro-in vivo extrapolation (IVIVE) with a pharmacokinetic-pharmacodynamic model to predict the warfarin maintenance dose in Han Chinese patients. The model incorporates demographic factors [sex, age, body weight (BW)] and the genetic polymorphisms of cytochrome P450 (CYP) 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1). Information on the various factors, mean warfarin daily dose and International Normalized Ratio (INR) was available for a cohort of 197 Han Chinese patients. Based on in vitro enzyme kinetic parameters for S-warfarin metabolism, demographic data for Han Chinese and some scaling factors, the S-warfarin clearance (CL) was predicted for patients in the cohort with different CYP2C9 genotypes using IVIVE. The plasma concentration of S-warfarin after a single oral dose was simulated using a one-compartment pharmacokinetic model with first-order absorption and a lag time and was combined with a mechanistic coagulation model to simulate the INR response. The warfarin maintenance dose was then predicted based on the demographic data and genotypes of CYP2C9 and VKORC1 for each patient and using the observed steady-state INR (INRss) as a target value. Finally, sensitivity analysis was carried out to determine which factor(s) affect the warfarin maintenance dose most strongly. The predictive performance of this mechanistic model is not inferior to that of our previous descriptive model. There were significant differences in the mean warfarin daily dose in patients with different CYP2C9 and VKORC1 genotypes. Using IVIVE, the predicted mean CL of S-warfarin for patients with CYP2C9*1/*3 (0.092 l/h, n = 11) was 57 % less than for those with wild-type *1/*1 (0.215 l/h, n

Effects of preoperative aspirin and clopidogrel therapy on perioperative blood loss and blood transfusion requirements in patients undergoing off-pump coronary artery bypass graft surgery.

Science.gov (United States)

Shim, Jae Kwang; Choi, Yong Seon; Oh, Young Jun; Bang, Sou Ouk; Yoo, Kyung Jong; Kwak, Young Lan

2007-07-01

Preoperative exposure to clopidogrel and aspirin significantly increases postoperative bleeding in patients undergoing on-pump coronary artery bypass graft surgery. Off-pump coronary bypass grafting has been proposed as an alternative technique to attenuate postoperative bleeding associated with clopidogrel. This study aimed to determine the effects of aspirin and clopidogrel therapy on perioperative blood loss and blood transfusion requirements in off-pump coronary artery bypass grafting. One hundred six patients scheduled for off-pump coronary artery bypass grafting were divided into three groups: aspirin and clopidogrel discontinued more than 6 days before surgery (group 1, n = 35), aspirin and clopidogrel continued until 3 to 5 days before surgery (group 2, n = 51), and both medications continued within 2 days of surgery (group 3, n = 20). Thromboelastographic tracings were analyzed before induction of anesthesia. Routine coagulation profiles were measured before and after surgery. A cell salvage device was used during surgery and salvaged blood was reinfused. Chest tube drainage and blood transfusion requirement were recorded postoperatively. Patient characteristics, operative data, and thromboelastographic tracings were similar among the groups. There were significant decreases in hematocrit level and platelet count and prolongation in prothrombin time postoperatively in all groups without any intergroup differences. The amounts of perioperative blood loss and blood transfusion required were all similar among the groups. Preoperative clopidogrel and aspirin exposure even within 2 days of surgery does not increase perioperative blood loss and blood transfusion requirements in patients undergoing elective off-pump coronary artery bypass grafting.

Clopidogrel bioactivation and risk of bleeding in patients cotreated with angiotensin-converting enzyme inhibitors after myocardial infarction

DEFF Research Database (Denmark)

Kristensen, K E; Zhu, H-J; Wang, X

2014-01-01

in vitro and linked the results with a pharmacoepidemiological study. In vitro, ACEIs inhibited CES1-mediated hydrolysis of a model substrate, and trandolapril and enalapril increased formation of clopidogrel active metabolite. In 70,934 patients with myocardial infarction, hazard ratios for clinically...... significant bleeding in ACEI-treated patients cotreated with or without clopidogrel were 1.10 (95% confidence interval (CI): 0.97-1.25, P = 0.124) and 0.90 (95% CI: 0.81-0.99, P = 0.025), respectively, as compared with patients who did not receive ACEIs. This difference was statistically significant (P = 0...

Warfarin maintenance dose in older patients: higher average dose and wider dose frequency distribution in patients of African ancestry than those of European ancestry.

Science.gov (United States)

Garwood, Candice L; Clemente, Jennifer L; Ibe, George N; Kandula, Vijay A; Curtis, Kristy D; Whittaker, Peter

2010-06-15

Studies report that warfarin doses required to maintain therapeutic anticoagulation decrease with age; however, these studies almost exclusively enrolled patients of European ancestry. Consequently, universal application of dosing paradigms based on such evidence may be confounded because ethnicity also influences dose. Therefore, we determined if warfarin dose decreased with age in Americans of African ancestry, if older African and European ancestry patients required different doses, and if their daily dose frequency distributions differed. Our chart review examined 170 patients of African ancestry and 49 patients of European ancestry cared for in our anticoagulation clinic. We calculated the average weekly dose required for each stable, anticoagulated patient to maintain an international normalized ratio of 2.0 to 3.0, determined dose averages for groups 80 years of age and plotted dose as a function of age. The maintenance dose in patients of African ancestry decreased with age (PAfrican ancestry required higher average weekly doses than patients of European ancestry: 33% higher in the 70- to 79-year-old group (38.2+/-1.9 vs. 28.8+/-1.7 mg; P=0.006) and 52% in the >80-year-old group (33.2+/-1.7 vs. 21.8+/-3.8 mg; P=0.011). Therefore, 43% of older patients of African ancestry required daily doses >5mg and hence would have been under-dosed using current starting-dose guidelines. The dose frequency distribution was wider for older patients of African ancestry compared to those of European ancestry (PAfrican ancestry indicate that strategies for initiating warfarin therapy based on studies of patients of European ancestry could result in insufficient anticoagulation and thereby potentially increase their thromboembolism risk. Copyright 2010 Elsevier Inc. All rights reserved.

Evaluation of a high-level waste radiological maintenance facility

International Nuclear Information System (INIS)

Collins, K.J.

1998-01-01

The Savannah River Site''s (SRS) Defense Waste Processing Facility (DWPF) near Aiken, SC is the nation''s first and world''s largest high level waste vitrification facility. DWPF began, operations in March 1996 to process radioactive waste, consisting of a matrixed predominantly 137 Cs precipitate and a predominately 90 Sr and alpha emitting sludge, into boro-silicate glass for long term storage. Presently, DWPF is processing only sludge waste and is preparing to process a combination of sludge and precipitate waste. During precipitate operations, canister dose rates are expected to exceed 10 Sv hr -1 (1000 rem hr -1 ). In sludge-only operations, canister contact gamma dose rates are approximately 15 mSv hr -1 (1500 mrem hr -1 ). Transferable contamination levels have been greater than 10 mSv hr -1 (100 cm 2 ) -1 for beta-gamma emitters and into the millions of Bq (100 cm 2 ) -1 for the alpha emitting radionuclides. This paper presents an evaluation of the radiological maintenance areas and their ability to support radiological work

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 ...

Evaluation of Low- Versus High-dose Valganciclovir for Prevention of Cytomegalovirus Disease in High-risk Renal Transplant Recipients.

Science.gov (United States)

Gabardi, Steven; Asipenko, Natalya; Fleming, James; Lor, Kevin; McDevitt-Potter, Lisa; Mohammed, Anisa; Rogers, Christin; Tichy, Eric M; Weng, Renee; Lee, Ruth-Ann

2015-07-01

Despite proven efficacy of prolonged cytomegalovirus (CMV) prophylaxis using valganciclovir 900 mg/day, some centers use 450 mg/day due to reported success and cost savings. This multicenter, retrospective study compared the efficacy and safety of 6 months of low-dose versus high-dose valganciclovir prophylaxis in high-risk, donor-positive/recipient-negative, renal transplant recipients (RTR). Two hundred thirty-seven high-risk RTR (low-dose group = valganciclovir 450 mg/day [n = 130]; high-dose group = valganciclovir 900 mg/day [n = s7]) were evaluated for 1-year CMV disease prevalence. Breakthrough CMV, resistant CMV, biopsy-proven acute rejection (BPAR), graft loss, opportunistic infections (OI), new-onset diabetes after transplantation (NODAT), premature valganciclovir discontinuation, renal function and myelosuppression were also assessed. Patient demographics and transplant characteristics were comparable. Induction and maintenance immunosuppression were similar, except for more early steroid withdrawal in the high-dose group. Similar proportions of patients developed CMV disease (14.6% vs 24.3%; P = 0.068); however, controlling CMV risk factor differences through multivariate logistic regression revealed significantly lower CMV disease in the low-dose group (P = 0.02; odds ratio, 0.432, 95% confidence interval, 0.211-0.887). Breakthrough and resistant CMV occurred at similar frequencies. There was no difference in renal function or rates of biopsy-proven acute rejection, graft loss, opportunistic infections, or new-onset diabetes after transplantation. The high-dose group had significantly lower mean white blood cell counts at months 5 and 6; however, premature valganciclovir discontinuation rates were similar. Low-dose and high-dose valganciclovir regimens provide similar efficacy in preventing CMV disease in high-risk RTR, with a reduced incidence of leukopenia associated with the low-dose regimen and no difference in resistant CMV. Low-dose valganciclovir

Static platelet adhesion, flow cytometry and serum TXB2 levels for monitoring platelet inhibiting treatment with ASA and clopidogrel in coronary artery disease: a randomised cross-over study

Science.gov (United States)

Eriksson, Andreas C; Jonasson, Lena; Lindahl, Tomas L; Hedbäck, Bo; Whiss, Per A

2009-01-01

Background Despite the use of anti-platelet agents such as acetylsalicylic acid (ASA) and clopidogrel in coronary heart disease, some patients continue to suffer from atherothrombosis. This has stimulated development of platelet function assays to monitor treatment effects. However, it is still not recommended to change treatment based on results from platelet function assays. This study aimed to evaluate the capacity of a static platelet adhesion assay to detect platelet inhibiting effects of ASA and clopidogrel. The adhesion assay measures several aspects of platelet adhesion simultaneously, which increases the probability of finding conditions sensitive for anti-platelet treatment. Methods With a randomised cross-over design we evaluated the anti-platelet effects of ASA combined with clopidogrel as well as monotherapy with either drug alone in 29 patients with a recent acute coronary syndrome. Also, 29 matched healthy controls were included to evaluate intra-individual variability over time. Platelet function was measured by flow cytometry, serum thromboxane B2 (TXB2)-levels and by static platelet adhesion to different protein surfaces. The results were subjected to Principal Component Analysis followed by ANOVA, t-tests and linear regression analysis. Results The majority of platelet adhesion measures were reproducible in controls over time denoting that the assay can monitor platelet activity. Adenosine 5'-diphosphate (ADP)-induced platelet adhesion decreased significantly upon treatment with clopidogrel compared to ASA. Flow cytometric measurements showed the same pattern (r2 = 0.49). In opposite, TXB2-levels decreased with ASA compared to clopidogrel. Serum TXB2 and ADP-induced platelet activation could both be regarded as direct measures of the pharmacodynamic effects of ASA and clopidogrel respectively. Indirect pharmacodynamic measures such as adhesion to albumin induced by various soluble activators as well as SFLLRN-induced activation measured by flow

Initiation and persistence with clopidogrel treatment after acute myocardial infarction: a nationwide study

DEFF Research Database (Denmark)

Sørensen, Rikke; Gislason, G H; Fosbøl, E L

2008-01-01

AIMS: To identify possible underuse by analysing initiation and persistence with clopidogrel treatment in an unselected population of patients admitted with myocardial infarction (MI) with or without subsequent percutaneous coronary intervention (PCI). METHODS: Patients admitted with first-time MI...... proportional hazard models. RESULTS: A total of 46,190 MI patients were included in the study, of whom 14,939 were treated with PCI. From 2000 to 2005 initiation of clopidogrel increased from 80.4 to 93.7% among MI patients with PCI and from 2.8 to 39.3% among MI patients without PCI. MI patients...... with concomitant heart failure received less treatment [odds ratio (OR) 0.49, confidence interval (CI) 0.43, 0.56 among patients with PCI and OR 0.90, CI 0.81, 0.99 among patients without PCI in 2002-2003, and OR 0.89, CI 0.80, 1.00 in 2004-2005, respectively]. Of MI patients with PCI, 77.5% completed 9 months...

Identificación de dos formas polimórficas cristalinas de clopidogrel bisulfato en materia prima farmacéutica

Directory of Open Access Journals (Sweden)

German Leonardo Madrigal Redondo

Full Text Available Introducción: el clopidogrel bisulfato existe en numerosas formas cristalinas, que varían en su estabilidad fisicoquímica, por lo que algunas de estas formas, patentadas o no, son útiles en la fabricación de medicamentos. Objetivo: identificar las formas cristalinas existentes en dos muestras de clopidogrel bisulfato materia prima comercializadas para la fabricación de medicamentos y el estado de pureza de ambas muestras. Métodos: las muestras de materia prima se obtuvieron de una industria nacional. Se examinaron mediante técnicas analíticas avanzadas como difracción de rayos X, calorimetría diferencial de barrido, termogravimetría y espectroscopia infrarroja. Se compararon los valores encontrados con los del estado del arte reconocidos en la literatura revisada para el clopidogrel bisulfato materias primas y tomados como referencia. Resultados: se obtuvieron los difractogramas, termogramas y espectros de absorción correspondientes a las muestras analizadas. Se utilizó el software TA Universal Analysis para obtener el porcentaje de descomposición, punto de fusión y picos identificadores en las muestras. Conclusiones: la muestra 1 contiene la forma cristalina I del bisulfato de clopidogrel, que no es pura ya que existe una banda característica de la presencia de contaminación con la forma cristalina II. La muestra 2 corresponde a la forma cristalina II del producto en forma pura.

Duration of clopidogrel treatment and risk of mortality and recurrent myocardial infarction among 11 680 patients with myocardial infarction treated with percutaneous coronary intervention: a cohort study

Directory of Open Access Journals (Sweden)

Køber Lars

2010-01-01

Full Text Available Abstract Background The optimal duration of clopidogrel treatment after percutaneous coronary intervention (PCI is unclear. We studied the risk of death or recurrent myocardial infarction (MI in relation to 6- and 12-months clopidogrel treatment among MI patients treated with PCI. Methods Using nationwide registers of hospitalizations and drug dispensing from pharmacies we identified 11 680 patients admitted with MI, treated with PCI and clopidogrel. Clopidogrel treatment was categorized in a 6-months and a 12-months regimen. Rates of death, recurrent MI or a combination of both were analyzed by the Kaplan Meier method and Cox proportional hazards models. Bleedings were compared between treatment regimens. Results The Kaplan Meier analysis indicated no benefit of the 12-months regimen compared with the 6-months in all endpoints. The Cox proportional hazards analysis confirmed these findings with hazard ratios for the 12-months regimen (the 6-months regimen used as reference for the composite endpoint of 1.01 (confidence intervals 0.81-1.26 and 1.24 (confidence intervals 0.95-1.62 for Day 0-179 and Day 180-540 after discharge. Bleedings occurred in 3.5% and 4.1% of the patients in the 6-months and 12-months regimen (p = 0.06. Conclusions We found comparable rates of death and recurrent MI in patients treated with 6- and 12-months' clopidogrel. The potential benefit of prolonged clopidogrel treatment in a real-life setting remains uncertain.

Increased mortality associated with low use of clopidogrel in patients with heart failure and acute myocardial infarction not undergoing percutaneous coronary intervention: a nationwide study

DEFF Research Database (Denmark)

Bonde, Lisbeth; Sorensen, Rikke; Fosbøl, Emil Loldrup

2010-01-01

We studied the association of clopidogrel with mortality in acute myocardial infarction (AMI) patients with heart failure (HF) not receiving percutaneous coronary intervention (PCI).......We studied the association of clopidogrel with mortality in acute myocardial infarction (AMI) patients with heart failure (HF) not receiving percutaneous coronary intervention (PCI)....

THE ROLE OF CLOPIDOGREL IN PATIENTS WITH ACUTE CORONARY SYNDROME AFTER THE EMERGENCE OF MORE POWERFUL INHIBITORS OF P2Y12 RECEPTOR

Directory of Open Access Journals (Sweden)

S. R. Gilyarevsky

2014-07-01

Full Text Available The role of P2Y12 receptor blocker clopidogrel after the introduction into clinical practice of new, more powerful and stable operating drugs belonging to this class of antiplatelet agents is discussed. The advantages and disadvantages of each of the currently used antiplatelet drugs that block the receptor P2Y12 are reviewed. On the basis of the analysis concludes that, despite the emergence of new antiplatelet agents clopidogrel, appears to be widely used for a long time in the treatment of patients with acute coronary syndrome and / or after coronary stenting. This is primarily due to the presence of large evidence base, and confirmation of safety of long-term therapy clopidogrel.

Different effects of clopidogrel and clarithromycin on the enantioselective pharmacokinetics of sibutramine and its active metabolites in healthy subjects.

Science.gov (United States)

Shinde, Dhananjay D; Kim, Ho-Sook; Choi, Jae-Seok; Pan, Wei; Bae, Soo Kyung; Yeo, Chang-Woo; Shon, Ji-Hong; Kim, Dong-Hyun; Shin, Jae Gook

2013-05-01

In this study, we assessed the effects of clopidogrel and clarithromycin, known CYP2B6 and CYP3A inhibitors, respectively, on the enantioselective disposition of racemic sibutramine in conjunction with CYP2B6 polymorphisms in humans. Sibutramine showed enantioselective plasma profiles with consistently higher concentrations of R-enantiomers. Clopidogrel and clarithromycin significantly increased the sibutramine plasma concentration, but their effects differed between enantiomers; a 2.2-fold versus 4.1-fold increase in the AUC in S-enantiomer and 1.8-fold versus 2.0-fold for the R-enantiomer, respectively. The AUCs of S- and R-desmethyl metabolites changed significantly during the clopidogrel phase (P sibutramine was higher in subjects with the CYP2B6*6/*6 genotype, but no statistical difference was observed among the CYP2B6 genotypes. These results suggest that the enantioselective disposition of sibutramine and its active metabolites are influenced by the altered genetic and environmental factors of CYP2B6 and CYP3A activity in vivo. © The Author(s) 2013.

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

Directory of Open Access Journals (Sweden)

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.

Evaluation of dose reduction versus standard dosing for maintenance of remission in patients with spondyloarthritis and clinical remission with anti-TNF (REDES-TNF): study protocol for a randomized controlled trial.

Science.gov (United States)

Pontes, Caridad; Gratacós, Jordi; Torres, Ferran; Avendaño, Cristina; Sanz, Jesús; Vallano, Antoni; Juanola, Xavier; de Miguel, Eugenio; Sanmartí, Raimon; Calvo, Gonzalo

2015-08-20

Dose reduction schedules of tumor necrosis factor antagonists (anti-TNF) as maintenance therapy in patients with spondyloarthritis are used empirically in clinical practice, despite the lack of clinical trials providing evidence for this practice. To address this issue the Spanish Society of Rheumatology (SER) and Spanish Society of Clinical Pharmacology (SEFC) designed a 3-year multicenter, randomized, open-label, controlled clinical trial (2 years for inclusion and 1 year of follow-up). The study is expected to include 190 patients with axial spondyloarthritis on stable maintenance treatment (≥4 months) with any anti-TNF agent at doses recommended in the summary of product characteristics. Patients will be randomized to either a dose reduction arm or maintenance of the dosing regimen as per the official labelling recommendations. Randomization will be stratified according to the anti-TNF agent received before study inclusion. Patient follow-up, visit schedule, and examinations will be maintained as per normal clinical practice recommendations according to SER guidelines. The study aims to test the hypothesis of noninferiority of the dose reduction strategy compared with standard treatment. The first patients were recruited in July 2012, and study completion is scheduled for the end of April 2015. The REDES-TNF study is a pragmatic clinical trial that aims to provide evidence to support a medical decision now made empirically. The study results may help inform clinical decisions relevant to both patients and healthcare decision makers. EudraCT 2011-005871-18 (21 December 2011).

Static platelet adhesion, flow cytometry and serum TXB2 levels for monitoring platelet inhibiting treatment with ASA and clopidogrel in coronary artery disease: a randomised cross-over study

Directory of Open Access Journals (Sweden)

Hedbäck Bo

2009-06-01

Full Text Available Abstract Background Despite the use of anti-platelet agents such as acetylsalicylic acid (ASA and clopidogrel in coronary heart disease, some patients continue to suffer from atherothrombosis. This has stimulated development of platelet function assays to monitor treatment effects. However, it is still not recommended to change treatment based on results from platelet function assays. This study aimed to evaluate the capacity of a static platelet adhesion assay to detect platelet inhibiting effects of ASA and clopidogrel. The adhesion assay measures several aspects of platelet adhesion simultaneously, which increases the probability of finding conditions sensitive for anti-platelet treatment. Methods With a randomised cross-over design we evaluated the anti-platelet effects of ASA combined with clopidogrel as well as monotherapy with either drug alone in 29 patients with a recent acute coronary syndrome. Also, 29 matched healthy controls were included to evaluate intra-individual variability over time. Platelet function was measured by flow cytometry, serum thromboxane B2 (TXB2-levels and by static platelet adhesion to different protein surfaces. The results were subjected to Principal Component Analysis followed by ANOVA, t-tests and linear regression analysis. Results The majority of platelet adhesion measures were reproducible in controls over time denoting that the assay can monitor platelet activity. Adenosine 5'-diphosphate (ADP-induced platelet adhesion decreased significantly upon treatment with clopidogrel compared to ASA. Flow cytometric measurements showed the same pattern (r2 = 0.49. In opposite, TXB2-levels decreased with ASA compared to clopidogrel. Serum TXB2 and ADP-induced platelet activation could both be regarded as direct measures of the pharmacodynamic effects of ASA and clopidogrel respectively. Indirect pharmacodynamic measures such as adhesion to albumin induced by various soluble activators as well as SFLLRN

Use of rank sum method in identifying high occupational dose jobs for ALARA implementation

International Nuclear Information System (INIS)

Cho, Yeong Ho; Kang, Chang Sun

1998-01-01

The cost-effective reduction of occupational radiation exposure (ORE) dose at a nuclear power plant could not be achieved without going through an extensive analysis of accumulated ORE dose data of existing plants. It is necessary to identify what are high ORE jobs for ALARA implementation. In this study, the Rank Sum Method (RSM) is used in identifying high ORE jobs. As a case study, the database of ORE-related maintenance and repair jobs for Kori Units 3 and 4 is used for assessment, and top twenty high ORE jobs are identified. The results are also verified and validated using the Friedman test, and RSM is found to be a very efficient way of analyzing the data. (author)

Moderate- vs high-dose methadone in the treatment of opioid dependence: a randomized trial.

Science.gov (United States)

Strain, E C; Bigelow, G E; Liebson, I A; Stitzer, M L

1999-03-17

Methadone hydrochloride treatment is the most common pharmacological intervention for opioid dependence, and recent interest has focused on expanding methadone treatment availability beyond traditional specially licensed clinics. However, despite recommendations regarding effective dosing of methadone, controlled clinical trials of higher-dose methadone have not been conducted. To compare the relative clinical efficacy of moderate- vs high-dose methadone in the treatment of opioid dependence. A 40-week randomized, double-blind clinical trial starting in June 1992 and ending in October 1995. Outpatient substance abuse treatment research clinic at the Johns Hopkins University Bayview Campus, Baltimore, Md. One hundred ninety-two eligible clinic patients. Daily oral methadone hydrochloride in the dose range of 40 to 50 mg (n = 97) or 80 to 100 mg (n = 95), with concurrent substance abuse counseling. Opioid-positive urinalysis results and retention in treatment. By intent-to-treat analysis through week 30 patients in the high-dose group had significantly lower rates of opioid-positive urine samples compared with patients in the moderate-dose group (53.0% [95% confidence interval [CI], 46.9%-59.2%] vs 61.9% [95% CI, 55.9%-68.0%]; P = .047. These differences persisted during withdrawal from methadone. Through day 210 no significant difference was evident between dose groups in treatment retention (high-dose group mean retention, 159 days; moderate-dose group mean retention, 157 days). Nineteen (33%) of 57 patients in the high-dose group and 11 (20%) of 54 patients in the moderate-dose group completed detoxification. Both moderate- and high-dose methadone treatment resulted in decreased illicit opioid use during methadone maintenance and detoxification. The high-dose group had significantly greater decreases in illicit opioid use.

Mechanisms of lower maintenance dose of tacrolimus in obese patients.

Science.gov (United States)

Sawamoto, Kazuki; Huong, Tran T; Sugimoto, Natsumi; Mizutani, Yuka; Sai, Yoshimichi; Miyamoto, Ken-ichi

2014-01-01

A retrospective analysis suggested that blood tacrolimus concentrations were consistent among patients with a body mass index (BMI) that was lean (maintenance dose of tacrolimus in patients with BMI ≥ 25 was significantly lower compared with that in patients with a BMI of less than 25. Lean and obese Zucker rats fed a normal diet were given tacrolimus intravenously or orally. The blood concentrations of tacrolimus in obese rats were significantly higher than those in lean rats after administration via both routes. The moment analysis has suggested that CLtot and Vdss of tacrolimus were not significantly different between lean and obese rats. The bioavailability was higher in obese rats, compared with that in lean rats. The protein expression of Cyp3a2 in the liver was significantly decreased in obese rats, compared with lean rats, while P-gp in the small intestine was also significantly decreased in obese rats. These results suggested that the steady-state trough concentration of tacrolimus in obese patients was well maintained by a relatively low dose compared with that in normal and lean patients, presumably due to increased bioavailability.

Maintenance Optimization of High Voltage Substation Model

Directory of Open Access Journals (Sweden)

Radim Bris

2008-01-01

Full Text Available The real system from practice is selected for optimization purpose in this paper. We describe the real scheme of a high voltage (HV substation in different work states. Model scheme of the HV substation 22 kV is demonstrated within the paper. The scheme serves as input model scheme for the maintenance optimization. The input reliability and cost parameters of all components are given: the preventive and corrective maintenance costs, the actual maintenance period (being optimized, the failure rate and mean time to repair - MTTR.

Effect of CYP2C9, VKORC1, CYP4F2 and GGCX genetic variants on warfarin maintenance dose and explicating a new pharmacogenetic algorithm in South Indian population.

Science.gov (United States)

Krishna Kumar, Dhakchinamoorthi; Shewade, Deepak Gopal; Loriot, Marie-Anne; Beaune, Philippe; Balachander, Jayaraman; Sai Chandran, B V; Adithan, Chandrasekaran

2014-01-01

To determine the influence of genetic polymorphisms on warfarin maintenance dose and to explicate an algorithm using the pharmacogenetic and clinical factors to determine the maintenance and/or starting dose of warfarin in South Indian patients receiving warfarin therapy. Patients receiving stabilized warfarin therapy (n=257) were included in the study. Single nucleotide polymorphisms (SNPs) of CYP2C9 (rs1799853 and rs1057910), VKORC1 (rs9923231, rs7196161, rs2884737, rs9934438, rs8050894, rs2359612 and rs7294), CYP4F2 (rs2108622) and GGCX (rs11676382) were genotyped by the quantitative real time-PCR method. The mean daily maintenance dose of warfarin was found to be 4.7 ± 2.1 mg/day. Patients with the CYP2C9*1/*2, *1/*3 and *2/*3 variant genotypes required a 51.0 (2.8 mg), 60.9 (2.3 mg) and 62.2 % (2.2 mg) lower daily maintenance dose of warfarin, respectively, than those patients with the CYP2C9*1/*1 wild-type genotype (5.2 mg) (pmaintenance dose. Genetic polymorphisms of CYP2C9, VKORC1, CYP4F2 and GGCX are important predictive factors of warfarin maintenance dose, and the developed algorithm will be useful to predict the required maintenance and/or starting warfarin dose in South Indian populations.

Effect of exercise on platelet activation during aspirin or clopidogrel intake in healthy men

DEFF Research Database (Denmark)

Hjorth Madsen, Esben; Christiansen, Morten Krogh; Schmidt, Erik Berg

2009-01-01

aggregometry. A significant increase in plasma von Willebrand Factor was also found in response to exercise. In conclusion, platelet activation occurs during exercise in healthy individuals. This activation is not prevented by use of aspirin or clopidogrel, and may partly be explained by an increase in plasma...

Tailored antiplatelet therapy to improve prognosis in patients exhibiting clopidogrel low-response prior to percutaneous coronary intervention for stable angina or non-ST elevation acute coronary syndrome

DEFF Research Database (Denmark)

Paarup Dridi, Nadia; Johansson, Pär I; Lønborg, Jacob T

2015-01-01

Abstract Aim: To investigate whether an intensified antiplatelet regimen could improve prognosis in stable or non-ST elevation in acute coronary syndrome (ACS) patients exhibiting high on-treatment platelet reactivity (HTPR) on clopidogrel and treated with percutaneous coronary intervention (PCI...

Clopidogrel discontinuation within the first year after coronary drug-eluting stent implantation

DEFF Research Database (Denmark)

Thim, Troels; Johansen, Martin Berg; Chisholm, Gro Egholm

2014-01-01

BACKGROUND: The impact of adherence to the recommended duration of dual antiplatelet therapy after first generation drug-eluting stent implantation is difficult to assess in real-world settings and limited data are available. METHODS: We followed 4,154 patients treated with coronary drug-eluting ......BACKGROUND: The impact of adherence to the recommended duration of dual antiplatelet therapy after first generation drug-eluting stent implantation is difficult to assess in real-world settings and limited data are available. METHODS: We followed 4,154 patients treated with coronary drug......-eluting stents in Western Denmark for 1 year and obtained data on redeemed clopidogrel prescriptions and major adverse cardiovascular events (MACE, i.e., cardiac death, myocardial infarction, or stent thrombosis) from medical databases. RESULTS: Discontinuation of clopidogrel within the first 3 months after...... stent implantation was associated with a significantly increased rate of MACE at 1-year follow-up (hazard ratio (HR) 2.06; 95% confidence interval (CI): 1.08-3.93). Discontinuation 3-6 months (HR 1.29; 95% CI: 0.70-2.41) and 6-12 months (HR 1.29; 95% CI: 0.54-3.07) after stent implantation were...

Influence of titration schedule and maintenance dose on the tolerability of adjunctive eslicarbazepine acetate: An integrated analysis of three randomized placebo-controlled trials.

Science.gov (United States)

Krauss, Gregory; Biton, Victor; Harvey, Jay H; Elger, Christian; Trinka, Eugen; Soares da Silva, Patrício; Gama, Helena; Cheng, Hailong; Grinnell, Todd; Blum, David

2018-01-01

To examine the influence of titration schedule and maintenance dose on the incidence and type of treatment-emergent adverse events (TEAEs) associated with adjunctive eslicarbazepine acetate (ESL). Data from three randomized, double-blind, placebo-controlled trials were analyzed. Patients with refractory partial-onset seizures were randomized to maintenance doses of ESL 400, 800, or 1200mg QD (dosing was initiated at 400 or 800mg QD) or placebo. The incidence of TEAEs was analyzed during the double-blind period (2-week titration phase; 12-week maintenance phase), according to the randomized maintenance dose and the titration schedule. 1447 patients were included in the analysis. During the first week of treatment, 62% of patients taking ESL 800mg QD had ≥1 TEAE, vs 35% of those taking 400mg QD and 32% of the placebo group; dizziness, somnolence, nausea, and headache were numerically more frequent in patients taking ESL 800mg than those taking ESL 400mg QD. During the double-blind period, the incidences of common TEAEs were lower in patients who initiated ESL at 400mg vs 800mg QD. For the 800 and 1200mg QD maintenance doses, rates of TEAEs leading to discontinuation were lower in patients who began treatment with 400mg than in those who began taking ESL 800mg QD. Initiation of ESL at 800mg QD is feasible. However, initiating treatment with ESL 400mg QD for 1 or 2 weeks is recommended, being associated with a lower incidence of TEAEs, and related discontinuations. For some patients, treatment may be initiated at 800mg QD, if the need for more immediate seizure reduction outweighs concerns about increased risk of adverse reactions during initiation. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Bleeding tendency in dual antiplatelet therapy with aspirin/clopidogrel: rescue of the template bleeding time in a single-center prospective study

Directory of Open Access Journals (Sweden)

Altman Raul

2012-01-01

Full Text Available Abstract Background Patients with heightened platelet reactivity in response to antiplatelet agents are at an increased risk of recurrent ischemic events. However, there is a lack of diagnostic criteria for increased response to combined aspirin/clopidogrel therapy. The challenge is to identify patients at risk of bleeding. This study sought to characterize bleeding tendency in patients treated with aspirin and clopidogrel. Patients/methods In a single-center prospective study, 100 patients under long-term aspirin/clopidogrel treatment, the effect of therapy was assayed by template bleeding time (BT and the inhibition of platelet aggregation (IPA by light transmission aggregometry (LTA. Arachidonic acid (0.625 mmol/L and adenosine diphosphate (ADP; 2, 4, and 8 μmol/L were used as platelet agonists. Results Bleeding episodes (28 nuisance, 2 hematuria [1 severe], 1 severe proctorrhagia, 1 severe epistaxis were significantly more frequent in patients with longer BT. Template BT ≥ 24 min was associated with bleeding episodes (28 of 32. Risk of bleeding increased 17.4% for each 1 min increase in BT. Correlation was found between BT and IPAmax in response to ADP 2 μmol/L but not to ADP 4 or 8 μmol/L. Conclusion In patients treated with dual aspirin/clopidogrel therapy, nuisance and internal bleeding were significantly associated with template BT and with IPAmax in response to ADP 2 μmol/L but not in response to ADP 4 μmol/L or 8 μmol/L.

Maintenance considerations of the Starfire Commercial Tokamak

International Nuclear Information System (INIS)

Trachael, C.A.; Zahn, H.S.; Field, R.E.; Stevens, H.C.

1979-01-01

An initial reactor design has been developed for the Starfire Tokamak reactor that incorporates maintenance features to permit reactor and plant operation with a 75% availability. All components of the reactor can be replaced utilizing highly automated remote maintenance techniques. Provisions for contact maintenance are included but would only be utilized on a contingency basis since it is believed that allowable dose rates will be decreased in future years. A modular design approach is used for the reactor and auxiliary subsystems to permit efficient use of remote maintenance. The modular approach minimizes the number of different maintenance operations required and can result in use of simple tasks such as push, pull, turn, etc., maneuvers for module removal. Fault isolation is provided for each replaceable module

Comparison of C-reactive protein levels with delivered dose of Kt/V in patients with end-stage renal disease on maintenance hemodialysis

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Humayun Rashid

2015-01-01

Full Text Available The objective of our study is to compare the C-reactive protein (CRP levels with the delivered dose of dialysis in terms of Kt/V in patients undergoing maintenance hemodialysis (HD. This is a comparative, cross-sectional survey. The study was conducted at the HD unit of the Shaikh Zayed Hospital, Lahore, Pakistan. Patients who fulfilled the inclusion and exclusion criteria were enrolled in this study. The delivered dose of HD (Kt/V was assessed by an online clearance module (OCM in Fresenius machines at the end of every dialysis session and the weekly Kt/V was determined by adding all three Kt/V values. The serum CRP sample was taken after each session of HD and the mean CRP was calculated and considered elevated if it was >6 mg/dL. Both weekly Kt/V and CRP values were entered in a pre-designed proforma. Data were analyzed by using statistical software SPSS and P-value £0.05 was considered significant. Of 100 patients on maintenance HD, high serum CRP level (>6 mg/dL was found in 38 patients. When the Kt/V was compared with the CRP level, there was a negative correlation between the two parameters (r = 0.212, P = 0.032. Low Kt/V means dialysis inadequacy, which is associated with chronic inflammatory state, resulting in high CRP levels. We suggest that the quality of life of dialysis patients can be improved by offering an adequate dose of HD reflected by Kt/V ≥3.6/week.

Two Different Maintenance Strategies in the Hospital Environment: Preventive Maintenance for Older Technology Devices and Predictive Maintenance for Newer High-Tech Devices

OpenAIRE

Sezdi, Mana

2016-01-01

A maintenance program generated through the consideration of characteristics and failures of medical equipment is an important component of technology management. However, older technology devices and newer high-tech devices cannot be efficiently managed using the same strategies because of their different characteristics. This study aimed to generate a maintenance program comprising two different strategies to increase the efficiency of device management: preventive maintenance for older tec...

ANALYSIS OF DOSE RATES DURING REPLACEMENT OF MANIPULATORS IN THE FFTF INTERIM EXAMINATION and MAINTENANCE (IEM) CELL

International Nuclear Information System (INIS)

NELSON, J.V.

2002-01-01

Replacement of a master-slave manipulator in the Interim Examination and Maintenance Cell at the Fast Flux Test Facility was carried out in August 2001. This operation created a 178-mm opening in the thick concrete wall of the hot cell. To aid in radiological work planning, dose rates outside the penetration in the wall were predicted using MCNP(trademark) photon transport calculations. The predicted dose rate was 7.7 mrem/h, which was reasonably close to the value of 10.4 mrem/h inferred from measurements

Aspirin Versus Aspirin Plus Clopidogrel as Antithrombotic Treatment Following Transcatheter Aortic Valve Replacement With a Balloon-Expandable Valve: The ARTE (Aspirin Versus Aspirin + Clopidogrel Following Transcatheter Aortic Valve Implantation) Randomized Clinical Trial.

