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Sample records for clopidogrel response evaluated

  1. Clopidogrel Responsiveness in Patients Undergoing Peripheral Angioplasty

    SciTech Connect

    Pastromas, Georgios Spiliopoulos, Stavros Katsanos, Konstantinos Diamantopoulos, Athanasios Kitrou, Panagiotis Karnabatidis, Dimitrios Siablis, Dimitrios

    2013-12-15

    Purpose: To investigate the incidence and clinical significance of platelet responsiveness in patients receiving clopidogrel after peripheral angioplasty procedures. Materials and Methods: This prospective study included patients receiving antiplatelet therapy with clopidogrel 75 mg after infrainguinal angioplasty or stenting and who presented to our department during routine follow-up. Clopidogrel responsiveness was tested using the VerifyNow P2Y12 Assay. Patients with residual platelet reactivity units (PRU) {>=} 235 were considered as nonresponders (NR group NR), whereas patients with PRU < 235 were considered as normal (responders [group R]). Primary end points were incidence of resistance to clopidogrel and target limb reintervention (TLR)-free survival, whereas secondary end points included limb salvage rates and the identification of any independent predictors influencing clinical outcomes. Results: In total, 113 consecutive patients (mean age 69 {+-} 8 years) with 139 limbs were enrolled. After clopidogrel responsiveness analysis, 61 patients (53.9 %) with 73 limbs (52.5 %) were assigned to group R and 52 patients (46.1 %) with 66 limbs (47.5 %) to group NR. Mean follow-up interval was 27.7 {+-} 22.9 months (range 3-95). Diabetes mellitus, critical limb ischemia, and renal disease were associated with clopidogrel resistance (Fisher's exact test; p < 0.05). According to Kaplan-Meier analysis, TLR-free survival was significantly superior in group R compared with group NR (20.7 vs. 1.9 %, respectively, at 7-year follow-up; p = 0.001), whereas resistance to clopidogrel was identified as the only independent predictor of decreased TLR-free survival (hazard rate 0.536, 95 % confidence interval 0.31-0.90; p = 0.01). Cumulative TLR rate was significantly increased in group NR compared with group R (71.2 % [52 of 73] vs. 31.8 % [21 of 66], respectively; p < 0.001). Limb salvage was similar in both groups. Conclusion: Clopidogrel resistance was related with

  2. Pharmacokinetic and Pharmacodynamic Responses to Clopidogrel: Evidences and Perspectives

    PubMed Central

    Zhang, Yan-Jiao; Li, Mu-Peng; Tang, Jie; Chen, Xiao-Ping

    2017-01-01

    Clopidogrel has significantly reduced the incidence of recurrent atherothrombotic events in patients with acute coronary syndrome (ACS) and in those undergoing percutaneous coronary intervention (PCI). However, recurrence events still remain, which may be partly due to inadequate platelet inhibition by standard clopidogrel therapy. Genetic polymorphisms involved in clopidogrel’s absorption, metabolism, and the P2Y12 receptor may interfere with its antiplatelet activity. Recent evidence indicated that epigenetic modification may also affect clopidogrel response. In addition, non-genetic factors such as demographics, disease complications, and drug-drug interactions can impair the antiplatelet effect of clopidogrel. The identification of factors contributing to the variation in clopidogrel response is needed to improve platelet inhibition and to reduce risk for cardiovascular events. This review encompasses the most recent updates on factors influencing pharmacokinetic and pharmacodynamic responses to clopidogrel. PMID:28335443

  3. Comparison of ticagrelor and high-dose clopidogrel on the platelet functions in patients with inadequate response to clopidogrel

    PubMed Central

    Gu, Xinshun; Fu, Xianghua; Wang, Yanbo; Zhang, Wenhui; Fan, Weize; Jiang, Yunfa; Hao, Guozhen; Miao, Qing; Li, Yi; Zhi, Wei

    2017-01-01

    Objective: To evaluate the effects of ticagrelor and high-dose clopidogrel on the platelet functions in patients with inadequate response to clopidogrel. Methods: In this prospective, randomized and controlled study, patients who had been diagnosed as acute coronary syndrome (ACS) with inadequate response to clopidogrel in the Second Hospital of Hebei Medical University from July 2015 to June 2016 were enrolled. Inadequate response to clopidogrel was defined as absolute reduction of platelet aggregation rate (PAR) <30% or PAR >70%. Eligible patients were randomly assigned to two groups, the high-dose group and the ticagrelor group. Clinical information and intervention protocols were compared. The PAR of the two groups were measured at the time of baseline, the 24th hour, 72nd hour, and the 7th day after treatments, the other platelet-related parameters were measured including platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW) at the same time points. Besides, the markers of platelet activation human P-selectin (CD62P) and thromboxane A2 (TXA2) were also recorded to compare. The incidence of major adverse cardiac events (MACE) and the side effects between two groups were followed up for three months. Results: A total of 74 patients were finally enrolled, 38 of whom were assigned to the ticagrelor group and the rest of them to the high-dose clopidogrel group. The baseline clinical and procedural characterists were similar. There were no significant differences in baseline levels of PAR between the two groups [(79.38±11.20)% vs. (73.97±12.74)%, P>0.05]. For both groups, the levels of PAR significantly decreased at each time point (P<0.001). Besides, the levels of PAR in ticagrelor group were lower than those in high-dose clopidogrel group at the 24th hour, 72nd hour and 7th day after treatments: [(25.92±10.31)% vs. (37.95±11.63)%, P<0.001], [(28.02±14.61)% vs. (30.64±10.73)%, P<0.001], [(37.17±11.11)% vs. (36.80±7.26)%, P<0

  4. Aspirin and clopidogrel response variability: review of the published literature.

    PubMed

    Ferguson, Angela D; Dokainish, Hisham; Lakkis, Nasser

    2008-01-01

    Antiplatelet resistance has been proposed as a possible mechanism to explain recurrent cardiovascular events in patients who have coronary artery disease and who are undergoing dual antiplatelet therapy. A comprehensive search on PubMed was conducted for literature that was printed in the English language between January 1996 and November 2007 on aspirin and clopidogrel resistance. Significant traits for aspirin hyporesponsiveness were female sex, older age, and lower levels of hemoglobin. Diabetes mellitus and elevated body mass index showed trends toward a higher incidence of resistance in some aspirin trials but did not reach statistical significance. Clopidogrel studies suggested that patients with type-2 diabetes mellitus are more likely to manifest inadequate response to the medication. Although 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors were initially suspected to decrease response to clopidogrel, later studies refuted this possibility. Patients with a suboptimal response to aspirin or clopidogrel seem to be at increased risk of recurrent cardiovascular events. Large clinical trials with standardized laboratory methods and well-defined protocols are needed to determine whether common features exist in patients with suspected hyporesponsiveness to antiplatelet therapy, and to validate the clinical relevance of response variability. A concise nonarbitrary definition of physiologic "resistance" is needed, and investigators should identify patients as having a variable response to antiplatelet therapy.

  5. Clopidogrel Response Variability: Review of the Literature and Practical Considerations.

    PubMed

    Oliphant, Carrie S; Trevarrow, Brian J; Dobesh, Paul P

    2016-02-01

    Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor is standard therapy following acute coronary syndrome and percutaneous coronary intervention. Despite the use of potent antiplatelet agents, vascular events continue to occur. Lack of response to clopidogrel therapy has been widely investigated using various methods of platelet function testing. These studies have consistently found an association between poor clopidogrel response and an increased risk of vascular events. Strategies to overcome this problem include higher clopidogrel doses or the use of an alternative P2Y12 agent. To date, the majority of studies investigating tailored antiplatelet therapy have failed to show any reduction in clinical events likely due to the low-risk population studied. Despite this lack of benefit from altering therapy, platelet function testing may be done in certain patient populations. Patients at high risk of deleterious outcomes from stent thrombosis may be an appropriate patient population for platelet function testing to ensure adequate response to therapy. In addition, emerging data suggests a potential role for platelet function testing to assess for bleeding risk. The purpose of this article is to review the key studies demonstrating response variability to clopidogrel therapy, strategies to overcome variability, and practical considerations for the clinician.

  6. Clopidogrel, a P2Y12 Receptor Antagonist, Potentiates the Inflammatory Response in a Rat Model of Peptidoglycan Polysaccharide-Induced Arthritis

    PubMed Central

    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. PMID:22028806

  7. The use of amlodipine, but not of P-glycoprotein inhibiting calcium channel blockers is associated with clopidogrel poor-response.

    PubMed

    Harmsze, Ankie M; Robijns, Karen; van Werkum, Jochem W; Breet, Nicoline J; Hackeng, Christian M; Ten Berg, Jurrien M; Ruven, Hendrik J T; Klungel, Olaf H; de Boer, Anthonius; Deneer, Vera H M

    2010-05-01

    Clopidogrel is a prodrug that has to be converted in vivo to its active metabolite by cytochrome (CYP)P450 iso-enzymes. As calcium channel blockers (CCBs) are inhibitors of CYP3A4, concomitant use of these drugs might play a role in the wide inter-individual variability in the response to clopidogrel. However, some CCBs also have strong inhibitory effects on the drug transporter P-glycoprotein (Pgp), which mediates clopidogrel's intestinal absorption. It was the aim of this study to evaluate the effect of co-administration of Pgp-inhibiting and non-Pgp-inhibiting CCBs on on-clopidogrel platelet reactivity in patients on dual antiplatelet therapy undergoing elective percutaneous coronary intervention (PCI). In a total of 623 consecutive patients undergoing elective PCI treated with clopidogrel and aspirin, platelet reactivity to 5 and 20 muM adenosine diphospate (ADP) and clopidogrel poor-response (defined as > 70% platelet aggregation to 20 muM ADP) were evaluated by light transmittance aggregometry. A total of 222 patients (35.6%) were on CCB treatment, of which 98 used Pgp-inhibiting CCBs (verapamil, nifedipine, diltiazem, barnidipine) and 124 patients used the non-Pgp-inhibiting CCB amlodipine. Adjusted mean ADP-induced on-clopidogrel platelet reactivity was significantly higher in both users of Pgp-inhibiting CCBs and amlodipine as compared to CCB non-users (all p<0.05). However, only the use of amlodipine was significantly associated with a 2.3-fold increased risk of clopidogrel poor-response. This study demonstrates that concomitant use of Pgp-inhibiting CCBs and amlodipine increases on-clopidogrel platelet reactivity. Only amlodipine was associated with clopidogrel poor-response. The drug-drug interaction between clopidogrel and amlodipine might be more clinically relevant as compared to P-glycoprotein-inhibiting CCBs.

  8. Hypersensitivity to ticagrelor and low response to clopidogrel: a case report

    PubMed Central

    Dai, Jing; Ge, Changjiang

    2017-01-01

    Ticagrelor is widely used to treat acute coronary syndrome. Hypersensitivity reaction of ticagrelor is rarely recognized. A low response to clopidogrel, which occurs in up to 23% of patients, is an independent risk factor for stent thrombosis. Management of patients with a low response to clopidogrel and ticagrelor hypersensitivity who are undergoing antithrombotic therapy remains to be a challenge. Herein, we report a patient with low response to clopidogrel and ticagrelor hypersensitivity, who was successfully managed using aspirin and warfarin. PMID:28154807

  9. Design, development and evaluation of clopidogrel bisulfate floating tablets

    PubMed Central

    Rao, K. Rama Koteswara; Lakshmi, K. Rajya

    2014-01-01

    Objective: The objective of the present work was to formulate and to characterize a floating drug delivery system for clopidogrel bisulphate to improve bioavailability and to minimize the side effects of the drug such as gastric bleeding and drug resistance development. Materials and Methods: Clopidogrel floating tablets were prepared by direct compression technique by the use of three polymers xanthan gum, hydroxypropyl methylcellulose (HPMC) K15M and HPMC K4M in different concentrations (20%, 25% and 30% w/w). Sodium bicarbonate (15% w/w) and microcrystalline cellulose (30% w/w) were used as gas generating agent and diluent respectively. Studies were carried out on floating behavior and influence of type of polymer on drug release rate. All the formulations were subjected to various quality control and in-vitro dissolution studies in 0.1 N hydrochloric acid (1.2 pH) and corresponding dissolution data were fitted to popular release kinetic equations in order to evaluate release mechanisms and kinetics. Results and Discussion: All the clopidogrel floating formulations followed first order kinetics, Higuchi drug release kinetics with diffusion as the dominant mechanism of drug release. As per Korsmeyer-Peppas equation, the release exponent “n” ranged 0.452-0.654 indicating that drug release from all the formulations was by non-Fickian diffusion mechanism. The drug release rate of clopidogrel was found to be affected by the type and concentration of the polymer used in the formulation (P < 0.05). As the concentration of the polymer was increased, the drug release was found to be retarded. Conclusion: Based on the results, clopidogrel floating tablets prepared by employing xanthan gum at concentration 25% w/w (formulation F2) was the best formulation with desired in-vitro floating time and drug dissolution. PMID:24678458

  10. Comparison of VerifyNow P2Y12 and thrombelastography for assessing clopidogrel response in stroke patients in China.

    PubMed

    Lv, Hui-Hui; Wu, Shuai; Liu, Xu; Yang, Xiao-Li; Xu, Jian-Feng; Guan, Yang-Tai; Dong, Qiang; Zheng, S Lilly; Jiang, Jian-Ming; Li, Shi-Xu; Luo, Zheng; Li, Li; An, Li-Xian; Han, Yan

    2016-02-01

    Poor response to clopidogrel is often associated with recurrent ischemic events, and reliable platelet function tests are needed to identify clopidogrel low response (CLR). The aim of the study was to compare the consistency of VerifyNow P2Y12 and thrombelastography (TEG) in acute ischemic stroke patients treated with clopidogrel. Patients hospitalized in Changhai Hospital from August 2012 to September 2013 and assigned to treatment with a daily 75-mg dose of clopidogrel. The blood samples were taken on the 5-7th day to assess the capability of VerifyNow P2Y12 and TEG for evaluation of clopidogrel response, and all instrument parameters were used to perform correlation analysis. Patients with CLR were detected by using the methods and criteria published earlier (PRU ≥ 230 assayed by VerifyNow P2Y12 or TEG-Inhib% ≤30 % measured by TEG). Totally 58 patients were enrolled for the study and there were wide varieties in parameters of VerifyNow P2Y12 and TEG. Results showed a total of 17 and 9 patients, respectively, identified as CLR assessed by VerifyNow P2Y12 and TEG, but only three patients were detected to be clopidogrel low responders with both tests. The kappa consistency analysis showed poor consistency between VerifyNow P2Y12 and TEG results in terms of CLR (Kappa = -0.0349, p = 0.7730). Linear regression also demonstrated poor correlation between VerifyNow-PRU/VerifyNow-Inhib% and TEG-Inhib% (p = 0.07901 and p = 0.3788, respectively). Our study demonstrated that there was poor correlation between VerifyNow P2Y12 and TEG results, and VerifyNow P2Y12 showed a larger proportion of CLR than TEG.

  11. Optimizing clopidogrel dose response: a new clinical algorithm comprising CYP2C19 pharmacogenetics and drug interactions

    PubMed Central

    Saab, Yolande B; Zeenny, Rony; Ramadan, Wijdan H

    2015-01-01

    Purpose Response to clopidogrel varies widely with nonresponse rates ranging from 4% to 30%. A reduced function of the gene variant of the CYP2C19 has been associated with lower drug metabolite levels, and hence diminished platelet inhibition. Drugs that alter CYP2C19 activity may also mimic genetic variants. The aim of the study is to investigate the cumulative effect of CYP2C19 gene polymorphisms and drug interactions that affects clopidogrel dosing, and apply it into a new clinical-pharmacogenetic algorithm that can be used by clinicians in optimizing clopidogrel-based treatment. Method Clopidogrel dose optimization was analyzed based on two main parameters that affect clopidogrel metabolite area under the curve: different CYP2C19 genotypes and concomitant drug intake. Clopidogrel adjusted dose was computed based on area under the curve ratios for different CYP2C19 genotypes when a drug interacting with CYP2C19 is added to clopidogrel treatment. A clinical-pharmacogenetic algorithm was developed based on whether clopidogrel shows 1) expected effect as per indication, 2) little or no effect, or 3) clinical features that patients experience and fit with clopidogrel adverse drug reactions. Results The study results show that all patients under clopidogrel treatment, whose genotypes are different from *1*1, and concomitantly taking other drugs metabolized by CYP2C19 require clopidogrel dose adjustment. To get a therapeutic effect and avoid adverse drug reactions, therapeutic dose of 75 mg clopidogrel, for example, should be lowered to 6 mg or increased to 215 mg in patients with different genotypes. Conclusion The implementation of clopidogrel new algorithm has the potential to maximize the benefit of clopidogrel pharmacological therapy. Clinicians would be able to personalize treatment to enhance efficacy and limit toxicity. PMID:26445541

  12. Does i-T744C P2Y12 Polymorphism Modulate Clopidogrel Response among Moroccan Acute Coronary Syndromes Patients?

    PubMed Central

    Hmimech, Wiam; El Khorb, Nada; Akoudad, Hafid; Habbal, Rachida; Nadifi, Sellama

    2017-01-01

    Background. An interindividual variability in response to Clopidogrel has been widely described in patients with acute coronary syndromes (ACS). The contribution of genetics on modulating this response was widely discussed. The objective of our study was to investigate the potential effect of i-T744C P2Y12 polymorphism on Clopidogrel response in a sample of Moroccan ACS patients. We tried also to determine the frequency of this polymorphism among Moroccan ACS compared to healthy subjects. Methods and Results. 77 ACS patients versus 101 healthy controls were recruited. DNA samples were genotyped by PCR-RFLP method. The VerifyNow assay was used to evaluate platelet function among ACS patients. Our results show that the mutant allele C was more frequent among ACS ST (+) than ST (−) patients (39% versus 19.8%, resp.), when the wild-type allele was more represented in the ACS ST (−) group (80.2%). The C allele frequency was higher among resistant than nonresistant patients (30% versus 20.8%, resp.). Comparison of ACS patients and healthy controls shows higher frequency of mutant C allele among cases compared to controls (22.73% versus 19.31%, resp.); there was a statistically significant association of the recessive and additive transmission models with the ACS development risk (OR [95% CI] = 1.78 [1.58–5.05], P = 0.01 and OR [95% CI] = 1.23 [0.74–2.03], P < 0.001, resp.), increasing thus the association of this polymorphism with the pathology. Conclusion. Our results suggest that this polymorphism may have a potential effect on Clopidogrel response among our Moroccan ACS patients and also on ACS development. PMID:28261502

  13. [Stent thrombosis and clopidogrel response variability: is the genetic test useful in clinical practice?].

    PubMed

    Notarangelo, Maria Francesca; Marziliano, Nicola; Giacalone, Rossella; Demola, Maria Antonietta; Conte, Giulio; Mantovani, Francesco; Ardissino, Diego

    2011-10-01

    The antiplatelet agent clopidogrel is an effective drug for the prevention of thrombotic events in patients with acute coronary syndrome and in those undergoing percutaneous coronary intervention with the deployment of a coronary stent. However, it has been reported that, despite adequate treatment, about 30% of patients continue to show the high degree of platelet reactivity that is central to the development of atherothrombotic complications and poorer clinical outcomes. Up to 13% of those taking clopidogrel experience a recurrent ischemic event during the first year after acute coronary syndrome, 1-3% experience subacute stent thrombosis after percutaneous coronary intervention probably due to a poor drug response, and about 1.5% experience major bleeding mainly due to an enhanced response. Recent research findings have highlighted the role of genetic variations in determining antiplatelet response variability, and this has aroused interest in genotyping all thienopyridine-eligible patients in order to identify those who would be at increased risk of harm if treated with clopidogrel. However, it remains to be determined whether this information is necessary or sufficient for risk stratification. Only when there are clinical data to support the hypothesis that genotype-guided therapy reduces the rate of ischemic and bleeding events will it be possible to justify the use of genetic testing in all potential patients. When that happens, genotype-guided antiplatelet therapy will also be available in the field of cardiovascular medicine.

  14. Decreased platelet responsiveness to clopidogrel correlates with CYP2C19 and PON1 polymorphisms in atherosclerotic patients.

    PubMed

    Marchini, J F M; Pinto, M R; Novaes, G C; Badran, A V; Pavão, R B; Figueiredo, G L; Lago, I M; Lima-Filho, M O; Lemos, D C; Tonani, M; Antloga, C M; Oliveira, L; Lorenzi, J C; Marin-Neto, J A

    2017-01-09

    Clopidogrel and aspirin are the most commonly used medications worldwide for dual antiplatelet therapy after percutaneous coronary intervention. However, clopidogrel hyporesponsiveness related to gene polymorphisms is a concern. Populations with higher degrees of genetic admixture may have increased prevalence of clopidogrel hyporesponsiveness. To assess this, we genotyped CYP2C19, ABCB1, and PON1 in 187 patients who underwent percutaneous coronary intervention. Race was self-defined by patients. We also performed light transmission aggregometry with adenosine diphosphate (ADP) and arachidonic acid during dual antiplatelet therapy. We found a significant difference for presence of the CYP2C19*2 polymorphism between white and non-white patients. Although 7% of patients had platelet resistance to clopidogrel, this did not correlate with any of the tested genetic polymorphisms. We did not find platelet resistance to aspirin in this cohort. Multivariate analysis showed that patients with PON1 and CYP2C19 polymorphisms had higher light transmission after ADP aggregometry than patients with native alleles. There was no preponderance of any race in patients with higher light transmission aggregometry. In brief, PON1 and CYP2C19 polymorphisms were associated with lower clopidogrel responsiveness in this sample. Despite differences in CYP2C19 polymorphisms across white and non-white patients, genetic admixture by itself was not able to identify clopidogrel hyporesponsiveness.

  15. Decreased platelet responsiveness to clopidogrel correlates with CYP2C19 and PON1 polymorphisms in atherosclerotic patients

    PubMed Central

    Marchini, J.F.M.; Pinto, M.R.; Novaes, G.C.; Badran, A.V.; Pavão, R.B.; Figueiredo, G.L.; Lago, I.M.; Lima-Filho, M.O.; Lemos, D.C.; Tonani, M.; Antloga, C.M.; Oliveira, L.; Lorenzi, J.C.; Marin-Neto, J.A.

    2017-01-01

    Clopidogrel and aspirin are the most commonly used medications worldwide for dual antiplatelet therapy after percutaneous coronary intervention. However, clopidogrel hyporesponsiveness related to gene polymorphisms is a concern. Populations with higher degrees of genetic admixture may have increased prevalence of clopidogrel hyporesponsiveness. To assess this, we genotyped CYP2C19, ABCB1, and PON1 in 187 patients who underwent percutaneous coronary intervention. Race was self-defined by patients. We also performed light transmission aggregometry with adenosine diphosphate (ADP) and arachidonic acid during dual antiplatelet therapy. We found a significant difference for presence of the CYP2C19*2 polymorphism between white and non-white patients. Although 7% of patients had platelet resistance to clopidogrel, this did not correlate with any of the tested genetic polymorphisms. We did not find platelet resistance to aspirin in this cohort. Multivariate analysis showed that patients with PON1 and CYP2C19 polymorphisms had higher light transmission after ADP aggregometry than patients with native alleles. There was no preponderance of any race in patients with higher light transmission aggregometry. In brief, PON1 and CYP2C19 polymorphisms were associated with lower clopidogrel responsiveness in this sample. Despite differences in CYP2C19 polymorphisms across white and non-white patients, genetic admixture by itself was not able to identify clopidogrel hyporesponsiveness. PMID:28076455

  16. Management Strategies for Clopidogrel Hypersensitivity.

    PubMed

    Beavers, Craig J; Carris, Nicolas W; Ruf, Kathryn M

    2015-06-01

    Clopidogrel is a cornerstone of dual antiplatelet therapy. Hypersensitivity reactions potentially limit the use of this treatment and present a significant clinical challenge. The authors have developed recommendations for the management of clopidogrel hypersensitivity with consideration for the etiology, pathophysiology, and critical evaluation of potential management strategies. The clopidogrel hypersensitivity reaction is complex in mechanism and presents generally around day 5 of treatment. Generalized reactions are most common, but the reaction may also be localized or systemic. Screening patients for hypersensitivity is not always possible because the type IV delayed reaction is not detected reliably by conventional skin prick, intradermal challenge, or patch testing. Proposed strategies for management of clopidogrel hypersensitivity include treatment of the reaction with corticosteroids, clopidogrel desensitization, substituting an alternative P2Y12 inhibitor, or clopidogrel avoidance. The safety, efficacy, and cost of each potential strategy must be considered when managing a patient with clopidogrel hypersensitivity.