Science.gov (United States)

Rodés-Cabau, Josep; Masson, Jean-Bernard; Welsh, Robert C; Garcia Del Blanco, Bruno; Pelletier, Marc; Webb, John G; Al-Qoofi, Faisal; Généreux, Philippe; Maluenda, Gabriel; Thoenes, Martin; Paradis, Jean-Michel; Chamandi, Chekrallah; Serra, Vicenç; Dumont, Eric; Côté, Mélanie

2017-07-10

The aim of this study was to compare aspirin plus clopidogrel with aspirin alone as antithrombotic treatment following transcatheter aortic valve replacement (TAVR) for the prevention of ischemic events, bleeding events, and death. Few data exist on the optimal antithrombotic therapy following TAVR. This was a randomized controlled trial comparing aspirin (80 to 100 mg/day) plus clopidogrel (75 mg/day) (dual antiplatelet therapy [DAPT]) versus aspirin alone (single-antiplatelet therapy [SAPT]) in patients undergoing TAVR with a balloon-expandable valve. The primary endpoint was the occurrence of death, myocardial infarction (MI), stroke or transient ischemic attack, or major or life-threatening bleeding (according to Valve Academic Research Consortium 2 definitions) within the 3 months following the procedure. The trial was prematurely stopped after the inclusion of 74% of the planned study population. A total of 222 patients were included, 111 allocated to DAPT and 111 to SAPT. The composite of death, MI, stroke or transient ischemic attack, or major or life-threatening bleeding tended to occur more frequently in the DAPT group (15.3% vs. 7.2%, p = 0.065). There were no differences between groups in the occurrence of death (DAPT, 6.3%; SAPT, 3.6%; p = 0.37), MI (DAPT, 3.6%; SAT, 0.9%; p = 0.18), or stroke or transient ischemic attack (DAPT, 2.7%; SAPT, 0.9%; p = 0.31) at 3 months. DAPT was associated with a higher rate of major or life-threatening bleeding events (10.8% vs. 3.6% in the SAPT group, p = 0.038). There were no differences between groups in valve hemodynamic status post-TAVR. This small trial showed that SAPT (vs. DAPT) tended to reduce the occurrence of major adverse events following TAVR. SAPT reduced the risk for major or life-threatening events while not increasing the risk for MI or stroke. Larger studies are needed to confirm these results. (Aspirin Versus Aspirin + Clopidogrel Following Transcatheter Aortic Valve Implantation: The ARTE

Cardiovascular outcomes associated with concomitant use of clopidogrel and proton pump inhibitors in patients with acute coronary syndrome in Taiwan

Science.gov (United States)

Lin, Chen-Fang; Shen, Li-Jiuan; Wu, Fe-Lin Lin; Bai, Chyi-Huey; Gau, Churn-Shiouh

2012-01-01

AIMS Our study aimed to examine the impact of concomitant use of proton pump inhibitors (PPIs) with clopidogrel on the cardiovascular outcomes of patients with acute coronary syndrome (ACS). Furthermore, we sought to quantify the effects of five individual PPIs when used concomitantly with clopidogrel. METHODS We conducted a retrospective cohort study of patients who were newly hospitalized for ACS between 1 January 2006 and 31 December 2007 retrieved from the Taiwan National Health Insurance Research Database (NHIRD) and who were prescribed clopidogrel (n= 37 099) during the follow-up period. A propensity score technique was used to establish a matched cohort in 1:1 ratio (n= 5173 for each group). The primary clinical outcome was rehospitalization for ACS, while secondary outcomes were rehospitalization for percutaneous transluminal coronary angioplasty (PTCA) with stent, PTCA without stent and revascularization (PTCA or coronary artery bypass graft surgery) after the discharge date for the index ACS event. RESULTS The adjusted hazard ratio of rehospitalization for ACS was 1.052 (95% confidence interval, 0.971–1.139; P= 0.214) in the propensity score matched cohort. Among all PPIs, only omeprazole was found to be statistically significantly associated with an increased risk of rehospitalization for ACS (adjusted hazard ratio, 1.226; 95% confidence interval, 1.066–1.410; P= 0.004). Concomitant use of esomeprazole, pantoprazole, rabeprazole and lansoprazole did not increase the risk. CONCLUSIONS Our study indicated no statistically significant increase in the risk of rehospitalization for ACS due to concurrent use of clopidogrel and PPIs overall. Among individual PPIs, only omeprazole was found to be statistically significantly associated with increased risk of rehospitalization for ACS. PMID:22364155

Prasugrel compared to clopidogrel in patients with acute coronary syndrome undergoing percutenaous coronary intervention: a Spanish model-based cost effectiveness analysis.

Science.gov (United States)

Davies, A; Sculpher, M; Barrett, A; Huete, T; Sacristán, J A; Dilla, T

2013-01-01

To assess the long-term cost-effectiveness of 12 months treatment of prasugrel compared to clopidogrel in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) in the Spanish health care system. A Markov state transition model was developed to estimate health outcomes, quality adjusted life years (QALYs), life years (LY), and costs over patients' lifetimes. Clinical inputs were based on an analysis of the TRITON-TIMI 38 clinical trial. Hospital readmissions captured during the trial in a sub-study of patients from eight countries (and subsequent re-hospitalisations modelled to accrue beyond the time horizon of the trial), were assigned to Spanish diagnosis-related group payment schedules to estimate hospitalisation costs. Mean total treatment costs were ?11,427 and ?10,910 for prasugrel and clopidogrel respectively. The mean cost of the study drug was ?538 higher for prasugrel vs. clopidogrel, but rehospitalisation costs at 12 months were ?79 lower for prasugrel due to reduced rates of revascularisation. Hospitalisation costs beyond 12 months were higher with prasugrel by ?55, due to longer life expectancy (+0.071 LY and +0.054 QALYs) associated with the decreased nonfatal myocardial infarction rate in the prasugrel group. The incremental cost per life year and QALY gained with prasugrel was ?7,198, and ?9,489, respectively. Considering a willingness-to-pay threshold of ?30,000/QALY gained in the Spanish setting, prasugrel represents a cost-effective option in comparison with clopidogrel among patients with ACS undergoing PCI. Copyright © 2013 SEFH. Published by AULA MEDICA. All rights reserved.

Clopidogrel (Plavix®), a P2Y(12) receptor antagonist, inhibits bone cell function in vitro and decreases trabecular bone in vivo

DEFF Research Database (Denmark)

Syberg, Susanne; Brandao-Burch, Andrea; Patel, Jessal J

2012-01-01

Clopidogrel (Plavix®), a selective P2Y(12) receptor antagonist, is widely prescribed to reduce the risk of heart attack and stroke and acts via the inhibition of platelet aggregation. Accumulating evidence now suggests that extracellular nucleotides, signalling through P2 receptors, play...... a significant role in bone, modulating both osteoblast and osteoclast function. In this study, we investigated the effects of clopidogrel treatment on (1) bone cell formation, differentiation and activity in vitro; and, (2) trabecular and cortical bone parameters in vivo. P2Y(12) receptor expression...

Vascular risk levels affect the predictive value of platelet reactivity for the occurrence of MACE in patients on clopidogrel. Systematic review and meta-analysis of individual patient data.

Science.gov (United States)

Reny, Jean-Luc; Fontana, Pierre; Hochholzer, Willibald; Neumann, Franz Josef; Ten Berg, Jurriën; Janssen, Paul W; Geisler, Tobias; Gawaz, Meinrad; Marcucci, Rossella; Gori, Anna-Maria; Cuisset, Thomas; Alessi, Marie-Christine; Berdagué, Philippe; Gurbel, Paul A; Yong, Gerald; Angiolillo, Dominick J; Aradi, Dániel; Beigel, Roy; Campo, Gianluca; Combescure, Christophe

2016-04-01

Prior studies have shown an association between high on-clopidogrel platelet reactivity (PR) and the risk of major adverse cardiovascular events (MACE). However, large intervention trials on PR-tailored treatments have been neutral. The role and usefulness of PR with regard to levels of cardiovascular risk are unclear. We undertook a systematic review and meta-analysis of individual patient data on MACE outcomes (acute coronary syndromes (ACS), ischaemic strokes, and vascular deaths) in relation to PR and its interaction with cardiovascular risk levels. PR was determined using ADP-induced light transmission aggregometry with a primary concentration of 20 µM ADP. Thirteen prospective studies totaled 6,478 clopidogrel-treated patients who experienced 421 MACE (6.5 %) during a median follow-up of 12 months. The strength of the association between the risk of MACE and PR increased significantly (p=0.04) with the number of risk factors present (age> 75 years, ACS at inclusion, diabetes, and hypertension). No association was detected in patients with no risk factor (p=0.48). In patients presenting one risk factor, only high-PR was associated with an increased risk of MACE (HR 3.2, p=0.001). In patients presenting ≥ 2 risk factors, the increase of risk started from medium-PR (medium-PR: HR=2.9, p=0.0004; high-PR: HR=3.7, p=0.0003). PR allowed the reclassification of 44 % of the total population to a different risk level for the outcome of MACE, mostly in intermediate or high risk patients. In conclusion, the magnitude of the association between PR and MACE risk is strongly dependent on the level of cardiovascular risk faced by patients on clopidogrel.

Occupational dose reduction developments and data collected at nuclear power plants

International Nuclear Information System (INIS)

Dionne, B.J.; Baum, J.W.

1984-01-01

Occupational dose reduction developments and data collected at nuclear power plants have been described. Written descriptions of repetitive high dose jobs, their collective dose equivalent ranges and list of dose reduction techniques will aid in reducing collective dose equivalents from these dose-reduction targets. Knowing which components contribute to high maintenance or repair dose will aid in reducing routine maintenance collective dose equivalents. The radwaste dose reduction improvements will aid in reducing radwaste operations collective dose equivalent and reduce the number of radwaste workers who exceed their administrative dose limits. The identification and rating of managers' and workers' ALARA incentives will provide the basis for recommendations to improve dose reduction incentives. Lastly, the identification and rating of the key components of an ALARA program will aid in the development and coordination of the nuclear station ALARA programs

Compact and maintenance-free radio probes for environmental surveillance of the gamma dose rate

International Nuclear Information System (INIS)

Genrich, V.

1998-01-01

The author reports on his experience with the operation of radio data networks for the continuous observation of the gamma dose rate in nuclear installations. Practically at every location (within) the installation the hermetically sealed probes can record the measurement values. Moreover, the probes have proved successful in environmental surveillance where they typically work in the form of measurement rings in 10 to 30 km distance. All measurement data are organized in the form of a data base. They can be disposed of in the form of an SQL-server in the computer network (LAN) of the power plant or the institution in charge of environmental surveillance. In comparison to conventional, e.g. cable-bound measurement networks with the new radio transmission technology there are numerous advantages: - minimal cost for projection - minimal cost for installation due to simple fixing - quasi-mobile use with highest possible flexibility - maintenance-free operation and high degree of operating reliability. (orig.) [de

Dose-associated changes in safety and efficacy parameters observed in a 24-week maintenance trial of olanzapine long-acting injection in patients with schizophrenia

Directory of Open Access Journals (Sweden)

Watson Susan B

2011-02-01

Full Text Available Abstract Background In a recently published 24-week maintenance study of olanzapine long-acting injection (LAI in schizophrenia (Kane et al., 2010, apparent dose-associated changes were noted in both efficacy and safety parameters. To help clinicians balance safety and efficacy when choosing a dose of olanzapine LAI, we further studied these changes. Methods Outpatients with schizophrenia who had maintained stability on open-label oral olanzapine for 4 to 8 weeks were randomly assigned to "low" (150 mg/2 weeks; N = 140, "medium" (405 mg/4 weeks; N = 318, or "high" (300 mg/2 weeks; N = 141 dosages of olanzapine LAI for 24 weeks. Potential relationships between dose and several safety or efficacy measures were examined via regression analysis, the Jonckheere-Terpstra test (continuous data, or the Cochran-Armitage test (categorical data. Results Safety parameters statistically significantly related to dose were mean weight change (low: +0.67 [SD = 4.38], medium: +0.89 [SD = 3.87], high: +1.70 [SD = 4.14] kg, p = .024; effect size [ES] = 0.264 high vs. low dose, mean change in prolactin (low: -5.61 [SD = 12.49], medium: -2.76 [SD = 19.02], high: +3.58 [SD = 33.78] μg/L, p = .001; ES = 0.410 high vs. low dose, fasting triglycerides change from normal at baseline to high (low: 3.2%, medium: 6.0%, high: 18.9%, p = .001; NNT = 7 high vs. low dose and fasting high-density lipoprotein cholesterol change from normal at baseline to low (low: 13.8%, medium: 19.6%, high: 30.7%, p = .019; NNT = 6 high vs. low dose. Efficacy measures significantly related to dose included Positive and Negative Syndrome Scale total score mean change (low: +2.66 [SD = 14.95], medium: -0.09 [SD = 13.47], high: -2.19 [SD = 13.11], p Conclusions Analyses of several safety and efficacy parameters revealed significant associations with dose of olanzapine LAI, with the highest dose generally showing greater efficacy as well as greater adverse changes in metabolic safety measures. When

Study of distribution of doses in maintenance operations and interventions in restricted areas of IPEN's radiopharmacy center, Brazil

International Nuclear Information System (INIS)

Machado, Jessica S.; Souza, Daiane C.; Rodrigues Junior, Orlando; Gerulis, Eduardo; Todo, Alberto S.

2013-01-01

This research was developed at the Radiopharmacy Center of the Nuclear and Energy Research Institute - IPEN/CNEN/SP, Brazil, that performs the production of radiopharmaceuticals with isotopes of the 131 I, 123 I, 201 Tl, 67 Ga, 18 F and 99 Mo for use in nuclear medicine. The radioisotopes are produced on an industrial scale and the installation was designed to meet radiation safety standards and quality control requirements. To ensure the production, there are skilled professionals who perform the tasks of maintenance of the equipment and instruments, installed in the cells of processing of radiopharmaceuticals, without which it is not possible to conduct the work with safety and quality. This study was done a survey called Survey of Variables, based on the maintenance operations and interventions in restricted areas of the Centre of Radiopharmacy and in the survey of the distribution of doses in these tasks, carried out during the period from 2005 to 2011. This research aims to identify and determine the main variables that have an impact on the worker's dose. The results are presented for the Occupationally Exposed Individual variable, variable operation, variable area/Cell, task and Feature variable and variable duration of operation, depending on the Dose variable. It is intended in this way to contribute to improvements in operations in restricted areas that may result in lower individual doses without causing significant changes in the routine of work

A polymorphism in NFKB1 is associated with improved effect of interferon-alpha maintenance treatment of patients with multiple myeloma after high-dose treatment with stem cell support

DEFF Research Database (Denmark)

Vangsted, Annette J; Klausen, Tobias W; Gimsing, Peter

2009-01-01

and Methods: In a retrospective study of 296 patients with multiple myelom undergoing high-dose therapy between 1994 and 2004, 146 patients were treated with interferon- as maintenance therapy. We tested the polymorphisms IL1B T-31C, IL6 G-174C, NFKB1-94ins/delATTG, CD3EAP G-21A and PPP1R13L IVS1 A4364G...... homozygous for the wild type G allele of IL6 G-174C who survived longer (p= 0.0074) than variant allele carriers. There was no association between the polymorphisms IL1B T-31C, CD3EAP G-21A and PPP1R13L IVS1 A4364G and treatment outcome for interferon-. Conclusions: Patients who are homozygous carriers...

Characterization of degradation products of amorphous and polymorphic forms of clopidogrel bisulphate under solid state stress conditions

DEFF Research Database (Denmark)

Raijada, Dhara K; Prasad, Bhagwat; Paudel, Amrit

2010-01-01

The present study deals with the stress degradation studies on amorphous and polymorphic forms of clopidogrel bisulphate. The objective was to characterize the degradation products and postulate mechanism of decomposition of the drug under solid state stress conditions. For that, amorphous form, ...

Gamma dosimetry of high doses

International Nuclear Information System (INIS)

Martinez C, T.; Galvan G, A.; Canizal, G.

1991-01-01

The gamma dosimetry of high doses is problematic in almost all the classic dosemeters either based on the thermoluminescence, electric, chemical properties, etc., because they are saturated to very high dose and they are no longer useful. This work carries out an investigation in the interval of high doses. The solid system of heptahydrate ferrous sulfate, can be used as solid dosemeter of routine for high doses of radiation. The proposed method is simple, cheap and it doesn't require sophisticated spectrophotometers or spectrometers but expensive and not common in some laboratories

Maintenance therapy of childhood acute lymphoblastic leukemia revisited-Should drug doses be adjusted by white blood cell, neutrophil, or lymphocyte counts?

Science.gov (United States)

Schmiegelow, Kjeld; Nersting, Jacob; Nielsen, Stine Nygaard; Heyman, Mats; Wesenberg, Finn; Kristinsson, Jon; Vettenranta, Kim; Schrøeder, Henrik; Weinshilboum, Richard; Jensen, Katrine Lykke; Grell, Kathrine; Rosthoej, Susanne

2016-12-01

6-Mercaptopurine (6MP) and methotrexate (MTX) based maintenance therapy is a critical phase of childhood acute lymphoblastic leukemia treatment. Wide interindividual variations in drug disposition warrant frequent doses adjustments, but there is a lack of international consensus on dose adjustment guidelines. To identify relapse predictors, we collected 28,255 data sets on drug doses and blood counts (median: 47/patient) and analyzed erythrocyte (Ery) levels of cytotoxic 6MP/MTX metabolites in 9,182 blood samples (median: 14 samples/patient) from 532 children on MTX/6MP maintenance therapy targeted to a white blood cell count (WBC) of 1.5-3.5 × 10 9 /l. After a median follow-up of 13.8 years for patients in remission, stepwise Cox regression analysis did not find age, average doses of 6MP and MTX, hemoglobin, absolute lymphocyte counts, thrombocyte counts, or Ery levels of 6-thioguanine nucleotides or MTX (including its polyglutamates) to be significant relapse predictors. The parameters significantly associated with risk of relapse (N = 83) were male sex (hazard ratio [HR] 2.0 [1.3-3.1], P = 0.003), WBC at diagnosis (HR = 1.04 per 10 × 10 9 /l rise [1.00-1.09], P = 0.048), the absolute neutrophil count (ANC; HR = 1.7 per 10 9 /l rise [1.3-2.4], P = 0.0007), and Ery thiopurine methyltransferase activity (HR = 2.7 per IU/ml rise [1.1-6.7], P = 0.03). WBC was significantly related to ANC (Spearman correlation coefficient, r s  = 0.77; P best hematological target for dose adjustments of maintenance therapy. © 2016 Wiley Periodicals, Inc.

Anti-inflammatory and anti-thrombotic intervention strategies using atorvastatin, clopidogrel and knock-down of CD40L do not modify radiation-induced atherosclerosis in ApoE null mice

Energy Technology Data Exchange (ETDEWEB)

Hoving, Saske [Division of Experimental Therapy, Netherlands Cancer Institute, Amsterdam (Netherlands); Heeneman, Sylvia [Department of Pathology, Cardiovascular Research Institute Maastricht (Netherlands); Gijbels, Marion J.J. [Department of Pathology, Cardiovascular Research Institute Maastricht (Netherlands); Department of Molecular Genetics, Cardiovascular Research Institute Maastricht (Netherlands); Poele, Johannes A.M. te [Division of Experimental Therapy, Netherlands Cancer Institute, Amsterdam (Netherlands); Pol, Jeffrey F.C.; Gabriels, Karen [Department of Pathology, Cardiovascular Research Institute Maastricht (Netherlands); Russell, Nicola S [Division of Radiotherapy, Netherlands Cancer Institute, Amsterdam (Netherlands); Daemen, Mat J.A.P. [Department of Pathology, Cardiovascular Research Institute Maastricht (Netherlands); Department of Pathology, AMC, Amsterdam (Netherlands); Stewart, Fiona A., E-mail: f.stewart@nki.nl [Division of Experimental Therapy, Netherlands Cancer Institute, Amsterdam (Netherlands)

2011-10-15

Background and purpose: We previously showed that irradiating the carotid arteries of ApoE{sup -/-} mice accelerated the development of macrophage-rich, inflammatory and thrombotic atherosclerotic lesions. In this study we investigated the potential of anti-inflammatory (atorvastatin, CD40L knockout) and anti-thrombotic (clopidogrel) intervention strategies to inhibit radiation-induced atherosclerosis. Material and methods: ApoE{sup -/-} mice were given 0 or 14 Gy to the neck and the carotid arteries were harvested at 4 or 28 weeks after irradiation. Atorvastatin (15 mg/kg/day) or clopidogrel (20 mg/kg/day) was given in the chow; control groups received regular chow. Clopidogrel inhibited platelet aggregation by 50%. CD40L{sup -/-}/ApoE{sup -/-} and ApoE{sup -/-} littermates were also given 0 or 14 Gy to the neck and the carotid arteries were harvested after 30 weeks. Results: Clopidogrel decreased MCP-1 expression in the carotid artery at 4 weeks after irradiation. Expression of VCAM-1, ICAM-1, thrombomodulin, tissue factor and eNOS was unchanged in atorvastatin and clopidogrel-treated mice. Neither drug inhibited either age-related or radiation-induced atherosclerosis. Furthermore, loss of the inflammatory mediator CD40L did not influence the development of age-related and radiation-induced atherosclerosis. Conclusions: The effects of radiation-induced atherosclerosis could not be circumvented by these specific anti-inflammatory and anti-coagulant therapies. This suggests that more effective drug combinations may be required to overcome the radiation stimulus, or that other underlying mechanistic pathways are involved compared to age-related atherosclerosis.

Anti-inflammatory and anti-thrombotic intervention strategies using atorvastatin, clopidogrel and knock-down of CD40L do not modify radiation-induced atherosclerosis in ApoE null mice

International Nuclear Information System (INIS)

Hoving, Saske; Heeneman, Sylvia; Gijbels, Marion J.J.; Poele, Johannes A.M. te; Pol, Jeffrey F.C.; Gabriels, Karen; Russell, Nicola S.; Daemen, Mat J.A.P.; Stewart, Fiona A.

2011-01-01

Background and purpose: We previously showed that irradiating the carotid arteries of ApoE −/− mice accelerated the development of macrophage-rich, inflammatory and thrombotic atherosclerotic lesions. In this study we investigated the potential of anti-inflammatory (atorvastatin, CD40L knockout) and anti-thrombotic (clopidogrel) intervention strategies to inhibit radiation-induced atherosclerosis. Material and methods: ApoE −/− mice were given 0 or 14 Gy to the neck and the carotid arteries were harvested at 4 or 28 weeks after irradiation. Atorvastatin (15 mg/kg/day) or clopidogrel (20 mg/kg/day) was given in the chow; control groups received regular chow. Clopidogrel inhibited platelet aggregation by 50%. CD40L −/− /ApoE −/− and ApoE −/− littermates were also given 0 or 14 Gy to the neck and the carotid arteries were harvested after 30 weeks. Results: Clopidogrel decreased MCP-1 expression in the carotid artery at 4 weeks after irradiation. Expression of VCAM-1, ICAM-1, thrombomodulin, tissue factor and eNOS was unchanged in atorvastatin and clopidogrel-treated mice. Neither drug inhibited either age-related or radiation-induced atherosclerosis. Furthermore, loss of the inflammatory mediator CD40L did not influence the development of age-related and radiation-induced atherosclerosis. Conclusions: The effects of radiation-induced atherosclerosis could not be circumvented by these specific anti-inflammatory and anti-coagulant therapies. This suggests that more effective drug combinations may be required to overcome the radiation stimulus, or that other underlying mechanistic pathways are involved compared to age-related atherosclerosis.

Buprenorphine/Naloxone Maintenance Therapy: an Observational Retrospective Report on the Effect of Dose on 18 months Retention in an Office-Based Treatment Program

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Theodore V Parran

2017-10-01

Full Text Available Context and objective: Buprenorphine has been available with few reports of the dose range necessary to adequately maintain patients. We report on the effect of 8 mg/d versus 16 mg/d of buprenorphine on long-term patient retention in office-based opioid maintenance (OBOMT. Design, setting, and participants: Case series, at an urban hospital-based primary care clinic providing OBOMT to 157 opiate-dependent, low socioeconomic status, uninsured, nonhomeless patients. Intervention: The OBOMT program operated by a comprehensive sobriety treatment program experienced State funding cuts. Thus, after 2 years, the program was required by the State funder to decrease the buprenorphine maintenance dose from 16 to 8 mg/d for all new admissions. We report on patient retention before and after dose reduction. Main outcome measures: The primary outcomes of this study were to measure and compare patient retention in the 2 cohorts at each point of treatment transition over the 18 months following OBOMT initiation. Results: No significant differences in patient retention were observed between the 16 and 8 mg/d patient cohorts. Lower dose buprenorphine maintenance (8 mg/d in uninsured patients enrolled in publicly funded long-term OBOMT combined with comprehensive sobriety counseling was as effective as higher dose therapy (16 mg/d in promoting patient retention throughout the study period. This lower dose resulted in a substantial saving to the public funding agency. Conclusions: In an observational retrospective report, retention in treatment of opiate-addicted patients was the same at 8 and 16 mg/d buprenorphine doses after 18 months. These data have implications for public and managed care funding of OBOMT, for the general prescribing of buprenorphine in outpatient care, and may be instructive in the ongoing debate about the relationship between buprenorphine dose.

The effectiveness, side effects and acceptability of locally available brand of Clopidogrel (Osvix as antiplatelet tablet in CABG patients

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Behzad Imani

2014-07-01

Conclusion: This study showed the Iranian brand of Clopidogrel (Osvix is significantly different from the original brand (Plavix in terms of performance factors in preventing platelet aggregation in patients undergoing coronary artery bypass grafting.

Dose-Dependent Effects of Methadone on QT interval in Patients under Methadone Maintenance Treatment

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Farzad Gheshlaghi

2013-03-01

Full Text Available Background: The role of methadone in QTc prolongation, Torsades de Pointes (TdP arrhythmia and sudden cardiac death has been debated. Because of widespread use of methadone in methadone maintenance treatment (MMT centers, we aimed to study dose-related effects of methadone on QTc prolongation. Methods: In a comparative observational study, 90 patients who were under MMT were evaluated. Patients were divided into three groups according to methadone daily dose (G1: 0-59 mg, G2: 60-109 mg, G3: 110-150 mg. Twelve-lead electrocardiograms (ECG were performed at baseline and two months later, after reaching the maximum daily dose of methadone. The QTc were calculated for each patient. Comparison of mean QTc and mean QTc prolongation between baseline and follow up ECGs were analyzed. Results: In total, mean (SD age was 32.4 (8.5. TdP was not detected in any patients. Mean QTc was 405.2 (17.0 and 418.5 (23.1 msec before and two months after MMT respectively. There was a significant difference between mean QTc in each group before and after treatment (P

Functional genetic polymorphisms in CYP2C19 gene in relation to cardiac side effects and treatment dose in a methadone maintenance cohort.

Science.gov (United States)

Wang, Sheng-Chang; Ho, Ing-Kang; Tsou, Hsiao-Hui; Liu, Sheng-Wen; Hsiao, Chin-Fu; Chen, Chia-Hui; Tan, Happy Kuy-Lok; Lin, Linen; Wu, Chi-Shin; Su, Lien-Wen; Huang, Chieh-Liang; Yang, Yi-Hong; Liu, Ming-Lun; Lin, Keh-Ming; Liu, Shu Chih; Wu, Hsiao-Yu; Kuo, Hsiang-Wei; Chen, Andrew C H; Chang, Yao-Sheng; Liu, Yu-Li

2013-10-01

Abstract Methadone maintenance therapy is an established treatment for heroin dependence. This study tested the influence of functional genetic polymorphisms in CYP2C19 gene encoding a CYP450 enzyme that contributes to methadone metabolism on treatment dose, plasma concentration, and side effects of methadone. Two single nucleotide polymorphisms (SNPs), rs4986893 (exon 4) and rs4244285 (exon 5), were selected and genotyped in 366 patients receiving methadone maintenance therapy in Taiwan. The steady-state plasma concentrations of both methadone and its EDDP metabolite enantiomers were measured. SNP rs4244285 allele was significantly associated with the corrected QT interval (QTc) change in the electrocardiogram (p=0.021), and the Treatment Emergent Symptom Scale (TESS) total score (p=0.021) in patients who continued using heroin, as demonstrated with a positive urine opiate test. Using the gene dose (GD) models where the CYP2C19 SNPs were clustered into poor (0 GD) versus intermediate (1 GD) and extensive (2 GD) metabolizers, we found that the extensive metabolizers required a higher dose of methadone (p=0.035), and showed a lower plasma R-methadone/methadone dose ratio (p=0.007) in urine opiate test negative patients, as well as a greater QTc change (p=0.008) and higher total scores of TESS (p=0.018) in urine opiate test positive patients, than poor metabolizers. These results in a large study sample from Taiwan suggest that the gene dose of CYP2C19 may potentially serve as an indicator for the plasma R-methadone/methadone dose ratio and cardiac side effect in patients receiving methadone maintenance therapy. Further studies of pharmacogenetic variation in methadone pharmacokinetics and pharmacodynamics are warranted in different world populations.

Analysis on the gamma dose distribution by major corrosion products during preventive maintenance period in nuclear power plant

International Nuclear Information System (INIS)

Ha, Wi Ho

2006-02-01

The information on dose distribution inside the containment building is an essential requirement to make a reduction of radiation exposure as well as effective operation and design of nuclear power plant. After reactor shutdown, radiation exposure to workers mainly occurs during preventive maintenance period due to inspection or repair works of major components. During that period, gamma doses are induced by major corrosion products in the primary coolant system. The radiation exposure to workers has been assessed by using the measurements. The measurements are, of course, a basic and reliable assessment. But the measurement has defect such as limitation of detecting area. In order to improve the defect of the measurements, system for assessment of gamma dose distribution during preventive maintenance period by using computational code was suggested in this study. First, activity of major corrosion products was calculated by using modified CRUDSIM code. Original CRUDSIM code was modified to add evaluation of other major corrosion products besides cobalt isotopes. Modeling of containment building for YGN Unit 3 was then performed. Gamma dose distribution by major corrosion products inside the containment building was calculated by using MCNPX code. Finally, the calculations were mapped for whole space inside the containment building and were compared with the measurements. As a result of this study, the defect of the measurement are supplemented by using computational calculation system, and it is expected that workers can make an effective work plan through providing dose distribution inside the containment building in advance. In addition, this study can be applied to technology development to make an effective containment shielding design of the next generation reactor as well as an improvement of the safety for workers in nuclear power plant

The possible role of maintenance treatment for primary central nervous system lymphoma.

Science.gov (United States)

Bairey, Osnat; Siegal, Tali

2018-03-11

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive brain tumor. The prognosis is poor, with high rates of relapse and disease progression after treatment. In addition, PCNSL affects a largely older population, so that a significant proportion of patients are ineligible for intensive therapies and high-dose chemotherapy. The elderly patients are also susceptible to the accelerated and detrimental cognitive side effects of whole-brain irradiation which is an alternative consolidation to high-dose chemotherapy. Maintenance therapy has been shown to be a promising strategy to prolong remission time in other hematopoietic malignancies. Herein, we discuss the place of maintenance treatment in PCNSL in view of perspective obtained from hematological malignancies and non-Hodgkin's lymphoma. Copyright © 2018 Elsevier Ltd. All rights reserved.

Ticagrelor versus clopidogrel in real-world patients with ST elevation myocardial infarction: 1-year results by propensity score analysis.

Science.gov (United States)

Vercellino, Matteo; Sànchez, Federico Ariel; Boasi, Valentina; Perri, Dino; Tacchi, Chiara; Secco, Gioel Gabrio; Cattunar, Stefano; Pistis, Gianfranco; Mascelli, Giovanni

2017-04-05

European guidelines recommend the use of ticagrelor versus clopidogrel in patients with ST elevation myocardial infarction (STEMI). This recommendation is based on inconclusive results and subanalyses from clinical trials. Few data are available on the effects of ticagrelor in a real-world population. To compare the effects of ticagrelor and clopidogrel in a real-world STEMI population, we conducted a pre-post case-control study examining all patients with STEMI included in the Cardio-STEMI Sanremo registry between February 2011 and June 2013. Cases and controls were defined according to P2Y 12 inhibitors, correcting the bias due to lack of randomization by propensity score analysis. Ticagrelor was introduced in 2012 in both in-hospital and pre-hospital settings independently of this study. Of the 416 patients enrolled in the Cardio-STEMI registry, 401 with a definite diagnosis of STEMI were included in this study. One hundred forty-two patients received ticagrelor and 259 received clopidogrel. Regarding clinical presentation and procedural data, those in the ticagrelor group had lower CRUSADE scores (23 [14-36] vs 27 [18-38]; p = 0.015] but a higher proportion of radial access (33% vs 14%; p word propensity score analysis, ticagrelor did not affect the risk of MACE during the hospital phase, or the incidence of hospital bleeding in patients with STEMI. However, in this mono-centric experience, ticagrelor resulted in improved 1-year survival, even after correction by propensity score.

Concomitant use of proton pump inhibitors and clopidogrel in patients with coronary, cerebrovascular, or peripheral artery disease in the factores de Riesgo y ENfermedad Arterial (FRENA) registry.

Science.gov (United States)

Muñoz-Torrero, Juan Francisco Sánchez; Escudero, Domingo; Suárez, Carmen; Sanclemente, Carmen; Pascual, Ma Teresa; Zamorano, José; Trujillo-Santos, Javier; Monreal, Manuel

2011-01-01

Among patients receiving clopidogrel for coronary artery disease, concomitant therapy with proton pump inhibitors (PPIs) has been associated with an increased risk for recurrent coronary events. Factores de Riesgo y ENfermedad Arterial (FRENA) is an ongoing, multicenter, observational registry of consecutive outpatients with coronary artery disease, cerebrovascular disease, or peripheral artery disease. We retrospectively examined the influence of concomitant use of PPIs on outcome in patients receiving clopidogrel. As of March 2009, 1222 patients were using clopidogrel: 595 had coronary artery disease, 329 cerebrovascular disease, and 298 had peripheral artery disease. Of these, 519 (42%) were concomitantly using PPIs. Over a mean follow-up of 15 months, 131 patients (11%) had 139 subsequent ischemic events: myocardial infarction 44, ischemic stroke 40, and critical limb ischemia 55. Seventeen of them (13%) died within 15 days of the subsequent event. PPI users had a higher incidence of myocardial infarction (rate ratio, 2.5; 95% confidence interval [CI], 1.3-4.8), ischemic stroke (rate ratio, 1.9; 95% CI, 1.03-3.7), and a nonsignificantly higher rate of critical limb ischemia (rate ratio, 1.6; 95% CI, 0.95-2.8) than nonusers. On multivariate analysis, concomitant use of clopidogrel and PPIs was independently associated with an increased risk for subsequent ischemic events both in the whole series of patients (hazard ratio, 1.8; 95% CI, 1.1-2.7) and in those with cerebrovascular disease or peripheral artery disease (hazard ratio, 1.5; 95% CI, 1.01-2.4). In patients with established arterial disease, concomitant use of PPIs and clopidogrel was associated with a nearly doubling of the incidence of subsequent myocardial infarction or ischemic stroke. This higher incidence persisted after multivariate adjustment.

External exposure dose of car mechanics during the maintenance of the cars from the risk cautionary area

International Nuclear Information System (INIS)

Kawakami, Hiroto; Yamada, Norikazu; Sasaki, Satoru; Kawasaki, Satoru

2011-12-01

At the request of the Local Nuclear Emergency Response Headquarters, JNES has estimated the effective external exposure dose of car mechanics during the maintenance of the cars from the risk cautionary area. JNES investigated the contamination of the cars from the risk cautionary area and of the average cars at Fukushima city cooperated by the Japan Automobile Dealers Association. Data of screed cars by the Local Nuclear Emergency Response Headquarters is also considered in. Effective external exposure dose of car mechanics treating the cars screened with the emergency situation screening level is estimated to be less than 1 mSv/y under the conservative conditions. This result shows that particular health concern isn't necessary for them. (author)

Biological dose estimation for accidental supra-high dose gamma-ray exposure

International Nuclear Information System (INIS)

Chen, Y.; Yan, X.K.; Du, J.; Wang, Z.D.; Zhang, X.Q.; Zeng, F.G.; Zhou, P.K.

2011-01-01

To correctly estimate the biological dose of victims accidentally exposed to a very high dose of 60 Co gamma-ray, a new dose-effect curve of chromosomal dicentrics/multicentrics and rings in the supra-high dose range was established. Peripheral blood from two healthy men was irradiated in vitro with doses of 60 Co gamma-rays ranging from 6 to 22 Gy at a dose rate of 2.0 Gy/min. Lymphocytes were concentrated, cultured and harvested at 52 h, 68 h and 72 h. The numbers of dic + r were counted. The dose-effect curves were established and validated using comparisons with doses from the Tokai-mura accident and were then applied to two victims of supra-high dose exposure accident. The results indicated that there were no significant differences in chromosome aberration frequency among the different culture times from 52 h to 72 h. The 6-22 Gy dose-effect curve was fitted to a linear quadratic model Y = -2.269 + 0.776D - 7.868 x l0 -3 D 2 . Using this mathematic model, the dose estimates were similar to data from Tokai-mura which were estimated by PCC ring. Whole body average doses of 9.7 Gy and 18.1 Gy for two victims in the Jining accident were satisfactorily given. We established and successfully applied a new dose-effect curve of chromosomal dicentrics plus ring (dic + r) after 6-22 Gy γ-irradiation from a supra-high dose 60 Co gamma-ray accident.

Defining predictive values using three different platelet function tests for CYP2C19 phenotype status on maintenance dual antiplatelet therapy after PCI.