  17. Cytochrome P450 3A4*22, PPAR-α, and ARNT polymorphisms and clopidogrel response.

    PubMed

    Kreutz, Rolf P; Owens, Janelle; Jin, Yan; Nystrom, Perry; Desta, Zeruesenay; Kreutz, Yvonne; Breall, Jeffrey A; Li, Lang; Chiang, Chienwei; Kovacs, Richard J; Flockhart, David A

    2013-01-01

    Recent candidate gene studies using a human liver bank and in vivo validation in healthy volunteers identified polymorphisms in cytochrome P450 (CYP) 3A4 gene (CYP3A4*22), Ah-receptor nuclear translocator (ARNT), and peroxisome proliferator-activated receptor-α (PPAR-α) genes that are associated with the CYP3A4 phenotype. We hypothesized that the variants identified in these genes may be associated with altered clopidogrel response, since generation of clopidogrel active metabolite is, partially mediated by CYP3A activity. Blood samples from 211 subjects, of mixed racial background, with established coronary artery disease, who had received clopidogrel, were analyzed. Platelet aggregation was determined using light transmittance aggregometry (LTA). Genotyping for CYP2C19*2, CYP3A4*22, PPAR-α (rs4253728, rs4823613), and ARNT (rs2134688) variant alleles was performed using Taqman® assays. CYP2C19*2 genotype was associated with increased on-treatment platelet aggregation (adenosine diphosphate 20 μM; P=0.025). No significant difference in on-treatment platelet aggregation, as measured by LTA during therapy with clopidogrel, was demonstrated among the different genotypes of CYP3A4*22, PPAR-α, and ARNT. These findings suggest that clopidogrel platelet inhibition is not influenced by the genetic variants that have previously been associated with reduced CYP3A4 activity.

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

    PubMed

    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 < 0.001). Receiver-operating characteristic curve analysis demonstrated that Au-min value >612.5 predicted the clopidogrel resistance with a sensitivity of 60% (OR: 100.65, %95 CI = 19.996-506.615 p < 0.001). Results of this study demonstrated that ADP responses were lower in smokers receiving clopidogrel and aspirin than in non-smokers receiving the same drug regimen. This finding indicates that smoking was related to an enhanced clopidogrel responsiveness in Turkish patients hospitalized due to ACS, suggesting that "smoker's paradox" probably exists in Turkish ACS patients.

  19. Development of a physiology-directed population pharmacokinetic and pharmacodynamic model for characterizing the impact of genetic and demographic factors on clopidogrel response in healthy adults.

    PubMed

    Jiang, Xi-Ling; Samant, Snehal; Lewis, Joshua P; Horenstein, Richard B; Shuldiner, Alan R; Yerges-Armstrong, Laura M; Peletier, Lambertus A; Lesko, Lawrence J; Schmidt, Stephan

    2016-01-20

    Clopidogrel (Plavix®), is a widely used antiplatelet agent, which shows high inter-individual variability in treatment response in patients following the standard dosing regimen. In this study, a physiology-directed population pharmacokinetic/pharmacodynamic (PK/PD) model was developed based on clopidogrel and clopidogrel active metabolite (clop-AM) data from the PAPI and the PGXB2B studies using a step-wise approach in NONMEM (version 7.2). The developed model characterized the in vivo disposition of clopidogrel, its bioactivation into clop-AM in the liver and subsequent platelet aggregation inhibition in the systemic circulation reasonably well. It further allowed the identification of covariates that significantly impact clopidogrel's dose-concentration-response relationship. In particular, CYP2C19 intermediate and poor metabolizers converted 26.2% and 39.5% less clopidogrel to clop-AM, respectively, compared to extensive metabolizers. In addition, CES1 G143E mutation carriers have a reduced CES1 activity (82.9%) compared to wild-type subjects, which results in a significant increase in clop-AM formation. An increase in BMI was found to significantly decrease clopidogrel's bioactivation, whereas increased age was associated with increased platelet reactivity. Our PK/PD model analysis suggests that, in order to optimize clopidogrel dosing on a patient-by-patient basis, all of these factors have to be considered simultaneously, e.g. by using quantitative clinical pharmacology tools.

  20. Positive clinical response to clopidogrel is independent of paraoxonase 1 Q192R and CYP2C19 genetic variants.

    PubMed

    Martínez-Quintana, Efrén; Medina-Gil, José M; Rodríguez-González, Fayna; Garay-Sánchez, Paloma; Limiñana, José M; Saavedra, Pedro; Tugores, Antonio

    2014-08-01

    There is increasing controversy about the influence of serum paraoxonase type 1 and cytochrome CYP2C19 in the conversion of clopidogrel to its pharmaceutically active metabolite. The effect of concomitant medication with the proton pump inhibitor omeprazole has been also subject of intense scrutiny. We present a cohort of 263 patients receiving anti-platelet aggregation treatment with clopidogrel and aspirin for 1 year. The paraoxonase 1 gene Q192R variant along with the presence of CYP2C19*2 and *3 loss of function alleles, concomitant medication with proton pump inhibitors and known cardiovascular risk factors were examined to determine their influence in disease relapse due to an ischaemic event during the 12 month treatment period. The low number of patients suffering a relapse (20 out of 263), indicates that double anti-aggregation therapy with aspirin and clopidogrel was very effective in our patients. Among the relapsers, evidence of coronary heart disease was the most influencial factor affecting response to therapy, while the presence of the paraoxonase 1 Q192R variant, loss of function of CYP2C19, and concomitant medication with omeprazole were non-significant.

  1. Evidence of platelet sensitization to ADP following discontinuation of clopidogrel therapy in patients with stable coronary artery disease.

    PubMed

    Lordkipanidzé, Marie; Diodati, Jean G; Schampaert, Erick; Palisaitis, Donald A; Pharand, Chantal

    2015-01-01

    Epidemiological studies have linked clopidogrel discontinuation with an increased incidence of ischemic events. This has led to the hypothesis that clopidogrel discontinuation may result in a pharmacological rebound. We evaluated the impact of clopidogrel discontinuation on platelet function. Platelet aggregation was measured by light transmission aggregometry (LTA) in response to adenosine diphosphate (ADP) 0.5, 1, 1.5, 2.5, 5 and 10 µM and by VerifyNow® P2Y12, in 37 clinically stable coronary artery disease (CAD) patients scheduled to discontinue clopidogrel treatment, and 37 clinically stable CAD patients not taking clopidogrel. Platelet function was assessed the day before clopidogrel cessation and 1, 3, 7, 14, 21 and 28 days after. Clopidogrel had been initiated a median of 555 days (ranging from 200 to 2280 days) before the treating cardiologist recommended its discontinuation. All participants were taking aspirin, most commonly 80 mg daily although a minority was prescribed 325 mg daily. Following clopidogrel discontinuation, VerifyNow® P2Y12 did not detect any rebound platelet activity, but ADP-induced LTA showed platelet sensitization to ADP, particularly at low ADP levels. Increased platelet activity was detectable seven days after clopidogrel cessation and remained higher than in controls 28 days after discontinuation. No clinical event occurred in any of the participants during the 28 days following clopidogrel cessation. In conclusion, platelet sensitization to ADP as a consequence of chronic clopidogrel administration may partially explain the recrudescence of ischemic events following clopidogrel discontinuation in otherwise stable coronary artery patients.

  2. New clopidogrel napadisilate salt and its solid dispersion with improved stability and bioequivalence to the commercial clopidogrel bisulphate salt in beagle dogs.

    PubMed

    Kim, Yong-Il; Kim, Kyung Soo; Suh, Kwee-Hyun; Shanmugam, Srinivasan; Woo, Jong Soo; Yong, Chul Soon; Choi, Han-Gon

    2011-08-30

    The purpose of this study was to develop a novel clopidogrel napadisilate-loaded solid dispersion with improved stability and bioequivalence to the clopidogrel bisulphate-loaded commercial product. Clopidogrel napadisilate prepared in this study appeared as a white crystalline powder unlike clopidogrel base. However, this salt did not improve the solubility of clopidogrel, even with improved stability compared to clopidogrel bisulphate. To improve the solubility of clopidogrel napadisilate, a novel clopidogrel napadisilate-loaded solid dispersion was prepared by the spray-drying technique using HPMC and colloidal silica, and the physicochemical properties, dissolution and bioavailability in beagle dogs were evaluated compared to the clopidogrel bisulphate-loaded commercial product. The solid dispersion composed of clopidogrel napadisilate, HPMC and colloidal silica at a weight ratio of 11.069/3/3.5 improved solubility by 6.5-fold compared to clopidogrel napadisilate, even if it did not improve drug solubility compared to clopidogrel bisulphate. However, unlike clopidogrel bisulphate, this formulation improved the stability of clopidogrel. Furthermore, the clopidogrel napadisilate solid dispersion-loaded tablet showed similar dissolution to the clopidogrel bisulphate-loaded commercial product and was bioequivalent to the commercial product in beagle dogs. Thus, this clopidogrel napadisilate-loaded solid dispersion could be a promising candidate for improving the stability and bioavailability of clopidogrel.

  3. Resistance to Clopidogrel among Iranian Patients Undergoing Angioplasty Intervention

    PubMed Central

    Haji Aghajani, Mohammad; Kobarfard, Farzad; Safi, Olia; Sheibani, Kourosh; Sistanizad, Mohammad

    2013-01-01

    To study the resistance to standard dosage of clopidogrel among Iranian patients following percutaneous coronary intervention measured by platelet aggregation test. Patients undergoing percutaneous coronary intervention in Imam Hussein Medical center, Tehran, Iran, who were under treatment with aspirin, but had no history of clopidogrel usage, entered the study. Patients received standard dosage of clopidogrel (Plavix®, Sanofi, France, 600 mg loading dose and 75 mg/day afterward). Platelet aggregation was measured using light transmission aggregometer. The response to the drug was categorized as complete resistance (platelet aggregation decreased less than 10%), intermediate resistance (platelet aggregation decreased between 10 to 30%) and complete response (platelet aggregation decreased to 30% or more). All patients were evaluated for major adverse cardio vascular events one month after the angioplasty based on MACE criteria by phone contact. Thirty-one patients with a mean age of 59 ± 13 entered the study. Sixty-five percent of patients showed complete response to clopidogrel (95% CI: 45% to 81%), 22% showed intermediate resistance (95% CI: 10-41%) and 13% showed complete resistance (95% CI: 4-30%). One month after the angioplasty, no major adverse cardiovascular event was recorded. Based on our findings, it seems that there is no major difference between Iranian population and other studies regarding the resistance to clopidogrel. Due to the limited number of participants in our study, further investigations with higher number of patients are recommended to more precisely calculate the percentage of resistance among Iranian patients. PMID:24250685

  4. PON1 Q192R genetic variant and response to clopidogrel and prasugrel: pharmacokinetics, pharmacodynamics, and a meta-analysis of clinical outcomes.

    PubMed

    Mega, Jessica L; Close, Sandra L; Wiviott, Stephen D; Man, Michael; Duvvuru, Suman; Walker, Joseph R; Sundseth, Scott S; Collet, Jean-Philippe; Delaney, Jessica T; Hulot, Jean-Sebastien; Murphy, Sabina A; Paré, Guillaume; Price, Matthew J; Sibbing, Dirk; Simon, Tabassome; Trenk, Dietmar; Antman, Elliott M; Sabatine, Marc S

    2016-04-01

    response to clopidogrel, nor was it associated with the response to prasugrel. The meta-analysis reinforced a lack of a significant association between Q192R and cardiovascular outcomes in clopidogrel-treated patients.

  5. Influence of Cyp2c19*2 Gene Variant on Therapeutic Response During Clopidogrel Treatment in Patients with Carotid Artery Stenosis

    PubMed Central

    Ignjatović, Svetlana; Rakićević, Ljiljana; Kusić-Tišma, Jelena; Radojković, Dragica; Čalija, Branko; Strugarević, Evgenija; Radak, Ðorđe; Kovač, Mirjana

    2016-01-01

    Summary Background Despite the proven clinical effect of oral antiplatelet drugs, a considerable number of patients do not have an adequate response to clopidogrel. The aim of our study was to determine the influence of CYP2C19*2 loss-of-function variant allele on clopidogrel responsiveness in patients with carotid artery stenosis. Methods One hundred and twelve patients with carotid artery stenosis undergoing endarterectomy were included in this one-year prospective study. All of them received clopidogrel (75 mg daily) for at least 30 days after the intervention. They were followed from the moment of hospital admission. CYP2C19*2 genotyping was performed by TaqMan Assay. The influence of CYP2C19*2 variant allele on clopidogrel platelet reactivity was determined using multiple-electrode aggregometry (MEA). Results Genotyping results showed that 82 (73.2%) patients were homozygous for wild type, 29 (25.9%) were heterozygous for the CYP2C19*2 allele and 1 (0.9%) was CYP2C19*2 homozygous. After 24 hours, among those with the wild type 29.3% were clopidogrel responders, and in those with the CYP2C19*2 alleles 10%. In the wild type group, 74.4% were clopidogrel responders after 7 days of taking the drug; 82.9% after 30 days of clopidogrel introduction, respectively. In patients with the CYP2C19*2 alleles the number of responders increased up to 46.7% after 7 days; 53.3% after 30 days of taking the drug, respectively. The risk for being a low-responder is higher for the patients heterozygous for the CYP2C19*2 allele vs. wild-type (OR 4.250, 95% CI 1.695-10.658, P<0.01). Conclusions The CYP2C19*2 loss-of-function variant allele has significant influence on clopidogrel response in patients with carotid artery stenosis undergoing endarterectomy. PMID:28356861

  6. Carboxylesterase 1 as a determinant of clopidogrel metabolism and activation.

    PubMed

    Zhu, Hao-Jie; Wang, Xinwen; Gawronski, Brian E; Brinda, Bryan J; Angiolillo, Dominick J; Markowitz, John S

    2013-03-01

    Clopidogrel pharmacotherapy is associated with substantial interindividual variability in clinical response, which can translate into an increased risk of adverse outcomes. Clopidogrel, a recognized substrate of hepatic carboxylesterase 1 (CES1), undergoes extensive hydrolytic metabolism in the liver. Significant interindividual variability in the expression and activity of CES1 exists, which is attributed to both genetic and environmental factors. We determined whether CES1 inhibition and CES1 genetic polymorphisms would significantly influence the biotransformation of clopidogrel and alter the formation of the active metabolite. Coincubation of clopidogrel with the CES1 inhibitor bis(4-nitrophenyl) phosphate in human liver s9 fractions significantly increased the concentrations of clopidogrel, 2-oxo-clopidogrel, and clopidogrel active metabolite, while the concentrations of all formed carboxylate metabolites were significantly decreased. As anticipated, clopidogrel and 2-oxo-clopidogrel were efficiently hydrolyzed by the cell s9 fractions prepared from wild-type CES1 transfected cells. The enzymatic activity of the CES1 variants G143E and D260fs were completely impaired in terms of catalyzing the hydrolysis of clopidogrel and 2-oxo-clopidogrel. However, the natural variants G18V, S82L, and A269S failed to produce any significant effect on CES1-mediated hydrolysis of clopidogrel or 2-oxo-clopidogrel. In summary, deficient CES1 catalytic activity resulting from CES1 inhibition or CES1 genetic variation may be associated with higher plasma concentrations of clopidogrel-active metabolite, and hence may enhance antiplatelet activity. Additionally, CES1 genetic variants have the potential to serve as a biomarker to predict clopidogrel response and individualize clopidogrel dosing regimens in clinical practice.

  7. Exome sequencing of extreme clopidogrel response phenotypes identifies B4GALT2 as a determinant of on-treatment platelet reactivity.

    PubMed

    Scott, S A; Collet, J-P; Baber, U; Yang, Y; Peter, I; Linderman, M; Sload, J; Qiao, W; Kini, A S; Sharma, S K; Desnick, R J; Fuster, V; Hajjar, R J; Montalescot, G; Hulot, J-S

    2016-09-01

    Interindividual variability in platelet aggregation is common among patients treated with clopidogrel and both high on-treatment platelet reactivity (HTPR) and low on-treatment platelet reactivity (LTPR) increase risks for adverse clinical outcomes. CYP2C19 influences clopidogrel response but only accounts for ∼12% of the variability in platelet reactivity. To identify novel variants implicated in on-treatment platelet reactivity, patients with coronary artery disease (CAD) with extreme pharmacodynamic responses to clopidogrel and wild-type CYP2C19 were subjected to exome sequencing. Candidate variants that clustered in the LTPR subgroup subsequently were genotyped across the discovery cohort (n = 636). Importantly, carriers of B4GALT2 c.909C>T had lower on-treatment P2Y12 reaction units (PRUs; P = 0.0077) and residual platelet aggregation (P = 0.0008) compared with noncarriers, which remained significant after adjusting for CYP2C19 and other clinical variables in both the discovery (P = 0.0298) and replication (n = 160; PRU: P = 0.0001) cohorts. B4GALT2 is a platelet-expressed galactosyltransferase, indicating that B4GALT2 c.909C>T may influence clopidogrel sensitivity through atypical cell-surface glycoprotein processing and platelet adhesion.

  8. Clinical, genetic and confounding factors determine the dynamics of the in vitro response/non response to clopidogrel.

    PubMed

    Gremmel, Thomas; Panzer, Simon

    2011-08-01

    Platelet inhibition by clopidogrel varies from one individual to the next. Further, in vitro high on-treatment residual adenosine-diphosphate inducible platelet reactivity (HRPR) is associated with an increased risk for major adverse cardiovascular events after percutaneous coronary intervention (PCI) with stent implantation. Recent studies identified numerous influencing factors for the antiplatelet effect of clopidogrel. Besides genetic predispositions, diverse clinical conditions as well as pharmacological interactions were shown to significantly impair clopidogrel-mediated platelet inhibition. Consequently, these influencing factors may affect clinical outcome after PCI and it is therefore desirable to identify cofounders of HRPR by platelet reactivity testing. It is apparent, that not all assays are sensitive to the same variables, and only cofounders of HRPR that are repeatedly identified by more than one test system may be clinically meaningful. However, treatment adjustment based on platelet function testing has not been associated with improved patients' outcome. This summary shall provide an overview over current knowledge on influencing factors for clopidogrel-mediated platelet inhibition and aid guidance for critical interpretation of in vitro obtained data on HRPR.

  9. The effects of clopidogrel and omeprazole on platelet function in normal dogs.

    PubMed

    Thames, B E; Lovvorn, J; Papich, M G; Wills, R; Archer, T; Mackin, A; Thomason, J

    2017-04-01

    Omeprazole is used concurrently with clopidogrel to reduce gastrointestinal adverse effects. In humans, the concurrent use of these two drugs can reduce the antiplatelet efficacy of clopidogrel. Our objective was to determine the effects of omeprazole and clopidogrel on platelet function in healthy dogs. A crossover study utilized turbidimetric aggregometry (ADP and collagen) and the PFA-100(®) with the collagen/ADP cartridge to evaluate platelet function in eight healthy dogs during the administration of clopidogrel (1 mg/kg/24 h p.o.), omeprazole (1 mg/kg/24 h p.o.), and a combination of clopidogrel and omeprazole. Drug metabolite concentrations were also measured. Compared to pretreatment, on Days 3 and 5, with ADP as the agonist, there was a significant decrease in maximum amplitude on aggregometry for both clopidogrel and clopidogrel/omeprazole groups. The following revealed no significant differences between clopidogrel and clopidogrel/omeprazole groups when compared on Days 3 and 5: maximum amplitude on aggregometry with ADP or collagen agonists, and PFA-100(®) closure times. When compared to the clopidogrel group, clopidogrel metabolite concentrations in the clopidogrel/omeprazole group were significantly higher on Days 3 and 5. The concurrent administration of omeprazole and clopidogrel in healthy dogs was associated with an increase in the plasma concentration of an inactive metabolite of clopidogrel, but does not significantly alter the antiplatelet effects of clopidogrel.

  10. Drug-drug interactions between clopidogrel and novel cardiovascular drugs.

    PubMed

    Pelliccia, Francesco; Rollini, Fabiana; Marazzi, Giuseppe; Greco, Cesare; Gaudio, Carlo; Angiolillo, Dominick J

    2015-10-15

    The combination of aspirin and the thienopyridine clopidogrel is a cornerstone in the prevention of atherothrombotic events. These two agents act in concert to ameliorate the prothrombotic processes stimulated by plaque rupture and vessel injury complicating cardiovascular disease. Guidelines recommend the use of clopidogrel in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention, and the drug remains the most utilized P2Y12 receptor inhibitor despite the fact that newer antiplatelet agents are now available. In recent years, numerous studies have shown inconsistency in the efficacy of clopidogrel to prevent atherothrombotic events. Studies of platelet function testing have shown variability in the response to clopidogrel. One of the major reason for this phenomenon lies in the interaction between clopidogrel and other drugs that may affect clopidogrel absorption, metabolism, and ultimately its antiplatelet action. Importantly, these drug-drug interactions have prognostic implications, since patients with high on-treatment platelet reactivity associated with reduced clopidogrel metabolism have an increased risk of ischemia. Previous systematic reviews have focused on drug-drug interactions between clopidogrel and specific pharmacologic classes, such as proton pump inhibitors, calcium channel blockers, and statins. However, more recent pieces of scientific evidence show that clopidogrel may also interact with newer drugs that are now available for the treatment of cardiovascular patients. Accordingly, the aim of this review is to highlight and discuss recent data on drug-drug interactions between clopidogrel and third-generation proton pump inhibitors, pantoprazole and lansoprazole, statins, pitavastatin, and antianginal drug, ranolazine.

  11. Potent and Orally Bioavailable Antiplatelet Agent, PLD-301, with the Potential of Overcoming Clopidogrel Resistance

    PubMed Central

    Chen, Jingyu; Wang, Michael Zhiyan

    2016-01-01

    PLD-301, a phosphate prodrug of clopidogrel thiolactone discovered by Prelude Pharmaceuticals with the aim to overcome clopidogrel resistance, was evaluated for its in vivo inhibitory effect on ADP-induced platelet aggregation in rats. The potency of PLD-301 was similar to that of prasugrel, but much higher than that of clopidogrel. The results of pharmacokinetic analysis showed that the oral bioavailability of clopidogrel thiolactone converted from PLD-301 was 4- to 5-fold higher than that of the one converted from clopidogrel, suggesting that in comparison with clopidogrel, lower doses of PLD-301 could be used clinically. In summary, PLD-301 presents a potent and orally bioavailable antiplatelet agent that might have some advantages over clopidogrel, such as overcoming clopidogrel resistance for CYP2C19-allele loss-of-function carriers, and lowering dose-related toxicity due to a much lower effective dose. PMID:27594816

  12. Von Willebrand Factor Antigen Predicts Response to Double Dose of Aspirin and Clopidogrel by PFA-100 in Patients Undergoing Primary Angioplasty for St Elevation Myocardial Infarction

    PubMed Central

    Gianetti, Jacopo; Parri, Maria Serena; Della Pina, Francesca; Marchi, Federica; Koni, Endrin; De Caterina, Alberto; Maffei, Stefano

    2013-01-01

    Von Willebrand factor (VWF) is an emerging risk factor in acute coronary syndromes. Platelet Function Analyzer (PFA-100) with Collagen/Epinephrine (CEPI) is sensitive to functional alterations of VWF and also identifies patients with high on-treatment platelet reactivity (HPR). The objective of this study was to verify the effect of double dose (DD) of aspirin and clopidogrel on HPR detected by PFA-100 and its relation to VWF and to its regulatory metalloprotease ADAMTS-13. Between 2009 and 2011 we enrolled 116 consecutive patients with ST elevation myocardial infarction undergoing primary PCI with HPR at day 5 after PCI. Patients recruited were then randomized between a standard dose (SD, n = 58) or DD of aspirin and clopidogrel (DD, n = 58), maintained for 6 months follow-up. Blood samples for PFA-100, light transmittance aggregometry, and VWF/ADAMTS-13 analysis were collected after 5, 30, and 180 days (Times 0, 1, and 2). At Times 1 and 2 we observed a significantly higher CEPI closure times (CT) in DD as compared to SD (P < 0.001). Delta of CEPI-CT (T1 − T0) was significantly related to VWF (P < 0.001) and inversely related to ADAMTS-13 (0.01). Responders had a significantly higher level of VWF at T0. Finally, in a multivariate model analysis, VWF and ADAMTS-13 in resulted significant predictors of CEPI-CT response (P = 0.02). HRP detected by PFA-100 in acute myocardial infarction is reversible by DD of aspirin and clopidogrel; the response is predicted by basal levels of VWF and ADAMTS-13. PFA-100 may be a useful tool to risk stratification in acute coronary syndromes given its sensitivity to VWF. PMID:24453831

  13. Relation between clopidogrel active metabolite levels and different platelet aggregation methods in patients receiving clopidogrel and aspirin.