Science.gov (United States)

Zhang, Hong-Zhe; Kim, Moo Hyun; Han, Jin-Yeong; Jeong, Young-Hoon

2014-01-01

Published data suggests that the presence of CYP2C19*2 or *3 loss of function (LOF) alleles is indicative of increased platelet aggregation and a higher risk of adverse cardiovascular events after clopidogrel administration. We sought to determine cut-off values using three different assays for prediction of the CYP2C19 phenotype in Korean percutaneous coronary intervention (PCI) patients. We enrolled 244 patients with drug-eluting stent implantation who were receiving clopidogrel and aspirin maintenance therapy for one month or more. Platelet reactivity was assessed with light transmittance aggregometry (LTA), multiple electrode aggregometry (MEA) and the VerifyNow P2Y12 assay (VN). The CYP2C19 genotype was analyzed by polymerase chain reaction (PCR) and snapshot method. The frequency of CYP2C19 LOF allele carriers was 58.6%. The cut-off values from LTA, MEA and VerifyNow for the identification of LOF allele carriers were as follows: 10 µM ADP-induced LTA ≥ 48 %, VN>242 PRU and MEA ≥ 37 U. Between the three tests, correlation was higher between LTA vs. VN assays (r=0.69) and LTA vs. MEA (r=0.56), with moderate agreement (κ=0.46 and κ=0.46), but between VN assay and MEA, both devices using whole blood showed a lower correlation (r=0.42) and agreement (κ=0.3). Our results provide guidance regarding cut-off levels for LTA, VerifyNow and MEA assays to detect the CYP2C19 LOF allele in patients during dual antiplatelet maintenance therapy.

Dose rate and total dose dependence of the 1/f noise performance of a GaAs operational amplifier during irradiation

International Nuclear Information System (INIS)

Hiemstra, D.M.

1995-01-01

A pictorial of a sectioned view of the torus of the International Thermonuclear Experimental Reactor (ITER) is shown. Maintenance and inspection of the reactor are required to be performed remotely. This is due to the high gamma radiation environment in vessel during inspection and maintenance activities. The custom GaAs operational amplifier is to be used to readout sensors on the in-vessel manipulator and inspection equipment. The gamma dose rate during maintenance and inspection is anticipated to be 3 Mrad(GaAs)/hour. Here, dose rate and total dose dependence of the 1/f noise performance of a custom GaAs MESFET operational amplifier during irradiation are presented. Dose rate dependent 1/f noise degradation during irradiation is believed to be due to electron trapping in deep levels, enhanced by backgating and shallow traps excited during irradiation. The reduction of this affect with accumulated total dose is believed to be due a reduction of deep level site concentration associated with substitutional oxygen. Post irradiation 1/f noise degradation is also presented.The generation-recombination noise observed post irradiation can be attributed to the production of shallow traps due to ionizing radiation

Radiation safety program in high dose rate brachytherapy facility at INHS Asvini

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Kirti Tyagi

2014-01-01

Full Text Available Brachytherapy concerns primarily the use of radioactive sealed sources which are inserted into catheters or applicators and placed directly into tissue either inside or very close to the target volume. The use of radiation in treatment of patients involves both benefits and risks. It has been reported that early radiation workers had developed radiation induced cancers. These incidents lead to continuous work for the improvement of radiation safety of patients and personnel The use of remote afterloading equipment has been developed to improve radiation safety in the delivery of treatment in brachytherapy. The widespread adoption of high dose rate brachytherapy needs appropriate quality assurance measures to minimize the risks to both patients and medical staff. The radiation safety program covers five major aspects: quality control, quality assurance, radiation monitoring, preventive maintenance, administrative measures and quality audit. This paper will discuss the radiation safety program developedfor a high dose rate brachytherapy facility at our centre which may serve as a guideline for other centres intending to install a similar facility.

Prasugrel versus clopidogrel for patients with unstable angina or non-ST-segment elevation myocardial infarction with or without angiography

DEFF Research Database (Denmark)

Wiviott, Stephen D; White, Harvey D; Ohman, E Magnus

2013-01-01

Treatment with prasugrel and aspirin improves outcomes compared with clopidogrel and aspirin for patients with acute coronary syndrome who have had angiography and percutaneous coronary intervention; however, no clear benefit has been shown for patients managed first with drugs only. We assessed ...

The long-term effects of switching from active intravenous bisphosphonate treatment to low-dose maintenance therapy in children with osteogenesis imperfecta.

Science.gov (United States)

Biggin, Andrew; Zheng, Linda; Briody, Julie N; Coorey, Craig P; Munns, Craig F

2015-01-01

Intravenous bisphosphonate therapy is the first-line treatment in moderate-to-severe osteogenesis imperfecta (OI), but there are varied treatment protocols with little data on long-term efficacy. This study evaluates the clinical outcomes when transitioning from active bisphosphonate treatment to maintenance therapy. A retrospective review was conducted on 17 patients before treatment, following active treatment (zoledronate 0.05 mg/kg 6-monthly or pamidronate 6-9 mg/kg/year) and after establishment on maintenance treatment for more than 2 years (zoledronate 0.025 mg/kg 6-monthly or pamidronate lean tissue mass increased during active treatment. These improvements were maintained during the period of maintenance treatment. Vertebral height improved in fractured thoracic vertebrae from pre-treatment to active therapy and improved further during maintenance treatment. Metacarpal cortical thickness and relative cortical area also increased over the treatment periods. Maintenance intravenous bisphosphonate therapy preserved the beneficial effects of active treatment at the doses stated above. Further studies are required to determine the optimal bisphosphonate treatment regimen in the management of children with OI. © 2015 S. Karger AG, Basel.

Radiation safety program in a high dose rate brachytherapy facility

International Nuclear Information System (INIS)

Rodriguez, L.V.; Hermoso, T.M.; Solis, R.C.

2001-01-01

The use of remote afterloading equipment has been developed to improve radiation safety in the delivery of treatment in brachytherapy. Several accidents, however, have been reported involving high dose-rate brachytherapy system. These events, together with the desire to address the concerns of radiation workers, and the anticipated adoption of the International Basic Safety Standards for Protection Against Ionizing Radiation (IAEA, 1996), led to the development of the radiation safety program at the Department of Radiotherapy, Jose R. Reyes Memorial Medical Center and at the Division of Radiation Oncology, St. Luke's Medical Center. The radiation safety program covers five major aspects: quality control/quality assurance, radiation monitoring, preventive maintenance, administrative measures and quality audit. Measures for evaluation of effectiveness of the program include decreased unnecessary exposures of patients and staff, improved accuracy in treatment delivery and increased department efficiency due to the development of staff vigilance and decreased anxiety. The success in the implementation required the participation and cooperation of all the personnel involved in the procedures and strong management support. This paper will discuss the radiation safety program for a high dose rate brachytherapy facility developed at these two institutes which may serve as a guideline for other hospitals intending to install a similar facility. (author)

Optimized dose distribution of a high dose rate vaginal cylinder

International Nuclear Information System (INIS)

Li Zuofeng; Liu, Chihray; Palta, Jatinder R.

1998-01-01

Purpose: To present a comparison of optimized dose distributions for a set of high-dose-rate (HDR) vaginal cylinders calculated by a commercial treatment-planning system with benchmark calculations using Monte-Carlo-calculated dosimetry data. Methods and Materials: Optimized dose distributions using both an isotropic and an anisotropic dose calculation model were obtained for a set of HDR vaginal cylinders. Mathematical optimization techniques available in the computer treatment-planning system were used to calculate dwell times and positions. These dose distributions were compared with benchmark calculations with TG43 formalism and using Monte-Carlo-calculated data. The same dwell times and positions were used for a quantitative comparison of dose calculated with three dose models. Results: The isotropic dose calculation model can result in discrepancies as high as 50%. The anisotropic dose calculation model compared better with benchmark calculations. The differences were more significant at the apex of the vaginal cylinder, which is typically used as the prescription point. Conclusion: Dose calculation models available in a computer treatment-planning system must be evaluated carefully to ensure their correct application. It should also be noted that when optimized dose distribution at a distance from the cylinder surface is calculated using an accurate dose calculation model, the vaginal mucosa dose becomes significantly higher, and therefore should be carefully monitored

Progress in high-dose radiation dosimetry

International Nuclear Information System (INIS)

Ettinger, K.V.; Nam, J.W.; McLaughlin, W.L.; Chadwick, K.H.

1981-01-01

The last decade has witnessed a deluge of new high-dose dosimetry techniques and expanded applications of methods developed earlier. Many of the principal systems are calibrated by means of calorimetry, although production of heat is not always the final radiation effect of interest. Reference systems also include a number of chemical dose meters: ferrous sulphate, ferrous-cupric sulphate, and ceric sulphate acidic aqueous solutions. Requirements for stable and reliable transfer dose meters have led to further developments of several important high-dose systems: amino acids and saccharides analysed by ESR or lyoluminescence, thermoluminescent materials, radiochromic dyes and plastics, ceric-cerous solutions analysed by potentiometry, and ethanol-chlorobenzene solutions analysed by high-frequency oscillometry. A number of other prospective dose meters are also treated in this review. In addition, an IAEA programme of high-dose standardization and intercomparison for industrial radiation processing is described. (author)

Salmeterol/fluticasone stable-dose treatment compared with formoterol/budesonide adjustable maintenance dosing: impact on health-related quality of life

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Williams Angela E

2007-07-01

Full Text Available Abstract Background Improving patients' health-related quality of life (HRQoL is recognized as a fundamental part of asthma management. The aims of this study were to evaluate the long-term efficacy (including symptom-free days and exacerbations and impact on HRQoL of a stable-dose regimen of salmeterol/fluticasone propionate (SAL/FP and an adjustable maintenance dosing (AMD regimen of formoterol/budesonide (FOR/BUD where treatment is adjusted based on symptoms [SAM40056]. Methods A total of 688 outpatients with asthma receiving regular low-dose inhaled corticosteroids (ICS plus a long-acting β2-agonist, or medium dose ICS alone participated in this randomized, double-blind, double-dummy, parallel-group, 1-year trial, which was conducted in 91 centers in 15 countries. Patients were randomized to receive 1 inhalation of SAL/FP 50/250 μg BID or 2 inhalations of FOR/BUD 6/200 μg BID during Weeks 1–4. For Weeks 5–52, patients meeting strict continuation criteria for stable asthma at Week 4 received AMD with FOR/BUD or stable-dose SAL/FP. Results The percentage of symptom-free days was significantly greater (58.8% vs 52.1%; p = 0.034 and the annual exacerbation rate was significantly lower (47%; p = 0.008 with stable-dose SAL/FP compared with FOR/BUD AMD. A total of 568 patients completed the Asthma Quality of Life Questionnaire (AQLQ at least once during the study. The mean change from baseline in AQLQ overall score was numerically greater with SAL/FP than FOR/BUD at week 28 and week 52, but did not reach statistical significance (p = 0.121 at Week 52. However, in a post hoc logistic regression analyses for any AQLQ improvement, significant benefits with SAL/FP were seen at both time points (p = 0.038 and p = 0.009, respectively. The minimally important difference of ≥ 0.5-point improvement in AQLQ overall score was achieved by a significantly greater number of patients receiving SAL/FP at Week 28 (68% vs 60%; p = 0.049; a trend for this

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.

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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

Intracranial meningiomas after high-dose irradiation

International Nuclear Information System (INIS)

Soffer, D.; Gomori, J.M.; Siegal, T.; Shalit, M.N.

1989-01-01

Three patients who presented with intracranial meningiomas 12, 15, and 20 years, respectively, after therapeutic high-dose irradiation of a primary brain tumor are described. Analysis of these cases and similar documented cases suggests that meningiomas after high-dose irradiation constitute a recognizable entity. Patients with such tumors received radiation therapy at a young age (mean age, 9.4 years). After a latent period of 2 to 47 years (mean, 19.8 years) they developed meningiomas at the site of irradiation, at a much younger age than patients with ''spontaneous'' meningiomas. Similar to the situation with meningiomas after low-dose irradiation, a relatively high proportion of meningiomas induced by high-dose irradiation tend to be malignant and biologically aggressive. A very young age at the time of irradiation seems to predispose to the induction of malignant meningiomas, rather than benign tumors. These unusual features provide indirect evidence that high-dose radiation may play a role in the pathogenesis of meningiomas.41 references

Optimization of radiation protection of cell maintenance of radiopharmaceutical production

International Nuclear Information System (INIS)

Machado, Jessica S.; Gerulis, Eduardo; Todo, Alberto S.; Rodrigues Junior, Orlando

2011-01-01

This paper performs a study of maintenance tasks realized in production cells to suggest improvements related to the occupational doses based on the optimization principle of the radioprotection. A data survey has been realized of the doses received by the workers during the maintenance. The average values of effective doses are lower than the limits established in the regulations, however can be optimized

Patient perception of methadone dose adequacy in methadone maintenance treatment: The role of perceived participation in dosage decisions.

Science.gov (United States)

Trujols, Joan; González-Saiz, Francisco; Manresa, María José; Alcaraz, Saul; Batlle, Francesca; Duran-Sindreu, Santiago; Pérez de Los Cobos, José

2017-05-01

In clinical practice, methadone maintenance treatment (MMT) entails tailoring the methadone dose to the patient's specific needs, thereby individualizing treatment. The aim of this study was to identify the independent factors that may significantly explain methadone dose adequacy from the patient's perspective. Secondary analysis of data collected in a treatment satisfaction survey carried out among a representative sample of MMT patients (n=122) from the region of La Rioja (Spain). As part of the original study protocol, participants completed a comprehensive battery to assess satisfaction with MMT, psychological distress, opinion of methadone as a medication, participation in dosage decisions, and perception of dose adequacy. Multivariate binary logistic regression showed that the only variable independently associated with the likelihood of a patient perceiving methadone dose as inadequate was the variable perceived-participation in methadone dosage decisions (OR=0.538, 95% CI=0.349-0.828). Patient participation in methadone dosage decisions was predictive of perceived adequacy of methadone dose beyond the contribution of other socio-demographic, clinical, and MMT variables. Patient participation in methadone dosage decision-making is valuable for developing a genuinely patient-centred MMT. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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...

High-dose irradiation of food

International Nuclear Information System (INIS)

Diehl, J.F.

1999-01-01

Studies performed on behalf of the International Project on Food Irradiation in the period from 1971 until 1980 resulted in the concluding statement that ''.the irradiation of any food commodity up to an overall average dose of 10 kGy presents no toxicological hazard; hence, toxicological testing of foods so treated is no longer required.'' Since then, licenses for food irradiation have been restricted to this maximum dose in any country applying this technology. Further testing programmes have been carried out investigating the wholesomeness or hazards of high-dose irradiation, but there has been little demand so far by the food industry for licensing of high-dose irradiation, as there is only a small range of products whose irradiation at higher doses offers advantages for given, intended use. These include eg. spices, dried herbs, meat products in flexible pouch packagings for astronauts, or patients with immune deficiencies. (orig./CB) [de

Maintenance and material aspects of DREAM reactor

International Nuclear Information System (INIS)

Ueda, S.; Nishio, S.; Yamada, R.; Seki, Y.; Kurihara, R.; Adachi, J.; Yamazaki, S.

2000-01-01

A concept of a commercial fusion power reactors (Fusion Power: 5.5 GW, electric output: 2.7 GW) having high environmental safety, high thermal efficiency and high availability has been studied in JAERI. The gross reactor configuration was designed to achieve good maintainability, high performance breeding blanket, high efficient power generation system and little radwastes. Design was based on the use of low activation structural material (SiC/SiC composites) and helium as a coolant. In this paper, maintenance and material aspects of DREAM reactor design is discussed. The concluding remarks are as follows. (1) The difficulty of development of maintenance tool is alleviated by sector replacement and the radiation dose environment less than 10 Gy/h in a reactor chamber. (2) Design requirement and present status of SiC/SiC composites was investigated. (3) The SiC/SiC composite development program is planned to satisfy the requirements of DREAM reactor

''Low dose'' and/or ''high dose'' in radiation protection: A need to setting criteria for dose classification

International Nuclear Information System (INIS)

Sohrabi, M.

1997-01-01

The ''low dose'' and/or ''high dose'' of ionizing radiation are common terms widely used in radiation applications, radiation protection and radiobiology, and natural radiation environment. Reading the title, the papers of this interesting and highly important conference and the related literature, one can simply raise the question; ''What are the levels and/or criteria for defining a low dose or a high dose of ionizing radiation?''. This is due to the fact that the criteria for these terms and for dose levels between these two extreme quantities have not yet been set, so that the terms relatively lower doses or higher doses are usually applied. Therefore, setting criteria for classification of radiation doses in the above mentioned areas seems a vital need. The author while realizing the existing problems to achieve this important task, has made efforts in this paper to justify this need and has proposed some criteria, in particular for the classification of natural radiation areas, based on a system of dose limitation. (author)

Experiences of occupational dose reduction at the Fugen nuclear power station

International Nuclear Information System (INIS)

Suzuki, Kazuya; Nakao, Hiromi; Naoi, Yohsuke; Takei, Hiroaki

1992-01-01

Occupational radiation dose has been effectively suppressed by efforts against both internal and external exposure in the Fugen nuclear power station. The tritium internal dose is completely suppressed by developments of high sensitivity tritium monitors with hollow fiber radon filters, comfortable tritium protection suits, and established working procedure for equipment maintenance of the heavy water system. The internal occupational dose has been suppressed to a negligible level comparing to the external dose. The external occupational dose had increased with dose rates of the primary cooling system. Establishment of radiation work procedure for maintenance works and development of chemical decontamination has been effectively saving the external occupational dose. The chemical decontaminations carried out in 1989 and 1991 are the first applications to the whole primary cooling system of operating power stations in Japan. This paper describes these efforts and effects on occupational dose reduction in Fugen. (author)

Maintenance therapy of childhood acute lymphoblastic leukemia revisited—Should drug doses be adjusted by white blood cell, neutrophil, or lymphocyte counts?

DEFF Research Database (Denmark)

Schmiegelow, Kjeld; Nersting, Jacob; Nielsen, Stine Nygaard

2016-01-01

BACKGROUND: 6-Mercaptopurine (6MP) and methotrexate (MTX) based maintenance therapy is a critical phase of childhood acute lymphoblastic leukemia treatment. Wide interindividual variations in drug disposition warrant frequent doses adjustments, but there is a lack of international consensus on dose...... levels of 6-thioguanine nucleotides or MTX (including its polyglutamates) to be significant relapse predictors. The parameters significantly associated with risk of relapse (N = 83) were male sex (hazard ratio [HR] 2.0 [1.3-3.1], P = 0.003), WBC at diagnosis (HR = 1.04 per 10 × 10(9) /l rise [1...

CYP2C19 and PON1 polymorphisms regulating clopidogrel bioactivation in Chinese, Malay and Indian subjects.

Science.gov (United States)

Chan, Mark Y; Tan, Karen; Tan, Huay-Cheem; Huan, Pei-Tee; Li, Bei; Phua, Qian-Hui; Lee, Hong-Kai; Lee, Chi-Hang; Low, Adrian; Becker, Richard C; Ong, Wen-Chong; Richards, Mark A; Salim, Agus; Tai, E-Shyong; Koay, Evelyn

2012-04-01

AIM, MATERIALS & METHODS: We investigated the functional significance of CYP2C19*2, *3, *17 and PON1 Q192R SNPs in 89 consecutive Asian patients on clopidogrel treatment and the prevalence of functionally significant polymorphisms among 300 Chinese, Malays and Asian Indians. Both CYP2C19 loss-of-function alleles (*2 or *3) were associated with higher platelet reactivity while the CYP2C19 gain-of-function allele (*17) had lower platelet reactivity. For PON1, the median PRI was not significantly different between the QQ, QR and RR groups. The allele frequencies of CYP2C19*2, CYP2C19*3 and CYP2C19*17 were 0.280, 0.065 and 0.010 (rare) for Chinese, 0.310, 0.050 and 0.025 for Malays, and 0.375, 0.010 (rare) and 0.165 for Indians, respectively. Our data suggest that genotyping studies to investigate clopidogrel response should include CYP2C19*2 and *3 but not *17 polymorphisms in Chinese, and CYP2C19*2 and *17 polymorphisms but not *3 in Indians. All three polymorphisms should preferably be genotyped in Malays.

Buprenorphine Maintenance Subjects Are Hyperalgesic and Have No Antinociceptive Response to a Very High Morphine Dose.

Science.gov (United States)

Athanasos, Peter; Ling, Walter; Bochner, Felix; White, Jason M; Somogyi, Andrew A

2018-03-05

Acute pain management in opioid-dependent persons is complicated because of tolerance and opioid-induced hyperalgesia. Very high doses of morphine are ineffective in overcoming opioid-induced hyperalgesia and providing antinociception to methadone-maintained patients in an experimental setting. Whether the same occurs in buprenorphine-maintained subjects is unknown. Randomized double-blind placebo-controlled. Subjects were tested on two occasions, at least five days apart, once with intravenous morphine and once with intravenous saline. Subjects were tested at about the time of putative trough plasma buprenorphine concentrations. Ambulatory. Twelve buprenorphine-maintained subjects: once daily sublingual dose (range = 2-22 mg); no dose change for 1.5-12 months. Ten healthy controls. Intravenous morphine bolus and infusions administered over two hours to achieve two separate pseudo-steady-state plasma concentrations one hour apart. Pain tolerance was assessed by application of nociceptive stimuli (cold pressor [seconds] and electrical stimulation [volts]). Ten blood samples were collected for assay of plasma morphine, buprenorphine, and norbuprenorphine concentrations until three hours after the end of the last infusion; pain tolerance and respiration rate were measured to coincide with blood sampling times. Cold pressor responses (seconds): baseline: control 34 ± 6 vs buprenorphine 17 ± 2 (P = 0.009); morphine infusion-end: control 52 ± 11(P = 0.04), buprenorphine 17 ± 2 (P > 0.5); electrical stimulation responses (volts): baseline: control 65 ± 6 vs buprenorphine 53 ± 5 (P = 0.13); infusion-end: control 74 ± 5 (P = 0.007), buprenorphine 53 ± 5 (P > 0.98). Respiratory rate (breaths per minute): baseline: control 17 vs buprenorphine 14 (P = 0.03); infusion-end: control 15 (P = 0.09), buprenorphine 12 (P < 0.01). Infusion-end plasma morphine concentrations (ng/mL): control 23 ± 1

Dose-reduction techniques for high-dose worker groups in nuclear power plants

International Nuclear Information System (INIS)

Khan, T.A.; Baum, J.W.; Dionne, B.J.

1991-03-01

This report summarizes the main findings of a study of the extent of radiation dose received by special work groups in the nuclear power industry. Work groups which chronically get large doses were investigated, using information provided by the industry. The tasks that give high doses to these work groups were examined and techniques described that were found to be particularly successful in reducing dose. Quantitative information on the extent of radiation doses to various work groups shows that significant numbers of workers in several critical groups receive doses greater than 1 and even 2 rem per year, particularly contract personnel and workers at BWR-type plants. The number of radiation workers whose lifetime dose is greater than their age is much less. Although the techniques presented would go some way in reducing dose, it is likely that a sizeable reduction to the high-dose work groups may require development of new dose-reduction techniques as well as major changes in procedures. 10 refs., 26 tabs

Performance of thermoluminescent materials for high dose dosimetry

International Nuclear Information System (INIS)

Texeira, Maria I.; Cecatti, Sonia G.P.; Caldas, Linda V.E.

2008-01-01

Cases involving high-doses of ionizing radiation are becoming increasingly common.The objective of this work was to characterize thermoluminescent materials for the dosimetry of workers exposed to high doses. Samples of TLD-200, TLD-400 and TLD-800 pellets from Thermo Electron Corporation were studied in gamma high-doses. Dose-response curves were obtained for doses between 100 mGy and 100 Gy. The reproducibility, the lower detection limits and dose-response curves were obtained for all three materials. The different kinds of detectors show usefulness for dosimetry of workers exposed accidentally to high doses. (author)

Prasugrel vs. clopidogrel in contemporary Western European patients with acute coronary syndromes receiving drug-eluting stents

DEFF Research Database (Denmark)

Wein, Bastian; Coslovsky, Michael; Jabbari, Reza

2017-01-01

BACKGROUND: Clinical and cost-effectiveness of prasugrel vs. clopidogrel in acute coronary syndrome (ACS) was only evaluated using TRITON-TIMI 38 event rates. A comparative analysis of both drugs in contemporary European ACS patients is lacking. METHODS: To address this issue, cardiac and bleedin......=0.255), but more major bleedings (4.0% vs. 1.7%, pexpenditures per patient: 1116.3 (DNK), 1063.5 (GER) and 880.8 (SUI) EURO, respectively. Accordingly, incremental cost...

Fiber optics in high dose radiation fields

International Nuclear Information System (INIS)

Partin, J.K.

1985-01-01

A review of the behavior of state-of-the-art optical fiber waveguides in high dose (greater than or equal to 10 5 rad), steady state radiation fields is presented. The influence on radiation-induced transmission loss due to experimental parameters such as dose rate, total dose, irradiation history, temperature, wavelength, and light intensity, for future work in high dose environments are given

Radiophotoluminescence light scope for high-dose dosimetry

International Nuclear Information System (INIS)

Sato, Fuminobu; Zushi, Naoki; Sakiyama, Tomoki; Kato, Yushi; Murata, Isao; Shimizu, Kikuo; Yamamoto, Takayoshi; Iida, Toshiyuki

2015-01-01

A radiophotoluminescence (RPL) light scope is a remote-sensing technique for measuring in situ the radiation dose in an RPL detector placed at a distance. The RPL light scope is mainly composed of an ultraviolet (UV) pulse laser, telescopic lenses, a photomultiplier tube, and camera modules. In a performance test, some RPL detectors were placed at distances up to 30 m and were illuminated with a pulsed UV laser beam. The photoluminescence responses of the RPL detectors were analyzed using this scope. Their radiation doses were determined from the amplitude of the given component of the photoluminescence responses. The RPL readout could be repeated without fading, and its amplitude exhibited good linearity at a dose ranging from 0.1 to 60 Gy. Furthermore, a two-dimensional distribution of radiation dose was obtained by laser scanning on an RPL detector. It was confirmed that the RPL light scope was a useful remote-sensing tool for high-dose dosimetry. - Highlights: • A radiophotoluminescence (RPL) light scope was developed for high-dose dosimetry. • The RPL light scope has high sensitivity and accuracy in high-dose dosimetry. • Two-dimensional radiation dose distribution was obtained by the RPL light scope.

A COMPARISON OF TWO DIFFERENT DOSES OF DEXMEDETOMIDINE INFUSION DURING MAINTENANCE OF GENERAL ANAESTHESIA IN PATIENTS UNDERGOING SPINE SURGERIES, FUNCTIONAL ENDOSCOPIC SINUS SURGERY AND MIDDLE EAR SURGERIES

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Bijay

2016-03-01

Full Text Available BACKGROUND This study is undertaken to compare the hemodynamic effects and reduction in the doses of volatile anaesthetics and muscle relaxants using two different doses of dexmedetomidine infusion during maintenance of anaesthesia in spine, functional endoscopic sinus surgery and middle ear surgeries. METHODS Sixty patients are randomly divided into 2 groups of 30 each. After shifting to the operation theatre baseline vitals were recorded. Anesthesia induced with thiopentone sodium and intubation done with the help of succinylcholine and maintained with oxygen, nitrous oxide and isoflurane. After 1 min of intubation, maintenance infusion of dexmedetomidine (0.4 mcg/kg/hr and 0.7 mcg/kg/hr for patients allotted in 2 separate groups was started and stopped 15 min before end of surgery. Hemodynamic parameters and any reduction in the doses of volatile anaesthetics and muscle relaxants was noted. RESULTS Dexmedetomidine infusion (0.4 mcg/kg/hr and 0.7 mcg/kg/hr in both groups reduced the requirements of muscle relaxants and volatile anaesthetics. Hemodynamic stability was better in the group receiving 0.4 mcg/kg/hr. Patients receiving 0.7 mcg/kg/hr had higher incidence of hypotension, bradycardia and delayed emergence from anaesthesia. CONCLUSION Dexmedetomidine infusion at 0.4 mcg/kg/hr during maintenance of anaesthesia in spine surgery, FESS and middle ear surgery would be good option to reduce the requirements of volatile anaesthetics, muscle relaxants and for better hemodynamic stability. OBJECTIVE OF STUDY: Primary Objective To compare and evaluate the hemodynamic effects and reduction in requirements of volatile anaesthetics and muscle relaxants with two different doses of dexmedetomidine infusion during maintenance of general anaesthesia in patients undergoing spine, FESS and middle ear surgeries.

High-dose dosimetry using natural silicate minerals

International Nuclear Information System (INIS)

Carmo, Lucas S. do; Mendes, Leticia; Watanabe, Shigueo; Rao, Gundu; Lucas, Natasha; Sato, Karina; Barbosa, Renata F.

2015-01-01

In the present study, certain natural silicate minerals such as aquamarine (AB), morganite (PB), goshenite (WB), white jadeite (JW), green jadeite (JG), pink tourmaline (PT) and two varieties of jadeite-like quartz, denoted here by JQ1 and JQ2, were investigated using the thermoluminescence technique to evaluate their potential for use as very-high- and high-dose dosimeters. These minerals respond to high doses of γ-rays of up to 1000 kGy and often to very high doses of up to 3000 kGy. The TL response of these minerals may be considered to be satisfactory for applications in high-dose dosimetry. Investigations of electron paramagnetic resonance and optically stimulated luminescence dosimetry are in progress. (author)

High-dose dosimetry using natural silicate minerals

Energy Technology Data Exchange (ETDEWEB)

Carmo, Lucas S. do; Mendes, Leticia, E-mail: isatiro@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Watanabe, Shigueo; Rao, Gundu; Lucas, Natasha; Sato, Karina, E-mail: lacifid@if.usp.br [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Instituto de Fisica. Departamento de Fisica Nuclear; Barbosa, Renata F., E-mail: profcelta@hotmail.com [Universidade Federal de Sao Paulo (UNIFESP), Santos, SP (Brazil). Departamento de Ciencias do Mar

2015-07-01

In the present study, certain natural silicate minerals such as aquamarine (AB), morganite (PB), goshenite (WB), white jadeite (JW), green jadeite (JG), pink tourmaline (PT) and two varieties of jadeite-like quartz, denoted here by JQ1 and JQ2, were investigated using the thermoluminescence technique to evaluate their potential for use as very-high- and high-dose dosimeters. These minerals respond to high doses of γ-rays of up to 1000 kGy and often to very high doses of up to 3000 kGy. The TL response of these minerals may be considered to be satisfactory for applications in high-dose dosimetry. Investigations of electron paramagnetic resonance and optically stimulated luminescence dosimetry are in progress. (author)

Polymorphisms of MDR1, CYP2C19 and P2Y12 genes in Indian population: Effects on clopidogrel response

Directory of Open Access Journals (Sweden)

Kavita K. Shalia

2013-03-01

Conclusion: The present study did show a trend toward impaired response of clopidogrel to inhibit platelet aggregation with variant genotypes of CYP2C19*2 and iT744C of P2Y12 compared to respective wild type genotype at 24 h.

Efficacy and safety of a therapeutic interchange from high-dose calcium channel blockers to a fixed-dose combination of amlodipine/benazepril in patients with moderate-to-severe hypertension.

Science.gov (United States)

Hilleman, D E; Reyes, A P; Wurdeman, R L; Faulkner, M

2001-08-01

Recent hypertension trials have demonstrated the importance of achieving goal blood pressures to reduce the risk of target organ damage. In patients with moderate to severe hypertension, the use of high-dose monotherapy and/or combinations of drugs are necessary to achieve these goals. Fixed-dose combination products may be useful in these patients by reducing the number of daily doses required to control blood pressure. The objective of the present study was to evaluate the efficacy and safety of a therapeutic interchange between high-dose calcium channel blocker therapy and a fixed-dose combination of amlodipine/ benazepril (Lotrel; Novartis Pharmaceuticals, USA) in patients with moderate to severe hypertension. A total of 75 patients were switched from amlodipine (n = 25), felodipine (n = 25), and nifedipine-GITS (n = 25) to amlodipine/benazepril. Twenty-eight of the 75 patients (37%) were taking either a beta-blocker or a diuretic in addition to the high-dose calcium channel blocker prior to the switch. Blood pressure control, side effects and the cost of the therapeutic interchange were evaluated in the year following the therapeutic interchange. Sixty-six of the 75 (88%) patients were successfully switched with maintenance of blood pressure control and without the development of new dose-limiting side effects. Reasons for treatment failure after the therapeutic interchange included loss of blood pressure control in five patients and the development of new dose-limiting side effects in four patients. These side effects included cough in three patients and rash in one patient. After accounting for differences in drug acquisition cost and costs related to the switch (clinic and emergency room and laboratory tests), a cost savings of $16030 for all 75 patients was realised in the first year. The per patient-per year cost savings was $214. Our data indicate that a therapeutic interchange from selected high-dose calcium channel blockers to a fixed-dose combination

Dose reduction and optimization studies (ALARA) at nuclear power facilities

International Nuclear Information System (INIS)

Baum, J.W.; Meinhold, C.B.

1983-01-01

Brookhaven National Laboratory (BNL) has been commissioned by the Nuclear Regulatory Commission (NRC) to study dose-reduction techniques and effectiveness of as low as reasonably achievable (ALARA) planning at LWR plants. These studies have the following objectives: identify high-dose maintenance tasks; identify dose-reduction techniques; examine incentives for dose reduction; evaluate cost-effectiveness and optimization of dose-reduction techniques; and compile an ALARA handbook on data, engineering modifications, cost-effectiveness calculations, and other information of interest to ALARA practioners

VKORC1 polymorphisms and warfarin maintenance dose in population of Sakha (Yakuts).

Science.gov (United States)

Chertovskikh, Y V; Malova, E U; Maksimova, N R; Popova, N V; Sychev, D A

2015-01-01

Vitamin K antagonists are effective in the prevention and treatment of thromboembolic disorders. Warfarin is one of the most widely prescribed vitamin K antagonists in the world [1, 2]. It has a narrow therapeutic range and a given dose may result in a large inter-individual variation of response. Insufficient dose may fail to prevent thromboembolism, while an overdose increases the risk of bleeding. Patient-specific factors (e.g., age, body size, race, concurrent diseases, and medications) explain some of the variability in warfarin dosage, but genetic factors influencing warfarin response explain a significantly higher proportion of this variability [3]. Molecular analysis of the gene that encodes the target enzyme vitamin K epoxide reductase complex 1 (VKORC1) strongly suggests that its genetic variations greatly affect the individual response to oral anticoagulants [4-7]. To evaluate effects of VKORC1 polymorphisms on warfarin dose excess anticoagulation (INR >4.0) in the population of Sakha (S) patients. 53 patients (29-women, 24-men) with atrial fibrillation (68%), congestive heart failure (60%), hypertension (49%) and cardiac valve replacement (26%) were recruited. The age range was 26-80 years, with a mean age of 62.87 ± 12.57 years.International normalized ratio and plasma warfarin concentrations were determined. Genotyping was carried out by RT-PCR (real-time PCR). The three genetic polymorphisms of the gene VKORC1 G3673A (rs9923231) were studied: normal (GG), heterozygous (GA) and homozygous (AA). Fisher exact probability test and chi-square test (with Yates correction) were applied to compare data among the AA and GG + GA groups; also Mann-Whitney test was used. The median maintenance daily dose of warfarin among AA carriers was 3.0 mg/day [1.25-7.5 mg], while in GG and GA patients it was 3.13 mg/day [1.88-7.92 mg]. The mean daily warfarin dosage was higher in GG and GA genotype carriers 4.05 mg/day (SD ± 1.7) than in patients with AA genotype 3

Doses from portable gauges

International Nuclear Information System (INIS)

Linauskas, S.H.

1988-08-01

Field studies to measure actual radiation exposures of operators of commercial moisture-density gauges were undertaken in several regions of Canada. Newly developed bubble detector dosimeter technology and conventional dosimetry such as thermoluminescent dosimeters (TLDs), integrating electronic dosimeters (DRDs), and CR-39 neutron track-etch detectors were used to estimate the doses received by 23 moisture-density gauge operators and maintenance staff. These radiation dose estimates were supported by mapping radiation fields and accounting for the time an operator was near a gauge. Major findings indicate that gauge maintenance and servicing workers were more likely than gauge operators to receive exposures above the level of 5 mSv, and that neutron doses were roughly the same as gamma doses. Gauge operators receive approximately 75% of their dose when transporting and carrying the gauge. Dose to their hands is similar to the dose to their trunks, but the dose to their feet area is 6 to 30 times higher. Gamma radiation is the primary source of radiation contributing to operator dose

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

High-precision relative position and attitude measurement for on-orbit maintenance of spacecraft

Science.gov (United States)

Zhu, Bing; Chen, Feng; Li, Dongdong; Wang, Ying

2018-02-01

In order to realize long-term on-orbit running of satellites, space stations, etc spacecrafts, in addition to the long life design of devices, The life of the spacecraft can also be extended by the on-orbit servicing and maintenance. Therefore, it is necessary to keep precise and detailed maintenance of key components. In this paper, a high-precision relative position and attitude measurement method used in the maintenance of key components is given. This method mainly considers the design of the passive cooperative marker, light-emitting device and high resolution camera in the presence of spatial stray light and noise. By using a series of algorithms, such as background elimination, feature extraction, position and attitude calculation, and so on, the high precision relative pose parameters as the input to the control system between key operation parts and maintenance equipment are obtained. The simulation results show that the algorithm is accurate and effective, satisfying the requirements of the precision operation technique.

High dose gamma-ray standard

International Nuclear Information System (INIS)

Macrin, R.; Moraru, R.

1999-01-01

The high gamma-ray doses produced in a gamma irradiator are used, mainly, for radiation processing, i.e. sterilization of medical products, processing of food, modifications of polymers, irradiation of electronic devices, a.s.o. The used absorbed doses depend on the application and cover the range 10 Gy to 100 MGy. The regulations in our country require that the response of the dosimetry systems, used for the irradiation of food and medical products, be calibrated and traceable to the national standards. In order to be sure that the products receive the desired absorbed dose, appropriate dosimetric measurements must be performed, including the calibration of the dosemeters and their traceability to the national standards. The high dose gamma-ray measurements are predominantly based on the use of reference radiochemical dosemeters. Among them the ferrous sulfate can be used as reference dosemeter for low doses (up to 400 Gy) but due to its characteristics it deserves to be considered a standard dosemeter and to be used for transferring the conventional absorbed dose to other chemical dosemeters used for absorbed doses up to 100 MGy. The study of the ferrous sulfate dosemeter consisted in preparing many batches of solution by different operators in quality assurance conditions and in determining for all batches the linearity, the relative intrinsic error, the repeatability and the reproducibility. The principal results are the following: the linear regression coefficient: 0.999, the relative intrinsic error: max.6 %, the repeatability (for P* = 95 %): max.3 %, the reproducibility (P* = 95%): max.5 %. (authors)

High dose of plasmid IL-15 inhibits immune responses in an influenza non-human primates immunogenicity model

International Nuclear Information System (INIS)

Yin Jiangmei; Dai Anlan; Laddy, Dominick J.; Yan Jian; Arango, Tatiana; Khan, Amir S.; Lewis, Mark G.; Andersen, Hanne; Kutzler, Michele A.; Draghia-Akli, Ruxandra; Weiner, David B.; Boyer, Jean D.