    PubMed

    Liang, Yan; Johnston, Marilyn; Hirsh, Jack; Pare, Guillaume; Li, Chunjian; Mehta, Shamir; Teo, Koon K; Sloane, Debi; Yi, Qilong; Zhu, Jun; Eikelboom, John W

    2012-11-01

    Clopidogrel is a prodrug that undergoes bioconversion via cytochrome P450 system to form an active metabolite (AM) that binds to the platelet ADP receptor. The antiplatelet effect of clopidogrel is commonly assessed by measuring the aggregatory response to 5 μM ADP by light transmission aggregation (LTA) or multiple electrode aggregometry (MEA) or by the vasodilator-stimulated phosphoprotein platelet reactivity index (VASP-PRI). To determine which of these three tests of platelet ADP receptor pathway inhibition most closely correlates with clopidogrel AM levels. We analyzed blood samples from 82 patients with coronary artery disease who were randomized to receive double-dose or standard dose clopidogrel for 2 weeks. We measured peak clopidogrel AM levels, platelet aggregation in response to ADP and VASP-PRI on days 1, and repeated all the measures on days 7 and 14. Linear regression analysis was used to examine the correlation between clopidogrel AM and LTA, MEA and VASP-PRI. Bland-Altman plots were used to explore the agreement between tests of the antiplatelet effects of clopidogrel. Clopidogrel AM on day 1 correlated most closely with VASP-PRI (r = -0.5767) and demonstrated weaker correlations with LTA (r = -0.4656) and MEA (r = -0.3384) (all p < 0.01). Intra-class correlation (ICC) between VASP-PRI and LTA was 0.6446; VASP-PRI and MEA was 0.4720; and LTA and MEA was 0.4693. Similar results were obtained on days 7 and 14. Commonly used pharmacodynamic measures of clopidogrel response are only moderately correlated with clopidogrel AM levels and may not be suitable to measure the adequacy of clopidogrel therapy.

  14. ABCB1 C3435T Polymorphism and Response to Clopidogrel Treatment in Coronary Artery Disease (CAD) Patients: A Meta-Analysis

    PubMed Central

    Su, Jia; Xu, Jin; Li, Xiaojing; Zhang, Han; Hu, Juwei; Fang, Renyuan; Chen, Xiaomin

    2012-01-01

    Background A number of investigators have evaluated the association between the ABCB1 polymorphism and clopidogrel responding, but the results have been inconclusive. To examine the risk of high platelet activity and poor clinical outcomes associated with the ABCB1 C3435T polymorphism in CAD patients on clopidogrel, all available studies were included in the present meta-analysis. Methods We performed a systematic search of PubMed, Scopus and the Cochrane library database for eligible studies. Articles meeting the inclusion criteria were comprehensively reviewed, and the available data were accumulated by the meta-analysis. Results It was demonstrated that the ABCB1 C3435T variation was associated with the risk of early major adverse cardiovascular events (MACE) (T vs. C OR, 1.34; 95% CI, 1.10 to 1.62; P = 0.003; TT vs. CC: OR, 1.77; 95% CI, 1.19 to 2.63; P = 0.005; CT + TT vs.CC: OR, 1.48; 95% CI, 1.06 to 2.06; P = 0.02) and the polymorphism was also associated with the risk of the long-term MACE in patients on clopidogrel LD 300 mg (T vs. C: OR, 1.28; 95% CI, 1.10 to 1.48; P = 0.001; TT vs. CC: OR, 1.59; 95% CI, 1.19 to 2.13; P = 0.002; CT + TT vs.CC: OR, 1.39; 95% CI, 1.08 to 1.79; P = 0.01). The comparison of TT vs. CC was associated with a reduction in the outcome of bleeding (TT vs. CC: OR, 0.51; 95% CI, 0.40 to 0.66; P<0.00001). However, the association between ABCB1 C3435T polymorphism and platelet activity and other risk of poor clinical outcomes was not significant. Conclusions The evidence from our meta-analysis indicated that the ABCB1 C3435T polymorphism might be a risk factor for the MACE in patients on clopidogrel LD 300 mg, and that TT homozygotes decreased the outcome of bleeding compared with CC homozygotes. PMID:23056288

  15. Paraoxonase 1 Gene Polymorphism Does Not Affect Clopidogrel Response Variability but Is Associated with Clinical Outcome after PCI

    PubMed Central

    Kang, Jeehoon; Jeon, Ki-Hyun; Kang, Si-Hyuck; Han, Jung-Kyu; Lee, Sang Eun; Yang, Han-Mo; Lee, Hae-Young; Kang, Hyun-Jae; Koo, Bon-Kwon; Oh, Byung-Hee; Park, Young-Bae; Kim, Hyo-Soo

    2013-01-01

    Background Paraoxonase (PON) is a high-density-lipoprotein (HDL) associated enzyme with antioxidative and anti-atherogenic property. Its function is associated with coronary artery disease and its activity genetically controlled. We evaluated whether genetic variation of PON-1 is associated with clinical outcome in a large cohort of Korean patients with drug-eluting stents implantation. Methods A total of 1676 patients with drug-eluting stent implantation were enrolled in the prospective CROSS-VERIFY cohort from June 2006 to June 2010. We genotyped the PON1-Q192R gene, measured clopidogrel on-treatment platelet reactivity (OPR), and analyzed lipid profiles. The primary endpoint was the composite of cardiac death, myocardial infarction, and stent thrombosis at 12 months. Results PON-1 genotyping data were available in 1336 patients. Since the Q-allele is associated with decreased PON-activity, we analyzed the outcome between patients with QQ/QR (815 patients, 61%) and those with RR-genotype (521 patients, 39%). After adjustment for common cardiac risk factors, the QQ/QR-genotype was an independent predictor of the primary thrombotic endpoint with an 11-fold increased risk (HR 11.6, 95% CI: 1.55–87.0), but not repeat revascularization (HR 1.12, 95% CI: 0.78–1.61). The QQ/QR-genotype was not associated with OPR (QQ/QR: 231±86 PRU vs. RR 236±82 PRU, p = 0.342) but higher small-dense LDL levels (1.20±0.12 mg/dL vs. 0.76±0.15 mg/dL, p = 0.027). The increased risk of thrombotic outcomes was more profound in acute coronary syndrome (ACS) patients compared with non-ACS patients. Conclusion PON1 Q-allele is an independent predictor of worse cardiovascular outcome independent of platelet function and is associated with significantly higher levels of small dense LDL-C. PMID:23418418

  16. Point-of-care platelet function assays demonstrate reduced responsiveness to clopidogrel, but not aspirin, in patients with Drug-Eluting Stent Thrombosis whilst on dual antiplatelet therapy

    PubMed Central

    Hobson, Alex R; Petley, Graham; Morton, Geraint; Dawkins, Keith D; Curzen, Nick P

    2008-01-01

    Background To test the hypothesis that point-of-care assays of platelet reactivity would demonstrate reduced response to antiplatelet therapy in patients who experienced Drug Eluting Stent (DES) ST whilst on dual antiplatelet therapy compared to matched DES controls. Whilst the aetiology of stent thrombosis (ST) is multifactorial there is increasing evidence from laboratory-based assays that hyporesponsiveness to antiplatelet therapy is a factor in some cases. Methods From 3004 PCI patients, seven survivors of DES ST whilst on dual antiplatelet therapy were identified and each matched with two patients without ST. Analysis was performed using (a) short Thrombelastogram PlateletMapping™ (TEG) and (b) VerifyNow Aspirin and P2Y12 assays. TEG analysis was performed using the Area Under the Curve at 15 minutes (AUC15) as previously described. Results There were no differences in responses to aspirin. There was significantly greater platelet reactivity on clopidogrel in the ST group using the Accumetrics P2Y12 assay (183 ± 51 vs. 108 ± 31, p = 0.02) and a trend towards greater reactivity using TEG AUC15 (910 ± 328 vs. 618 ± 129, p = 0.07). 57% of the ST group by TEG and 43% of the ST cases by Accumetrics PRU had results > two standard deviations above the expected mean in the control group. Conclusion This study demonstrates reduced platelet response to clopidogrel in some patients with DES ST compared to matched controls. The availability of point-of-care assays that can detect these responses raises the possibility of prospectively identifying DES patients at risk of ST and manipulating their subsequent risk. PMID:18312665

  17. CYP2C19 but not CYP2B6, CYP3A4, CYP3A5, ABCB1, PON1 or P2Y12 genetic polymorphism impacts antiplatelet response after clopidogrel in Koreans.

    PubMed

    Zhang, Hong-Zhe; Kim, Moo Hyun; Guo, Long-Zhe; Serebruany, Victor

    2017-01-01

    Clopidogrel response variability (CRV) is well documented, and may affect clinical outcomes. Impact of genetic polymorphisms is important for assessing and predicting CRV. The extensive evidence indicates the importance of CYP2C19 variants in reducing efficacy of clopidogrel. This study defined the impact of numerous genetic polymorphisms on CRV before and after percutaneous coronary interventions (PCI) exclusively in a Korean cohort assuming less genetic variability noise. One hundred and thirty-six patients of Korean origin undergoing PCI were included. Platelet reactivity was measured by VerifyNow assay before and after PCI. Genetic polymorphism of seven single nucleotides of CYP2B6, CYP2C19, CYP3A4, CYP3A5, ABCB1, PON1, and P2Y12 were evaluated and matched with platelet reactivity. Carriers of at least one CYP2C19*2 or *3 allele uniformly exhibited higher platelet reactivity compared to 0-carrier pre-PCI (odds ratio 3.1, 95% confidence interval 1.4-6.9, P < 0.01) and post-PCI (odds ratio 3.4, 95% confidence interval 1.7-6.8, P < 0.001). The carriers of other gene allele variants lack uniformed impact on CRV. The Korean carriers of CYP2C19*2 or *3 allele are linked to CRV, whereas CYP2B6, CYP3A4, CYP3A5, ABCB1, PON1, and P2Y12 failed to predict CRV. The exact clinical utility of these findings is uncertain, and requires a large randomized national trial for proof of concept.

  18. Intrinsic platelet reactivity before start with clopidogrel as predictor for on-clopidogrel platelet function and long-term clinical outcome.

    PubMed

    Hochholzer, Willibald; Valina, Christian M; Bömicke, Timo; Amann, Michael; Stratz, Christian; Nührenberg, Thomas; Trenk, Dietmar; Neumann, Franz-Josef

    2015-07-01

    High on-clopidogrel platelet reactivity is associated with worse clinical outcome. Previous data suggest that intrinsic platelet reactivity before initiation of clopidogrel contributes significantly to on-clopidogrel platelet reactivity. It is unknown whether intrinsic reactivity can sufficiently predict on-clopidogrel reactivity and therefore identify patients with insufficient response to clopidogrel before initiation of treatment and at risk for worse clinical outcome. This analysis included 765 consecutive patients undergoing elective coronary stent implantation. Platelet reactivity was assessed by light transmission aggregometry (5 µM ADP) before administration of clopidogrel 600mg and after intake of first maintenance dose of clopidogrel on day 1 following coronary stenting. Patients were followed for up to seven years. The combined primary endpoint was death of any cause or non-fatal myocardial infarction. Intrinsic and on-clopidogrel platelet reactivity were significant correlated (r=0.31; p < 0.001). Among all tested clinical and genetic factors including the cytochrome P450 2C19*2 polymorphism, intrinsic platelet reactivity was the strongest predictor for on-clopidogrel platelet reactivity. However, intrinsic platelet reactivity could only explain 8 % of variability of on-clopidogrel platelet function. Only on-treatment platelet reactivity was predictive for long-term clinical outcome (HR 1.47, 95 % CI 1.05-2.05; p = 0.02) whereas intrinsic platelet reactivity was not (HR 1.03, 95 % CI 0.74-1.43; p = 0.86). In conclusion, intrinsic platelet reactivity before initiation of clopidogrel is the strongest predictor of early on-clopidogrel platelet reactivity but can only explain a minor proportion of its variability and is not significantly associated with clinical outcome. Thus, baseline testing cannot substitute on-clopidogrel platelet function testing.

  19. High clopidogrel dose in patients with chronic kidney disease having clopidogrel resistance after percutaneous coronary intervention.

    PubMed

    Liang, Jing; Wang, Zhijian; Shi, Dongmei; Liu, Yuyang; Zhao, Yingxin; Han, Hongya; Li, Yueping; Liu, Wei; Zhang, Linlin; Yang, Lixia; Zhou, Yujie

    2015-04-01

    We evaluated the impact of clopidogrel 150 mg/d in patients with chronic kidney disease (CKD) having clopidogrel resistance (CR) after percutaneous coronary intervention (PCI); 1076 consecutive patients with coronary artery disease (CAD) having CKD were enrolled. Maximal platelet aggregation (MPA) was assessed before, 24 hours, and 30 days after a 300-mg loading dose of clopidogrel prior to PCI. After PCI, 370 patients with CR were randomized to receive clopidogrel 75 mg/d (n = 184) or 150 mg/d (n = 186) for 30 days. Stent thrombosis (ST), major adverse cardiac events (MACEs), and bleeding were analyzed after 1 month. Patients in the 150 mg group had significant lower rates of ST and MACE. There was no significant difference in major or minor bleeding. Patients in the 150 mg group had lower MPA and greater inhibition of platelet aggregation. One-month administration of 150 mg/d of clopidogrel decreases the rate of ST and MACE without increasing bleeding in patients with CKD having CR after PCI.

  20. Clopidogrel use After Myocardial Revascularization: Prevalence, Predictors, and One-Year Survival Rate

    PubMed Central

    Prates, Paulo Roberto L.; Williams, Judson B.; Mehta, Rajendra H.; Stevens, Susanna R.; Thomas, Laine; Smith, Peter K.; Newby, L. Kristin; Kalil, Renato A. K.; Alexander, John H.; Lopes, Renato D.

    2016-01-01

    Introduction Antiplatelet therapy after coronary artery bypass graft (CABG) has been used. Little is known about the predictors and efficacy of clopidogrel in this scenario. Objective Identify predictors of clopidogrel following CABG. Methods We evaluated 5404 patients who underwent CABG between 2000 and 2009 at Duke University Medical Center. We excluded patients undergoing concomitant valve surgery, those who had postoperative bleeding or death before discharge. Postoperative clopidogrel was left to the discretion of the attending physician. Adjusted risk for 1-year mortality was compared between patients receiving and not receiving clopidogrel during hospitalization after undergoing CABG. Results At hospital discharge, 931 (17.2%) patients were receiving clopidogrel. Comparing patients not receiving clopidogrel at discharge, users had more comorbidities, including hyperlipidemia, hypertension, heart failure, peripheral arterial disease and cerebrovascular disease. Patients who received aspirin during hospitalization were less likely to receive clopidogrel at discharge (P≤0.0001). Clopidogrel was associated with similar 1-year mortality compared with those who did not use clopidogrel (4.4% vs. 4.5%, P=0.72). There was, however, an interaction between the use of cardiopulmonary bypass and clopidogrel, with lower 1-year mortality in patients undergoing off-pump CABG who received clopidogrel, but not those undergoing conventional CABG (2.6% vs 5.6%, P Interaction = 0.032). Conclusion Clopidogrel was used in nearly one-fifth of patients after CABG. Its use was not associated with lower mortality after 1 year in general, but lower mortality rate in those undergoing off-pump CABG. Randomized clinical trials are needed to determine the benefit of routine use of clopidogrel in CABG. PMID:27556308

  1. Chiral Stability of an Extemporaneously Prepared Clopidogrel Bisulfate Oral Suspension

    PubMed Central

    Tynes, Clay R.; Livingston, Brad; Patel, Hetesh; Arnold, John J.

    2014-01-01

    OBJECTIVES The purpose of this study was to evaluate the chiral stability of clopidogrel bisulfate in an extemporaneously compounded oral suspension for a period of 60 days. METHODS A 5 mg/mL oral suspension of clopidogrel bisulfate was prepared from commercially available Plavix tablets. The clopidogrel suspension was then evenly divided between two light-resistant prescription bottles and stored either under refrigeration (4°C) or at room temperature (25°C). Samples were drawn from the stored suspensions immediately after preparation and on days 7, 14, 28, and 60. Samples were subsequently analyzed at each time point by high-performance liquid chromatography using a reversed-phase column, with chemical stability defined as the retention of at least 90% of the initial intact clopidogrel concentration measured. To determine the chiral stability of the suspension, samples were also analyzed by high-performance liquid chromatography using a chiral column to investigate possible enantiomeric inversion. Chiral stability was defined as the retention of at least 90% of the initial concentration of the suspension as the S-enantiomer, the active moiety of Plavix. RESULTS Regardless of storage conditions, the oral suspension of clopidogrel retained at least 98% of the active S-enantiomer for 60 days after preparation. Compared with the clopidogrel suspension stored in the refrigerator, more chiral inversion was noted in the clopidogrel suspension stored at room temperature. CONCLUSIONS Our investigation of chiral stability indicates that a 5 mg/mL clopidogrel oral suspension stored under refrigeration and at room temperature maintains chiral stability as the active S-enantiomer. PMID:24782688

  2. Rationale and design of the randomized, double-blind trial testing INtraveNous and Oral administration of elinogrel, a selective and reversible P2Y(12)-receptor inhibitor, versus clopidogrel to eVAluate Tolerability and Efficacy in nonurgent Percutaneous Coronary Interventions patients (INNOVATE-PCI).

    PubMed

    Leonardi, Sergio; Rao, Sunil V; Harrington, Robert A; Bhatt, Deepak L; Gibson, C Michael; Roe, Matthew T; Kochman, Janusz; Huber, Kurt; Zeymer, Uwe; Madan, Mina; Gretler, Daniel D; McClure, Matthew W; Paynter, Gayle E; Thompson, Vivian; Welsh, Robert C

    2010-07-01

    Despite current dual-antiplatelet therapy with aspirin and clopidogrel, adverse clinical events continue to occur during and after percutaneous coronary intervention (PCI). The failure of clopidogrel to provide optimal protection may be related to delayed onset of action, interpatient variability in its effect, and an insufficient level of platelet inhibition. Furthermore, the irreversible binding of clopidogrel to the P2Y(12) receptor for the life span of the platelet is associated with increased bleeding risk especially during urgent or emergency surgery. Novel antiplatelet agents are required to improve management of patients undergoing PCI. Elinogrel is a potent, direct-acting (ie, non-prodrug), selective, competitive, and reversible P2Y(12) inhibitor available in both intravenous and oral formulations. The INNOVATE-PCI study is a phase 2 randomized, double-blind, clopidogrel-controlled trial to evaluate the safety, tolerability, and preliminary efficacy of this novel antiplatelet agent in patients undergoing nonurgent PCI.

  3. Clopidogrel and genetic testing: is it necessary for everyone?

    PubMed

    Goswami, Sweta; Cheng-Lai, Angela; Nawarskas, James

    2012-01-01

    Clopidogrel is a widely used antiplatelet agent to treat and prevent a variety of atherothrombotic diseases. More than a decade after its initial Food and Drug Administration approval, studies have emerged raising concerns regarding its possible reduced efficacy in patients who have impaired conversion of clopidogrel to its active metabolite (ie, poor metabolizers). Research has implicated genetic variations in the CYP2C19 isozyme as at least partly responsible for the variable antiplatelet response seen with clopidogrel. Studies have shown that patients possessing genetic variants of the CYP2C19 isozyme may be at increased risk of adverse cardiovascular events due to impaired clopidogrel efficacy, although this has not been definitively demonstrated. The Food and Drug Administration has issued a boxed warning regarding this concern. However, specific recommendations on genetic testing and alternative therapeutic strategies are not currently available. Genetic testing is commercially available to test patients for variability in the CYP2C19 isozyme, but altering antiplatelet therapy based on the results of this testing has not been adequately studied, and it is therefore not clear how to adjust therapy based on the results of this genetic testing. In addition, there are many other factors that may contribute to the variability in antiplatelet effect seen with clopidogrel besides CYP2C19 genetic polymorphisms. Ongoing trials dealing with adjusting antiplatelet therapy based on genetic testing will hopefully provide more useful information on how to appropriately integrate pharmacogenomics with the care of patients with atherothrombotic disease.

  4. Association of Cytochrome P450 Genetic Variants with Clopidogrel Resistance and Outcomes in Acute Ischemic Stroke

    PubMed Central

    Yi, Xingyang; Wang, Yanfen; Zhou, Qiang; Wang, Chun; Cheng, Wen; Chi, Lifen

    2016-01-01

    Aims: Clopidogrel is an antiplatelet drug primarily used to treat or prevent acute ischemic stroke (IS) or myocardial infarction (MI). This prodrug requires biotransformation to an active metabolite by cytochrome P450 (CYP) enzymes, and CYP single nucleotide polymorphisms (SNPs) could affect the efficiency of such biotransformation. Methods: A total of 375 consecutive IS patients were genotyped for eight CYP SNPs using mass spectrometry. Platelet aggregation activity was measured before and after the 7 – 10 day treatment. Gene–gene interactions were analyzed using generalized multifactor dimensionality reduction (GMDR) analysis. All patients received clopidogrel therapy and were followed up for six months. Primary outcomes were evaluated as a composite of recurrent ischemic stroke (RIS), MI, and death. The secondary outcome was the modified Rankin Scale (mRS). Results: Clopidogrel resistance occurred in 153 patients (40.8%). The frequency of CYP3A5 (rs776746) GG/AG and CYP2C19*2 (rs4244285) AA/AG genotypes was significantly higher in clopidogrel-resistant patients than in sensitive patients. There was a significant gene-gene interaction between CYP3A5 (rs776746) and CYP2C19*2 (rs4244285). CYP2C19*2 AA and its interaction with CYP3A5 GG were independent predictors of clopidogrel resistance and affected the activity of platelet aggregation. Diabetes mellitus, CYP2C19*2 (rs4244285), clopidogrel resistance, and the interaction of CYP2C19*2 with CYP3A5 were all independent risk factors for the primary outcomes of clopidogrel treatment. Clopidogrel-resistant patients were more likely to have poor outcomes (mRS > 2 points) compared with clopidogrel-sensitive patients. Conclusion: CYP SNPs and their interactions are associated with drug resistance and outcomes in acute IS patients. PMID:26961113

  5. Sulfonylureas and on-clopidogrel platelet reactivity in type 2 diabetes mellitus patients.

    PubMed

    Harmsze, Ankie M; Van Werkum, Jochem W; Moral, Fulya; Ten Berg, Jurri N M; Hackeng, Christian M; Klungel, Olaf H; De Boer, Anthonius; Deneer, Vera H M

    2011-01-01

    Clopidogrel is a prodrug that needs to be converted in?vivo by several cytochrome (CYP) P450 iso-enzymes to become active. Both clopidogrel and the oral hypoglycemic drug class sulfonylureas are metabolized by the iso-enzyme CYP2C9. The objective of the study was to evaluate the relationship of sulfonylureas and on-clopidogrel platelet reactivity in type 2 diabetes mellitus patients undergoing elective coronary stent implantation. In this prospective, observational study, on-clopidogrel platelet reactivity was quantified using adenosine diphosphate (ADP)-induced light transmittance aggregometry in 139 type 2 diabetes mellitus patients undergoing elective coronary stent implantation treated with clopidogrel and aspirin. High on-clopidogrel platelet reactivity was defined as >70.7% platelet reactivity to 20 μmol/L ADP. A total of 53 patients (38.1%) were on concomitant treatment with sulfonylureas. The remaining 86 patients were on other hypoglycemic drugs. On-clopidogrel platelet reactivity was significantly higher in patients with concomitant sulfonylurea treatment as compared to patients without concomitant sulfonylurea treatment (for 5 μmol/L ADP: 46.0% ± 11.8 vs. 40.6% ± 16.0; p=0.035, adjusted p=0.032 and for 20 μmol/L ADP: 64.6% ± 10.8 vs. 58.7% ± 15.5; p=0.019, adjusted p=0.017). The concomitant use of sulfonylureas was associated with a 2.2-fold increased risk of high on-clopidogrel platelet reactivity (OR 2.2, 95% CI 1.1-4.7, p=0.039 and after adjustment for confounders: OR(adj) 2.0, 95% CI 1.0-5.7, p=0.048). Concomitant treatment with sulfonylureas might be associated with decreased platelet inhibition by clopidogrel in type 2 diabetes mellitus patients on dual antiplatelet therapy undergoing elective coronary stent implantation.

  6. Program Evaluation Particularly Responsive Evaluation

    ERIC Educational Resources Information Center

    Stake, Robert E.