2009-01-01

Interleukin (IL)-15, is a cytokine that is important for the maintenance of long-lasting, high-avidity T cell response to invading pathogens and has, therefore, been used in vaccine and therapeutic platforms as an adjuvant. In addition to pure protein delivery, plasmids encoding the IL-15 gene have been utilized. However, it is critical to determine the appropriate dose to maximize the adjuvanting effects. We immunized rhesus macaques with different doses of IL-15 expressing plasmid in an influenza non-human primate immunogenicity model. We found that co-immunization of rhesus macaques with a Flu DNA-based vaccine and low doses of plasmid encoding macaque IL-15 enhanced the production of IFN-γ (0.5 mg) and the proliferation of CD4 + and CD8 + T cells, as well as T CM levels in proliferating CD8 + T cells (0.25 mg). Whereas, high doses of IL-15 (4 mg) decrease the production of IFN-γ and the proliferation of CD4 + and CD8 + T cells and T CM levels in the proliferating CD4 + and CD8 + T cells. In addition, the data of hemagglutination inhibition (HI) antibody titer suggest that although not significantly different, there appears to be a slight increase in antibodies at lower doses of IL-15. Importantly, however, the higher doses of IL-15 decrease the antibody levels significantly. This study demonstrates the importance of optimizing DNA-based cytokine adjuvants.

Methamphetamine treatment during development attenuates the dopaminergic deficits caused by subsequent high-dose methamphetamine administration.

Science.gov (United States)

McFadden, Lisa M; Hoonakker, Amanda J; Vieira-Brock, Paula L; Stout, Kristen A; Sawada, Nicole M; Ellis, Jonathan D; Allen, Scott C; Walters, Elliot T; Nielsen, Shannon M; Gibb, James W; Alburges, Mario E; Wilkins, Diana G; Hanson, Glen R; Fleckenstein, Annette E

2011-08-01

Administration of high doses of methamphetamine (METH) causes persistent dopaminergic deficits in both nonhuman preclinical models and METH-dependent persons. Noteworthy, adolescent [i.e., postnatal day (PND) 40] rats are less susceptible to this damage than young adult (PND90) rats. In addition, biweekly treatment with METH, beginning at PND40 and continuing throughout development, prevents the persistent dopaminergic deficits caused by a "challenge" high-dose METH regimen when administered at PND90. Mechanisms underlying this "resistance" were thus investigated. Results revealed that biweekly METH treatment throughout development attenuated both the acute and persistent deficits in VMAT2 function, as well as the acute hyperthermia, caused by a challenge METH treatment. Pharmacokinetic alterations did not appear to contribute to the protection afforded by the biweekly treatment. Maintenance of METH-induced hyperthermia abolished the protection against both the acute and persistent VMAT2-associated deficits suggesting that alterations in thermoregulation were caused by exposure of rats to METH during development. These findings suggest METH during development prevents METH-induced hyperthermia and the consequent METH-related neurotoxicity. Copyright © 2011 Wiley-Liss, Inc.

QT response after a test dose and during maintenance therapy with AZD1305 in patients with atrial fibrillation: a double-blind, randomized, placebo-controlled trial

DEFF Research Database (Denmark)

Egstrup, Kenneth; Bergfeldt, Lennart; Duris, Tibor

2011-01-01

AZD1305 is an investigational antiarrhythmic agent that prolongs refractoriness through combined potassium and sodium channel inhibition. This study aimed to explore the utility of a test dose in predicting QT interval corrected according to Fridericia's formula (QTcF) during subsequent maintenance...

Estimation of the transit dose component in high dose rate brachytherapy

International Nuclear Information System (INIS)

Garcia Romero, A.; Millan Cebrian, E.; Lozano Flores, F.J.; Lope Lope, R.; Canellas Anoz, M.

2001-01-01

Current high dose rate brachytherapy (HDR) treatment planning systems usually calculate dose only from source stopping positions (stationary component), but fails to account for the administered dose when the source is moving (dynamic component or transit dose). Numerical values of this transit dose depends upon the source velocity, implant geometry, source activity and prescribed dose. In some HDR treatments using particular geometry the transit dose cannot be ignored because it increases the dose at the prescriptions points and also could increase potential late tissue complications as predicted by the linear quadratic model. International protocols recommend to verify this parameter. The aim of this paper has been to establish a procedure for the transit dose calculation for the Gammamed 12i equipment at the RT Department in the Clinical University Hospital (Zaragoza-Spain). A numeric algorithm was implemented based on a dynamic point approximation for the moving HDR source and the calculated results for the entrance-exit transit dose was compared with TLD measurements made in some discrete points. (author) [es

ELDRS Characterization for a Very High Dose Mission

Science.gov (United States)

Harris, Richard D.; McClure, Steven S.; Rax, Bernard G.; Kenna, Aaron J.; Thorbourn, Dennis O.; Clark, Karla B.; Yan, Tsun-Yee

2010-01-01

Evaluation of bipolar linear parts which may have Enhanced Low Dose Rate Sensitivity (ELDRS) is problematic for missions that have very high dose radiation requirements. The accepted standards for evaluating parts that display ELDRS require testing at a very low dose rate which could be prohibitively long for very high dose missions. In this work, a methodology for ELDRS characterization of bipolar parts for mission doses up to 1 Mrad(Si) is evaluated. The procedure employs an initial dose rate of 0.01 rad(Si)/s to a total dose of 50 krad(Si) and then changes to 0.04 rad(Si)/s to a total dose of 1 Mrad(Si). This procedure appears to work well. No change in rate of degradation with dose has been observed when the dose rate is changed from 0.01 to 0.04 rad(Si)/s. This is taken as an indication that the degradation due to the higher dose rate is equivalent to that at the lower dose rate at the higher dose levels, at least for the parts studied to date. In several cases, significant parameter degradation or functional failure not observed at HDR was observed at fairly high total doses (50 to 250 krad(Si)) at LDR. This behavior calls into question the use of dose rate trend data and enhancement factors to predict LDR performance.

Weldon Spring historical dose estimate

International Nuclear Information System (INIS)

Meshkov, N.; Benioff, P.; Wang, J.; Yuan, Y.

1986-07-01

This study was conducted to determine the estimated radiation doses that individuals in five nearby population groups and the general population in the surrounding area may have received as a consequence of activities at a uranium processing plant in Weldon Spring, Missouri. The study is retrospective and encompasses plant operations (1957-1966), cleanup (1967-1969), and maintenance (1969-1982). The dose estimates for members of the nearby population groups are as follows. Of the three periods considered, the largest doses to the general population in the surrounding area would have occurred during the plant operations period (1957-1966). Dose estimates for the cleanup (1967-1969) and maintenance (1969-1982) periods are negligible in comparison. Based on the monitoring data, if there was a person residing continually in a dwelling 1.2 km (0.75 mi) north of the plant, this person is estimated to have received an average of about 96 mrem/yr (ranging from 50 to 160 mrem/yr) above background during plant operations, whereas the dose to a nearby resident during later years is estimated to have been about 0.4 mrem/yr during cleanup and about 0.2 mrem/yr during the maintenance period. These values may be compared with the background dose in Missouri of 120 mrem/yr

Weldon Spring historical dose estimate

Energy Technology Data Exchange (ETDEWEB)

Meshkov, N.; Benioff, P.; Wang, J.; Yuan, Y.

1986-07-01

This study was conducted to determine the estimated radiation doses that individuals in five nearby population groups and the general population in the surrounding area may have received as a consequence of activities at a uranium processing plant in Weldon Spring, Missouri. The study is retrospective and encompasses plant operations (1957-1966), cleanup (1967-1969), and maintenance (1969-1982). The dose estimates for members of the nearby population groups are as follows. Of the three periods considered, the largest doses to the general population in the surrounding area would have occurred during the plant operations period (1957-1966). Dose estimates for the cleanup (1967-1969) and maintenance (1969-1982) periods are negligible in comparison. Based on the monitoring data, if there was a person residing continually in a dwelling 1.2 km (0.75 mi) north of the plant, this person is estimated to have received an average of about 96 mrem/yr (ranging from 50 to 160 mrem/yr) above background during plant operations, whereas the dose to a nearby resident during later years is estimated to have been about 0.4 mrem/yr during cleanup and about 0.2 mrem/yr during the maintenance period. These values may be compared with the background dose in Missouri of 120 mrem/yr.

Prospective observational study of the effect of dual antiplatelet therapy with tranexamic acid treatment on platelet function and bleeding after cardiac surgery.

Science.gov (United States)

Amour, J; Garnier, M; Szymezak, J; Le Manach, Y; Helley, D; Bertil, S; Ouattara, A; Riou, B; Gaussem, P

2016-12-01

The bleeding impact of dual antiplatelet therapy (DAPT), aspirin and clopidogrel, maintained until coronary artery bypass graft surgery (CABG), is still a matter of debate. The lack of preoperative antiplatelet activity measurement and heterogeneity of antifibrinolytic protocols in prior studies make the conclusions questionable. The aim of this prospective study was to determine, after preoperative antiplatelet activity measurement, if the maintenance of DAPT until CABG increases bleeding in patients treated with tranexamic acid (TA). This observational study included 150 consecutive patients, 89 treated with aspirin and 61 treated with DAPT, undergoing a first-time planned on-pump CABG with TA treatment. Antiplatelet activity was measured with platelet aggregation tests and quantification of VASP phosphorylation. Postoperative bleeding at 24 h was recorded and propensity score analysis was performed. Based on VASP assay, 54% of patients showed high on-clopidogrel platelet activity inhibition. Postoperative bleeding at 24 h increased by 22% in the DAPT group, compared with the aspirin group (680 [95% CI: 360-1670] vs 558 [95%CI: 267-1270] ml, P < 0.01), consistent with increased blood transfusion (21% vs 7%, P = 0.01); a higher incidence of mediastinitis did not reach statistical significance (15% vs 4%, P = 0.05). Bleeding correlated with the extent of clopidogrel antiplatelet effect, with the best correlation for the VASP assay. Maintenance of DAPT until the day of CABG in patients treated with TA, increased postoperative bleeding at 24 h in parallel with preoperative antiplatelet activity induced by clopidogrel. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Benefit of Clopidogrel Therapy in Patients With Myocardial Infarction and Chronic Kidney Disease

DEFF Research Database (Denmark)

Blicher, Thalia Marie; Hommel, Kristine; Kristensen, Søren Lund

2014-01-01

to percutaneous coronary intervention (PCI) treatment.A total of 69 082 incident MI patients in the period 2002-2011 were included. Clopidogrel treatment was associated with hazard ratios (HRs) for the combined endpoint of all-cause mortality and recurrent MI in PCI-treated patients of 0.90 (95% confidence...... interval [CI], 0.47 to 1.72) in renal replacement therapy (RRT) patients, 0.59 (95% CI: 0.40 to 0.88) in non-end-stage CKD patients and 0.69 (95% CI, 0.61 to 0.77) in patients without kidney disease (P for interaction=0.60). In patients not treated with PCI, HRs were 0.90 (95% CI, 0.68 to 1.21) in RRT...

Quality control of 192Ir high dose rate after loading brachytherapy dose veracity

International Nuclear Information System (INIS)

Feng Zhongsu; Xu Xiao; Liu Fen

2008-01-01

Recently, 192 Ir high dose rate (HDR) afterloading are widely used in brachytherapy. The advantage of using HDR systems over low dose rate systems are shorter treatment time and higher fraction dose. To guarantee the veracity of the delivery dose, several quality control methods are deseribed in this work. With these we can improve the position precision, time precision and dose precision of the brachytherapy. (authors)

Pharmacokinetically guided dosing of (high-dose) chemotherapeutic agents

NARCIS (Netherlands)

Attema-de Jonge, M.E. (Milly Ellen)

2004-01-01

Due to variation in drug distribution, metabolism and elimination processes between patients, systemic exposure to chemotherapeutic agents may be highly variable from patient to patient after administration of similar doses. This pharmacokinetic variability may explain in part the large variability

Interval of Routine Maintenance and Maintenance Performance: A Literature Review

Directory of Open Access Journals (Sweden)

Au-Yong Cheong Peng

2016-01-01

Full Text Available In high-rise residential buildings, the quality of facilities management services is significant to the normal operation of the facilities. Unfortunately, lack of concern towards building maintenance, especially preventive maintenance, happens in domestic housing industry in Malaysia. Majority of the maintenance operations of condominiums suffer from lack of planning, lack of proactive maintenance plan, and lack of proper implementation. Thus, this paper reviews the implementation of preventive maintenance strategy, routine maintenance in specific. An extensive review of literature published in 1987 to 2014 is performed for the purpose of this research. The publications are sourced from journal articles, conference proceedings and books. The literature analysis confirms that the routine maintenance of facilities and building services is vital and it can be influential towards the maintenance performance. Subsequently, a theoretical framework is developed, which shows the relationship between routine maintenance of building facilities & services and maintenance performance. The building facilities & services are divided into two categories. They are essential facilities & services that ensure the safety, health, habitability, and operability of buildings; while value-added facilities & services deal with property value, return on investment, and quality living of buildings. Based on the findings, a future research is proposed, which aims to identify the appropriate routine of maintenance for the facilities and services in high-rise residential buildings to improve the maintenance performance.

Development and Validation of an HPLC Method for Simultaneous Quantification of Clopidogrel Bisulfate, Its Carboxylic Acid Metabolite, and Atorvastatin in Human Plasma: Application to a Pharmacokinetic Study

Directory of Open Access Journals (Sweden)

Octavian Croitoru

2015-01-01

Full Text Available A simple, sensitive, and specific reversed phase liquid chromatographic method was developed and validated for simultaneous quantification of clopidogrel, its carboxylic acid metabolite, and atorvastatin in human serum. Plasma samples were deproteinized with acetonitrile and ibuprofen was chosen as internal standard. Chromatographic separation was performed on an BDS Hypersil C18 column (250 × 4.6 mm; 5 μm via gradient elution with mobile phase consisting of 10 mM phosphoric acid (sodium buffer solution (pH = 2.6 adjusted with 85% orthophosphoric acid : acetonitrile : methanol with flow rate of 1 mL·min−1. Detection was achieved with PDA detector at 220 nm. The method was validated in terms of linearity, sensitivity, precision, accuracy, limit of quantification, and stability tests. Calibration curves of the analytes were found to be linear in the range of 0.008–2 μg·mL−1 for clopidogrel, 0.01–4 μg·mL−1 for its carboxylic acid metabolite, and 0.005–2.5 μg·mL−1 for atorvastatin. The results of accuracy (as recovery with ibuprofen as internal standard were in the range of 96–98% for clopidogrel, 94–98% for its carboxylic acid metabolite, and 90–99% for atorvastatin, respectively.

Mercaptopurine/Methotrexate Maintenance Therapy of Childhood Acute Lymphoblastic Leukemia: Clinical Facts and Fiction

Science.gov (United States)

Nielsen, Stine N.; Frandsen, Thomas L.; Nersting, Jacob

2014-01-01

The antileukemic mechanisms of 6-mercaptopurine (6MP) and methotrexate (MTX) maintenance therapy are poorly understood, but the benefits of several years of myelosuppressive maintenance therapy for acute lymphoblastic leukemia are well proven. Currently, there is no international consensus on drug dosing. Because of significant interindividual and intraindividual variations in drug disposition and pharmacodynamics, vigorous dose adjustments are needed to obtain a target degree of myelosuppression. As the normal white blood cell counts vary by patients’ ages and ethnicity, and also within age groups, identical white blood cell levels for 2 patients may not reflect the same treatment intensity. Measurements of intracellular levels of cytotoxic metabolites of 6MP and MTX can identify nonadherent patients, but therapeutic target levels remains to be established. A rise in serum aminotransferase levels during maintenance therapy is common and often related to high levels of methylated 6MP metabolites. However, except for episodes of hypoglycemia, serious liver dysfunction is rare, the risk of permanent liver damage is low, and aminotransferase levels usually normalize within a few weeks after discontinuation of therapy. 6MP and MTX dose increments should lead to either leukopenia or a rise in aminotransferases, and if neither is experienced, poor treatment adherence should be considered. The many genetic polymorphisms that determine 6MP and MTX disposition, efficacy, and toxicity have precluded implementation of pharmacogenomics into treatment, the sole exception being dramatic 6MP dose reductions in patients who are homozygous deficient for thiopurine methyltransferase, the enzyme that methylates 6MP and several of its metabolites. In conclusion, maintenance therapy is as important as the more intensive and toxic earlier treatment phases, and often more challenging. Ongoing research address the applicability of drug metabolite measurements for dose adjustments

Industrial Maintenance Strategies

International Nuclear Information System (INIS)

Sajjad Akbar

2006-01-01

Industrial plants have become more complex due to technological advancement. This has made the task of maintenance more difficult. The maintenance costs in terms of resources and downtime loss are so high that maintenance function has become a critical factor in a plant's profitability. Industry should devote as much forethought to the management of maintenance function as to production. Maintenance has grown from an art to a precise, technical engineering science. Planning, organizing scheduling and control of maintenance using modern techniques pays dividends in the form of reduced costs and increased reliability. The magnitude and the dimension of maintenance have multiplied due to development in the engineering technologies. Production cost and capacities are directly affected by the breakdown time. Total operating cost including the maintenance cost plays an important role in replacement dimension. The integrated system approach would bring forth the desired results of high maintenance standards. The standards once achieved and sustained, would add to the reliability of the plan and relieve heavy stresses and strains on the engineering logistic support. (author)

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

Physiological and immunological changes following exposure to low versus high-dose ionizing irradiation; comparative analysis with dose rate and cumulative dose

International Nuclear Information System (INIS)

Heesun, Kim; Heewon, Jang; Soungyeon, Song; Shinhye, Oh; Cukcheul, Shin; Meeseon, Jeong; Chasoon, Kim; Kwnaghee, Yang; Seonyoung, Nam; Jiyoung, Kim; Youngwoo, Jin; Changyoung, Cha

2008-01-01

Full text: While high-dose of ionizing radiation is generally harmful and causes damage to living organisms some reports suggest low-dose of radiation may not be as damaging as previously thought. Despite increasing evidence regarding the protective effect of low-dose radiation, no studies have directly compared the exact dose-response pattern by high- and low-dose of radiation exposed at high-and low-dose rate. This study aims to explore the cellular and molecular changes in mice exposed to low- and high-dose of radiation exposed at low- and high-dose rate. When C57BL/6 mice (Female, 6 weeks) were exposed at high-dose rate, 0.8 Gy/min, no significant change on the level of WBC, RBC, or platelets was observed up to total dose of 0.5 Gy. However, 2 Gy of radiation caused dramatic reduction in the level of white blood cells (WBC) and platelets. This reduction was accompanied by increased DNA damage in hematopoietic environments. The reduction of WBC was mainly due to the reduction in the number of CD4+ T cells and CD19+ B cells. CD8+ T cells and NK cells appeared to be relatively resistant to high-dose of radiation. This change was also accompanied by the reduction of T- and B- progenitor cells in the bone marrow. In contrast, no significant changes of the number of CD4+ T, CD8+ T, NK, and B cells were observed in the spleen of mice exposed at low-dose-rate (0.7 m Gy/h or 3.95 mGy/h) for up to 2 Gy, suggesting that low-dose radiation does not alter cellular distribution in the spleen. Nevertheless, mice exposed to low-dose radiation exhibited elevation of VEGF, MCP-1, IL-4, Leptin, IL-3, and Tpo in the peripheral blood and slight increases in MIP-2, RANTES, and IL-2 in the spleen. This suggests that chronic γ-radiation can stimulate immune function without causing damage to the immune components of the body. Taken together, these data indicate hormesis of low-dose radiation, which could be attributed to the stimulation of immune function. Dose rate rather than total

Dose volume assessment of high dose rate 192IR endobronchial implants

International Nuclear Information System (INIS)

Cheng, B. Saw; Korb, Leroy J.; Pawlicki, Todd; Wu, Andrew

1996-01-01

Purpose: To study the dose distributions of high dose rate (HDR) endobronchial implants using the dose nonuniformity ratio (DNR) and three volumetric irradiation indices. Methods and Materials: Multiple implants were configured by allowing a single HDR 192 Ir source to step through a length of 6 cm along an endobronchial catheter. Dwell times were computed to deliver a dose of 5 Gy to points 1 cm away from the catheter axis. Five sets of source configurations, each with different dwell position spacings from 0.5 to 3.0 cm, were evaluated. Three-dimensional (3D) dose distributions were then generated for each source configuration. Differential and cumulative dose-volume curves were generated to quantify the degree of target volume coverage, dose nonuniformity within the target volume, and irradiation of tissues outside the target volume. Evaluation of the implants were made using the DNR and three volumetric irradiation indices. Results: The observed isodose distributions were not able to satisfy all the dose constraints. The ability to optimally satisfy the dose constraints depended on the choice of dwell position spacing and the specification of the dose constraint points. The DNR and irradiation indices suggest that small dwell position spacing does not result in a more homogeneous dose distribution for the implant. This study supports the existence of a relationship between the dwell position spacing and the distance from the catheter axis to the reference dose or dose constraint points. Better dose homogeneity for an implant can be obtained if the spacing of the dwell positions are about twice the distance from the catheter axis to the reference dose or dose constraint points

Teachers' High Maintenance Behaviour as Perceived by University Students in Taiwan, and Their Coping Strategies

Science.gov (United States)

Hong, Fu-Yuan; Cheng, Kuang-Tsan

2014-01-01

Using a questionnaire survey, this study probed into interpersonal cues and characteristics of teachers' high maintenance behaviors perceived by university students and their coping strategies, and then analyzed the relationship between their perceived high maintenance behaviors and the dimensions of their coping strategies. The Scale of Teachers'…

Braquiterapia de alta taxa de dose no Brasil High-dose rate brachytherapy in Brazil

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Sérgio Carlos Barros Esteves

2004-10-01

Full Text Available A braquiterapia de alta taxa de dose foi introduzida em nosso meio em janeiro de 1991. Desde então, houve uma mudança significativa na abordagem das neoplasias malignas em relação às vantagens do novo método, e também resolução da demanda reprimida de braquiterapia para as neoplasias ginecológicas. Nos primeiros dez anos de atividade, o Brasil tratou, em 31 serviços, 26.436 pacientes com braquiterapia, sendo mais de 50% das pacientes portadoras de neoplasias do colo uterino. Este estudo mostra o número e o perfil de pacientes tratados com esse método e a sua distribuição no território nacional, deixando explícito o benefício da braquiterapia de alta taxa de dose para o Brasil.High-dose rate brachytherapy was first introduced in Brazil in January 1991. Significant changes in the management of malignant neoplasms were observed since utilization of high-dose rate brachytherapy. The high number of gynecological patients awaiting for brachytherapy also decreased during this period. In the first ten years 26,436 patients were treated with high-dose rate brachytherapy. More than 50% of these patients presented neoplasms of the uterine cervix. In this study we present the number and profile of the patients treated with high-dose rate brachytherapy as well as the distribution of these patients in the Brazilian territory, proving the benefit of the use of high-dose rate brachytherapy in Brazil.

Associations Between Complex PCI and Prasugrel or Clopidogrel Use in Patients With Acute Coronary Syndrome Who Undergo PCI: From the PROMETHEUS Study.

Science.gov (United States)

Chandrasekhar, Jaya; Baber, Usman; Sartori, Samantha; Aquino, Melissa; Kini, Annapoorna S; Rao, Sunil; Weintraub, William; Henry, Timothy D; Farhan, Serdar; Vogel, Birgit; Sorrentino, Sabato; Ge, Zhen; Kapadia, Samir; Muhlestein, Joseph B; Weiss, Sandra; Strauss, Craig; Toma, Catalin; DeFranco, Anthony; Effron, Mark B; Keller, Stuart; Baker, Brian A; Pocock, Stuart; Dangas, George; Mehran, Roxana

2018-03-01

Potent P2Y 12 inhibitors might offer enhanced benefit against thrombotic events in complex percutaneous coronary intervention (PCI). We examined prasugrel use and outcomes according to PCI complexity, as well as analyzing treatment effects according to thienopyridine type. PROMETHEUS was a multicentre observational study that compared clopidogrel vs prasugrel in acute coronary syndrome patients who underwent PCI (n = 19,914). Complex PCI was defined as PCI of the left main, bifurcation lesion, moderate-severely calcified lesion, or total stent length ≥ 30 mm. Major adverse cardiac events (MACE) were a composite of death, myocardial infarction, stroke, or unplanned revascularization. Outcomes were adjusted using multivariable Cox regression for effect of PCI complexity and propensity-stratified analysis for effect of thienopyridine type. The study cohort included 48.9% (n = 9735) complex and 51.1% (n = 10,179) noncomplex patients. Second generation drug-eluting stents were used in 70.1% complex and 66.2% noncomplex PCI patients (P PCI was associated with greater adjusted risk of 1-year MACE (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.20-1.39; P PCI patients (P = 0.30). Compared with clopidogrel, prasugrel significantly decreased adjusted risk for 1-year MACE in complex PCI (HR, 0.79; 95% CI, 0.68-0.92) but not noncomplex PCI (HR, 0.91; 95% CI, 0.77-1.08), albeit there was no evidence of interaction (P interaction = 0.281). Despite the use of contemporary techniques, acute coronary syndrome patients who undergo complex PCI had significantly higher rates of 1-year MACE. Adjusted magnitude of treatment effects with prasugrel vs clopidogrel were consistent in complex and noncomplex PCI without evidence of interaction. Copyright © 2018. Published by Elsevier Inc.

Maintenance management at the High Flux Isotope Reactor

International Nuclear Information System (INIS)

Farrar, M.B.

1982-02-01

Maintenance procedures are described for mechanical and electrical equipment; nuclear and process instrumentation; operational maintenance; equipment and systems inspections; and HFIR quality assurance

Dose control during decommissioning stage 1.2 of decommissioning SGHWR facility

Energy Technology Data Exchange (ETDEWEB)

Rodgers, M.J. [AEA Technology (United Kingdom)

1995-12-31

Dose control during decommissioning stage 1.2 of the SGHWR facility, i.e preparation for an extended period of care and maintenance, is discussed. The method of control of dose uptake is described and also the systems of dose uptake review, the use of dose restraint objections and other tools for limitation of dose uptake. Dose uptake data are presented for periods of maintenance shutdowns. Finally the option of chemical clearing of the circuit following shutdown is considered. (UK).

Endorectal high dose rate brachytherapy quality assurance

International Nuclear Information System (INIS)

Devic, S.; Vuong, T.; Evans, M.; Podgorsak, E.

2008-01-01

We describe our quality assurance method for preoperative high dose rate (HDR) brachytherapy of endorectal tumours. Reproduction of the treatment planning dose distribution on a daily basis is crucial for treatment success. Due to the cylindrical symmetry, two types of adjustments are necessary: applicator rotation and dose distribution shift along the applicator axis. (author)

Dose escalation using conformal high-dose-rate brachytherapy improves outcome in unfavorable prostate cancer

International Nuclear Information System (INIS)

Martinez, Alvaro A.; Gustafson, Gary; Gonzalez, Jose; Armour, Elwood; Mitchell, Chris; Edmundson, Gregory; Spencer, William; Stromberg, Jannifer; Huang, Raywin; Vicini, Frank

2002-01-01

Purpose: To overcome radioresistance for patients with unfavorable prostate cancer, a prospective trial of pelvic external beam irradiation (EBRT) interdigitated with dose-escalating conformal high-dose-rate (HDR) prostate brachytherapy was performed. Methods and Materials: Between November 1991 and August 2000, 207 patients were treated with 46 Gy pelvic EBRT and increasing HDR brachytherapy boost doses (5.50-11.5 Gy/fraction) during 5 weeks. The eligibility criteria were pretreatment prostate-specific antigen level ≥10.0 ng/mL, Gleason score ≥7, or clinical Stage T2b or higher. Patients were divided into 2 dose levels, low-dose biologically effective dose 93 Gy (149 patients). No patient received hormones. We used the American Society for Therapeutic Radiology and Oncology definition for biochemical failure. Results: The median age was 69 years. The mean follow-up for the group was 4.4 years, and for the low and high-dose levels, it was 7.0 and 3.4 years, respectively. The actuarial 5-year biochemical control rate was 74%, and the overall, cause-specific, and disease-free survival rate was 92%, 98%, and 68%, respectively. The 5-year biochemical control rate for the low-dose group was 52%; the rate for the high-dose group was 87% (p<0.001). Improvement occurred in the cause-specific survival in favor of the brachytherapy high-dose level (p=0.014). On multivariate analysis, a low-dose level, higher Gleason score, and higher nadir value were associated with increased biochemical failure. The Radiation Therapy Oncology Group Grade 3 gastrointestinal/genitourinary complications ranged from 0.5% to 9%. The actuarial 5-year impotency rate was 51%. Conclusion: Pelvic EBRT interdigitated with transrectal ultrasound-guided real-time conformal HDR prostate brachytherapy boost is both a precise dose delivery system and a very effective treatment for unfavorable prostate cancer. We demonstrated an incremental beneficial effect on biochemical control and cause

Radiation Protection Practices during the Helium Circulator Maintenance of the 10 MW High Temperature Gas-Cooled Reactor-Test Module (HTR-10

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Chengxiang Guo

2016-01-01

Full Text Available Current radiation protection methodology offers abundant experiences on light-water reactors, but very few studies on high temperature gas-cooled reactor (HTR. To fill this gap, a comprehensive investigation was performed to the radiation protection practices in the helium circulator maintenance of the Chinese 10 MW HTR test module (HTR-10 in this paper. The investigation reveals the unique behaviour of HTR-10’s radiation sources in the maintenance as well as its radionuclide species and presents the radiation protection methods that were tailored to these features. Owing to these practices, the radioactivity level was kept low throughout the maintenance and only low-level radioactive waste was generated. The quantitative analysis further demonstrates that the decontamination efficiency was over 89% for surface contamination and over 34% for γ dose rate and the occupational exposure was much lower than both the limits of regulatory and the exposure levels in comparable literature. These results demonstrate the effectiveness of the reported radiation protection practices, which directly provides hands-on experience for the future HTR-PM reactor and adds to the completeness of the radiation protection methodology.

Maintaining occupational dose ALARA through work management

International Nuclear Information System (INIS)

Khan, A. H.

1999-01-01

Canadian philosophy in keeping occupational dose ALARA has been to train staff in radiation safety so that they can be fully responsible for participating in minimizing the risks associated with the hazardous work. Senior managers actively promote high standards of performance in dose reduction techniques as a means for integrating ALARA into the operation and maintenance of the station by all personnel. Minimizing radiation dose is accomplished by applying cost effective work management techniques such as Job Safety Analysis, pre-job briefings and establishing and achieving radiation dose goals. Radiation dose goals are used as a management tool for involving all work groups in reducing doses as well as providing a means of assessing the effectiveness of dose reduction actions. ALARA, along with conventional safety, is used as a lever to raise the standard of quality of work and to overall build a safety culture. (author). 4 figs

Low dose radiation enhance the anti-tumor effect of high dose radiation on human glioma cell U251

International Nuclear Information System (INIS)

Wang Chang; Wang Guanjun; Tan Yehui; Jiang Hongyu; Li Wei

2008-01-01

Objective: To detect the effect on the growth of human glioma cell U251 induced by low dose irradiation and low dose irradiation combined with large dose irradiation. Methods: Human glioma cell line U251 and nude mice carried with human glioma were used. The tumor cells and the mice were treated with low dose, high dose, and low dose combined high dose radiation. Cells growth curve, MTT and flow cytometry were used to detect the proliferation, cell cycle and apoptosis of the cells; and the tumor inhibition rate was used to assess the growth of tumor in vivo. Results: After low dose irradiation, there was no difference between experimental group and control group in cell count, MTT and flow cytometry. Single high dose group and low dose combined high dose group both show significantly the suppressing effect on tumor cells, the apoptosis increased and there was cell cycle blocked in G 2 period, but there was no difference between two groups. In vivo apparent anti-tumor effect in high dose radiation group and the combining group was observed, and that was more significant in the combining group; the prior low dose radiation alleviated the injury of hematological system. There was no difference between single low dose radiation group and control. Conclusions: There is no significant effect on human glioma cell induced by low dose radiation, and low dose radiation could not induce adaptive response. But in vivo experience, low dose radiation could enhance the anti-tumor effect of high dose radiation and alleviated the injury of hematological system. (authors)

Unmasking of Partial Diabetes Insipidus during Stress but Not Maintenance Dosing of Glucocorticoids in an Infant with Septo-Optic Dysplasia

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Loechner KarenJ

2011-03-01

Full Text Available Background. It is well acknowledged that glucocorticoid (GC replacement can unmask diabetes insipidus (DI in subjects with hypopituitarism. Objective. To increase the awareness and monitoring for transient and symptomatic DI in children with partial hypopituitarism during periods in which increased GC needs are required. Methods/Case. A 2-month-old female infant with septo-optic dysplasia (SOD; on thyroid and maintenance GC replacement therapy at 8 mg/m2/day developed transient DI during 2 separate episodes of stress (one hypothermia, one febrile when stress dosing of GC (25 mg/m2/day was instituted. Conclusion. Children not diagnosed with DI during initial evaluation for hypopituitarism may benefit from rescreening of serum sodium levels during acute periods of stress that demand "stress" GC dosing. This will permit treatment and/or increased vigilance for ensuing permanent DI.

Inventory-transportation integrated optimization for maintenance spare parts of high-speed trains

Science.gov (United States)

Wang, Jiaxi; Wang, Huasheng; Wang, Zhongkai; Li, Jian; Lin, Ruixi; Xiao, Jie; Wu, Jianping

2017-01-01

This paper presents a 0–1 programming model aimed at obtaining the optimal inventory policy and transportation mode for maintenance spare parts of high-speed trains. To obtain the model parameters for occasionally-replaced spare parts, a demand estimation method based on the maintenance strategies of China’s high-speed railway system is proposed. In addition, we analyse the shortage time using PERT, and then calculate the unit time shortage cost from the viewpoint of train operation revenue. Finally, a real-world case study from Shanghai Depot is conducted to demonstrate our method. Computational results offer an effective and efficient decision support for inventory managers. PMID:28472097

Use of and inhospital outcomes after early clopidogrel therapy in patients not undergoing an early invasive strategy for treatment of non-ST-segment elevation myocardial infarction: results from Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the American College of Cardiology/American Heart Association guidelines (CRUSADE).

Science.gov (United States)

Alexander, Deepu; Ou, Fang-Shu; Roe, Matthew T; Pollack, Charles V; Ohman, E Magnus; Cannon, Christopher P; Gibler, W Brian; Fintel, Dan J; Peterson, Eric D; Brown, David L

2008-09-01

Although current guidelines recommend early initiation of clopidogrel in patients with non-ST-segment elevation myocardial infarction (NSTEMI), the degree to which it has been adopted in clinical practice remains unclear. We sought to determine patterns of early (vs 9.5%, P = .90). Until recently, up to 50% of NSTEMI patients in contemporary practice in the United States not undergoing PCI within 24 hours of arrival in the United States are not treated according to guideline recommendations. Among a high-risk NSTEMI population not undergoing PCI within 24 hours of arrival, the nonrandomized short-term use of clopidogrel is associated with a lower risk of inhospital mortality without an increased risk of major bleeding.

NIST high-dose calibration services

International Nuclear Information System (INIS)

Humphreys, J.C.

1989-01-01

There is a need for the standardization of high-dose measurements used in the radiation-processing industry in order to provide assured traceability to national standards. NIST provides dosimetry calibration services to this industry. One of these services involves administration of known absorbed doses of gamma rays to customer-supplied dosimeters. The dosimeters are packaged to provide electron equilibrium conditions and are irradiated in a standard 60 Co calibration facility; this provides a calibration of that batch of dosimeters. Another service consists of supplying to a customer calibrated transfer dosimeters for irradiation with the customer's radiation source. The irradiated transfer dosimeters are then returned to NIST for analysis; the results are reported to the customer, providing a calibration of the dose rate of the customer's source. (orig.)

Rectal dose assessment in patients submitted to high-dose-rate brachytherapy for uterine cervix cancer

International Nuclear Information System (INIS)

Oliveira, Jetro Pereira de; Batista, Delano Valdivino Santos; Bardella, Lucia Helena; Carvalho, Arnaldo Rangel

2009-01-01

Objective: The present study was aimed at developing a thermoluminescent dosimetric system capable of assessing the doses delivered to the rectum of patients submitted to high-dose-rate brachytherapy for uterine cervix cancer. Materials and methods: LiF:Mg,Ti,Na powder was the thermoluminescent material utilized for evaluating the rectal dose. The powder was divided into small portions (34 mg) which were accommodated in a capillary tube. This tube was placed into a rectal probe that was introduced into the patient's rectum. Results: The doses delivered to the rectum of six patients submitted to high-dose-rate brachytherapy for uterine cervix cancer evaluated by means of thermoluminescent dosimeters presented a good agreement with the planned values based on two orthogonal (anteroposterior and lateral) radiographic images of the patients. Conclusion: The thermoluminescent dosimetric system developed in the present study is simple and easy to be utilized as compared to other rectal dosimetry methods. The system has shown to be effective in the evaluation of rectal doses in patients submitted to high-dose-rate brachytherapy for uterine cervix cancer. (author)

Dose escalation using conformal high-dose-rate brachytherapy improves outcome in unfavorable prostate cancer.