    2011-01-01

    In this paper, the author talks about some recent developments in the methodology of program evaluation and about what he calls "responsive evaluation." He discusses two models for program evaluation, namely (1) informal study or self-study; and (2) the pretest/posttest model. Then, he describes an approach that he has been working on, which will…

  7. Inflammatory and Antioxidant Pattern Unbalance in “Clopidogrel-Resistant” Patients during Acute Coronary Syndrome

    PubMed Central

    Gori, Anna Maria; Cecchettini, Antonella; Parodi, Guido; Marcucci, Rossella; Parolini, Marina; Romagnuolo, Ilaria; Citti, Lorenzo; Abbate, Rosanna

    2015-01-01

    Background. In acute coronary syndrome (ACS), inflammation and redox response are associated with increased residual platelet reactivity (RPR) on clopidogrel therapy. We investigated whether clopidogrel interaction affects platelet function and modulates factors related to inflammation and oxidation in ACS patients differently responding to clopidogrel. Material and Methods. Platelet aggregation was measured in 29 ACS patients on dual (aspirin/clopidogrel) antiplatelet therapy. Nonresponders (NR) were defined as RPR ≥70% by ADP. Several inflammatory and redox parameters were assayed and platelet proteome was determined. Results. Eight (28%) out of 29 ACS patients resulted NR to clopidogrel. At 24 hours, the levels of Th2-type cytokines IL-4, IFNγ, and MCP-1 were higher in NR, while blood GSH (r-GSHbl) levels were lower in NR than responders (R). Proteomic analysis evidenced an upregulated level of platelet adhesion molecule, CD226, and a downregulation of the antioxidant peroxiredoxin-4. In R patients the proinflammatory cytokine IL-6 decreased, while the anti-inflammatory cytokine IL-1Ra increased. Conclusions. In patients with high RPR on clopidogrel therapy, an unbalance of inflammatory factors, platelet adhesion molecules, and circulatory and platelet antioxidant molecules was observed during the acute phase. Proinflammatory milieu persists in nonresponders for a long time after the acute event while antioxidant blood factors tend to conform to normal responsiveness. PMID:25873769

  8. An allele-specific PCR system for rapid detection and discrimination of the CYP2C19∗4A, ∗4B, and ∗17 alleles: implications for clopidogrel response testing.

    PubMed

    Scott, Stuart A; Tan, Qian; Baber, Usman; Yang, Yao; Martis, Suparna; Bander, Jeffrey; Kornreich, Ruth; Hulot, Jean-Sébastien; Desnick, Robert J

    2013-11-01

    CYP2C19 is involved in the metabolism of clinically relevant drugs, including the antiplatelet prodrug clopidogrel, which has prompted interest in clinical CYP2C19 genotyping. The CYP2C19∗4B allele is defined by both gain-of-function [c.-806C>T (∗17)] and loss-of-function [c.1A>G (∗4)] variants on the same haplotype; however, current genotyping and sequencing assays are unable to determine the phase of these variants. Thus, the aim of this study was to develop an assay that could rapidly detect and discriminate the related ∗4A, ∗4B, and ∗17 alleles. An allele-specific PCR assay, composed of four unique primer mixes that specifically interrogate the defining ∗17 and ∗4 variants, was developed by using samples (n = 20) with known genotypes, including the ∗4A, ∗4B, and/or ∗17 alleles. The assay was validated by testing 135 blinded samples, and the results were correlated with CYP2C19 genotyping and allele-specific cloning/sequencing. Importantly, among the six ∗4 carriers in the validation cohort, after allele-specific PCR testing both samples with a ∗1/∗4 genotype were reclassified to ∗1/∗4A, all three samples with a ∗4/∗17 genotype were reclassified to ∗1/∗4B, and a sample with a ∗4/∗17/∗17 genotype was reclassified to ∗4B/∗17. In conclusion, this rapid and robust allele-specific PCR assay can refine CYP2C19 genotyping and metabolizer phenotype classification by determining the phase of the defining ∗17 and ∗4 variants, which may have utility when testing CYP2C19 for clopidogrel response.

  9. Switching from Clopidogrel to Prasugrel in patients undergoing PCI: A meta-analytic overview.

    PubMed

    Verdoia, Monica; Barbieri, Lucia; Suryapranata, Harry; De Luca, Giuseppe

    2016-01-01

    Despite the demonstrated benefits of Prasugrel, a new generation thienopyridine, in the prevention of thrombotic complications after percutaneous coronary interventions (PCI) for Acute Coronary Syndromes (ACS), its use is still precluded to those many patients arriving to the cath lab pre-treated with Clopidogrel. Conclusive data on the strategy of switching from Clopidogrel to Prasugrel are still missing, therefore we aimed to perform a meta-analysis of current studies evaluating the safety and efficacy of switching from Clopidogrel to Prasugrel (PS) as compared to a standard thienopyridine therapy with Clopidogrel or Prasugrel in patients undergoing PCI. Literature archives and main scientific sessions' abstracts were scanned for studies comparing a switching strategy from Clopidogrel to Prasugrel vs. Prasugrel or Clopidogrel. Primary efficacy endpoint was overall mortality. Secondary endpoints were: non-fatal myocardial infarction and definite/probable stent thrombosis. Safety endpoint was the rate of major bleedings according to a per-protocol definition. A total of 12 studies, involving 3956 patients, were included. Among them, 1396 patients (35.3%), received Prasugrel after a Clopidogrel treatment (PS), while 2560 (64.7%) received either Prasugrel or Clopidogrel. The switch from Clopidogrel to Prasugrel was in the majority of the studies periprocedural. The mortality was numerically lower, but not statistically significant, in the PS group as compared with patients who did not switch (1.7% vs. 3.8%, OR [95% CI] = 0.68 [0.40,1.15], p = 0.15, phet = 0.61), without any relationship with patients' risk profile (r = -0.68 [-2.09, 0.73], p = 0.35). Similar results were obtained for secondary efficacy endpoints and at sensitivity analysis in the majority of subgroups evaluated. Moreover, the PS strategy did not increase major bleedings as compared with standard therapy (1.4% vs. 2.5%, OR [95% CI = 0.70 [0.39, 1.25], p = 0.23, phet = 0.6). The present meta

  10. Responsive Evaluation: An Interpretation.

    ERIC Educational Resources Information Center

    Lewy, Arieh

    1977-01-01

    Stake's concept of responsive evaluation is designed to provide various decision makers with the kind of information desired and in the form most helpful for making decisions. Compared with formal research procedures, this approach has both advantages and disadvantages. It may also provide a valuable supplement to formal evaluation. (CTM)

  11. Effects of genetic factors to stent thrombosis due to clopidogrel resistance after coronary stent placement.

    PubMed

    Kirac, D; Erdem, A; Avcilar, T; Yesilcimen, K; Guney, A I; Emre, A; Yazici, S; Terzi, S; Kaspar, E C; Cetin, S E; Isbir, T

    2016-01-19

    Stent thrombosis (ST) is considered as a multifactorial problem which is mostly occurs due to clopidogrel resistance. It may be due to some CYP450 enzyme deficiencies which play role in clopidogrel metabolism. Therefore the aim of this study is to detect the mutations in CYP2C19 and CYP2C9 genes which may cause ST, and to investigate the relation between other risk factors and ST. 50 individuals who have stent thrombosis and 50 individuals who haven't got any complication were enrolled as patient and control group respectively. *2,*3,*4,*5,*17 mutations in CYP2C19 gene and *2 ve *3 mutations in CYP2C9 gene were investigated with RT-PCR. Clopidogrel and aspirin resistance were investigated with multiple electrode platelet aggregometry. Results were evaluated statistically. CYP2C19*2 mutation was found statistically higher in patients (% 18), whereas CYP2C19*17 was found statistically higher in controls (% 36)(p<0.05). Additionally, it was found that patients who have clopidogrel and/or aspirin resistance also have CYP2C19*1/*2 or CYPC19*2/*2 genotype. These relations were also found statistically significant. (p=0,000005 for clopidogrel resistance and p=0,000059 for aspirin resistance). In conclusion, it was suggested that there is a relation between CYP2C19*2 mutations and ST due to clopidogrel resistance, and CYP2C19*17 may have a protective role in this process. The use of novel and more potent drug or high clopidogrel maintenance dosing before stent implantation may be beneficial treatment options for antiplatelet therapy in CYP2C19*2 carriers.

  12. Increased Postoperative Bleeding Risk among Patients with Local Flap Surgery under Continued Clopidogrel Therapy

    PubMed Central

    Eichhorn, Wolfgang; Haase, Martina; Kluwe, Lan; Zeuch, Jürgen; Smeets, Ralf; Hanken, Henning; Wehrmann, Manfred; Gröbe, Alexander; Heiland, Max; Birkelbach, Moritz; Rendenbach, Carsten

    2015-01-01

    Purpose. The purpose of the study was to evaluate the influence of a continued antiplatelet therapy with clopidogrel on postoperative bleeding risk in patients undergoing skin tumor resection and reconstruction with local flaps or skin grafts under outpatient conditions. Patients and Methods. The authors designed and implemented a retrospective clinical cohort study at the General Hospital Balingen. The primary endpoint was the bleeding ratio in patients with clopidogrel treatment in comparison to patients without any anticoagulant or antiplatelet therapy. Wound healing was evaluated on days 1, 3, 5, 7, 10, and 14. Results. 650 procedures were performed, 123 of them under continued clopidogrel therapy. There were significantly more postoperative bleeding complications among patients with continued antiplatelet therapy. Regarding the whole study population, malignant lesions, a larger defect size, and skin grafts were accompanied by a higher rate of bleeding incidents. However, there were no significant findings in the univariate analysis of the clopidogrel group. All bleeding incidents were easily manageable. Conclusion. Despite an increased bleeding ratio among patients under continued clopidogrel therapy, the performance of simple surgical procedures can be recommended. However, cautious preparation and careful hemostasis are indispensable. PMID:26345612

  13. Pharmacogenetic Selection of Volunteers Increases Stringency of Bioequivalence Studies; The Case of Clopidogrel

    PubMed Central

    Garcés-Eisele, J.; Ruiz-Argüelles, A.; Estrada-Marín, Larisa; Reyes-Núñez, Virginia; Vázquez-Pérez, R.; Guzmán-García, Olga; Coutiño-Medina, R.; Acosta-Sandria, Leticia; Cedillo-Carvallo, Beatriz

    2014-01-01

    Clinical response to clopidogrel varies widely due to under-dosing, drug interactions and intrinsic interindividual differences resulting from genetic polymorphisms. Cytochrome P450-2C19 is the principal enzyme involved in the activation of the prodrug and loss-of-function alleles have been described. Upon expiration of the pharmaceutical patent of clopidogrel, generic manufacturers have started to subject interchangeable formulations to bioequivalence studies. The purpose of the current investigation was to study the effect of selection of volunteers homozygous for the CYP2C19*1 haplotype on the bioavailability of clopidogrel. A regular 2×2 bioequivalence study between two formulations of clopidogrel was performed in volunteers selected and unselected for relevant CYP2C19 haplotypes for the Mexican population. It was found that selection of volunteers homozygous for the CYP2C19*1 haplotype, increased the stringency of bioequivalence statistics and resulted in bioinequivalence of a generic clopidogrel compound that otherwise proved equivalent when tested in an open unselected population. Augmentation of bioequivalence strictness is expected to result from pharmacogenetic selection of volunteers. PMID:25284925

  14. Pharmacogenetic selection of volunteers increases stringency of bioequivalence studies; the case of clopidogrel.

    PubMed

    Garcés-Eisele, J; Ruiz-Argüelles, A; Estrada-Marín, Larisa; Reyes-Núñez, Virginia; Vázquez-Pérez, R; Guzmán-García, Olga; Coutiño-Medina, R; Acosta-Sandria, Leticia; Cedillo-Carvallo, Beatriz

    2014-07-01

    Clinical response to clopidogrel varies widely due to under-dosing, drug interactions and intrinsic interindividual differences resulting from genetic polymorphisms. Cytochrome P450-2C19 is the principal enzyme involved in the activation of the prodrug and loss-of-function alleles have been described. Upon expiration of the pharmaceutical patent of clopidogrel, generic manufacturers have started to subject interchangeable formulations to bioequivalence studies. The purpose of the current investigation was to study the effect of selection of volunteers homozygous for the CYP2C19*1 haplotype on the bioavailability of clopidogrel. A regular 2×2 bioequivalence study between two formulations of clopidogrel was performed in volunteers selected and unselected for relevant CYP2C19 haplotypes for the Mexican population. It was found that selection of volunteers homozygous for the CYP2C19*1 haplotype, increased the stringency of bioequivalence statistics and resulted in bioinequivalence of a generic clopidogrel compound that otherwise proved equivalent when tested in an open unselected population. Augmentation of bioequivalence strictness is expected to result from pharmacogenetic selection of volunteers.

  15. Clopidogrel

    MedlinePlus

    ... Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for ...

  16. Stent Thrombosis Patients with Hyporesponsiveness to Clopidogrel, Prasugrel, and Ticagrelor: A Case Series Using Short Thromboelastography

    PubMed Central

    Sambu, Nalyaka; Mahmoudi, Michael; Curzen, Nick

    2016-01-01

    Patients after percutaneous coronary intervention (PCI) with stent implantation and functional hyporesponsiveness to P2Y12 inhibitors are at higher risk of ischaemic events, particularly stent thrombosis (ST). It is currently not routine practice to assess the functional response to these agents. However, concern over functional hyporesponsiveness to clopidogrel has led to widespread uptake of prasugrel and ticagrelor as the default P2Y12 inhibitor after stent implantation in patients with acute coronary syndrome. Here we report, for the first time, 3 cases in which patients who have had ST exhibit hyporesponsiveness to clopidogrel, prasugrel, and ticagrelor. PMID:27799942

  17. Additive antithrombotic effect of ASP6537, a selective cyclooxygenase (COX)-1 inhibitor, in combination with clopidogrel in guinea pigs.