Science.gov (United States)

Martinez, Alvaro A; Gustafson, Gary; Gonzalez, José; Armour, Elwood; Mitchell, Chris; Edmundson, Gregory; Spencer, William; Stromberg, Jannifer; Huang, Raywin; Vicini, Frank

2002-06-01

To overcome radioresistance for patients with unfavorable prostate cancer, a prospective trial of pelvic external beam irradiation (EBRT) interdigitated with dose-escalating conformal high-dose-rate (HDR) prostate brachytherapy was performed. Between November 1991 and August 2000, 207 patients were treated with 46 Gy pelvic EBRT and increasing HDR brachytherapy boost doses (5.50-11.5 Gy/fraction) during 5 weeks. The eligibility criteria were pretreatment prostate-specific antigen level >or=10.0 ng/mL, Gleason score >or=7, or clinical Stage T2b or higher. Patients were divided into 2 dose levels, low-dose biologically effective dose 93 Gy (149 patients). No patient received hormones. We used the American Society for Therapeutic Radiology and Oncology definition for biochemical failure. The median age was 69 years. The mean follow-up for the group was 4.4 years, and for the low and high-dose levels, it was 7.0 and 3.4 years, respectively. The actuarial 5-year biochemical control rate was 74%, and the overall, cause-specific, and disease-free survival rate was 92%, 98%, and 68%, respectively. The 5-year biochemical control rate for the low-dose group was 52%; the rate for the high-dose group was 87% (p failure. The Radiation Therapy Oncology Group Grade 3 gastrointestinal/genitourinary complications ranged from 0.5% to 9%. The actuarial 5-year impotency rate was 51%. Pelvic EBRT interdigitated with transrectal ultrasound-guided real-time conformal HDR prostate brachytherapy boost is both a precise dose delivery system and a very effective treatment for unfavorable prostate cancer. We demonstrated an incremental beneficial effect on biochemical control and cause-specific survival with higher doses. These results, coupled with the low risk of complications, the advantage of not being radioactive after implantation, and the real-time interactive planning, define a new standard for treatment.

Investigation of polymer composite for high dose dosimetry

International Nuclear Information System (INIS)

Pereira, E.L.M.; Batista, A.S.M.; Ribeiro, F.A.S.; Santos, A.P.; Faria, L.O.; Oliveira, A.H.

2017-01-01

Introduction: This paper presents the efficacy evaluation of PVDF and nanocomposites of the PVDF films for high gamma dosimetry. Our scope in this first part of our studies is the selection of the most promising film for future dosimetry trials, where the proportionality of response of the selected material will be investigated over a large range of doses and dose rates. Methods: Was prepared nanocomposites made by mixing Poly(vinylidene fluoride) (PVDF), zirconium oxide (ZrO 2 ) and multi-walled carbon nanotubes (MWCNTs) aiming to find dosimetric properties for applications in high dose dosimetry. The samples were irradiated with a Co-60 source at constant dose rate (16.7 kGy/h), with doses ranging from 100 to 2750 kGy. The UV-Vis and FTIR spectrophotometry have been used to monitor the appearing of C=C conjugated bonds and radio-oxidation of carbon (C=O). Results: FTIR spectrometry has that the absorbance intensities at 1715 cm -1 and 1730 cm -1 can be used for high dosimetry purposes for gamma doses ranging from 400 to 2750 kGy. In this range, it is possible to observe a linear relationship between Abs & Dose. Fading of signal was evaluated for one month and reproducibility in 2000 kGy dose. Conclusion: FTIR spectroscopic data revealed two optical absorption bands at 1715 cm -1 and 1730 cm -1 whose intensities are unambiguously related to gamma delivered dose ranging from 400 kGy to 2750 kGy. (author)

Using adaptive model predictive control to customize maintenance therapy chemotherapeutic dosing for childhood acute lymphoblastic leukemia.

Science.gov (United States)

Noble, Sarah L; Sherer, Eric; Hannemann, Robert E; Ramkrishna, Doraiswami; Vik, Terry; Rundell, Ann E

2010-06-07

Acute lymphoblastic leukemia (ALL) is a common childhood cancer in which nearly one-quarter of patients experience a disease relapse. However, it has been shown that individualizing therapy for childhood ALL patients by adjusting doses based on the blood concentration of active drug metabolite could significantly improve treatment outcome. An adaptive model predictive control (MPC) strategy is presented in which maintenance therapy for childhood ALL is personalized using routine patient measurements of red blood cell mean corpuscular volume as a surrogate for the active drug metabolite concentration. A clinically relevant mathematical model is developed and used to describe the patient response to the chemotherapeutic drug 6-mercaptopurine, with some model parameters being patient-specific. During the course of treatment, the patient-specific parameters are adaptively identified using recurrent complete blood count measurements, which sufficiently constrain the patient parameter uncertainty to support customized adjustments of the drug dose. While this work represents only a first step toward a quantitative tool for clinical use, the simulated treatment results indicate that the proposed mathematical model and adaptive MPC approach could serve as valuable resources to the oncologist toward creating a personalized treatment strategy that is both safe and effective. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Statistical behavior of high doses in medical radiodiagnosis

International Nuclear Information System (INIS)

Barboza, Adriana Elisa

2014-01-01

This work has as main purpose statistically estimating occupational exposure in medical diagnostic radiology in cases of high doses recorded in 2011 at national level. For statistical survey of this study, doses of 372 IOE's diagnostic radiology in different Brazilian states were evaluated. Data were extracted from the work of monograph (Research Methodology Of High Doses In Medical Radiodiagnostic) that contains the database's information Sector Management doses of IRD/CNEN-RJ, Brazil. The identification of these states allows the Sanitary Surveillance (VISA) responsible, becomes aware of events and work with programs to reduce these events. (author)

Study of teflon pads as high doses dosemeters

International Nuclear Information System (INIS)

Teixeira, Maria Ines; Caldas, Linda V.E.

2013-01-01

The aim of this work is to study the Teflon, which is used as a binder in the manufacture of dosimetric tablets, for the feasibility of this material as high dose dosemeter. In this paper we used the technique of thermally stimulated luminescence (OSL) to characterize the dosimetric properties of Teflon. Teflon samples were exposed to different doses of radiation, using a source of gamma radiation ( 60 Co). It was obtained dose-response curve between 100 Gy to 50 kGy and reproducibility of OSL response. The preliminary results show that Teflon is a useful material to high dose dosimetry

High-Dose Vitamin C Injection to Cancer Patients May Promote Thrombosis Through Procoagulant Activation of Erythrocytes.

Science.gov (United States)

Kim, Keunyoung; Bae, Ok-Nam; Koh, Sung-Hee; Kang, Seojin; Lim, Kyung-Min; Noh, Ji-Yoon; Shin, Sue; Kim, Inho; Chung, Jin-Ho

2015-10-01

Potential risk of high-dose vitamin C consumption is often ignored. Recently, gram-dose vitamin C is being intravenously injected for the treatment of cancer, which can expose circulating blood cells to extremely high concentrations of vitamin C. As well as platelets, red blood cells (RBCs) can actively participate in thrombosis through procoagulant activation. Here, we examined the procoagulant and prothrombotic risks associated with the intravenous injection of gram-dose vitamin C. Vitamin C (0.5-5 mM) increased procoagulant activity of freshly isolated human RBCs via the externalization of phosphatidylserine (PS) to outer cellular membrane and the formation of PS-bearing microvesicles. PS exposure was induced by the dysregulation of key enzymes for the maintenance of membrane phospholipid asymmetry, which was from vitamin C-induced oxidative stress, and resultant disruption of calcium and thiol homeostasis. Indeed, the intravenous injection of vitamin C (0.5-1.0 g/kg) in rats in vivo significantly increased thrombosis. Notably, the prothrombotic effects of vitamin C were more prominent in RBCs isolated from cancer patients, who are at increased risks of thrombotic events. Vitamin C-induced procoagulant and prothrombotic activation of RBCs, and increased thrombosis in vivo. RBCs from cancer patients exhibited increased sensitivity to the prothrombotic effects of vitamin C, reflecting that intravenous gram-dose vitamin C therapy needs to be carefully revisited. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Renewal and maintenance of a nuclear structure data file used for the calculations of dose conversion factors

International Nuclear Information System (INIS)

Togawa, Orihiko; Yamaguchi, Yukichi

1996-02-01

The ENSDF decay data are used as fundamental data to compute radiation data in the DOSDAC code system, which was developed at JAERI, for the calculation of dose conversion factors. The ENSDF decay data have been periodically revised by reviewing new experimental data in the literature under an international network. The use of this data file enables us to calculate radiation data from information which is the newest and internationally recognized. In spite of this advantage, the decay data file is seldom used in applied fields. This is due to some problems to be solved from a viewpoint of the calculation of radiation data, as well as its complicated structure. This report describes methods for renewal and maintenance of the ENSDF decay data used for the calculation of dose conversion factors. In case that the decay data are used directly, attention should be sometimes paid to some problems, for example defects in data. In renewing and using the ENSDF decay data, the DOSDAC code system tries to avoid wrong calculations of radiation data by check and modification of defects in data through four supporting computer codes. (author)

Ionization chamber for high dose measurements

International Nuclear Information System (INIS)

Rodrigues Junior, Ary de Araujo

2005-01-01

Industrial gamma irradiators facilities are designed for processing large amounts of products, which are exposed to large doses of gamma radiation. The irradiation, in industrial scale, is usually carried out in a dynamic form, where the products go through a 60 Co gamma source with activity of TBq to P Bq (k Ci to MCi). The dose is estimated as being directly proportional to the time that the products spend to go through the source. However, in some situations, mainly for research purposes or for validation of customer process following the ISO 11137 requirements, it is required to irradiate small samples in a static position with fractional deliver doses. The samples are put inside the irradiation room at a fixed distance from the source and the dose is usually determined using dosimeters. The dose is only known after the irradiation, by reading the dosimeter. Nevertheless, in the industrial irradiators, usually different kinds of products with different densities go through between the source and the static position samples. So, the dose rate varies in function of the product density. A suitable methodology would be to monitor the samples dose in real time, measuring the dose on line with a radiation detector, which would improve the dose accuracy and avoid the overdose. A cylindrical ionization chamber of 0.9 cm 3 has been developed for high-doses real-time monitoring, during the sample irradiation at a static position in a 60 Co gamma industrial plant. Nitrogen and argon gas at pressure of 10 exp 5 Pa (1 bar) was utilized to fill the ionization chamber, for which an appropriate configuration was determined to be used as a detector for high-dose measurements. To transmit the signal generated in the ionization chamber to the associated electronic and processing unit, a 20 m mineral insulated cable was welded to the ionization chamber. The signal to noise ratio produced by the detector was about 100. The dosimeter system was tested at a category I gamma

Warfarin Dosing Algorithms Underpredict Dose Requirements in Patients Requiring ≥7 mg Daily: A Systematic Review and Meta-analysis.

Science.gov (United States)

Saffian, S M; Duffull, S B; Wright, Dfb

2017-08-01

There is preliminary evidence to suggest that some published warfarin dosing algorithms produce biased maintenance dose predictions in patients who require higher than average doses. We conducted a meta-analysis of warfarin dosing algorithms to determine if there exists a systematic under- or overprediction of dose requirements for patients requiring ≥7 mg/day across published algorithms. Medline and Embase databases were searched up to September 2015. We quantified the proportion of over- and underpredicted doses in patients whose observed maintenance dose was ≥7 mg/day. The meta-analysis included 47 evaluations of 22 different warfarin dosing algorithms from 16 studies. The meta-analysis included data from 1,492 patients who required warfarin doses of ≥7 mg/day. All 22 algorithms were found to underpredict warfarin dosing requirements in patients who required ≥7 mg/day by an average of 2.3 mg/day with a pooled estimate of underpredicted doses of 92.3% (95% confidence interval 90.3-94.1, I 2 = 24%). © 2017 American Society for Clinical Pharmacology and Therapeutics.

Development of computerized dose planning system and applicator for high dose rate remote afterloading irradiation

Energy Technology Data Exchange (ETDEWEB)

Choi, T. J. [Keimyung Univ., Taegu (Korea); Kim, S. W. [Fatima Hospital, Taegu (Korea); Kim, O. B.; Lee, H. J.; Won, C. H. [Keimyung Univ., Taegu (Korea); Yoon, S. M. [Dong-a Univ., Pusan (Korea)

2000-04-01

To design and fabricate of the high dose rate source and applicators which are tandem, ovoids and colpostat for OB/Gyn brachytherapy includes the computerized dose planning system. Designed the high dose rate Ir-192 source with nuclide atomic power irradiation and investigated the dose characteristics of fabricated brachysource. We performed the effect of self-absorption and determining the gamma constant and output factor and determined the apparent activity of designed source. he automated computer planning system provided the 2D distribution and 3D includes analysis programs. Created the high dose rate source Ir-192, 10 Ci(370GBq). The effective attenuation factor from the self-absorption and source wall was examined to 0.55 of the activity of bare source and this factor is useful for determination of the apparent activity and gamma constant 4.69 Rcm{sup 2}/mCi-hr. Fabricated the colpostat was investigated the dose distributions of frontal, axial and sagittal plane in intra-cavitary radiation therapy for cervical cancer. The reduce dose at bladder and rectum area was found about 20 % of original dose. The computerized brachytherapy planning system provides the 2-dimensional isodose and 3-D include the dose-volume histogram(DVH) with graphic-user-interface mode. emoted afterloading device was built for experiment of created Ir-192 source with film dosimetry within {+-}1 mm discrepancy. 34 refs., 25 figs., 11 tabs. (Author)

Pharmacogenetics and Pharmacokinetics in high-dose alkylating chemotherapy

NARCIS (Netherlands)

Ekhart, G.C. (Corine)

2008-01-01

High-dose chemotherapy in combination with peripheral blood progenitor cell transplantation has been developed as a possible curative treatment modality in several solid tumours. A frequently used high-dose regimen in the Netherlands is the CTC regimen, which is a 4-day course of cyclophosphamide,

Establishment and verification of dose-response curve of chromosomal aberrations after exposure to very high dose γ-ray

International Nuclear Information System (INIS)

Chen Ying; Luo Yisheng; Cao Zhenshan; Liu Xiulin

2006-01-01

To estimate accurately biological dose of the victims exposed to high dose, the dose-response curves of chromosome aberration induced by 6-22 Gy 60 Co γ-ray were established. Human peripheral blood in vitro was irradiated, then lymphocytes were concentrated, cultured 52h, 68h and 72h and harvested. The frequencies of dicentrics (multi-centrics) and rings were counted and compared between different culture times. The dose-response curves and equations were established, as well as verified with high dose exposure accidents. The experiment showed that the culture time should be prolonged properly after high dose exposure, and no significant differences were observed between 52-72h culture. The dose-response curve of 6-22 Gy fitted to linear-square model Y=-2.269 + 0.776D - 7.868 x 10 -3 D 2 and is reliable through verification of the accident dose estimations. In this study, the dose-response curve and equation of chromosome dic + r after 6-22 Gy high dose irradiation were established firstly, and exact dose estimation can be achieved according to it. (authors)

Nonlinear model of high-dose implantation

International Nuclear Information System (INIS)

Danilyuk, A.

2001-01-01

The models of high-dose implantation, using the distribution functions, are relatively simple. However, they must take into account the variation of the function of distribution of the implanted ions with increasing dose [1-4]. This variation takes place owing to the fact that the increase of the concentration of the implanted ions results in a change of the properties of the target. High-dose implantation is accompanied by sputtering, volume growth, diffusion, generation of defects, formation of new phases, etc. The variation of the distribution function is determined by many factors and is not known in advance. The variation within the framework of these models [1-4] is taken into account in advance by the introduction of intuitive assumptions on the basis of implicit considerations. Therefore, these attempts should be regarded as incorrect. The model prepared here makes it possible to take into account the sputtering of the target, volume growth and additional declaration on the implanted ions. Without any assumptions in relation to the variation of the distribution function with increasing dose. In our model it is assumed that the type of distribution function for small doses in a pure target substance is the same as in substances with implanted ions. A second assumption relates to the type of the distribution function valid for small doses in the given substances. These functions are determined as a result of a large number of theoretical and experimental investigations and are well-known at the present time. They include the symmetric and nonsymmetric Gauss distribution, the Pearson distribution, and others. We examine implantation with small doses of up to 10 14 - 10 15 cm -2 when the accurately known distribution is valid

High-dose gadolinium-enhanced MRI for diagnosis of meningeal metastases

International Nuclear Information System (INIS)

Kallmes, D.F.; Gray, L.; Glass, J.P.

1998-01-01

We compared high-dose (0.3 mmol/kg) and standard-dose (0.1 mmol/kg) gadolinium-enhanced MRI for diagnosis of meningeal metastases in 12 patients with suspected meningeal metastases. They were imaged with both standard-dose and high-dose gadolinium. All patients with abnormal meningeal enhancement underwent at least one lumbar puncture for cerebrospinal fluid (CSF) cytology, while patients with normal meningeal enhancement were followed clinically. All patients with negative CSF cytology also were followed clinically. A single observer reviewed all the images, with specific attention to the enhancement pattern of the meninges. Abnormal leptomeningeal enhancement was present in three cases, and abnormal pachymeningeal enhancement in three other patients. All of these patients had abnormal CSF analyses. In two of the three cases of abnormal leptomeningeal enhancement the disease was more evident on high-dose than on standard-dose imaging; in one case the abnormal enhancement was visible only on high-dose imaging. In one of the three cases with abnormal pachymeningeal enhancement, the disease was evident prospectively only with high-dose imaging. (orig.)

A randomized trial using motivational interviewing for maintenance of blood pressure improvements in a community-engaged lifestyle intervention: HUB city steps

Science.gov (United States)

Landry, Alicia; Madson, Michael; Thomson, Jessica; Zoellner, Jamie; Connell, Carol; Yadrick, Kathleen

2015-01-01

Little is known about the effective dose of motivational interviewing for maintaining intervention-induced health outcome improvements. The purpose of this study was to compare effects of two doses of motivational interviewing for maintaining blood pressure improvements in a community-engaged lifestyle intervention conducted with African-Americans. Participants were tracked through a 12-month maintenance phase following a 6-month intervention targeting physical activity and diet. For the maintenance phase, participants were randomized to receive a low (4) or high (10) dose of motivational interviewing delivered via telephone by trained research staff. Generalized linear models were used to test for group differences in blood pressure. Blood pressure significantly increased during the maintenance phase. No differences were apparent between randomized groups. Results suggest that 10 or fewer motivational interviewing calls over a 12-month period may be insufficient to maintain post-intervention improvements in blood pressure. Further research is needed to determine optimal strategies for maintaining changes. PMID:26590242

Investigation of polymer composite for high dose dosimetry

Energy Technology Data Exchange (ETDEWEB)

Pereira, E.L.M.; Batista, A.S.M., E-mail: adriananuclear@yahoo.com.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil); Ribeiro, F.A.S.; Santos, A.P.; Faria, L.O.; Oliveira, A.H. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

2017-07-01

Introduction: This paper presents the efficacy evaluation of PVDF and nanocomposites of the PVDF films for high gamma dosimetry. Our scope in this first part of our studies is the selection of the most promising film for future dosimetry trials, where the proportionality of response of the selected material will be investigated over a large range of doses and dose rates. Methods: Was prepared nanocomposites made by mixing Poly(vinylidene fluoride) (PVDF), zirconium oxide (ZrO{sub 2}) and multi-walled carbon nanotubes (MWCNTs) aiming to find dosimetric properties for applications in high dose dosimetry. The samples were irradiated with a Co-60 source at constant dose rate (16.7 kGy/h), with doses ranging from 100 to 2750 kGy. The UV-Vis and FTIR spectrophotometry have been used to monitor the appearing of C=C conjugated bonds and radio-oxidation of carbon (C=O). Results: FTIR spectrometry has that the absorbance intensities at 1715 cm{sup -1} and 1730 cm{sup -1} can be used for high dosimetry purposes for gamma doses ranging from 400 to 2750 kGy. In this range, it is possible to observe a linear relationship between Abs & Dose. Fading of signal was evaluated for one month and reproducibility in 2000 kGy dose. Conclusion: FTIR spectroscopic data revealed two optical absorption bands at 1715 cm{sup -1} and 1730 cm{sup -1} whose intensities are unambiguously related to gamma delivered dose ranging from 400 kGy to 2750 kGy. (author)

Methodology of high dose research in medical radiodiagnostic

International Nuclear Information System (INIS)

Barboza, Adriana E.; Martins, Cintia P. de S.

2013-01-01

This work has as main purpose to study occupational exposure in diagnostic radiology in medical cases of high doses recorded in 2011 at the national level . These doses were recorded by monitoring individual of the occupationally exposed individuals (OEI's). This monitoring of the doses received by ionizing radiation has as main objective to ensure that the principle of dose limitation is respected. In this study it were evaluated doses of 372 OEI's radiology in different Brazilian states. Doses were extracted from the database of Sector Management Doses of the Institute for Radioprotection and Dosimetry - IRD/CNEN-RJ, Brazil. The information from the database provide reports of doses from several states, which allows to quantify statistically, showing those with the highest doses in four areas: dose greater than or equal to 20 mSv apron and chest and dose greater than or equal to 100 mSv apron and chest. The identification of these states allows the respective Sanitary Surveillance (VISA), be aware of the events and make plans to reduce them. This study clarified the required procedures when there is a record of high dose emphasizing the importance of using protective radiological equipment, dosimeter and provide a safety environment work by maintaining work equipment. Proposes the ongoing training of professionals, emphasizing the relevance of the concepts of radiation protection and the use of the questionnaire with their investigative systematic sequence, which will allow quickly and efficiently the success the investigations

High-dose preoperative radiation for cancer of the rectum: Impact of radiation dose on patterns of failure and survival

International Nuclear Information System (INIS)

Ahmad, N.R.; Mohiuddin, M.; Marks, G.

1993-01-01

A variety of dose-time schedules are currently used for preoperative radiation therapy of rectal cancer. An analysis of patients treated with high-dose preoperative radiation therapy was undertaken to determine the influence of radiation dose on the patterns of failure, survival, and complications. Two hundred seventy-five patients with localized rectal cancer were treated with high-dose preoperative radiation therapy. One hundred fifty-six patients received 45 Gy (low-dose group). Since 1985, 119 patients with clinically unfavorable cancers were given a higher dose, 55 Gy using a shrinking field technique (high-dose group). All patients underwent curative resection. Median follow-up was 66 months in the low-dose group and 28 months in the high-dose group. Patterns of failure, survival, and complications were analyzed as a function of radiation dose. Fourteen percent of the total group developed a local recurrence; 20% in the low-dose group as compared with 6% in the high-dose group. The actuarial local recurrence rate at 5 years was 20% for the low-dose group and 8% for the high-dose group, and approached statistical significance with p = .057. For tethered/fixed tumors the actuarial local recurrence rates at 5 years were 28% and 9%, respectively, with p = .05. Similarly, for low-lying tumors (less than 6 cm from the anorectal junction) the rates were 24% and 9%, respectively, with p = .04. The actuarial rate of distant metastasis was 28% in the low-dose group and 20% in the high-dose group and was not significantly different. Overall actuarial 5-year survival for the total group of patients was 66%. No significant difference in survival was observed between the two groups, despite the higher proportion of unfavorable cancers in the high-dose group. The incidence of complications was 2%, equally distributed between the two groups. High-dose preoperative radiation therapy for rectal cancer results in excellent local control rates. 27 refs., 2 figs., 8 tabs

Acute renal failure in high dose carboplatin chemotherapy

NARCIS (Netherlands)

Frenkel, J.; Kool, G.; de Kraker, J.

1995-01-01

Carboplatin has been reported to cause acute renal failure when administered in high doses to adult patients. We report a 4 1/2-year-old girl who was treated with high-dose carboplatin for metastatic parameningeal embryonal rhabdomyosarcoma. Acute renal failure developed followed by a slow partial

Dose intercomparison studies for standardization of high-dose dosimetry in Viet Nam

International Nuclear Information System (INIS)

Mai Hoang Hoa; Duong Nguyen Dinh; Kojima, T.

1999-01-01

The Irradiation Center of the Vietnam Atomic Energy Commission (IC-VAEC) is planning to establish a traceability system for high-dose dosimetry and to provide high-dose standards as a secondary standard dosimetry laboratory (SSDL) level in Vietnam. For countries which do not have a standard dosimetry laboratory, the participation in the International Dose Assurance Service (IDAS) operated by the International Atomic Energy Agency (IAEA) is the most common means to verify own dosimetry performance with a certain uncertainty. This is, however, only one-direction dose intercomparison with evaluation by IAEA including unknown parameter at participant laboratories. The SSDL level laboratory should have traceability as well as compatibility, ability to evaluate uncertainties of its own dosimetry performance by itself In the present paper, we reviewed our dosimetry performance through two-way dose intercomparison studies and self-evaluation of uncertainty in our dosimetry procedure. The performance of silver dichromate dosimeter as reference transfer dosimeter in IC-VAEC was studied through two-way blind dose intercomparison experiments between the IC-VAEC and JAERI. As another channel of dose intercomparison with IAEA, alanine dosimeters issued by IDAS were simultaneously irradiated with the IC-VAEC dichromate dosimeters at IC-VAEC and analyzed by IAEA. Dose intercomparison between IC-VAEC and JAERI results into a good agreement (better than ±2.5%), and IDAS results also show similar agreement within ±3.0%. The uncertainty was self-estimated on the basis of the JAERI alanine dosimetry, and a preliminary value of about 1.86% at a 68% confidence level is established. The results from these intercomparisons and our estimation of the uncertainty are consistent. We hope that our experience is valuable to other countries which do not have dosimetry standard laboratories and/or are planning to establish them. (author)

Maintenance management for nuclear power plant 'Integrated valve maintenance'

International Nuclear Information System (INIS)

Gerner, P.; Zanner, G.

2001-01-01

The deregulation of Europe's power market does force many utilities, and especially nuclear power plant operators, to introduce extensive cost-cutting measures in order to be able to compete within this new environment. The optimization of plant outages provides considerable potential for raising plant availability but can also lower operating costs by reducing e.g. expenditure on maintenance. Siemens Nuclear Power GmbH, in cooperation with plant operators, is currently implementing new and improved service concepts which can have a major effect on the way in which maintenance will be performed in the future. Innovative service packages for maintenance in nuclear power plants are available which can be used to perform a time- and cost-effective maintenance. The concepts encompass optimization of the overall sequence from planning in advance to the individual measures including reduction of the scope of maintenance activities, identification of cost cutting potential and bundling of maintenance activities. The main features of these maintenance activities are illustrated here using the examples of outage planning and integrated valve maintenance. In nuclear power plants approx. 5000 valves are periodically preventively, condition-based or breakdown-based maintained. Because of this large number of valves to be maintained a high potential of improvements and cost reductions can be achieved by performing an optimized, cost-effective maintenance based on innovative methods and tools. Siemens Nuclear Power GmbH has developed and qualified such tools which allow to reduce service costs while maintaining high standards of safety and availability. By changing from preventive to predictive (condition-based) maintenance - the number of valves to be maintained may be reduced considerably. The predictive maintenance is based on the Siemens Nuclear Power GmbH diagnostic and evaluation method (ADAM). ADAM is used to monitor the operability of valves by analytical verification of

High-dose contrast-enhanced MRI in multiple sclerosis

International Nuclear Information System (INIS)

Koudriavtseva, T.; Pozzilli, C.; Di Biasi, C.; Iannilli, M.; Trasimeni, G.; Gasperini, C.; Argentino, C.; Gualdi, G.F.

1996-01-01

Contrast-enhanced MRI is effective for assessing disease activity in multiple sclerosis (MS) and may provide an outcome measure for testing the efficacy of treatment in clinical trials. To compare the sensitivity of high-dose gadolinium-HP-DO3A with that of a standard dose of gadolinium-DTPA, we studied 16 patients with relapsing-remitting MS in the acute phase of the disease. Each underwent two MRI examinations within at most 48 h. The initial MRI study was with a standard dose of gadolinium-DTPA (0.1 mmol/kg), and the second one an experimental dose of gadolinium-HP-DO3A (0.3 mmol/kg). No adverse effects were attributed to the contrast media. The high-dose study revealed more enhancing lesions than the standard-dose study (56 vs 38). This difference was found to be more relevant for infratentorial and small lesions. Furthermore, with the higher dose, there was a marked qualitative improvement in the visibility and delineation of the lesions. (orig.). With 4 figs., 2 tabs

High-dose contrast-enhanced MRI in multiple sclerosis

Energy Technology Data Exchange (ETDEWEB)

Koudriavtseva, T. [Department of Neurosciences, University of Rome ``La Sapienza`` Rome (Italy); Pozzilli, C. [Department of Neurosciences, University of Rome ``La Sapienza`` Rome (Italy); Di Biasi, C. [MR Unit, Clinica Medica 1, University of Rome ``La Sapienza``, Rome (Italy); Iannilli, M. [MR Unit, Clinica Medica 1, University of Rome ``La Sapienza``, Rome (Italy); Trasimeni, G. [MR Unit, Clinica Medica 1, University of Rome ``La Sapienza``, Rome (Italy); Gasperini, C. [Department of Neurosciences, University of Rome ``La Sapienza`` Rome (Italy); Argentino, C. [Department of Neurosciences, University of Rome ``La Sapienza`` Rome (Italy); Gualdi, G.F. [MR Unit, Clinica Medica 1, University of Rome ``La Sapienza``, Rome (Italy)

1996-05-01

Contrast-enhanced MRI is effective for assessing disease activity in multiple sclerosis (MS) and may provide an outcome measure for testing the efficacy of treatment in clinical trials. To compare the sensitivity of high-dose gadolinium-HP-DO3A with that of a standard dose of gadolinium-DTPA, we studied 16 patients with relapsing-remitting MS in the acute phase of the disease. Each underwent two MRI examinations within at most 48 h. The initial MRI study was with a standard dose of gadolinium-DTPA (0.1 mmol/kg), and the second one an experimental dose of gadolinium-HP-DO3A (0.3 mmol/kg). No adverse effects were attributed to the contrast media. The high-dose study revealed more enhancing lesions than the standard-dose study (56 vs 38). This difference was found to be more relevant for infratentorial and small lesions. Furthermore, with the higher dose, there was a marked qualitative improvement in the visibility and delineation of the lesions. (orig.). With 4 figs., 2 tabs.

Standardization of high-dose measurement of electron and gamma ray absorbed doses and dose rates

International Nuclear Information System (INIS)

McLaughlin, W.L.

1985-01-01

Intense electron beams and gamma radiation fields are used for sterilizing medical devices, treating municipal wastes, processing industrial goods, controlling parasites and pathogens, and extending the shelf-life of foods. Quality control of such radiation processes depends largely on maintaining measurement quality assurance through sound dosimetry procedures in the research leading to each process, in the commissioning of that process, and in the routine dose monitoring practices. This affords documentation as to whether satisfactory dose uniformity is maintained throughout the product and throughout the process. Therefore, dosimetry at high doses and dose rates must in many radiation processes be standardized carefully, so that 'dosimetry release' of a product is verified. This standardization is initiated through preliminary dosimetry intercomparison studies such as those sponsored recently by the IAEA. This is followed by establishing periodic exercises in traceability to national or international standards of absorbed dose and dose rate. Traceability is achieved by careful selection of dosimetry methods and proven reference dosimeters capable of giving sufficiently accurate and precise 'transfer' dose assessments: (1) they must be calibrated or have well-established radiation-yield indices; (2) their radiation response characteristics must be reproducible and cover the dose range of interest; (3) they must withstand the rigours of back-and-forth mailing between a central standardizing laboratory and radiation processing facilities, without excessive errors arising due to instabilities, dosimeter batch non-uniformities, and environmental and handling stresses. (author)

Building relationships for better maintenance.

Science.gov (United States)

Lee, Hackman Hon Yin; Scott, David

2009-02-01

Effective management of building maintenance is a vital ingredient in ensuring a high quality built environment for any building's occupiers. However, maintenance is not high on the list of priorities for most organisations. Communication between top management personnel looking at maintenance issues from a strategic standpoint and maintenance staff considering them at an operational level is often not as good as it should be. When planning maintenance activities maintenance personnel often draw too heavily on their technical experience and expertise without taking sufficient account of wider organisational objectives or consulting effectively with top management. Senior managers also regularly complain about lack of managerial input from maintenance departments. Such barriers contribute to communication difficulties between top management at a strategic level and maintenance personnel at an operational level. Identifying where the key differences lie in senior managers' and maintenance personnel's viewpoints on maintenance strategy can prove invaluable in achieving some convergence of opinions and optimising the efficiency of the overall building maintenance process.

A Phase I Trial of High-Dose Lenalidomide and Melphalan as Conditioning for Autologous Stem Cell Transplantation in Relapsed or Refractory Multiple Myeloma.

Science.gov (United States)

Mark, Tomer M; Guarneri, Danielle; Forsberg, Peter; Rossi, Adriana; Pearse, Roger; Perry, Arthur; Pekle, Karen; Tegnestam, Linda; Greenberg, June; Shore, Tsiporah; Gergis, Usama; Mayer, Sebastian; Van Besien, Koen; Ely, Scott; Jayabalan, David; Sherbenou, Daniel; Coleman, Morton; Niesvizky, Ruben

2017-06-01

Autologous stem cell transplantation (ASCT) conditioned with high-dose chemotherapy has long been established as the standard of care for eligible patients with newly diagnosed multiple myeloma. Despite recent therapeutic advances, high-dose melphalan (HDM) remains the chemotherapy regimen of choice in this setting. Lenalidomide (LEN) in combination with low-dose dexamethasone is recognized as a standard of care for patients with relapsed or refractory multiple myeloma (RRMM), and there is growing support for the administration of LEN as maintenance therapy post-ASCT. In view of the above, the present phase I clinical trial was designed to evaluate the safety and tolerability of high-dose LEN (HDLEN) in patients with RRMM, and to determine the maximum tolerated dose of HDLEN when added to HDM before ASCT. Despite administering HDLEN at doses of up to 350 mg/day, the maximum tolerated dose could not be determined, owing to an insufficient number of dose-limiting toxicities in the 21 patients enrolled in the trial. Conditioning with HDLEN plus HDM was associated with a favorable tolerability profile. Adverse events following ASCT were as expected with HDM. Median progression-free and overall survival were 10 months and 22 months, respectively, in this population of heavily pretreated patients. Our findings suggest that HDLEN in combination with HDM may offer significant potential as a conditioning regimen before ASCT in patients with RRMM. These preliminary findings are now being evaluated further in an ongoing phase II clinical trial. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Update on pediatric resuscitation drugs: high dose, low dose, or no dose at all.

Science.gov (United States)

Sorrentino, Annalise

2005-04-01

Pediatric resuscitation has been a topic of discussion for years. It is difficult to keep abreast of changing recommendations, especially for busy pediatricians who do not regularly use these skills. This review will focus on the most recent guidelines for resuscitation drugs. Three specific questions will be discussed: standard dose versus high-dose epinephrine, amiodarone use, and the future of vasopressin in pediatric resuscitation. The issue of using high-dose epinephrine for cardiopulmonary resuscitation refractory to standard dose epinephrine has been a topic of debate for many years. Recently, a prospective, double-blinded study was performed to help settle the debate. These results will be reviewed and compared with previous studies. Amiodarone is a medication that was added to the pediatric resuscitation algorithms with the most recent recommendations from the American Heart Association in 2000. Its use and safety will also be discussed. Another topic that is resurfacing in resuscitation is the use of vasopressin. Its mechanism and comparisons to other agents will be highlighted, although its use in the pediatric patient has not been thoroughly studied. Pediatric resuscitation is a constantly evolving subject that is on the mind of anyone taking care of sick children. Clinicians are continually searching for the most effective methods to resuscitate children in terms of short- and long-term outcomes. It is important to be familiar with not only the agents being used but also the optimal way to use them.

Traditional clinical risk factors predict clopidogrel hypo-responsiveness in unselected patients undergoing non-emergent percutaneous coronary intervention

DEFF Research Database (Denmark)

Ratcovich, Hanna; Holmvang, Lene; Johansson, Pär Inge

2016-01-01

patients with HPR and LPR. Nine hundred and twenty-three consecutive patients undergoing non-emergent PCI were enrolled. Platelet reactivity (PR) was determined using Multiplate assays. Patients were grouped into quintiles based on their PR values. Upper and lower quintiles defined HPR and LPR......, respectively, whereas quintiles 2-4 defined normal responders. All patients were assigned PREDICT score points in clinical categories (age > 65, reduced left ventricular function, reduced kidney function, acute coronary syndrome (ACS) and diabetes). We found an association between the cumulative number...... of PREDICT score variables and the incidence of HPR for clopidogrel (HPR (ADP)) (p 

Lean Maintenance Applied to Improve Maintenance Efficiency in Thermoelectric Power Plants

OpenAIRE

Orlando Duran; Andrea Capaldo; Paulo Andrés Duran Acevedo

2017-01-01

Thermoelectric power plants consist of a set of critical equipment that require high levels of availability and reliability. Due to this, maintenance of these physical assets is gaining momentum in industry. Maintenance is considered as an activity that contributes to improving the availability, efficiency and productivity of each piece of equipment. Several techniques have been used to achieve greater efficiencies in maintenance, among which we can find the lean maintenance philosophy. Despi...

Chromatographic determination of clopidogrel bisulfate; detection and quantification of counterfeit Plavix® tablets

Directory of Open Access Journals (Sweden)

Mona E. ElTantawy

2014-06-01

Full Text Available Counterfeiting of pharmaceutical products is a global problem. Upon using quality-ensuring methods of international pharmacopoeias, additional impurities and the low content of the active pharmaceutical ingredients were detected. In this paper, two chromatographic HPLC and TLC-densitometric methods were proposed as fast and reliable methods for detection and quantitation of counterfeit Plavix® tablets. These tablets were chemically counterfeited by aspirin, its degradate salicylic acid and metronidazole which were separated, besides the active ingredient clopidogrel bisulfate, by the proposed methods. Also, counterfeit was in packaging, strips and tablets’ color and these could be seen by visual inspection compared to original drug. The proposed methods can easily differentiate genuine from counterfeited tablets without need of prior separation. The proposed methods were validated according to ICH guidelines and applied to eleven batches, also were compared statistically with the reported one.

Development of maintenance equipment for nuclear material fabrication equipment in a highly active hot cell

International Nuclear Information System (INIS)

Park, J. J.; Yang, M. S.; Kim, K. H. and others

2000-09-01

This report presents the development of a maintenance system for a highly contaminated nuclear material handling equipment at a hot-cell. This maintenance system has mainly three subsystems - a gamma-radiation measurement module for detecting a gamma-radiation level and identifying its distribution in-situ, a dry-type decontamination device for cleaning up contaminated particles, and a maintenance chamber for isolating contaminated equipment. The mechanical design considerations, controller, capabilities and remote operation and manipulation of the maintenance system are described. Such subsystems developed were installed and tested in the IMEF (Irradiated Material Examination Facility) M6 hot-cell after mock-up tests and performed their specific tasks successfully

Development of maintenance equipment for nuclear material fabrication equipment in a highly active hot cell

Energy Technology Data Exchange (ETDEWEB)

Park, J. J.; Yang, M. S.; Kim, K. H. and others

2000-09-01

This report presents the development of a maintenance system for a highly contaminated nuclear material handling equipment at a hot-cell. This maintenance system has mainly three subsystems - a gamma-radiation measurement module for detecting a gamma-radiation level and identifying its distribution in-situ, a dry-type decontamination device for cleaning up contaminated particles, and a maintenance chamber for isolating contaminated equipment. The mechanical design considerations, controller, capabilities and remote operation and manipulation of the maintenance system are described. Such subsystems developed were installed and tested in the IMEF (Irradiated Material Examination Facility) M6 hot-cell after mock-up tests and performed their specific tasks successfully.

Study of distribution of doses in maintenance operations and interventions in restricted areas of IPEN's radiopharmacy center, Brazil; Estudo da distribuicao de doses em operacoes de manutencao e intervencao em areas restritas no Centro de Radiofarmacia do IPEN

Energy Technology Data Exchange (ETDEWEB)

Machado, Jessica S.; Souza, Daiane C.; Rodrigues Junior, Orlando; Gerulis, Eduardo; Todo, Alberto S., E-mail: jsmachado@ipen.br, E-mail: dcsouza@ipen.br, E-mail: rodrijr@ipen.br, E-mail: egerulis@ipen.br, E-mail: astodo@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (lPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2013-07-01

This research was developed at the Radiopharmacy Center of the Nuclear and Energy Research Institute - IPEN/CNEN/SP, Brazil, that performs the production of radiopharmaceuticals with isotopes of the {sup 131}I, {sup 123}I, {sup 201}Tl, {sup 67}Ga, {sup 18}F and {sup 99}Mo for use in nuclear medicine. The radioisotopes are produced on an industrial scale and the installation was designed to meet radiation safety standards and quality control requirements. To ensure the production, there are skilled professionals who perform the tasks of maintenance of the equipment and instruments, installed in the cells of processing of radiopharmaceuticals, without which it is not possible to conduct the work with safety and quality. This study was done a survey called Survey of Variables, based on the maintenance operations and interventions in restricted areas of the Centre of Radiopharmacy and in the survey of the distribution of doses in these tasks, carried out during the period from 2005 to 2011. This research aims to identify and determine the main variables that have an impact on the worker's dose. The results are presented for the Occupationally Exposed Individual variable, variable operation, variable area/Cell, task and Feature variable and variable duration of operation, depending on the Dose variable. It is intended in this way to contribute to improvements in operations in restricted areas that may result in lower individual doses without causing significant changes in the routine of work.

Retrospective analysis of dose delivery in intra-operative high dose rate brachytherapy

International Nuclear Information System (INIS)

Oh, M.; Avadhani, J.S.; Malhotra, H.K.; Cunningham, B.; Tripp, P.; Jaggernauth, W.; Podgorsak, M.B.

2007-01-01

Background. This study was performed to quantify the inaccuracy in clinical dose delivery due to the incomplete scatter conditions inherent in intra-operative high dose rate (IOHDR) brachytherapy. Methods. Treatment plans of 10 patients previously treated in our facility, which had irregular shapes of treated areas, were used. Treatment geometries reflecting each clinical case were simulated using a phantom assembly with no added build-up on top of the applicator. The treatment planning geometry (full scatter surrounding the applicator) was subsequently simulated for each case by adding bolus on top of the applicator. Results. For geometries representing the clinical IOHDR incomplete scatter environment, measured doses at the 5 mm and 10 mm prescription depths were lower than the corresponding prescribed doses by about 7.7% and 11.1%, respectively. Also, for the two prescription methods, an analysis of the measured dose distributions and their corresponding treatment plans showed average decreases of 1.2 mm and 2.2 mm in depth of prescription dose, respectively. Conclusions. Dosimetric calculations with the assumption of an infinite scatter environment around the applicator and target volume have shown to result in dose delivery errors that significantly decrease the prescription depth for IOHDR treatment.(author)

Fertility of Tall Girls Treated with High-Dose Estrogen, a Dose-Response Relationship

NARCIS (Netherlands)

Hendriks, A. E. J.; Drop, S. L. S.; Laven, J. S. E.; Boot, A. M.

Context: High-dose estrogen treatment to reduce final height of tall girls increases their risk for infertility in later life. Objective: The aim was to study the effect of estrogen dose on fertility outcome of these women. Design/Setting: We conducted a retrospective cohort study of university

Influence of microenvironment pH, humidity, and temperature on the stability of polymorphic and amorphous forms of clopidogrel bisulfate

DEFF Research Database (Denmark)

Raijada, Dhara K; Singh, Saranjit; Bansal, Arvind K

2010-01-01

The effect of microenvironment pH, humidity, and temperature was evaluated on the stability of polymorphic and amorphous forms of clopidogrel bisulfate, when present alone or in combinations. Oxalic acid and sodium carbonate were used as solid stressors to create acidic and alkaline p...... more degradation than the individual forms above critical relative humidity (85% RH). Similar higher degradation was observed between 75% RH and 85% RH in case of acid-stressed samples. In alkaline microenvironment, all the samples showed identical decomposition attributed to conversion of bisulfate...

High-dose thiamine therapy counters dyslipidemia and advanced glycation of plasma protein in streptozotocin-induced diabetic rats.

Science.gov (United States)

Karachalias, Nikolaos; Babaei-Jadidi, Roya; Kupich, Christian; Ahmed, Naila; Thornalley, Paul J

2005-06-01

The streptozotocin-induced (STZ) diabetic rat experimental model of diabetes on insulin maintenance therapy exhibits dyslipidemia, mild thiamine deficiency, and increased plasma protein advanced glycation end products (AGEs). The reversal of thiamine deficiency by high-dose thiamine and S-benzoylthiamine monophosphate (benfotiamine) prevented the development of incipient nephropathy. Recently, we reported that high-dose thiamine (but not benfotiamine) countered diabetic dyslipidemia. To understand further the differences between the effects of thiamine and benfotiamine therapy, we quantified the levels of the AGEs in plasma protein. We found hydroimidazolone AGE residues derived from glyoxal and methylglyoxal, G-H1 and MG-H1, were increased 115% and 68% in STZ diabetic rats, with respect to normal controls, and were normalized by both thiamine and benfotiamine; whereas N-carboxymethyl-lysine (CML) and N-carboxyethyl-lysine (CEL) residues were increased 74% and 118% in STZ diabetic rats and were normalized by thiamine only. The lack of effect of benfotiamine on plasma CML and CEL residue concentrations suggests there may be important precursors of plasma protein CML and CEL residues other than glyoxal and methylglyoxal. These are probably lipid-derived aldehydes.

Radiation effects of high and low doses

International Nuclear Information System (INIS)

El-Naggar, A.M.

1998-01-01

The extensive proliferation of the uses and applications of atomic and nuclear energy resulted in possible repercussions on human health. The prominent features of the health hazards that may be incurred after exposure to high and low radiation doses are discussed. The physical and biological factors involved in the sequential development of radiation health effects and the different cellular responses to radiation injury are considered. The main criteria and features of radiation effects of high and low doses are comprehensively outlined

High daily doses of benzodiazepines among Quebec seniors: prevalence and correlates

Directory of Open Access Journals (Sweden)

Moride Yola

2001-11-01

Full Text Available Abstract Background Use of high daily doses of benzodiazepines is generally contraindicated for seniors. While both patient and physician factors may influence the use of high daily doses, previous research on the effect of patient factors has been extremely limited. The objectives of this study were to determine the one year prevalence of use of high daily doses of benzodiazepines, and examine physician and patient correlates of such use among Quebec community-dwelling seniors. Methods Patient information for 1423 community-dwelling Quebec seniors who participated in the Canadian Study of Health and Aging was linked to provincial health insurance administrative data bases containing detailed information on prescriptions received and prescribers. Results The standardized one year period prevalence of use of high daily doses of benzodiazepines was 7.9%. Use of high daily doses was more frequent among younger seniors and those who had reported anxiety during the previous year. Patients without cognitive impairment were more likely to receive high dose prescriptions from general practitioners, while those with cognitive impairment were more likely to receive high dose prescriptions from specialists. Conclusion High dose prescribing appears to be related to both patient and physician factors.

Proximity correction of high-dosed frame with PROXECCO

Science.gov (United States)

Eisenmann, Hans; Waas, Thomas; Hartmann, Hans

1994-05-01

Usefulness of electron beam lithography is strongly related to the efficiency and quality of methods used for proximity correction. This paper addresses the above issue by proposing an extension to the new proximity correction program PROXECCO. The combination of a framing step with PROXECCO produces a pattern with a very high edge accuracy and still allows usage of the fast correction procedure. Making a frame with a higher dose imitates a fine resolution correction where the coarse part is disregarded. So after handling the high resolution effect by means of framing, an additional coarse correction is still needed. Higher doses have a higher contribution to the proximity effect. This additional proximity effect is taken into account with the help of the multi-dose input of PROXECCO. The dose of the frame is variable, depending on the deposited energy coming from backscattering of the proximity. Simulation proves the very high edge accuracy of the applied method.

Clopidogrel-Proton Pump Inhibitor Drug-Drug Interaction and Risk of Adverse Clinical Outcomes Among PCI-Treated ACS Patients: A Meta-analysis.

Science.gov (United States)

Serbin, Michael A; Guzauskas, Gregory F; Veenstra, David L

2016-08-01

Uncertainty regarding clopidogrel effectiveness attenuation because of a drug-drug interaction with proton pump inhibitors (PPI) has led to conflicting guidelines on concomitant therapy. In particular, the effect of this interaction in patients who undergo a percutaneous coronary intervention (PCI), a population known to have increased risk of adverse cardiovascular events, has not been systematically evaluated. To synthesize the evidence of the effect of clopidogrel-PPI drug interaction on adverse cardiovascular outcomes in a PCI patient population. We conducted a systematic literature review for studies reporting clinical outcomes in patients who underwent a PCI and were initiated on clopidogrel with or without a PPI. Studies were included in the analysis if they reported at least 1 of the clinical outcomes of interest (major adverse cardiovascular event [MACE], cardiovascular death, all-cause death, myocardial infarction, stroke, stent thrombosis, and bleed events). We excluded studies that were not exclusive to PCI patients or had no PCI subgroup analysis and/or did not report at least a 6-month follow-up. Statistical and clinical heterogeneity were evaluated and HRs and 95% CIs for adverse clinical events were pooled using the DerSimonian and Laird random-effects meta-analysis method. We identified 12 studies comprising 50,277 PCI patients that met our inclusion and exclusion criteria. Our analysis included retrospective analyses of randomized controlled trials (2), health registries (3), claims databases (2), and institutional records (5); no prospective studies of PCI patients were identified. On average, patients were in their mid-60s, male, and had an array of comorbidities, including hyperlipidemia, diabetes, hypertension, and smoking history. Concomitant therapy following PCI resulted in statistically significant increases in composite MACE (HR = 1.28; 95% CI = 1.24-1.32), myocardial infarction (HR = 1.51; 95% CI = 1.40-1.62), and stroke (HR = 1.46; 95

Impact of catheter reconstruction error on dose distribution in high dose rate intracavitary brachytherapy and evaluation of OAR doses

International Nuclear Information System (INIS)

Thaper, Deepak; Shukla, Arvind; Rathore, Narendra; Oinam, Arun S.

2016-01-01

In high dose rate brachytherapy (HDR-B), current catheter reconstruction protocols are relatively slow and error prone. The purpose of this study is to evaluate the impact of catheter reconstruction error on dose distribution in CT based intracavitary brachytherapy planning and evaluation of its effect on organ at risk (OAR) like bladder, rectum and sigmoid and target volume High risk clinical target volume (HR-CTV)

High-temperature absorbed dose measurements in the megagray range

International Nuclear Information System (INIS)

Balian, P.; Ardonceau, J.; Zuppiroli, L.

1988-01-01

Organic conductors of the tetraselenotetracene family have been tested as ''high-temperature'' absorbed dose dosimeters. They were heated up to 120 0 C and irradiated at this temperature with 1-MeV electrons in order to simulate, in a short time, a much longer γ-ray irradiation. The electric resistance increase of the crystal can be considered a good measurement of the absorbed dose in the range 10 6 Gy to a few 10 8 Gy and presumably one order of magnitude more. This dosimeter also permits on-line (in-situ) measurements of the absorbed dose without removing the sensor from the irradiation site. The respective advantages of organic and inorganic dosimeters at these temperature and dose ranges are also discussed. In this connection, we outline new, but negative, results concerning the possible use of silica as a high-temperature, high-dose dosimeter. (author)

High-dose MeV electron irradiation of Si-SiO2 structures implanted with high doses Si+

Science.gov (United States)

Kaschieva, S.; Angelov, Ch; Dmitriev, S. N.

2018-03-01

The influence was studied of 22-MeV electron irradiation on Si-SiO2 structures implanted with high-fluence Si+ ions. Our earlier works demonstrated that Si redistribution is observed in Si+-ion-implanted Si-SiO2 structures (after MeV electron irradiation) only in the case when ion implantation is carried out with a higher fluence (1016 cm-2). We focused our attention on the interaction of high-dose MeV electron irradiation (6.0×1016 cm-2) with n-Si-SiO2 structures implanted with Si+ ions (fluence 5.4×1016 cm-2 of the same order magnitude). The redistribution of both oxygen and silicon atoms in the implanted Si-SiO2 samples after MeV electron irradiation was studied by Rutherford back-scattering (RBS) spectroscopy in combination with a channeling technique (RBS/C). Our results demonstrated that the redistribution of oxygen and silicon atoms in the implanted samples reaches saturation after these high doses of MeV electron irradiation. The transformation of amorphous SiO2 surface into crystalline Si nanostructures (after MeV electron irradiation) was evidenced by atomic force microscopy (AFM). Silicon nanocrystals are formed on the SiO2 surface after MeV electron irradiation. The shape and number of the Si nanocrystals on the SiO2 surface depend on the MeV electron irradiation, while their size increases with the dose. The mean Si nanocrystals height is 16-20 nm after irradiation with MeV electrons at the dose of 6.0×1016 cm-2.

A novel theory of radiation damage at high doses

International Nuclear Information System (INIS)

Seeger, A.; Stuttgart Univ.

1989-01-01

Deviations of radiation damage (in the case of metals usually monitored by the residual electrical resistivity) from proportionality with the irradiation dose have so far been analysed almost exclusively in terms of extensions of models originally developed for small doses. The present theory considers the opposite limit i.e. the quasi-saturated state. It is argued that at high doses the Lueck-Sizmann effect may result in a self-organization of clusters of vacancies and self-interstitials, forming a heterogeneous froth. Possible structures of this froth and its effect on the electrical resistivity of metals are discussed. The model is shown to account for the dependence of the ''saturation resistivity'' on the nature of the irradiation as well as for several other hitherto poorly explained observations. Among them are the electrical-resistivity variation induced by high-dose irradiation with heavy ions, the amorphization of certain alloys by high-dose electron irradiation, and the occurrence of ordered arrays of stacking-fault tetrahedra after in-situ irradiations in high-voltage electron microscopes. (author)

Recommendations to designers aimed at minimizing radiation dose incurred in operation, maintenance, inspection and repair of light-water reactors

International Nuclear Information System (INIS)

1978-01-01

In the framework of the exchange of experience between nuclear power plant operators organized by the services of the Commission of the European Communities an ad-hoc working party elaborated recommendations particularly directed to those concerned with design of light water reactor plants. The necessary design measures which should be followed to minimize radiation dose incurred in operation, maintenance, inspection and repair of such reactors are listed. The recommendations are based on recent views expressed by operating utilities within the Community. It is intended to revise these recommendations at suitable intervals in order to make use of the most recent experience and to keep the report up to date with the actual state of art in nuclear technology

Radiobiological aspects of continuous low dose-rate irradiation and fractionated high dose-rate irradiation

International Nuclear Information System (INIS)

Turesson, I.

1990-01-01

The biological effects of continuous low dose-rate irradiation and fractionated high dose-rate irradiation in interstitial and intracavitary radiotherapy and total body irradiation are discussed in terms of dose-rate fractionation sensitivity for various tissues. A scaling between dose-rate and fraction size was established for acute and late normal-tissue effects which can serve as a guideline for local treatment in the range of dose rates between 0.02 and 0.005 Gy/min and fraction sizes between 8.5 and 2.5 Gy. This is valid provided cell-cycle progression and proliferation can be ignored. Assuming that the acute and late tissue responses are characterized by α/β values of about 10 and 3 Gy and a mono-exponential repair half-time of about 3 h, the same total doses given with either of the two methods are approximately equivalent. The equivalence for acute and late non-hemopoietic normal tissue damage is 0.02 Gy/min and 8.5 Gy per fraction; 0.01 Gy/min and 5.5 Gy per fraction; and 0.005 Gy/min and 2.5Gy per fraction. A very low dose rate, below 0.005 Gy/min, is thus necessary to simulate high dose-rate radiotherapy with fraction sizes of about 2Gy. The scaling factor is, however, dependent on the repair half-time of the tissue. A review of published data on dose-rate effects for normal tissue response showed a significantly stronger dose-rate dependence for late than for acute effects below 0.02 Gy/min. There was no significant difference in dose-rate dependence between various acute non-hemopoietic effects or between various late effects. The consistent dose-rate dependence, which justifies the use of a general scaling factor between fraction size and dose rate, contrasts with the wide range of values for repair half-time calculated for various normal-tissue effects. This indicates that the model currently used for repair kinetics is not satisfactory. There are also few experimental data in the clinical dose-rate range, below 0.02 Gy/min. It is therefore

Statistical behavior of high doses in medical radiodiagnosis; Comportamento estatistico das altas doses em radiodiagnostico medico

Energy Technology Data Exchange (ETDEWEB)

Barboza, Adriana Elisa, E-mail: adrianaebarboza@gmail.com, E-mail: elisa@bolsista.ird.gov.br [Instituto de Radioprotecao e Dosimetria, (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

2014-07-01

This work has as main purpose statistically estimating occupational exposure in medical diagnostic radiology in cases of high doses recorded in 2011 at national level. For statistical survey of this study, doses of 372 IOE's diagnostic radiology in different Brazilian states were evaluated. Data were extracted from the work of monograph (Research Methodology Of High Doses In Medical Radiodiagnostic) that contains the database's information Sector Management doses of IRD/CNEN-RJ, Brazil. The identification of these states allows the Sanitary Surveillance (VISA) responsible, becomes aware of events and work with programs to reduce these events. (author)

The effect of a low-fat, high-protein or high-carbohydrate ad libitum diet on weight loss maintenance and metabolic risk factors.

Science.gov (United States)

Claessens, M; van Baak, M A; Monsheimer, S; Saris, W H M

2009-03-01

High-protein (HP) diets are often advocated for weight reduction and weight loss maintenance. The aim was to compare the effect of low-fat, high-carbohydrate (HC) and low-fat, HP ad libitum diets on weight maintenance after weight loss induced by a very low-calorie diet, and on metabolic and cardiovascular risk factors in healthy obese subjects. Forty-eight subjects completed the study that consisted of an energy restriction period of 5-6 weeks followed by a weight maintenance period of 12 weeks. During weight maintenance subjects received maltodextrin (HC group) or protein (HP group) (casein (HPC subgroup) or whey (HPW subgroup)) supplements (2 x 25 g per day), respectively and consumed a low-fat diet. Subjects in the HP diet group showed significantly better weight maintenance after weight loss (2.3 kg difference, P=0.04) and fat mass reduction (2.2 kg difference, P=0.02) than subjects in the HC group. Triglyceride (0.6 mM difference, P=0.01) and glucagon (9.6 pg ml(-1) difference, P=0.02) concentrations increased more in the HC diet group, while glucose (0.3 mM difference, P=0.02) concentration increased more in the HP diet group. Changes in total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, insulin, HOMAir index, HbA1c, leptin and adiponectin concentrations did not differ between the diets. No differences were found between the casein- or whey-supplemented HP groups. These results show that low-fat, high-casein or whey protein weight maintenance diets are more effective for weight control than low-fat, HC diets and do not adversely affect metabolic and cardiovascular risk factors in weight-reduced moderately obese subjects without metabolic or cardiovascular complications.

Design of casks: incorporating operational feedback from maintenance

Energy Technology Data Exchange (ETDEWEB)

Bimet, F.; Hartenstein, M. [COGEMA Logistics, Saint Quentin (France)

2004-07-01

Casks are designed to conform to regulations and to client specifications. Essential areas such as easy operation, low costs of maintenance, low operation and maintenance doses, limited waste, are not explicitly covered. Notwithstanding, COGEMA LOGISTICS uses all feedback available, so that casks are designed to be easy, safe and economical to operate and maintain. Maintenance is an activity where you do spot items that old-time designers could have made better, and things that users should not have done. Thanks to quality assurance, there are a number of data available, waiting to be collected and exploited; they have to be identified, located, retrieved, and analysed. Using information such as wear, damage, use of spare parts, access problems helps to make casks ever better. It leads to more efficient concepts, and to upgrades on existing designs; it also allows to integrate environmental considerations, inter alia in the choice of materials and in maintenance methods. It is necessary for the designer to interact with the users, the cask owners, the maintenance providers, in order to gather all relevant information and events. This is made easier when all these actors are ''under one roof'', or have very close ties. This paper presents COGEMA LOGISTICS methods for collecting and analysing all these experiences waiting to be used. It explains our process for analysing data, preparing yearly reports that are made available to our designers. It describes how each new design is subject to a maintainability study, using this feedback, so that the cask safety is always assured, that radiological doses are kept to a minimum, and that operating and maintenance costs will remain as low as possible.

Design of casks: incorporating operational feedback from maintenance

International Nuclear Information System (INIS)

Bimet, F.; Hartenstein, M.

2004-01-01

Casks are designed to conform to regulations and to client specifications. Essential areas such as easy operation, low costs of maintenance, low operation and maintenance doses, limited waste, are not explicitly covered. Notwithstanding, COGEMA LOGISTICS uses all feedback available, so that casks are designed to be easy, safe and economical to operate and maintain. Maintenance is an activity where you do spot items that old-time designers could have made better, and things that users should not have done. Thanks to quality assurance, there are a number of data available, waiting to be collected and exploited; they have to be identified, located, retrieved, and analysed. Using information such as wear, damage, use of spare parts, access problems helps to make casks ever better. It leads to more efficient concepts, and to upgrades on existing designs; it also allows to integrate environmental considerations, inter alia in the choice of materials and in maintenance methods. It is necessary for the designer to interact with the users, the cask owners, the maintenance providers, in order to gather all relevant information and events. This is made easier when all these actors are ''under one roof'', or have very close ties. This paper presents COGEMA LOGISTICS methods for collecting and analysing all these experiences waiting to be used. It explains our process for analysing data, preparing yearly reports that are made available to our designers. It describes how each new design is subject to a maintainability study, using this feedback, so that the cask safety is always assured, that radiological doses are kept to a minimum, and that operating and maintenance costs will remain as low as possible

Maintenance of BWR control rod drive mechanisms

International Nuclear Information System (INIS)

Greene, R.H.

1991-01-01

Control rod drive mechanism (CRDM) replacement and rebuilding is one of the highest dose, most physically demanding, and complicated maintenance activities routinely accomplished by BWR utilities. A recent industry workshop sponsored by the Oak Ridge National Laboratory, which dealt with the effects of CRDM aging, revealed enhancements in maintenance techniques and tooling which have reduced ALARA, improved worker comfort and productivity, and have provided revised guidelines for CRDM changeout selection. Highlights of this workshop and ongoing research on CRDM aging are presented in this paper

Effects of low priming dose irradiation on cell cycle arrest of HepG2 cells caused by high dose irradiation

International Nuclear Information System (INIS)

Xia Jingguang; Jin Xiaodong; Chinese Academy of Sciences, Beijing; Li Wenjian; Wang Jufang; Guo Chuanling; Gao Qingxiang

2005-01-01

Human hepatoma cells hepG2 were irradiated twice by 60 Co γ-rays with a priming dose of 5 cGy and a higher dose of 3 Gy performed 4h or 8h after the low dose irradiation. Effects of the priming dose irradiation on cell cycle arrest caused by high dose were examined with flow cytometry. Cells in G 2 /M phase accumulated temporarily after the 5 cGy irradiation, and proliferation of tumor cells was promoted significantly by the low dose irradiation. After the 3 Gy irradiation, G 2 phase arrest occurred, and S phase delayed temporally. In comparison with 3 kGy irradiation only, the priming dose delivered 4h prior to the high dose irradiation facilitated accumulation of hepG2 cells in G 2 /M phase, whereas the priming dose delivered 8h prior to the high dose irradiation helped the cells to overcome G 2 arrest. It was concluded that effects of the priming dose treatment on cell cycle arrest caused by high dose irradiation were dependent on time interval between the two irradiations. (authors)

A clinical comparison of high dose and low dose of Suxamethonium

Directory of Open Access Journals (Sweden)

RK Yadav

2014-01-01

Full Text Available Background: Suxamethonium having its rapid onset and short duration of action makes this drug unique amongst the neuromuscular blocking drugs described so far. However, use of suxamethonium is associated with a large number of undesirable side effects. Objective: To evaluate clinical effects of high and low dose of suxamethonium and to determine whether lower dose of suxamethonium can be used for any beneficial effects in terms of its various adverse effects e.g. cardiovascular responses, post-operative muscle pains and intraocular pressure. Methods: A total of 100 patients were included in this prospective study. All these patients on preoperative clinical evaluation were assessed to have adequate airway. All the patients were divided in two groups, low dose group (group I and High dose group (group II with 50 patients in each at random. A standard anesthetic technique was adhered to all the patients and following parameters were observed on comparative basis: a. Fasciculation and post operative myalgia. b. Cardiovascular effects, c. Intraocular pressure. Observation: The incidence of post Suxamethonium pain was significantly greater in group II. Increase in heart rate from baseline was significant in both groups. There was no significant difference between the two groups in the diastolic pressure but rise in systolic blood pressure was significant at all assessment times in both groups. This rise from control was statistically significant. Conclusion: Suxamethonium can be used in lower doses (0.5 mg/kg in elective cases without airway compromise. It gives benefits of reduced muscle pains, cardiovascular responses and intraocular hypertension. Journal of College of Medical Sciences-Nepal, 2013, Vol-9, No-2, 1-8 DOI: http://dx.doi.org/10.3126/jcmsn.v9i2.9677

Cumulative high doses of inhaled formoterol have less systemic effects in asthmatic children 6-11 years-old than cumulative high doses of inhaled terbutaline

DEFF Research Database (Denmark)

Kaae, Rikke; Agertoft, Lone; Pedersen, Sören

2004-01-01

OBJECTIVES: To evaluate high dose tolerability and relative systemic dose potency between inhaled clinically equipotent dose increments of formoterol and terbutaline in children. METHODS: Twenty boys and girls (6-11 years-old) with asthma and normal ECGs were studied. Ten doses of formoterol (Oxi...

Dosimetric systems of high dose, dose rate and dose uniformity in food and medical products

International Nuclear Information System (INIS)

Vargas, J.; Vivanco, M.; Castro, E.

2014-08-01

In the Instituto Peruano de Energia Nuclear (IPEN) we use the chemical dosimetry Astm-E-1026 Fricke as a standard dosimetric system of reference and different routine dosimetric systems of high doses, according to the applied doses to obtain the desired effects in the treated products and the doses range determined for each type of dosimeter. Fricke dosimetry is a chemical dosimeter in aqueous solution indicating the absorbed dose by means an increase in absorbance at a specific wavelength. A calibrated spectrophotometer with controlled temperature is used to measure absorbance. The adsorbed dose range should cover from 20 to 400 Gy, the Fricke solution is extremely sensitive to organic impurities, to traces of metal ions, in preparing chemical products of reactive grade must be used and the water purity is very important. Using the referential standard dosimetric system Fricke, was determined to March 5, 2013, using the referential standard dosimetric system Astm-1026 Fricke, were irradiated in triplicate Fricke dosimeters, to 5 irradiation times (20; 30; 40; 50 and 60 seconds) and by linear regression, the dose rate of 5.400648 kGy /h was determined in the central point of the irradiation chamber (irradiator Gamma cell 220 Excel), applying the decay formula, was compared with the obtained results by manufacturers by means the same dosimetric system in the year of its manufacture, being this to the date 5.44691 kGy /h, with an error rate of 0.85. After considering that the dosimetric solution responds to the results, we proceeded to the irradiation of a sample of 200 g of cereal instant food, 2 dosimeters were placed at the lateral ends of the central position to maximum dose and 2 dosimeters in upper and lower ends as minimum dose, they were applied same irradiation times; for statistical analysis, the maximum dose rate was 6.1006 kGy /h and the minimum dose rate of 5.2185 kGy /h; with a dose uniformity of 1.16. In medical material of micro pulverized bone for

EPR design for maintenance

International Nuclear Information System (INIS)

Krugmann, U.

1998-01-01

Preventive maintenance is very important in achieving high plant availability. For the European Pressurized Reactor (EPR) preventive maintenance has been carefully addressed in the design stage. This is particularly necessary because of the traditionally different maintenance strategies employed in France and Germany. This paper emphasizes the following features introduced in the ERP design to minimize the duration of the refueling outage: (1) containment accessibility during power operation; (2) overall plant layout to facilitate inspections and maintenances within the containment; and (3) safety system design for enabling preventive maintenance during power operation. (author)

Accelerated Irradiations for High Dose Microstructures in Fast Reactor Alloys

Energy Technology Data Exchange (ETDEWEB)

Jiao, Zhijie [Univ. of Michigan, Ann Arbor, MI (United States)

2017-03-31

The objective of this project is to determine the extent to which high dose rate, self-ion irradiation can be used as an accelerated irradiation tool to understand microstructure evolution at high doses and temperatures relevant to advanced fast reactors. We will accomplish the goal by evaluating phase stability and swelling of F-M alloys relevant to SFR systems at very high dose by combining experiment and modeling in an effort to obtain a quantitative description of the processes at high and low damage rates.

An analysis of the radiation field characteristics for extremity dose assessment during maintenance periods at nuclear power plants in Korea

International Nuclear Information System (INIS)

Kim, H. G.; Kong, T. Y.

2012-01-01

Workers who maintain the water chambers of steam generators during maintenance periods in nuclear power plants (NPPs) have a higher likelihood of high radiation exposure, even if they are exposed for a short period of time. In particular, it is expected that the hands of workers would receive the highest radiation exposure as a consequence of hand contact with radioactive materials. In this study, a characteristic analysis of inhomogeneous radiation fields for contact operations was conducted using thermoluminescent dosemeters for the whole body and extremities during maintenance periods at Korean NPPs. It was observed that inhomogeneous radiation fields for contact operations at NPPs were dominated by high-energy photons. (authors)

Dose conversion coefficients for high-energy photons, electrons, neutrons and protons

International Nuclear Information System (INIS)

Sakamoto, Yukio

2005-01-01

Dose conversion coefficients for photons, electrons and neutrons based on new ICRP recommendations were cited in the ICRP Publication 74, but the energy ranges of these data were limited and there are no data for high energy radiations produced in accelerator facilities. For the purpose of designing the high intensity proton accelerator facilities at JAERI, the dose evaluation code system of high energy radiations based on the HERMES code was developed and the dose conversion coefficients of effective dose were evaluated for photons, neutrons and protons up to 10 GeV, and electrons up to 100 GeV. The dose conversion coefficients of effective dose equivalent were also evaluated using quality factors to consider the consistency between radiation weighting factors and Q-L relationship. The effective dose conversion coefficients obtained in this work were in good agreement with those recently evaluated by using FLUKA code for photons and electrons with all energies, and neutrons and protons below 500 MeV. There were some discrepancy between two data owing to the difference of cross sections in the nuclear reaction models. The dose conversion coefficients of effective dose equivalents for high energy radiations based on Q-L relation in ICRP Publication 60 were evaluated only in this work. The previous comparison between effective dose and effective dose equivalent made it clear that the radiation weighting factors for high energy neutrons and protons were overestimated and the modification was required. (author)

Evaluation of the dose uniformity for double-plane high dose rate interstitial breast implants with the use of dose reference points and dose non-uniformity ratio

International Nuclear Information System (INIS)

MAjor, T.; Polgar, C.; Somogyi, A.; Nemeth, G.

2000-01-01

This study investigated the influence of dwell time optimizations on dose uniformity characterized by dose values in dose points and dose non-uniformity ratio (DNR) and analyzed which implant parameters have influence on the DNR. Double-plane breast implants with catheters arranged in triangular pattern were used for the calculations. At a typical breast implant, dose values in dose reference points inside the target volume and volumes enclosed by given isodose surfaces were calculated and compared for non-optimized and optimized implants. The same 6-cm treatment length was used for the comparisons. Using different optimizations plots of dose non-uniformity ratio as a function of catheter separation, source step size, number of catheters, length of active sections were drawn and the minimum DNR values were determined. Optimization resulted in less variation in dose values over dose points through the whole volume and in the central plane only compared to the non-optimized case. At implant configurations consisting of seven catheters with 15-mm separation, 5-mm source step size and various active lengths adapted according to the type of optimization, the no optimization, geometrical (volume mode) and dose point (on dose points and geometry) optimization resulted in similar treatment volumes, but an increased high dose volume was observed due to the optimization. The dose non-uniformity ratio always had the minimum at average dose over dose normalization points, defined in the midpoints between the catheters through the implant volume. The minimum value of DNR depended on catheter separation, source step size, active length and number of catheters. The optimization had only a small influence on DNR. In addition to the reference points in the central plane only, dose points positioned in the whole implant volume can be used for evaluating the dose uniformity of interstitial implants. The dose optimization increases not only the dose uniformity within the implant but

Neuroprotective potential of high-dose biotin.

Science.gov (United States)

McCarty, Mark F; DiNicolantonio, James J

2017-11-01

A recent controlled trial has established that high-dose biotin supplementation - 100 mg, three times daily - has a stabilizing effect on progression of multiple sclerosis (MS). Although this effect has been attributed to an optimization of biotin's essential cofactor role in the brain, a case can be made that direct stimulation of soluble guanylate cyclase (sGC) by pharmacological concentrations of biotin plays a key role in this regard. The utility of high-dose biotin in MS might reflect an anti-inflammatory effect of cGMP on the cerebral microvasculature, as well on oligodendrocyte differentiation and on Schwann cell production of neurotrophic factors thought to have potential for managing MS. But biotin's ability to boost cGMP synthesis in the brain may have broader neuroprotective potential. In many types of neurons and neural cells, cGMP exerts neurotrophic-mimetic effects - entailing activation of the PI3K-Akt and Ras-ERK pathways - that promote neuron survival and plasticity. Hippocampal long term potentiation requires nitric oxide synthesis, which in turn promotes an activating phosphorylation of CREB via a pathway involving cGMP and protein kinase G (PKG). In Alzheimer's disease (AD), amyloid beta suppresses this mechanism by inhibiting sGC activity; agents which exert a countervailing effect by boosting cGMP levels tend to restore effective long-term potentiation in rodent models of AD. Moreover, NO/cGMP suppresses amyloid beta production within the brain by inhibiting expression of amyloid precursor protein and BACE1. In conjunction with cGMP's ability to oppose neuron apoptosis, these effects suggest that high-dose biotin might have potential for the prevention and management of AD. cGMP also promotes neurogenesis, and may lessen stroke risk by impeding atherogenesis and hypertrophic remodeling in the cerebral vasculature. The neuroprotective potential of high-dose biotin likely could be boosted by concurrent administration of brain

Lean Maintenance Applied to Improve Maintenance Efficiency in Thermoelectric Power Plants

Directory of Open Access Journals (Sweden)

Orlando Duran

2017-10-01

Full Text Available Thermoelectric power plants consist of a set of critical equipment that require high levels of availability and reliability. Due to this, maintenance of these physical assets is gaining momentum in industry. Maintenance is considered as an activity that contributes to improving the availability, efficiency and productivity of each piece of equipment. Several techniques have been used to achieve greater efficiencies in maintenance, among which we can find the lean maintenance philosophy. Despite the wide diffusion of lean maintenance, there is no structured method that supports the prescription of lean tools applied to the maintenance function. This paper presents the experience gathered in two lean maintenance projects in thermoelectric power plants. The application of lean techniques was based on using a previously developed multicriterial decision making process that uses the Fuzzy Analytic Hierarchy Process (AHP methodology to carry out a diagnosis and prescription tasks. That methodology allowed the prescription of the appropriated lean techniques to resolve the main deficiencies in maintenance function. The results of applying such lean tools show that important results can be obtained, making the maintenance function in thermoelectric power plants more efficient and lean.

Polybutadiene and Styrene-Butadiene rubbers for high-dose dosimetry

Energy Technology Data Exchange (ETDEWEB)

Oliveira, Lucas N. [Instituto Federal de Educacao, Ciencia e Tecnologia de Goias-IFG,Campus Goiania, Goiania -GO (Brazil); Instituto de Pesquisas Energeticas e Nucleares -IPEN, Sao Paulo-SP (Brazil); Vieira, Silvio L. [Instituto de Fisica, Universidade Federal de Goias-UFG, Campus Samambaia, Goiania-GO (Brazil); Schimidt, Fernando [Instituto Federal de Educacao, Ciencia e Tecnologia de Goias-IFG,Campus Inhumas, Inhumas-GO (Brazil); Antonio, Patricia L.; Caldas, Linda V.E. [Instituto de Pesquisas Energeticas e Nucleares -IPEN, Sao Paulo-SP (Brazil)

2015-07-01

Polybutadiene and Styrene-Butadiene are synthetical rubbers used widely for pneumatic tires manufacturing. In this research, the dosimeter characteristics of those rubbers were studied for application in high-dose dosimetry. The rubber samples were irradiated with doses of 10 Gy up to 10 kGy, using a {sup 60}Co Gamma Cell-220 system (dose rate of 1.089 kGy/h) and their readings were taken on a Fourier Transform Infrared Spectroscopy-FTIR system (model Frontier/Perkin Elmer). The ratios of two absorbance peaks were taken for each kind of rubber spectrum, Polybutadiene (1306/1130 cm{sup -1}) and Styrene-Butadiene (1449/1306 cm{sup -1}). The ratio calculated was used as the response to the irradiation, and is not uniform across the sample. From the results, it can be concluded for both rubbers: a) the dose-response curves may be useful for high-dose dosimetry (greater than 250 Gy); b) their response for reproducibility presented standard deviations lower than 2.5%; c) the relative sensitivity was higher for Styrene-Butadiene (1.86 kGy{sup -1}) than for Polybutadiene (1.81 kGy{sup -1}), d) for doses of 10 kGy to 200 kGy, there was no variation in the dosimetric response. Both types of rubber samples showed usefulness as high-dose dosimeters. (authors)

Assessments for high dose radionuclide therapy treatment planning

International Nuclear Information System (INIS)

Fisher, D.R.

2003-01-01

Advances in the biotechnology of cell specific targeting of cancer and the increased number of clinical trials involving treatment of cancer patients with radiolabelled antibodies, peptides, and similar delivery vehicles have led to an increase in the number of high dose radionuclide therapy procedures. Optimised radionuclide therapy for cancer treatment is based on the concept of absorbed dose to the dose limiting normal organ or tissue. The limiting normal tissue is often the red marrow, but it may sometimes be the lungs, liver, intestinal tract, or kidneys. Appropriate treatment planning requires assessment of radiation dose to several internal organs and tissues, and usually involves biodistribution studies in the patient using a tracer amount of radionuclide bound to the targeting agent and imaged at sequential timepoints using a planar gamma camera. Time-activity curves are developed from the imaging data for the major organ tissues of concern, for the whole body and sometimes for selected tumours. Patient specific factors often require that dose estimates be customised for each patient. In the United States, the Food and Drug Administration regulates the experimental use of investigational new drugs and requires 'reasonable calculation of radiation absorbed dose to the whole body and to critical organs' using the methods prescribed by the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine. Review of high dose studies shows that some are conducted with minimal dosimetry, that the marrow dose is difficult to establish and is subject to large uncertainties. Despite the general availability of software, internal dosimetry methods often seem to be inconsistent from one clinical centre to another. (author)

Effect of a high-protein diet on maintenance of blood pressure levels achieved after initial weight loss

DEFF Research Database (Denmark)

Engberink, M F; Geleijnse, J M; Bakker, S J L

2015-01-01

Randomized trials have shown significant blood pressure (BP) reductions after increased protein compared with carbohydrate intake, but the effect on BP maintenance after initial weight loss is unclear. We examined the effect of a high-protein diet on the maintenance of reduced BP after weight loss......(-2), BP was 118/73 mm Hg and 28 subjects (6.5%) used antihypertensive agents. Systolic BP during 26 weeks of weight maintenance dietary intervention increased in both treatment groups, but it was 2.2 mm Hg less (95% CI: -4.6 to 0.2 mm Hg, P=0.08) in the high-protein group than in the lower...

Safety and tolerability of high doses of glucocorticoides

Directory of Open Access Journals (Sweden)

Rakić Branislava D.

2016-01-01

Full Text Available Introduction: Treatment of acute lymphoblastic leukemia includes the use of high doses of glucocorticoides (prednisone and dexamethasone, which significantly increase the success of therapy due to lymphocytolitic effect. The aim: The aim of the study was to determine tolerability of high doses of prednisone and dexamethasone in children with acute lymphoblastic leukemia and the structure and the intensity of adverse effects, occurred after application of these medicines. Subjects and methods: In a prospective study, we analyzed adverse effects of high doses of glucocorticoides in children suffering acute lymphoblastic leukemia treated in the Institute for Child and Youth Health Care of Vojvodina, since December 2010. until October 2014, were analyzed. This study included 18 patients, aged from 2 to 15 years. Results: Hyperglycemia appeared in 89% of patients treated with prednisone and in 61% of patients treated with dexamethasone. In order to control the high blood glucose level (above 10 mmol /L, in 11% of patients insulin was used. Hypertension appeared in 28% patients treated with prednisone and dexamethasone. Antihypertensives were needed for regulation in 17% patients. Hypopotassemia and hypocalcaemia were significantly more expressed after the use of prednisone in comparison to dexamethasone. In 11% of patients, the treatment with dexamethasone caused depressive behavior, followed by agitation. Conclusion: Adverse effects of dexamethasone and prednisone, administered in high doses in children with ALL were known, expected and reversible. Adverse reactions usually disappeared spontaneously or after short-term symptomatic therapy.

Dose conversion coefficients for high-energy photons, electrons, neutrons and protons

CERN Document Server

Sakamoto, Y; Sato, O; Tanaka, S I; Tsuda, S; Yamaguchi, Y; Yoshizawa, N

2003-01-01

In the International Commission on Radiological Protection (ICRP) 1990 Recommendations, radiation weighting factors were introduced in the place of quality factors, the tissue weighting factors were revised, and effective doses and equivalent doses of each tissues and organs were defined as the protection quantities. Dose conversion coefficients for photons, electrons and neutrons based on new ICRP recommendations were cited in the ICRP Publication 74, but the energy ranges of theses data were limited and there are no data for high energy radiations produced in accelerator facilities. For the purpose of designing the high intensity proton accelerator facilities at JAERI, the dose evaluation code system of high energy radiations based on the HERMES code was developed and the dose conversion coefficients of effective dose were evaluated for photons, neutrons and protons up to 10 GeV, and electrons up to 100 GeV. The dose conversion coefficients of effective dose equivalent were also evaluated using quality fact...

High-dose secondary calibration laboratory accreditation program

Energy Technology Data Exchange (ETDEWEB)

Humphreys, J.C. [National Institute of Standards and Technology, Gaithersburg, MD (United States)

1993-12-31

There is a need for high-dose secondary calibration laboratories to serve the multi-billion dollar radiation processing industry. This need is driven by the desires of industry for less costly calibrations and faster calibration-cycle response time. Services needed include calibration irradiations of routine processing dosimeters and the supply of reference standard transfer dosimeters for irradiation in the production processing facility. In order to provide measurement quality assurance and to demonstrate consistency with national standards, the high-dose secondary laboratories would be accredited by means of an expansion of an existing National Voluntary Laboratory Accreditation Program. A laboratory performance criteria document is under development to implement the new program.

High-dose secondary calibration laboratory accreditation program

International Nuclear Information System (INIS)

Humphreys, J.C.

1993-01-01

There is a need for high-dose secondary calibration laboratories to serve the multi-billion dollar radiation processing industry. This need is driven by the desires of industry for less costly calibrations and faster calibration-cycle response time. Services needed include calibration irradiations of routine processing dosimeters and the supply of reference standard transfer dosimeters for irradiation in the production processing facility. In order to provide measurement quality assurance and to demonstrate consistency with national standards, the high-dose secondary laboratories would be accredited by means of an expansion of an existing National Voluntary Laboratory Accreditation Program. A laboratory performance criteria document is under development to implement the new program

Relevance of high-dose chemotherapy in solid tumours

NARCIS (Netherlands)

Nieboer, P; de Vries, EGE; Mulder, NH; van der Graaf, WTA

Drug resistance is a major problem in the treatment of solid tumours. Based on a steep dose-response relationship for especially alkylating agents on tumour cell survival, high-dose chemotherapy was considered of interest for the treatment of solid tumours. Results of phase 1 and 2 studies with

High-dose erythropoietin for tissue protection

DEFF Research Database (Denmark)

Lund, Anton; Lundby, Carsten; Olsen, Niels Vidiendal

2014-01-01

BACKGROUND: The discovery of potential anti-apoptotic and cytoprotective effects of recombinant human erythropoietin (rHuEPO) has led to clinical trials investigating the use of high-dose, short-term rHuEPO therapy for tissue protection in conditions such as stroke and myocardial infarction....... Experimental studies have been favourable, but the clinical efficacy has yet to be validated. MATERIALS AND METHODS: We have reviewed clinical studies regarding the use of high-dose, short-term rHuEPO therapy for tissue protection in humans with the purpose to detail the safety and efficacy of r...... no effect of rHuEPO therapy on measures of tissue protection. Five trials including 1025 patients reported safety concerns in the form of increased mortality or adverse event rates. No studies reported reduced mortality. CONCLUSIONS: Evidence is sparse to support a tissue-protective benefit of r...

Remote assembly and maintenance of fusion reactors

International Nuclear Information System (INIS)

Becquet, M.C.; Farfaletti-Casali, F.

1991-01-01

This paper intend to present the state of the art in the field of remote assembly and maintenance, including system analysis design and operation for controlled fusion device such as JET, and the next NET and ITER reactors. The operational constraints of fusion reactors with respect to temperature, radiations dose rates and cumulated doses are considered with the resulting design requirements. Concepts like articulated boom, in-vessel vehicle and blanket handling device are presented. The close relations between computer simulations and experimental validation of those concepts are emphasized to ensure reliability of the operational behavior. Mockups and prototypes in reduced and full scale, as operating machines are described to illustrate the progress in remote operations for fusion reactors. The developments achieved at the Institute for System Engineering and Informatics of the Joint Research Center, in the field of remote blanket maintenance, reliability assessment of RH systems and remote cut and welding of lips joints are considered. (author)

Investigation of PBAT dosimetric properties for high gamma dose dosimetry

International Nuclear Information System (INIS)

Cunha, Elisete L.; Schimitberger, Thiago

2017-01-01

Poly(butylene adipate-co-terephthalate) (PBAT) is an aliphatic-aromatic copolyester which is biodegradable. It is a non-photoluminescent copolyester that becomes photoluminescent after previous exposure to gamma doses higher than 100 kGy. After the previous high energy irradiation, the material shows the highest photo-stimulated luminescence emission when excited with a LED source at wavelengths ranging from 370 to 405 nm. In this work we investigated the enhancement of the photoluminescence (PL) and dosimetric properties of PBAT, after exposure to high doses of gamma radiation ranging from 50 to 4,000 kGy. In this investigation we demonstrate that increasing the PBAT film thickness by 100 μm enhances the PL output by 3.5 times, when irradiated with 500 kGy. Also, besides the already known color green brightness, the PL intensity can also be used for high dose dosimetry purposes for doses ranging from 50 to 750 kGy. The FTIR analysis has demonstrated that the there is a linear relationship between peak intensity and dose for doses ranging from 100 and 2,000 kGy for the absorbance peaks at 3,241 cm -1 and 3271 cm -1 , with linear correlation coefficients of 0.9981 and 0.9992, respectively. The results indicate that PBAT has great potential for applications in bio-imaging devices and high gamma dose dosimetry. (author)

Investigation of PBAT dosimetric properties for high gamma dose dosimetry

Energy Technology Data Exchange (ETDEWEB)

Cunha, Elisete L.; Schimitberger, Thiago, E-mail: elisete.cunha@cdtn.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Departamento de Engenharia Nuclear; Oliveira, Cristiana M.; Faria, Luiz O., E-mail: farialo@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

2017-07-01

Poly(butylene adipate-co-terephthalate) (PBAT) is an aliphatic-aromatic copolyester which is biodegradable. It is a non-photoluminescent copolyester that becomes photoluminescent after previous exposure to gamma doses higher than 100 kGy. After the previous high energy irradiation, the material shows the highest photo-stimulated luminescence emission when excited with a LED source at wavelengths ranging from 370 to 405 nm. In this work we investigated the enhancement of the photoluminescence (PL) and dosimetric properties of PBAT, after exposure to high doses of gamma radiation ranging from 50 to 4,000 kGy. In this investigation we demonstrate that increasing the PBAT film thickness by 100 μm enhances the PL output by 3.5 times, when irradiated with 500 kGy. Also, besides the already known color green brightness, the PL intensity can also be used for high dose dosimetry purposes for doses ranging from 50 to 750 kGy. The FTIR analysis has demonstrated that the there is a linear relationship between peak intensity and dose for doses ranging from 100 and 2,000 kGy for the absorbance peaks at 3,241 cm{sup -1} and 3271 cm{sup -1}, with linear correlation coefficients of 0.9981 and 0.9992, respectively. The results indicate that PBAT has great potential for applications in bio-imaging devices and high gamma dose dosimetry. (author)

Paranal maintenance and CMMS experience

Science.gov (United States)

Montano, Nelson

2004-10-01

During the last four years of operations, low technical downtime has been one of the relevant records of the Paranal Observatory. From the beginning of the Very Large Telescope (VLT) project, European Southern Observatory (ESO) has considered the implementation of a proper maintenance strategy a fundamental point in order to ensure low technical down time and preserve the Observatory's assets. The implementation of the maintenance strategy was based on the following aspects: - Strong maintenance sense during the design stage. Line Replacement Unit (LRU) concept, standardization and modularity of the Observatory equipment - Creation of a dedicated team for Maintenance - The implementation of a Computerized Maintenance Management System After four operational years, the result of these aspects has exceeded the expectations; the Observatory has been operating with high availability under a sustainable strategy. The strengths of the maintenance strategy have been based on modern maintenance concepts applied by regular production companies, where any minute of down time involves high cost. The operation of the actual Paranal Maintenance System is based mainly on proactive activities, such as regular inspections, preventive maintenance (PM) and predictive maintenance (PdM) plans. Nevertheless, it has been necessary to implement a strong plan for corrective maintenance (CM). The Spare Parts Strategy has also been an important point linked to the Maintenance Strategy and CMMS implementation. At present, almost 4,000 items related to the Observatory spare parts are loaded into the CMMS database. Currently, we are studying the implementation of a Reliability Centered Maintenance (RCM) project in one of our critical systems The following document presents the actual status of the Paranal Maintenance Strategy and which have been the motivations to implement the established strategy.

Remote maintenance considerations for swimming pool tokamak reactor

International Nuclear Information System (INIS)

Niikura, S.; Yamada, M.; Kasai, M.

1983-01-01

Swimming Pool Tokamak Reactor (SPTR) is one of the candidate devices which are expected to demonstrate physical and engineering feasibility for fusion power reactors. In SPTR, water shield is adopted instead of solid shield structures. Among the advantages of SPTR are, from viewpoint of remote maintenance, small handling weight and high space availability between TF coils and a vacuum vessel. On the other hand, high dose rate during reactor repair and adverse effects on remote maintenance equipment by the shielding water might be the disadvantage of SPTR, where it is assumed that the shielding water is drained during reactor repair. Since the design of SPTR is still at the preliminary stage, for remote maintenance, much effort has been directed to clarification of design conditions such as environment and handling weight. As for the remote maintenance system concepts, studies have been focussed on those for a vacuum vessel and its internal structure (blanket, divertor and protection walls) expected to be repaired more frequently. The vacuum vessel assembly is divided into 21 sectors and number of TF coils is 14. A pair of TF coils are connected with each other by antitorque beams on the whole side surface. Vacuum vessel cassettes and associated blanket, divertor and protection walls are replaced through seven windows between TF coils pairs. Therefore each vacuum vessel cassette is required moving mechanisms in toroidal and radial directions. Options for slide mechanisms are wheels, balls, rollers and water bearings. Options for driving the cassette are self-driving by hydraulic motors and external driving by rack-pinion, wires or specific vehicles. As a result of studies, the moving mechanism with wheels and hydraulic motors has been selected for the reference design, and the system with water bearings and rack-pinion as an alternative. Furthermore typical concepts have been obtained for remote maintenance equipment such as wall-mounted manipulators, tools for

High-dose infliximab for treatment of pediatric ulcerative colitis: A survey of clinical practice

Institute of Scientific and Technical Information of China (English)

Roy Nattiv; Janet M Wojcicki; Elizabeth A Garnett; Neera Gupta; Melvin B Heyman

2012-01-01

AIM:TO assess attitudes and trends regarding the use of high-dose infliximab among pediatric gastroenterologists for treatment of pediatric ulcerative colitis (UC).METHODS:A 19-item survey was distributed to subscribers of the pediatric gastroenterology (PEDSGI)listserv.Responses were submitted anonymously and results compiled in a secure website.RESULTS:A total of 113 subscribers (88％ based in the United States) responded (101 pediatric gastroenterology attendings and 12 pediatric gastroenterology fellows).There were 46％ in academic medical institutions and 39％ in hospital-based practices.The majority (91％) were treating ＞10 patients with UC; 13％ were treating ＞100 patients with UC; 91％ had prescribed infliximab (IFX) 5 mg/kg for UC; 72％ had prescribed IFX 10 mg/kg for UC.Using a 5-point Likert scale,factors that influenced the decision not to increase IFX dosing in patients with UC included:"improvement on initial dose of IFX" (mean:3.88) and "decision to move to colectomy" (3.69).Lowest mean Likert scores were:"lack of guidelines or literature regarding increased IFX dosing" (1.96) and "insurance authorization or other insurance issues" (2.34)."Insurance authorization or other insurance issues" was identified by 39％ as at least somewhat of a factor (Likert score ≥ 3) in their decision not to increase the IFX dose.IFX 10 mg/kg was more commonly used for the treatment of pediatric UC among responders based in the United States (75/100) compared to non-United States responders (6/13,P =0.047).Induction of remission was reported by 78％ of all responders and 81％ reported maintenance of remission with IFX 10 mg/kg.One responder reported one death with IFX 10 mg/kg.CONCLUSION:IFX 10 mg/kg is more commonly used in the United States to treat pediatric UC.Efficacy and safety data are required to avoid insurance barriers for its use.

Influence of CYP3A5 genetic variation on everolimus maintenance dosing after cardiac transplantation.

Science.gov (United States)

Lesche, Dorothea; Sigurdardottir, Vilborg; Setoud, Raschid; Englberger, Lars; Fiedler, Georg M; Largiadèr, Carlo R; Mohacsi, Paul; Sistonen, Johanna

2015-12-01

Everolimus (ERL) has become an alternative to calcineurin inhibitors (CNIs) due to its renal-sparing properties, especially in heart transplant (HTx) recipients with kidney dysfunction. However, ERL dosing is challenging due to its narrow therapeutic window combined with high interindividual pharmacokinetic variability. Our aim was to evaluate the effect of clinical and genetic factors on ERL dosing in a pilot cohort of 37 HTx recipients. Variants in CYP3A5, CYP3A4, CYP2C8, POR, NR1I2, and ABCB1 were genotyped, and clinical data were retrieved from patient charts. While ERL trough concentration (C0 ) was within the targeted range for most patients, over 30-fold variability in the dose-adjusted ERL C0 was observed. Regression analysis revealed a significant effect of the non-functional CYP3A5*3 variant on the dose-adjusted ERL C0 (p = 0.031). ERL dose requirement was 0.02 mg/kg/d higher in patients with CYP3A5*1/*3 genotype compared to patients with CYP3A5*3/*3 to reach the targeted C0 (p = 0.041). ERL therapy substantially improved estimated glomerular filtration rate (28.6 ± 6.6 mL/min/1.73 m(2)) in patients with baseline kidney dysfunction. Everolimus pharmacokinetics in HTx recipients is highly variable. Our preliminary data on patients on a CNI-free therapy regimen suggest that CYP3A5 genetic variation may contribute to this variability. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

High-Dose Statin Pretreatment Decreases Periprocedural Myocardial Infarction and Cardiovascular Events in Patients Undergoing Elective Percutaneous Coronary Intervention: A Meta-Analysis of Twenty-Four Randomized Controlled Trials

Science.gov (United States)

Wang, Le; Peng, Pingan; Zhang, Ou; Xu, Xiaohan; Yang, Shiwei; Zhao, Yingxin; Zhou, Yujie

2014-01-01

Background Evidence suggests that high-dose statin pretreatment may reduce the risk of periprocedural myocardial infarction (PMI) and major adverse cardiac events (MACE) for certain patients; however, previous analyses have not considered patients with a history of statin maintenance treatment. In this meta-analysis of randomized controlled trials (RCTs), we reevaluated the efficacy of short-term high-dose statin pretreatment to prevent PMI and MACE in an expanded set of patients undergoing elective percutaneous coronary intervention. Methods We searched the PubMed/Medline database for RCTs that compared high-dose statin pretreatment with no statin or low-dose statin pretreatment as a prevention of PMI and MACE. We evaluated the incidence of PMI and MACE, including death, spontaneous myocardial infarction, and target vessel revascularization at the longest follow-up for each study for subgroups stratified by disease classification and prior low-dose statin treatment. Results Twenty-four RCTs with a total of 5,526 patients were identified. High-dose statin pretreatment was associated with 59% relative reduction in PMI (odds ratio [OR]: 0.41; 95% confidence interval [CI]: 0.34–0.49; Pstatin pretreatment on MACE was significant for statin-naive patients (OR: 0.69; 95% CI: 0.50–0.95; P = 0.02) and prior low dose statin-treated patients (OR: 0.28; 95% CI: 0.12–0.65; P = 0.003); and for patients with acute coronary syndrome (OR: 0.52; 95% CI: 0.34–0.79; P = 0.003), but not for patients with stable angina (OR: 0.71; 95% CI 0.45–1.10; P = 0.12). Long-term effects on survival were less obvious. Conclusions High-dose statin pretreatment can result in a significant reduction in PMI and MACE for patients undergoing elective PCI. The positive effect of high-dose statin pretreatment on PMI and MACE is significant for statin-naïve patients and patients with prior treatment. The positive effect of high-dose statin pretreatment on MACE is significant for

Methodology of high dose research in medical radiodiagnostic; Metodologia de investigacao de doses elevadas em radiodiagnostico medico

Energy Technology Data Exchange (ETDEWEB)

Barboza, Adriana E.; Martins, Cintia P. de S., E-mail: ird@ird.gov.br [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

2013-11-01

This work has as main purpose to study occupational exposure in diagnostic radiology in medical cases of high doses recorded in 2011 at the national level . These doses were recorded by monitoring individual of the occupationally exposed individuals (OEI's). This monitoring of the doses received by ionizing radiation has as main objective to ensure that the principle of dose limitation is respected. In this study it were evaluated doses of 372 OEI's radiology in different Brazilian states. Doses were extracted from the database of Sector Management Doses of the Institute for Radioprotection and Dosimetry - IRD/CNEN-RJ, Brazil. The information from the database provide reports of doses from several states, which allows to quantify statistically, showing those with the highest doses in four areas: dose greater than or equal to 20 mSv apron and chest and dose greater than or equal to 100 mSv apron and chest. The identification of these states allows the respective Sanitary Surveillance (VISA), be aware of the events and make plans to reduce them. This study clarified the required procedures when there is a record of high dose emphasizing the importance of using protective radiological equipment, dosimeter and provide a safety environment work by maintaining work equipment. Proposes the ongoing training of professionals, emphasizing the relevance of the concepts of radiation protection and the use of the questionnaire with their investigative systematic sequence, which will allow quickly and efficiently the success the investigations.

Pharmacokinetics of and short-term virologic response to low-dose 400-milligram once-daily raltegravir maintenance therapy.

NARCIS (Netherlands)

Ananworanich, J.; Gorowara, M.; Avihingsanon, A.; Kerr, S.J.; Heesch, N. van; Khongpetch, C.; Uanithirat, A.; Hill, A.; Ruxrungtham, K.; Burger, D.M.

2012-01-01

Because studies showed similar viral suppression with lower raltegravir doses and because Asians usually have high antiretroviral concentrations, we explored low-dose raltegravir therapy in Thais. Nineteen adults on raltegravir at 400 mg twice daily (BID) with HIV RNA loads of <50 copies/ml were

Condition-based maintenance for complex systems : Coordinating maintenance and logistics planning for the process industries

NARCIS (Netherlands)

Olde Keizer, Minou Catharina Anselma

2016-01-01

Maintenance planning in the process industries is extremely complex for various reasons. Plants often run nonstop, allowing little time for performing preventive maintenance. Failures should be prevented, however, as they can lead to system downtime and high losses of revenue. Corrective maintenance

Teflon pastille use in high dose dosimetry; Utilizacao de pastilhas de teflon em dosimetria de doses altas

Energy Technology Data Exchange (ETDEWEB)

Teixeira, Maria Ines [Associacao Educacional Nove de Julho (UNINOVE), Sao Paulo, SP (Brazil); Caldas, Linda V.E., E-mail: miteixeira@ipen.b, E-mail: lcaldas@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2011-10-26

This paper study the Teflon, which is used as aglomerant in the confection of dosimetric pastilles, for the viabilization of this material as high dose dosimeter. This paper used the OSL technique for the characterization of dosimetric properties of Teflon. The doses-response curve has been obtained for {sup 60}Co radiation between 100 Gy and 50 kGy, and the OSL answer reproducibility. The preliminary results shown that the Teflon is a material which can be used for high dose dosimetry

measurement of high dose radiation using yellow perspex dosimeter

International Nuclear Information System (INIS)

Thamrin, M Thoyib; Sofyan, Hasnel

1996-01-01

Measurement of high dose radiation using yellow perspex dosemeter has been carried out. Dose range used was between 0.1 to 3.0 kGy. Measurement of dose rate against Fricke dosemeter as a standard dose meter From the irradiation of Fricke dosemeter with time variation of 3,6,9,12,15 and 18 minute, it was obtained average dose rate of 955.57 Gy/hour, linear equation of dose was Y= 2.333+15.776 X with its correlation factor r = 0.9999. Measurement result using yellow perspex show that correlation between net optical density and radiation dose was not linear with its equation was ODc exp. [Bo + In(dose).Bi] Value of Bo = -0.215 and Bi=0.5020. From the experiment it was suggested that routine dosimeter (yellow perspex) should be calibrated formerly against standard dosemeters

Space Telescope maintenance and refurbishment

Science.gov (United States)

Trucks, H. F.

1983-01-01

The Space Telescope (ST) represents a new concept regarding spaceborne astronomical observatories. Maintenance crews will be brought to the orbital worksite to make repairs and replace scientific instruments. For major overhauls the telescope can be temporarily returned to earth with the aid of the Shuttle. It will, thus, be possible to conduct astronomical studies with the ST for two decades or more. The five first-generation scientific instruments used with the ST include a wide field/planetary camera, a faint object camera, a faint object spectrograph, a high resolution spectrograph, and a high speed photometer. Attention is given to the optical telescope assembly, the support systems module, aspects of mission and science operations, unscheduled maintenance, contingency orbital maintenance, planned on-orbit maintenance, ground maintenance, ground refurbishment, and ground logistics.

TPX remote maintenance and shielding

International Nuclear Information System (INIS)

Rennich, M.J.; Nelson, B.E.

1994-01-01

The Tokamak Physics Experiment machine design incorporates comprehensive planning for efficient and safe component maintenance. Three programmatic decisions have been made to insure the successful implementation of this objective. First, the tokamak incorporates radiation shielding to reduce activation of components and limit the dose rate to personnel working on the outside of the machine. This allows most of the ex-vessel equipment to be maintained through conventional ''hands-on'' procedures. Second, to the maximum extent possible, low activation materials will be used inside the shielding volume. This resulted in the selection of Titanium (Ti-6Al-4V) for the vacuum vessel and PFC structures. The third decision stipulated that the primary in-vessel components will be replaced or repaired via remote maintenance tools specifically provided for the task. The component designers have been given the responsibility of incorporating maintenance design and for proving the maintainability of the design concepts in full-scale mockup tests prior to the initiation of final fabrication. Remote maintenance of the TPX machine is facilitated by general purpose tools provided by a special purpose design team. Major tools will include an in-vessel transporter, a vessel transfer system and a large component transfer container. In addition, tools such as manipulators and remotely operable impact wrenches will be made available to the component designers by this group. Maintenance systems will also provide the necessary controls for this equipment

Increased platelet aggregation and turnover in the acute phase of ST-elevation myocardial infarction

DEFF Research Database (Denmark)

Jensen, Kristian Løkke Funck; Dalsgaard, Jens; Grove, Erik Lerkevang

2013-01-01

Newly produced platelets are present in the acute phase of ST-elevation myocardial infarction (STEMI). This may influence the antiplatelet effect of aspirin and clopidogrel administered prior to primary percutaneous coronary intervention (PPCI). The aims of this study were to investigate the anti...... turnover may partly explain the reduced efficacy of antiplatelet drugs in the acute phase of STEMI....... the antiplatelet effect of aspirin and clopidogrel and evaluate platelet turnover in the acute phase of STEMI compared to a stable phase 3 months later. In this observational follow-up study on 48 STEMI patients transferred for PPCI, loading doses of aspirin (300 mg) and clopidogrel (600 mg) were given orally...... in the ambulance. Blood samples were obtained immediately prior to PPCI, at 4 and 12 hours after administration of bolus doses and at follow-up after 3 months. Residual platelet aggregation was evaluated by Multiplate® and VerifyNow® aggregometry. Platelet turnover was evaluated by automated flow cytometry...

Protocol of source shielding maintenance in a level measurement systems

International Nuclear Information System (INIS)

Gonzales, E.; Figueroa, J.

1996-01-01

Maintenance labor of the source shielding and locking system is not performed in many Venezuelan enterprises that employ radioactive level gauge in large container. The lack of maintenance and the ambient long lasting action have produced impairment of many devices and their given parts rise to economical and radiological protection problems. In order to help to solve the mentioned problems, principally to reduce the unjustified dose to workers, the IVIC Health Physics Service worked out a protocol to perform, in a safety way, the maintenance of source shielding and its locking system. This protocol is presented in this paper. (authors)

Impact of smoking status on platelet function and clinical outcomes with prasugrel vs. clopidogrel in patients with acute coronary syndromes managed without revascularization

DEFF Research Database (Denmark)

Cornel, Jan H; Ohman, E Magnus; Neely, Benjamin

2014-01-01

managed medically without revascularization. METHODS AND RESULTS: A total of 7062 patients aged ..., or stroke in current smokers was significantly lower with prasugrel (11.7%) vs. clopidogrel (18.6%), but there was no difference in non-smokers (13.8% vs. 13.7%), with significant interaction between treatment and baseline smoking status (P = .0002). Bleeding events occurred more frequently in prasugrel......-treated patients with no significant interaction between treatment and baseline smoking status. CONCLUSIONS: Among medically managed ACS patients

Optimizing preventive maintenance with maintenance templates

International Nuclear Information System (INIS)

Dozier, I.J.

1996-01-01

Rising operating costs has caused maintenance professionals to rethink their strategy for preventive maintenance (PM) programs. Maintenance Templates are pre-engineered PM task recommendations for a component type based on application of the component. Development of the maintenance template considers the dominant failure cause of the component and the type of preventive maintenance that can predict or prevent the failure from occurring. Maintenance template development also attempts to replace fixed frequency tasks with condition monitoring tasks such as vibration analysis or thermography. For those components that have fixed frequency PM intervals, consideration is given to the maintenance drivers such as criticality, environment and usage. This helps to maximize the PM frequency intervals and maximize the component availability. Maintenance Templates have been used at PECO Energy's Limerick Generating Station during the Reliability Centered Maintenance (RCM) Process to optimize their PM program. This paper describes the development and uses of the maintenance templates

Diagnosis of cerebral metastases by means of standard doses of Gadobutrol versus a high-dose protocol. Intraindividual evaluation of a phase-II high-dose study

International Nuclear Information System (INIS)

Vogl, T.J.; Friebe, C.E.; Balzer, T.; Mack, M.G.; Steiner, S.; Schedel, H.; Pegios, W.; Lanksch, W.; Banzer, D.; Felix, R.

1995-01-01

In a clinical phase-II study 20 patients who had been diagnosed as having brain metastases with CT or MRT were studied prospectively with Gadobutrol, a new nonionic, low osmolality contrast agent. Each patient received an initial injection of 0.1 mmol/kg body weight and an additional dose of 0.2 mmol/kg Gadobutrol 10 min later. Spinecho images were obtained before and after the two applications of Gadobutrol. Dynamic scanning (Turbo-FLASH) was performed for 3 min after each injection of the contrast agent. Both quantitative and qualitative data were intraindividually evaluated. The primary tumor was a bronchial carcinoma in 11 cases; in 9 other cases there were different primary tumors. Forty-eight hours after the use of Gadobutrol there were no adverse signs in the clinical examination, vital signs or blood and urine chemistry. Statistical analysis (Friedman test and Wilcoxon test) of the C/N ratios between tumor and white matter, percentage enhancement, and visual assessment rating revealed statistically significant superiority of high-dose Gadobutrol injection in comparison to the standard dose. The percentage enhancement increased on average from 104% after 0.1 mmol/kg to 162% after 0.3 mmol/kg Gadobutrol. Qualitative delineation and contrast of the lesions increased significantly. The use of high-dose Gadobutrol improved the detection of 36 additional lesions in 6 patients. (orig./VHE) [de

High-resolution CT of the lung in asbestos-exposed subjects. Comparison of low-dose and high-dose HRCT

International Nuclear Information System (INIS)

Majurin, M.L.; Varpula, M.; Kurki, T.; Pakkala, L.

1994-01-01

The lowest possible mAs settings for high-resolution CT (HRCT) were studied on 45 individuals with suspected asbestos-related lung disease. All patients were investigated with 5 to 6 high-dose HRCT images (120 kVp/160 mA/2 s) at 3-cm intervals. At a selected level 4 additional low-dose images were obtained on each patient with lower mAs settings (100 mA/2 s, 80 mA/2 s, 60 mA/2 s, 30 mA/2 s). Thirty-seven subjects out of 45 had HRCT lesions compatible with asbestosis. HRCT images obtained with as low as 60 mA/2 s settings clearly showed pleural tractions and thickenings, parenchymal bands, honeycombing and subpleural curvilinear shadows, whereas in the evaluation of subpleural short lines and ground glass findings 80 mA/2 s were required. The lowest setting, 30 mA/2 s, was sufficient only in detecting and evaluating pleural tractions and thickenings. We conclude that 160 mAs yield good quality HRCT images, with substantial decrease of radiation dose, for the evaluation of asbestos-related lesions. (orig.)

The clinical pharmacology of alkylating agents in high-dose chemotherapy

NARCIS (Netherlands)

Huitema, A. D.; Smits, K. D.; Mathôt, R. A.; Schellens, J. H.; Rodenhuis, S.; Beijnen, J. H.

2000-01-01

Alkylating agents are widely used in high-dose chemotherapy regimens in combination with hematological support. Knowledge about the pharmacokinetics and pharmacodynamics of these agents administered in high doses is critical for the safe and efficient use of these regimens. The aim of this review is

Radiobiological modelling of dose-gradient effects in low dose rate, high dose rate and pulsed brachytherapy

International Nuclear Information System (INIS)

Armpilia, C; Dale, R G; Sandilos, P; Vlachos, L

2006-01-01

This paper presents a generalization of a previously published methodology which quantified the radiobiological consequences of dose-gradient effects in brachytherapy applications. The methodology uses the linear-quadratic (LQ) formulation to identify an equivalent biologically effective dose (BED eq ) which, if applied uniformly to a specified tissue volume, would produce the same net cell survival as that achieved by a given non-uniform brachytherapy application. Multiplying factors (MFs), which enable the equivalent BED for an enclosed volume to be estimated from the BED calculated at the dose reference surface, have been calculated and tabulated for both spherical and cylindrical geometries. The main types of brachytherapy (high dose rate (HDR), low dose rate (LDR) and pulsed (PB)) have been examined for a range of radiobiological parameters/dimensions. Equivalent BEDs are consistently higher than the BEDs calculated at the reference surface by an amount which depends on the treatment prescription (magnitude of the prescribed dose) at the reference point. MFs are closely related to the numerical BED values, irrespective of how the original BED was attained (e.g., via HDR, LDR or PB). Thus, an average MF can be used for a given prescribed BED as it will be largely independent of the assumed radiobiological parameters (radiosensitivity and α/β) and standardized look-up tables may be applicable to all types of brachytherapy treatment. This analysis opens the way to more systematic approaches for correlating physical and biological effects in several types of brachytherapy and for the improved quantitative assessment and ranking of clinical treatments which involve a brachytherapy component

Optimization of radiation protection of cell maintenance of radiopharmaceutical production; Otimizacao da radioprotecao em manutencoes de celas de producao de radiofarmacos

Energy Technology Data Exchange (ETDEWEB)

Machado, Jessica S.; Gerulis, Eduardo; Todo, Alberto S.; Rodrigues Junior, Orlando, E-mail: jsmachado@ipen.b, E-mail: egerulis@ipen.b, E-mail: astodo@ipen.b, E-mail: rodrijr@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), SP (Brazil)

2011-10-26

This paper performs a study of maintenance tasks realized in production cells to suggest improvements related to the occupational doses based on the optimization principle of the radioprotection. A data survey has been realized of the doses received by the workers during the maintenance. The average values of effective doses are lower than the limits established in the regulations, however can be optimized

Basic policy of maintenance for the power conversion system of the gas turbine high temperature reactor 300 (GTHTR300)

International Nuclear Information System (INIS)

Kosugiyama, Shinichi; Takizuka, Takakazu; Kunitomi, Kazuhiko; Yan, Xing; Katanishi, Shoji; Takada, Shoji

2003-01-01

Basic policy of maintenance was determined for major equipment in the power conversion system of the Gas Turbine High Temperature Reactor 300 (GTHTR300). It was developed based on the current maintenance practice in Light Water Reactors (LWRs), High Temperature Engineering Test Reactor (HTTR) and conventional combined cycle power plants while taking into account of unique design features of GTHTR300. First, potential degradation phenomena in operations were identified and corresponding maintenance approaches were proposed for the equipment. Such degradations encountered typically in LWRs as corrosion, erosion and stress corrosion cracking are unlikely to occur since the working fluid of GTHTR300 is inert helium. Main causes of the degradations are high operating temperature and pressure. The gas turbine, compressor, generator, control valves undergo opening and dismantling maintenance in a suitable time interval. The power conversion vessel, heat exchanger vessel, primary system piping and heat exchanging tubes of precooler are subjected to in-service inspections similar to those done in LWRs. As turbine blades represent the severest material degradation because of their high-temperature and high-stress operating conditions, a lifetime management scheme was suggested for them. The longest interval of open-casing maintenance of the gas turbine is estimated to be six to seven years from technical point of view. Present study is entrusted from the Ministry of Education, Culture, Sports, Science and Technology of Japan. (author)

Calcium carbonate as a possible dosimeter for high irradiation doses

International Nuclear Information System (INIS)

Negron M, A.; Ramos B, S.; Camargo R, C.; Uribe, R. M.; Gomez V, V.; Kobayashi, K.

2014-08-01

The aim of this work is to analyze the interactions of 5 MeV electron beam radiation and a 290 MeV/u Carbon beam with calcium carbonate (powder) at 298 K and at different irradiation doses, for the potential use of calcium carbonate as a high-dose dosimeter. The irradiation doses with the electron beam were from 0.015 to 9 MGy, and with Carbon beam from 1.5 kGy to 8 kGy. High-energy radiation induces the formation of free radicals in solid calcium carbonate that can be detected and measured by electron paramagnetic resonance (EPR). An increase of the EPR response for some of the free radicals produced in the sample was observed as a function of the irradiation dose. The response of one of the radicals decreased with the dose. These measurements are reproducible; the preparation of the sample is simple and inexpensive; and the signal is stable for several months. The response curves show that the dosimeter tends to saturate at 10 MGy. Based on these properties, we propose this chemical compound as a high-dose dosimeter, mainly for electron irradiation. (author)

Calcium carbonate as a possible dosimeter for high irradiation doses

Energy Technology Data Exchange (ETDEWEB)

Negron M, A.; Ramos B, S.; Camargo R, C. [UNAM, Instituto de Ciencias Nucleares, Ciudad Universitaria, 04510 Mexico D. F. (Mexico); Uribe, R. M. [Kent State University, College of Technology, Kent OH (United States); Gomez V, V. [UNAM, Instituto de Quimica, Ciudad Universitaria, 04510 Mexico D. F. (Mexico); Kobayashi, K., E-mail: negron@nucleares.unam.mx [Yokohama National University (Japan)

2014-08-15

The aim of this work is to analyze the interactions of 5 MeV electron beam radiation and a 290 MeV/u Carbon beam with calcium carbonate (powder) at 298 K and at different irradiation doses, for the potential use of calcium carbonate as a high-dose dosimeter. The irradiation doses with the electron beam were from 0.015 to 9 MGy, and with Carbon beam from 1.5 kGy to 8 kGy. High-energy radiation induces the formation of free radicals in solid calcium carbonate that can be detected and measured by electron paramagnetic resonance (EPR). An increase of the EPR response for some of the free radicals produced in the sample was observed as a function of the irradiation dose. The response of one of the radicals decreased with the dose. These measurements are reproducible; the preparation of the sample is simple and inexpensive; and the signal is stable for several months. The response curves show that the dosimeter tends to saturate at 10 MGy. Based on these properties, we propose this chemical compound as a high-dose dosimeter, mainly for electron irradiation. (author)

Calibration of high-dose radiation facilities (Handbook)

International Nuclear Information System (INIS)

Gupta, B.L.; Bhat, R.M.

1986-01-01

In India at present several high intensity radiation sources are used. There are 135 teletheraphy machines and 65 high intensity cobalt-60 sources in the form of gamma chambers (2.5 Ci) and PANBIT (50 Ci). Several food irradiation facilities and a medical sterilization plant ISOMED are also in operation. The application of these high intensity sources involve a wide variation of dose from 10 Gy to 100 kGy. Accurate and reproducible radiation dosimetry is essential in the use of these sources. This handbook is especially compiled for calibration of high-dose radiation facilities. The first few chapters discuss such topics as interaction of radiation with matter, radiation chemistry, radiation processing, commonly used high intensity radiation sources and their special features, radiation units and dosimetry principles. In the chapters which follow, chemical dosimeters are discussed in detail. This discussion covers Fricke dosimeter, FBX dosimeter, ceric sulphate dosimeter, free radical dosimetry, coloured indicators for irrdiation verification. A final chapter is devoted to practical hints to be followed in calibration work. (author)

Plasma Doping - Enabling Technology for High Dose Logic and Memory Applications

International Nuclear Information System (INIS)

Miller, T.; Godet, L.; Papasouliotis, G. D.; Singh, V.

2008-01-01

As logic and memory device dimensions shrink with each generation, there are more high dose implants at lower energies. Examples include dual poly gate (also referred to as counter-doped poly), elevated source drain and contact plug implants. Plasma Doping technology throughput and dopant profile benefits at these ultra high dose and lower energy conditions have been well established [1,2,3]. For the first time a production-worthy plasma doping implanter, the VIISta PLAD tool, has been developed with unique architecture suited for precise and repeatable dopant placement. Critical elements of the architecture include pulsed DC wafer bias, closed-loop dosimetry and a uniform low energy, high density plasma source. In this paper key performance metrics such as dose uniformity, dose repeatability and dopant profile control will be presented that demonstrate the production-worthiness of the VIISta PLAD tool for several high dose applications.

Spectroscopic gamma camera for use in high dose environments

Energy Technology Data Exchange (ETDEWEB)

Ueno, Yuichiro, E-mail: yuichiro.ueno.bv@hitachi.com [Research and Development Group, Hitachi, Ltd., Hitachi-shi, Ibaraki-ken 319-1221 (Japan); Takahashi, Isao; Ishitsu, Takafumi; Tadokoro, Takahiro; Okada, Koichi; Nagumo, Yasushi [Research and Development Group, Hitachi, Ltd., Hitachi-shi, Ibaraki-ken 319-1221 (Japan); Fujishima, Yasutake; Kometani, Yutaka [Hitachi Works, Hitachi-GE Nuclear Energy, Ltd., Hitachi-shi, Ibaraki-ken (Japan); Suzuki, Yasuhiko [Measuring Systems Engineering Dept., Hitachi Aloka Medical, Ltd., Ome-shi, Tokyo (Japan); Umegaki, Kikuo [Faculty of Engineering, Hokkaido University, Sapporo-shi, Hokkaido (Japan)

2016-06-21

We developed a pinhole gamma camera to measure distributions of radioactive material contaminants and to identify radionuclides in extraordinarily high dose regions (1000 mSv/h). The developed gamma camera is characterized by: (1) tolerance for high dose rate environments; (2) high spatial and spectral resolution for identifying unknown contaminating sources; and (3) good usability for being carried on a robot and remotely controlled. These are achieved by using a compact pixelated detector module with CdTe semiconductors, efficient shielding, and a fine resolution pinhole collimator. The gamma camera weighs less than 100 kg, and its field of view is an 8 m square in the case of a distance of 10 m and its image is divided into 256 (16×16) pixels. From the laboratory test, we found the energy resolution at the 662 keV photopeak was 2.3% FWHM, which is enough to identify the radionuclides. We found that the count rate per background dose rate was 220 cps h/mSv and the maximum count rate was 300 kcps, so the maximum dose rate of the environment where the gamma camera can be operated was calculated as 1400 mSv/h. We investigated the reactor building of Unit 1 at the Fukushima Dai-ichi Nuclear Power Plant using the gamma camera and could identify the unknown contaminating source in the dose rate environment that was as high as 659 mSv/h.

Calibration procedure for thermoluminescent dosemeters in water absorbed doses for Iridium-192 high dose rate sources

International Nuclear Information System (INIS)

Reyes Cac, Franky Eduardo

2004-10-01

Thermoluminescent dosimeters are used in brachytherapy services quality assurance programs, with the aim of guaranteeing the correct radiation dose supplied to cancer patients, as well as with the purpose of evaluating new clinical procedures. This work describes a methodology for thermoluminescent dosimeters calibration in terms of absorbed dose to water for 192 Ir high dose rate sources. The reference dose used is measured with an ionization chamber previously calibrated for 192 Ir energy quality, applying the methodology proposed by Toelli. This methodology aims to standardizing the procedure, in a similar form to that used for external radiotherapy. The work evolves the adaptation of the TRS-277 Code of the International Atomic Energy Agency, for small and big cavities, through the introduction for non-uniform experimental factor, for the absorbed dose in the neighborhood of small brachytherapy sources. In order to simulate a water medium around the source during the experimental work, an acrylic phantom was used. It guarantees the reproducibility of the ionization chamber and the thermoluminescent dosimeter's location in relation to the radiation source. The values obtained with the ionization chamber and the thermoluminescent dosimeters, exposed to a 192 Ir high dose rate source, were compared and correction factors for different source-detector distances were determined for the thermoluminescent dosimeters. A numeric function was generated relating the correction factors and the source-detector distance. These correction factors are in fact the thermoluminescent dosimeter calibration factors for the 192 Ir source considered. As a possible application of this calibration methodology for thermoluminescent dosimeters, a practical range of source-detector distances is proposed for quality control of 192 Ir high dose rate sources. (author)

Biological dose estimation and comet analysis of the victims in a high dose 60Co radiation accident

International Nuclear Information System (INIS)

Chen Ying; Liu Xiulin; Luo Yisheng; Li You; Yao Bo

2007-01-01

Objective: To explore the methods of chromosome preparation in human peripheral blood and bone marrow after very high dose exposure and fit the dose-response curve of dicentrics and tings in the range of high doses over 6 Gy for estimating biological dose and detecting DNA damage in the victims of '10.21' accident. Methods: The samples of peripheral blood and bone marrow in 2 victims were collected to prepare chromosome mataphases and dicentrics (multicentrics) + rings were counted. The dose-response curve and equation of human blood irradiated between 6-22 Gy in vitro were established and applied to assess biological dose of 2 victims. In addition, their DNA damages were tested by alkaline single cell gel electrophoresis. Results: The dicentric + ring numbers of 4.47 per cell in victims B's peripheral blood lymphocytes and 9.15 per cell in victim A's bone marrow who had no mitosis in peripheral blood cell. The whole body average doses of victims B and A estimated by 6-22 Gy equation arrived at 9.4 Gy and 19.5 Gy, respectively. The serious DNA damages were expressed by small head and large tail comet figures. Conclusions: The biological doses of 2 victims estimated by 6-22 Gy dose-response curve have reached the levels of extreme grave bone marrow and intestinal ARS, respectively. (authors)

Integrated maintenance program (IMP)

International Nuclear Information System (INIS)

Zemdegs, R.T.; Chout, Q.B.

1998-01-01

Approaches to the maintenance of nuclear power plants have undergone significant change in the past several decades. The traditional breakdown approach has been displaced by preventive (calendar-based) maintenance and more recently, by condition-based maintenance (CBM). This is largely driven by the fact that traditional maintenance programs, derived primarily from equipment vendor recommendations, are generally unsuccessful in controlling maintenance costs or equipment failures. Many advances in the maintenance field have taken place since the maintenance plans for Ontario Hydro's nuclear plants were initially established. Ontario Hydro nuclear plant operating costs can be substantially reduced and Incapability Factor improved with the application of modern maintenance processes and tools. Pickering is designated as the lead station for IMP. Of immediate concern is the fact that Pickering Nuclear Division has been experiencing a significant backlog of Operating Preventive Maintenance Callups. This backlog, over 2000, is unacceptable to both station management and the nuclear regulator, the Atomic Energy Control Board. In addition there are over 500 callups in various stages of revision (in hyperspace) without an adequate control nor reporting system to manage their completion. There is also considerable confusion about the classification of l icensing c allups, e.g. callups which are mandatory as a result of legal requirements. Furthermore the ineffectiveness of the Preventive Maintenance (PM) has been the subject of peer audits and Atomic Energy Control Board (AECB) findings over the past several years. The current preventive maintenance ratio PM2 /(PM+CM3) at Pickering ND is less than 20%, due to the current high load of equipment breakdown. This past summer, an Independent Integrated Performance Assessment (IIPA) review at Ontario Hydro confirmed these concerns. Over the past several years, Ontario Hydro nuclear staff have evaluated several programs to improve

Preservation of Minced Meats by Using Medium and High-doses Irradiation

International Nuclear Information System (INIS)

Hammad, A.A.I.; Swailam, H.M.H.; Taha, S.M.A.

2003-01-01

The effect of medium (2.5-10 kGy) dose irradiation and high(20-70 kGy) dose irradiation on the microbiological, chemical and organoleptic properties of minced meat samples was studied. It was found that irradiation dose of only 5 kGy greatly reduced all microbial counts and completely eliminated all non-spore forming pathogenic bacteria contaminated minced meat samples. Consequently this irradiation dose extended the refrigerated (3 degree ±1) storage life of these products for more than 8 weeks. This irradiation dose almost did not affect the chemical composition, particularly the main amino acids and main fatty acids of minced meat samples. Panelists could not differentiate between irradiated minced meat samples at this dose and unirradiated samples. High doses irradiation, i.e.40 and 70 kGy were sufficient and efficient in sterilization of minced meat samples and in obtaining long-stable minced meat products (Two years) at ambient temperature. These irradiation doses slightly reduced (not more than 7%) aspartic acid, glutamic acid, methionine and lysine of minced meat. It also decreased the relative percentage of total unsaturated fatty acids by not more than 17 % . These high irradiation doses caused loss of C 18:3 and C 20:1

Dose management: weighing up the costs and benefits of remote maintenance

International Nuclear Information System (INIS)

Lefaure, C.; Lochard, J.; Blain, A.

1989-01-01

Reducing occupational exposure during maintenance, while at the same time preserving the economic viability of nuclear power plants, will be one of the major challenges to be faced by the industry over the next decade. Increased use of robotics is a possibility. The costs and benefits are examined in this paper. (author)

Efficacy and tolerability of high-dose phenobarbital in children with focal seizures.

Science.gov (United States)

Okumura, Akihisa; Nakahara, Eri; Ikeno, Mitsuru; Abe, Shinpei; Igarashi, Ayuko; Nakazawa, Mika; Takasu, Michihiko; Shimizu, Toshiaki

2016-04-01

We retrospectively reviewed the outcomes of children with focal epilepsy treated with oral high-dose phenobarbital. We reviewed data on children (agedphenobarbital (>5 mg/kg/day to maintain a target serum level >40 μg/mL) for at least 6 months. Seizure frequency was evaluated after phenobarbital titration, and 1 and 2 years after high-dose phenobarbital treatment commenced. Treatment was judged effective when seizure frequencies fell by ⩾75%. Seven boys and eight girls were treated. The median age at commencement of high-dose phenobarbital therapy was 30 months. The maximal serum phenobarbital level ranged from 36.5 to 62.9 μg/mL. High-dose PB was effective in seven. In two patients, treatment was transiently effective, but seizure frequency later returned to the baseline. High-dose PB was ineffective in six. No significant association between effectiveness and any clinical variable was evident. Drowsiness was recorded in nine patients, but no patient developed a behavioral problem or hypersensitivity. Oral high-dose phenobarbital was effective in 7 of 15 patients with focal epilepsy and well tolerated. High-dose PB may be useful when surgical treatment is difficult. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

A proactive condition-based maintenance strategy with both perfect and imperfect maintenance actions

International Nuclear Information System (INIS)

Do, Phuc; Voisin, Alexandre; Levrat, Eric; Iung, Benoit

2015-01-01

This paper deals with a proactive condition-based maintenance (CBM) considering both perfect and imperfect maintenance actions for a deteriorating system. Perfect maintenance actions restore completely the system to the ‘as good as new’ state. Their related cost are however often high. The first objective of the paper is to investigate the impacts of imperfect maintenance actions. In fact, both positive and negative impacts are considered. Positive impact means that the imperfect maintenance cost is usually low. Negative impact implies that (i) the imperfect maintenance restores a system to a state between good-as-new and bad-as-old and (ii) each imperfect preventive action may accelerate the speed of the system's deterioration process. The second objective of the paper is to propose an adaptive maintenance policy which can help to select optimally maintenance actions (perfect or imperfect actions), if needed, at each inspection time. Moreover, the time interval between two successive inspection points is determined according to a remaining useful life (RUL) based-inspection policy. To illustrate the use of the proposed maintenance policy, a numerical example finally is introduced. - Highlights: • A new imperfect maintenance model for deterioration system is proposed. • Both positive and negative impacts of an imperfect maintenance action are investigated. • An adaptive condition-based maintenance policy is introduced. • The optimal number of useful imperfect maintenance actions for each life cycle is optimally provided

Novel high dose rate lip brachytherapy technique to improve dose homogeneity and reduce toxicity by customized mold

International Nuclear Information System (INIS)

Feldman, Jon; Appelbaum, Limor; Sela, Mordechay; Voskoboinik, Ninel; Kadouri, Sarit; Weinberger, Jeffrey; Orion, Itzhak; Meirovitz, Amichay

2014-01-01

The purpose of this study is to describe a novel brachytherapy technique for lip Squamous Cell Carcinoma, utilizing a customized mold with embedded brachytherapy sleeves, which separates the lip from the mandible, and improves dose homogeneity. Seven patients with T2 lip cancer treated with a “sandwich” technique of High Dose Rate (HDR) brachytherapy to the lip, consisting of interstitial catheters and a customized mold with embedded catheters, were reviewed for dosimetry and outcome using 3D planning. Dosimetric comparison was made between the “sandwich” technique to “classic” – interstitial catheters only plan. We compared dose volume histograms for Clinical Tumor Volume (CTV), normal tissue “hot spots” and mandible dose. We are reporting according to the ICRU 58 and calculated the Conformal Index (COIN) to show the advantage of our technique. The seven patients (ages 36–81 years, male) had median follow-up of 47 months. Four patients received Brachytherapy and External Beam Radiation Therapy, 3 patients received brachytherapy alone. All achieved local control, with excellent esthetic and functional results. All patients are disease free. The Customized Mold Sandwich technique (CMS) reduced the high dose region receiving 150% (V150) by an average of 20% (range 1–47%), The low dose region (les then 90% of the prescribed dose) improved by 73% in average by using the CMS technique. The COIN value for the CMS was in average 0.92 as opposed to 0.88 for the interstitial catheter only. All differences (excluding the low dose region) were statistically significant. The CMS technique significantly reduces the high dose volume and increases treatment homogeneity. This may reduce the potential toxicity to the lip and adjacent mandible, and results in excellent tumor control, cosmetic and functionality

Chromosomal Aberrations in Normal and AT Cells Exposed to High Dose of Low Dose Rate Irradiation

Science.gov (United States)

Kawata, T.; Shigematsu, N.; Kawaguchi, O.; Liu, C.; Furusawa, Y.; Hirayama, R.; George, K.; Cucinotta, F.

2011-01-01

Ataxia telangiectasia (A-T) is a human autosomally recessive syndrome characterized by cerebellar ataxia, telangiectases, immune dysfunction, and genomic instability, and high rate of cancer incidence. A-T cell lines are abnormally sensitive to agents that induce DNA double strand breaks, including ionizing radiation. The diverse clinical features in individuals affected by A-T and the complex cellular phenotypes are all linked to the functional inactivation of a single gene (AT mutated). It is well known that cells deficient in ATM show increased yields of both simple and complex chromosomal aberrations after high-dose-rate irradiation, but, less is known on how cells respond to low-dose-rate irradiation. It has been shown that AT cells contain a large number of unrejoined breaks after both low-dose-rate irradiation and high-dose-rate irradiation, however sensitivity for chromosomal aberrations at low-dose-rate are less often studied. To study how AT cells respond to low-dose-rate irradiation, we exposed confluent normal and AT fibroblast cells to up to 3 Gy of gamma-irradiation at a dose rate of 0.5 Gy/day and analyzed chromosomal aberrations in G0 using fusion PCC (Premature Chromosomal Condensation) technique. Giemsa staining showed that 1 Gy induces around 0.36 unrejoined fragments per cell in normal cells and around 1.35 fragments in AT cells, whereas 3Gy induces around 0.65 fragments in normal cells and around 3.3 fragments in AT cells. This result indicates that AT cells can rejoin breaks less effectively in G0 phase of the cell cycle? compared to normal cells. We also analyzed chromosomal exchanges in normal and AT cells after exposure to 3 Gy of low-dose-rate rays using a combination of G0 PCC and FISH techniques. Misrejoining was detected in the AT cells only? When cells irradiated with 3 Gy were subcultured and G2 chromosomal aberrations were analyzed using calyculin-A induced PCC technique, the yield of unrejoined breaks decreased in both normal and AT

Dose finding study of granisetron in patients receiving high-dose cisplatin chemotherapy. The Granisetron Study Group.

Science.gov (United States)

Riviere, A.

1994-01-01

The efficacy and safety of three different doses of granisetron (2 micrograms kg-1, group A; 10 micrograms kg-1, group B; 40 micrograms kg-1, group C) were compared in a randomised, double-blind study of 157 patients due to receive high-dose cisplatin therapy (mean dose > 97 mg m-2). In each group, up to two 3 mg rescue doses of granisetron were allowed if more than mild nausea or vomiting occurred. In group A 30.8%, in group B 61.5% and in group C 67.9% of patients were complete responders (i.e. no vomiting or nothing worse than mild nausea) during the first 24 h. These differences are significant between groups A and B, and A and C. There were no statistically significant differences in any efficacy variable between the 10 micrograms kg-1 and 40 micrograms kg-1 groups, although in each case the trend favoured the higher dose. Additional rescue doses resulted in resolved or improved symptoms in 95.3% for the first rescue dose and 93.3% for the second. Over the 7 days of the study, 82.7%, 82.7% and 86.8% of patients in groups A, B and C respectively were treated with granisetron alone. Headache was the most common side-effect, reported by 9.6% of patients; the majority of headaches were mild. There was no difference between the treatment groups regarding the adverse event rate. We concluded that prophylactic doses of 10 or 40 micrograms kg-1 lead to a safe and satisfactory degree of control of nausea and vomiting induced by high-dose cisplatin. PMID:8180032

Overall asthma control achieved with budesonide/formoterol maintenance and reliever therapy for patients on different treatment steps

Directory of Open Access Journals (Sweden)

Östlund Ollie

2011-04-01

Full Text Available Abstract Background Adjusting medication for uncontrolled asthma involves selecting one of several options from the same or a higher treatment step outlined in asthma guidelines. We examined the relative benefit of introducing budesonide/formoterol (BUD/FORM maintenance and reliever therapy (Symbicort SMART® Turbuhaler® in patients previously prescribed treatments from Global Initiative for Asthma (GINA Steps 2, 3 or 4. Methods This is a post hoc analysis of the results of five large clinical trials (>12000 patients comparing BUD/FORM maintenance and reliever therapy with other treatments categorised by treatment step at study entry. Both current clinical asthma control during the last week of treatment and exacerbations during the study were examined. Results At each GINA treatment step, the proportion of patients achieving target levels of current clinical control were similar or higher with BUD/FORM maintenance and reliever therapy compared with the same or a higher fixed maintenance dose of inhaled corticosteroid/long-acting β2-agonist (ICS/LABA (plus short-acting β2-agonist [SABA] as reliever, and rates of exacerbations were lower at all treatment steps in BUD/FORM maintenance and reliever therapy versus same maintenance dose ICS/LABA (P Conclusions BUD/FORM maintenance and reliever therapy may be a preferable option for patients on Steps 2 to 4 of asthma guidelines requiring a more effective treatment and, compared with other fixed dose alternatives, is most effective in the higher treatment steps.

Estimation of dynamic treatment strategies for maintenance therapy of children with acute lymphoblastic leukaemia: an application of history-adjusted marginal structural models

DEFF Research Database (Denmark)

Rosthøj, Susanne; Keiding, Niels; Schmiegelow, Kjeld

2012-01-01

Childhood acute lymphoblastic leukaemia is treated with long-term intensive chemotherapy. During the latter part of the treatment, the maintenance therapy, the patients receive oral doses of two cytostatics. The doses are tailored to blood counts measured on a weekly basis, and the treatment is t...... of the methods in relation to the formulation of alternative dosing strategies for the maintenance therapy....

Does High-Dose Antimicrobial Chemotherapy Prevent the Evolution of Resistance?

Science.gov (United States)

Day, Troy; Read, Andrew F.

2016-01-01

High-dose chemotherapy has long been advocated as a means of controlling drug resistance in infectious diseases but recent empirical studies have begun to challenge this view. We develop a very general framework for modeling and understanding resistance emergence based on principles from evolutionary biology. We use this framework to show how high-dose chemotherapy engenders opposing evolutionary processes involving the mutational input of resistant strains and their release from ecological competition. Whether such therapy provides the best approach for controlling resistance therefore depends on the relative strengths of these processes. These opposing processes typically lead to a unimodal relationship between drug pressure and resistance emergence. As a result, the optimal drug dose lies at either end of the therapeutic window of clinically acceptable concentrations. We illustrate our findings with a simple model that shows how a seemingly minor change in parameter values can alter the outcome from one where high-dose chemotherapy is optimal to one where using the smallest clinically effective dose is best. A review of the available empirical evidence provides broad support for these general conclusions. Our analysis opens up treatment options not currently considered as resistance management strategies, and it also simplifies the experiments required to determine the drug doses which best retard resistance emergence in patients. PMID:26820986

High-dose zolpidem dependence - Psychostimulant effects? A case report and literature review

Directory of Open Access Journals (Sweden)

Abhijna Chandan Chattopadhyay

2016-01-01

Full Text Available Zolpidem, an imidazoline nonbenzodiazepine sedative drug, is used widely. Initial reports showed minimal abuse potential. However, multiple reports have appeared of dose escalation and abuse. Subjective effects of high-dose zolpidem are not known. In light of accumulating evidence of abuse potential, we hereby report a case of high-dose dependence and a review of relevant literature. A 33-year-old male presented with 5 years of daily use of 600–1700 mg of zolpidem tartrate. He reported subjective effects of euphoria, intense craving, and inability to stop use. Loss of receptor specificity, pharmacokinetic factors, and different receptor distributions can explain paradoxical stimulatory effects of high-dose zolpidem. Further studies are required to characterize subjective effects of high-dose zolpidem.

Concomitant chemoradiotherapy with high dose rate brachytherapy ...

African Journals Online (AJOL)

Concomitant chemoradiotherapy with high dose rate brachytherapy as a definitive treatment modality for locally advanced cervical cancer. T Refaat, A Elsaid, N Lotfy, K Kiel, W Small Jr, P Nickers, E Lartigau ...

Phosphorus-32 in polycythemia vera with and without maintenance treatment. Intermediate follow-up results

International Nuclear Information System (INIS)

Najean, Y.; Rain, J.D.

1995-01-01

Three-hundred and seventy-two patients with polycythemia vera, aged 65 years or more or with a high risk of vascular complications, were openly treated between 1979 and 1994 with 32 P or a combination of 32 P plus a small maintenance dose (7,5 mg/kg/day) of hydroxy urea. Although only a small number of patients was followed long enough to allow definite conclusions, some results are already significant in this intermediary study performed in November 1994. Maintenance treatment with hydroxy urea led to a significant prolongation of the intervals between 32 P administrations and to a decreased annual mean dose of radiophosphorus. Median survival does not differ between to the two treatment groups, 10,7 years compared to 10,0 years. The rate of vascular complications did not differ between groups. At 10 years follow-up, the risk of developing (epithelial) cancer was increased in the group of patients who received maintenance treatment, 30% compared to 10%. Similarly, development of myelodysplasia, acute leukemia or lymphoma was more common in patients receiving hydroxy urea, 25% compared to 12%. Myeloid transformation of the spleen occurred with the same frequency. Our intermediate follow-up results show that addition of hydroxy urea to 32 P treatment does not change survival or vascular complications in polycythemia vera patients, but probably increases the risk of developing cancer or leukemia. (authors). 2 refs., 4 figs

Study on radioactive waste management scenarios in regular maintenance of a fusion reactor

International Nuclear Information System (INIS)

Someya, Youji; Tobita, Kenji; Yanagihara, Satoshi

2015-01-01

Low-level radioactive waste is generated in large amounts in the operation of a fusion reactor. For this reason, there are needs for the study of radioactive waste management scenarios, as well as the clarification of the function of waste handling facilities in the design phase. This paper describes the management scenarios with a focus on the radioactive waste generated at the time of scheduled maintenance of a nuclear fusion prototype reactor. Based on the temporal change of the residual heat and dose rate of the blanket and diverter, as the furnace equipment associated with induced radioactivity, management period was determined. At this time, the attenuation rate of dose rate and the like of each device are different. So, if maintenance cycle is established for each device and thus storage area is minimized, the control area can be optimized. Based on the 'principle for minimizing radioactive waste,' the reuse of devices is effective in reducing waste. So, in view of a commercial reactor, research and development is required for the establishment of reuse process under high-dose. Since the commitment to radioactive waste is considered to be an important factor in the future for the social acceptance of nuclear fusion reactor development, comprehensive study including the disposal of waste and the reuse of equipment is important. (A.O.)

Radiation exposure for 'caregivers' during high-dose outpatient radioiodine therapy

International Nuclear Information System (INIS)

Marriott, C. J.; Webber, C. E.; Gulenchyn, K. Y.

2007-01-01

On 27 occasions, radiation doses were measured for a family member designated as the 'caregiver' for a patient receiving high-dose radioiodine outpatient therapy for differentiated thyroid carcinoma. For 25 of the administrations, patients received 3.7 GBq of 131 I. Radiation doses for the designated caregivers were monitored on an hourly basis for 1 week using electronic personal dosemeters. The average penetrating dose was 98±64 μSv. The maximum penetrating dose was 283 μSv. Measured dose rate profiles showed that, on average, one-third of the caregiver dose was received during the journey home from hospital. The mean dose rate profile showed rapid clearance of 131 I with three distinct phases. The corresponding clearance half-times were 131 I contaminating the home. (authors)

Remote handling maintenance of ITER

International Nuclear Information System (INIS)

Haange, R.

1999-01-01

The remote maintenance strategy and the associated component design of the International Thermonuclear Experimental Reactor (ITER) have reached a high degree of completeness, especially with respect to those components that are expected to require frequent or occasional remote maintenance. Large-scale test stands, to demonstrate the principle feasibility of the remote maintenance procedures and to develop the required equipment and tools, were operational at the end of the Engineering Design Activities (EDA) phase. The initial results are highly encouraging: major remote equipment deployment and component replacement operations have been successfully demonstrated. (author)

High-Dose versus Low-Dose Vitamin D Supplementation and Arterial Stiffness among Individuals with Prehypertension and Vitamin D Deficiency

Directory of Open Access Journals (Sweden)

Amanda Zaleski

2015-01-01

Full Text Available Introduction. Vitamin D deficiency is associated with the onset and progression of hypertension and cardiovascular disease (CVD. However, mechanisms underlying vitamin D deficiency-mediated increased risk of CVD remain unknown. We sought to examine the differential effect of high-dose versus low-dose vitamin D supplementation on markers of arterial stiffness among ~40 vitamin D deficient adults with prehypertension. Methods. Participants were randomized to high-dose (4000 IU/d versus low-dose (400 IU/d oral vitamin D3 for 6 months. 24 hr ambulatory blood pressure (BP, carotid-femoral pulse wave velocity, and pulse wave analyses were obtained at baseline and after 6 months of vitamin D supplementation. Results. There were no changes in resting BP or pulse wave velocity over 6 mo regardless of vitamin D dose (all p>0.202. High-dose vitamin D decreased augmentation index and pressure by 12.3 ± 5.3% (p=0.047 and 4.0 ± 1.5 mmHg (p=0.02, respectively. However, these decreases in arterial stiffness were not associated with increases in serum 25-hydroxyvitamin D over 6 mo (p=0.425. Conclusion. High-dose vitamin D supplementation appears to lower surrogate measures of arterial stiffness but not indices of central pulse wave velocity. Clinical Trial Registration. This trial is registered with www.clinicaltrials.gov (Unique Identifier: NCT01240512.

Status of fusion maintenance

International Nuclear Information System (INIS)

Fuller, G.M.

1984-01-01

Effective maintenance will be an essential ingredient in determining fusion system productivity. This level of productivity will result only after close attention is paid to the entire system as an entity and appropriate integration of the elements is made. The status of fusion maintenance is reviewed in the context of the entire system. While there are many challenging developmental tasks ahead in fusion maintenance, the required technologies are available in several high-technology industries, including nuclear fission

High dose calibrations at the Pacific Northwest Laboratory

International Nuclear Information System (INIS)

McDonald, J.C.; Fox, R.A.

1988-10-01

The need is increasing for both high radiation exposures and calibration measurements that provide traceability of such exposures to national standards. The applications of high exposures include: electronic component damage studies, sterilization of medical products and food irradiation. Accurate high exposure measurements are difficult to obtain and cannot, in general, be carried out with a single dose measurement system or technique because of the wide range of doses and the variety of materials involved. This paper describes the dosimetric measurement and calibration techniques used at the Pacific Northwest Laboratory (PNL) that make use of radiochromic dye films, thermoluminescent dosimeters (TLDs), ionization chambers, and calorimetric dosimeters. The methods used to demonstrate the consistency of PNL calibrations with national standards will also be discussed. 4 refs

SU-F-P-19: Fetal Dose Estimate for a High-Dose Fluoroscopy Guided Intervention Using Modern Data Tools

Energy Technology Data Exchange (ETDEWEB)

Moirano, J [University of Washington, Seattle, WA (United States)

2016-06-15

Purpose: An accurate dose estimate is necessary for effective patient management after a fetal exposure. In the case of a high-dose exposure, it is critical to use all resources available in order to make the most accurate assessment of the fetal dose. This work will demonstrate a methodology for accurate fetal dose estimation using tools that have recently become available in many clinics, and show examples of best practices for collecting data and performing the fetal dose calculation. Methods: A fetal dose estimate calculation was performed using modern data collection tools to determine parameters for the calculation. The reference point air kerma as displayed by the fluoroscopic system was checked for accuracy. A cumulative dose incidence map and DICOM header mining were used to determine the displayed reference point air kerma. Corrections for attenuation caused by the patient table and pad were measured and applied in order to determine the peak skin dose. The position and depth of the fetus was determined by ultrasound imaging and consultation with a radiologist. The data collected was used to determine a normalized uterus dose from Monte Carlo simulation data. Fetal dose values from this process were compared to other accepted calculation methods. Results: An accurate high-dose fetal dose estimate was made. Comparison to accepted legacy methods were were within 35% of estimated values. Conclusion: Modern data collection and reporting methods ease the process for estimation of fetal dose from interventional fluoroscopy exposures. Many aspects of the calculation can now be quantified rather than estimated, which should allow for a more accurate estimation of fetal dose.

The Steroids in the Maintenance of Remission of Proliferative Lupus Nephritis (SIMPL Pilot Trial

Directory of Open Access Journals (Sweden)

Lauren Galbraith

2014-11-01

Full Text Available Background: Patients with proliferative lupus nephritis are at risk of frequent relapses. Whether low- dose prednisone prevents relapses is uncertain. Objectives: We undertook a pilot RCT to determine the feasibility of a larger trial. Design: Pilot randomized controlled trial. Setting: Single center Canadian outpatient nephrology clinic. Patients: Participants with systemic lupus erythematosus (SLE and a history of class III or IV lupus nephritis that achieved at least partial remission and remained on prednisone were eligible. Measurements: Feasibility: proportion of eligible patients randomized and adherence to tapering regimen. Clinical: occurrence of renal or major non-renal flare of SLE. Methods: We conducted a blinded, two-parallel-group randomized controlled trial of prednisone 7.5 mg/day (continuation compared to a matching placebo (withdrawal. Results: Of nineteen eligible patients screened, 15 (79% were recruited and randomized; 8 to prednisone continuation and seven to withdrawal. All participants adhered to the tapering protocol to their assigned withdrawal or low-dose maintenance target. Over 36 months, the primary outcome occurred in four (50% patients in the continuation group (three renal and one major non-renal flare, compared with one patient (14% in the withdrawal group (one renal flare. Three participants (38% in the continuation group had minor flares, while no patients in the withdrawal group did. Limitations: This pilot RCT was small and not designed to assess the efficacy or safety of maintenance with low-dose prednisone. Conclusions: The high proportion of eligible patients recruited, and success of protocol adherence suggest a large trial of prednisone maintenance therapy compared to withdrawal is feasible. Trial registration: Current Controlled Trials ISRCTN31327267.

Comparative study of SOI/Si hybrid substrates fabricated using high-dose and low-dose oxygen implantation

International Nuclear Information System (INIS)

Dong Yemin; Chen Meng; Chen Jing; Wang Xiang; Wang Xi

2004-01-01

Hybrid substrates comprising both silicon-on-insulator (SOI) and bulk Si regions have been fabricated using the technique of patterned separation by implantation of oxygen (SIMOX) with high-dose (1.5 x 10 18 cm -2 ) and low-dose ((1.5-3.5) x 10 17 cm -2 ) oxygen ions, respectively. Cross-sectional transmission electron microscopy (XTEM) was employed to examine the microstructures of the resulting materials. Experimental results indicate that the SOI/Si hybrid substrate fabricated using high-dose SIMOX is of inferior quality with very large surface height step and heavily damaged transitions between the SOI and bulk regions. However, the quality of the SOI/Si hybrid substrate is enhanced dramatically by reducing the implant dose. The defect density in transitions is reduced considerably. Moreover, the expected surface height difference does not exist and the surface is exceptionally flat. The possible mechanisms responsible for the improvements in quality are discussed