    PubMed

    Sakata, Chinatsu; Suzuki, Ken-Ichi; Morita, Yoshiaki; Kawasaki, Tomihisa

    2017-03-05

    Clopidogrel (Plavix(®), Sanofi-Aventis), the adenosine diphosphate P2Y12 receptor antagonist, is reported to be effective in the prevention of cardiovascular events and is often used in combination with aspirin, particularly in high-risk patients. ASP6537 is a reversible cyclooxygenase (COX)-1 inhibitor that is under investigation as an anti-platelet agent. First, we investigated the reversibility of the antiplatelet effect of ASP6537 and its interaction with ibuprofen to compare the usability of ASP6537 with that of aspirin. We then evaluated the antithrombotic effect of ASP6537 in combination with clopidogrel using a FeCl3-induced thrombosis model in guinea pigs. ASP6537 exerted reversible antiplatelet activity, and no pharmacodynamic interaction with ibuprofen was noted. When administered as monotherapy, ASP6537 exerted a significant antithrombotic effect at ≥3mg/kg, while aspirin inhibited thrombosis at 100mg/kg. ASP6537 exerted significant additive effects in combination with clopidogrel, and the minimum antithrombotic dose was reduced by concomitant administration of clopidogrel. Our study showed that ASP6537 did not interact with ibuprofen and has clear additive effects in combination with clopidogrel. ASP6537 may therefore represent a promising antiplatelet agent for use in clinical settings in combination with clopidogrel.

  18. Non-Carriers of Reduced-Function CYP2C19 Alleles are Most Susceptible to Impairment of the Anti-Platelet Effect of Clopidogrel by Proton-Pump Inhibitors: A Pilot Study

    PubMed Central

    Lee, Jen-Kuang; Wu, Cho-Kai; Juang, Jyh-Ming; Tsai, Chia-Ti; Hwang, Juey-Jen; Lin, Jiuun-Lee; Chiang, Fu-Tien

    2016-01-01

    Background The phenomenon of CYP2C19 polymorphism affects the metabolism of both clopidogrel and proton-pump inhibitors (PPI). However, concomitant use of both drugs may reduce the desired therapeutic effects. In this study, we evaluated whether individuals with different numbers of reduced-function CYP2C19 alleles were equally affected and whether PPIs with different dependencies on CYP2C19 metabolism were equally involved. Methods Thirty healthy volunteers were recruited to a six-week regimen of clopidogrel. Three PPIs with different metabolic dependencies on CYP2C19 were included and separately administered in this order. Each PPI was given for a week, followed by a one-week washout period before the intervention of the next PPI. The anti-platelet effect was examined by Thromboelastography Platelet MappingTM (TEG®) and vasodilator-stimulated phosphoprotein (VASP) assays. Results Both TEG® and VASP tests showed the same general qualitative trend, but TEG® detected a statistically significant fluctuation of platelet aggregation in response to different drug interventions. The TEG® results also demonstrated that non-carriers experienced the most significant impairment of anti-platelet effect of clopidogrel after concomitant use of PPIs. This impairment was closely related to the metabolic dependence on CYP2C19 of PPI. Conclusions Our study indicated that non-carriers of reduced-function CYP2C19 alleles are most susceptible to impairment of the anti-platelet effect of clopidogrel after concomitant PPI use. Individual subjects are not equally affected, and PPIs are not equally involved. However, large-scale randomized clinical trials are needed to evaluate the clinical outcome. PMID:27122952

  19. Multi-parameter assessment of platelet inhibition and its stability during aspirin and clopidogrel therapy

    PubMed Central

    Timur, A. Anil; Murugesan, Gurunathan; Zhang, Li; Barnard, John; Bhatt, Deepak L.; Kottke-Marchant, Kandice

    2014-01-01

    Introduction Poor response to antiplatelet drugs is associated with adverse outcomes. We assessed platelet inhibition and its stability and tested correlation and agreement between platelet function assays. Methods Peripheral blood from 58 patients on both aspirin and clopidogrel who underwent percutaneous coronary intervention (PCI) was collected at hospital discharge (visit-1) and at 30–90 days (visit-2). Platelet function was measured using light transmission aggregometry (LTA-AA and LTA-ADP), VerifyNow (Aspirin; ARU and P2Y12; PRU), ex vivo TxB2, urinary 11dhTxB2, and VASP (PRI) assays. Data were analyzed as continuous, quartiles and binary. Patients were defined as aspirin poor responder (PR) with ARU ≥550, LTA-AA maximum ≥20%, TxB2 ≥1 ng/mL or 11dhTxB2 ≥1,500 pg/mg of creatinine and as clopidogrel PR with PRU ≥240, PRU ≥208, LTA-ADP maximum ≥40%, PRI ≥50%, or PRI ≥66%. Results Aspirin PR was 3–33% and clopidogrel PR was 10–35% in visit-1. LTA-AA, 11dhTxB2, and all clopidogrel-response measures showed correlation and agreement between visit-1 and visit-2. The highest agreement between two visits was revealed by PRU ≥240 and PRI ≥66% (PRU-κ=0.7, 95% CI=0.47, 0.93; PRI-κ=0.69, 95% CI=0.42, 0.95, p-values<0.001). Comparison of platelet function assays in a single visit (Visit-1) revealed a poor correlation between LTA-AA and 11dhTxB2 assays and no agreement among aspirin-response assays. The highest correlation and agreement were obtained between VerifyNow P2Y12 and VASP assays (rho=0.7, p-value<0.001 and PRU ≥208-PRI-κ=0.41–0.42, 95% CI=0.13, 0.69, p-values<0.001). Conclusions Platelet inhibition is stable during aspirin and clopidogrel treatment. Clopidogrel-response assays correlate and agree with each other better than aspirin-response assays. PMID:24852729

  20. The Evaluator's Responsibility for Utilization.

    ERIC Educational Resources Information Center

    Patton, Michael Quinn

    1988-01-01

    The role of the evaluator in insuring utilization and quality of evaluation results is discussed. Topics covered include a utilization-focused vision of accountability, overcoming staff fears of evaluation, eliciting the right information from users, situational responsiveness, and advocacy. (TJH)

  1. The pharmacokinetic and pharmacodynamic interaction of clopidogrel and cilostazol in relation to CYP2C19 and CYP3A5 genotypes

    PubMed Central

    Kim, Ho‐Sook; Lim, Younghae; Oh, Minkyung; Ghim, Jong‐lyul; Kim, Eun‐Young; Kim, Dong‐Hyun

    2015-01-01

    Aim The primary objective of the present study was to evaluate the pharmacokinetic and pharmacodynamic interactions between clopidogrel and cilostazol in relation to the CYP2C19 and CYP3A5 genotypes. Methods In a randomized, three‐way crossover study, 27 healthy subjects were administered clopidogrel (300 mg), cilostazol (100 mg) or clopidogrel + cilostazol orally. Plasma concentrations of clopidogrel, cilostazol and their active metabolites (clopidogrel thiol metabolite, 3,4‐dehydrocilostazol and 4″‐trans‐hydroxycilostazol), and adenosine diphosphate‐induced platelet aggregation were measured for pharmacokinetic and pharmacodynamic assessment. Results The area under the plasma concentration–time curve (AUC) of the active thiol metabolite of clopidogrel was highest in the CYP2C19 extensive metabolizers (EM) and lowest in the poor metabolizers (PM). Cilostazol decreased the thiol metabolite AUC by 29% in the CYP3A5*1/*3 genotype [geometric mean ratio (GMR) 0.71; 90% confidence interval (CI) 0.58, 0.86; P = 0.020] but not in the CYP3A5*3/*3 genotype (GMR 0.93; 90% CI 0.80, 1.10; P = 0.446). Known effects of the CYP2C19 and CYP3A5 genotypes on the exposure of cilostazol and its metabolites were observed but there was no significant difference in the AUC of cilostazol and 3,4‐dehydrocilostazol between cilostazol and clopidogrel + cilostazol. The inhibition of platelet aggregation from 4 h to 24 h (IPA4–24) following the administration of clopidogrel alone was highest in the CYP2C19 EM genotype and lowest in the CYP2C19 PM genotype (59.05 ± 18.95 vs. 36.74 ± 13.26, P = 0.023). However, the IPA of the CYP2C19 PM following co‐administration of clopidogrel and cilostazol was comparable with that of the CYP2C19 EM and intermediate metabolizers (IM) only in CYP3A5*3/*3 subjects. Conclusions The additive antiplatelet effect of cilostazol plus clopidogrel is maximized in subjects with both the CYP2C19 PM and CYP3A5*3/*3 genotypes because

  2. Efficacy of Leflunomide, Telmisartan, and Clopidogrel for Immunoglobulin A Nephropathy: A Randomized Controlled Trial

    PubMed Central

    Wu, Jie; Duan, Shu-Wei; Sun, Xue-Feng; Li, Wen-Ge; Wang, Ya-Ping; Liu, Wen-Hu; Zhang, Jian-Rong; Lun, Li-De; Li, Xue-Mei; Zhou, Chun-Hua; Li, Ji-Jun; Liu, Shu-Wen; Xie, Yuan-Sheng; Cai, Guang-Yan; Ma, Lu; Huang, Wen; Wu, Hua; Jia, Qiang; Chen, Xiang-Mei

    2016-01-01

    Background: The efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for immunoglobulin A nephropathy (IgAN) are unclear. This study was designed to evaluate the efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for IgAN. Methods: It is a multicenter, prospective, double-dummy randomized controlled trial. Primary IgAN patients were recruited in 13 renal units across Beijing, China, from July 2010 to June 2012. After a 4-week telmisartan (80 mg/d) wash-in, 400 patients continuing on 80 mg/d telmisartan were randomly assigned to additionally receive placebo (Group A), 50 mg/d clopidogrel (Group B), 20 mg/d leflunomide (Group C), or 50 mg/d clopidogrel and 20 mg/d leflunomide (Group D). The 24-week intervention was completed by 360 patients. The primary endpoint was change in 24-h proteinuria at 24 weeks. A linear mixed-effect model was used to analyze the changes at 4, 12, and 24 weeks. Generalized estimating equations were used to evaluate changes in hematuria grade. This trial was registered at the Chinese Clinical Trial Registry. Results: The effects of telmisartan combined with leflunomide on changes in proteinuria (0.36 [95% confidence interval (CI) 0.18–0.55] g/d, P < 0.001), in serum uric acid (76.96 [95% CI 57.44–96.49] μmol/L, P < 0.001), in serum creatinine (9.49 [95% CI 6.54–12.44] μmol/L, P < 0.001), and in estimated glomerular filtration rate (−6.72 [95% CI −9.46 to −3.98] ml∙min−1∙1.73 m−2, P < 0.001) were statistically significant, whereas they were not statistically significant on changes in systolic and diastolic blood pressure and weight (P > 0.05). Telmisartan combined with clopidogrel had no statistical effect on any outcome, and there was no interaction between the interventions. No obvious adverse reactions were observed. Conclusions: Telmisartan combined with leflunomide, not clopidogrel, is safe and effective for decreasing proteinuria in certain

  3. Cangrelor inhibits the binding of the active metabolites of clopidogrel and prasugrel to P2Y12 receptors in vitro.

    PubMed

    Judge, Heather M; Buckland, Robert J; Jakubowski, Joseph A; Storey, Robert F

    2016-01-01

    Cangrelor is a rapid-acting, direct-binding, and reversible P2Y12 antagonist which has been studied for use during percutaneous coronary intervention (PCI) in patients with or without pretreatment with an oral P2Y12 antagonist. As cangrelor is administered intravenously, it is necessary to switch to an oral P2Y12 antagonist following PCI, such as the thienopyridines clopidogrel, and prasugrel or the non-pyridine ticagrelor. Previous studies have suggested a negative pharmacodynamic interaction between cangrelor and thienopyridines. This in vitro study evaluated the receptor-level interaction between cangrelor and the active metabolite (AM) of clopidogrel or prasugrel by assessing functional P2Y12 receptor number using a (33)P-2MeSADP binding assay. All P2Y12 antagonists studied resulted in strong P2Y12 receptor blockade (cangrelor: 93.6%; clopidogrel AM: 93.0%; prasugrel AM: 97.9%). Adding a thienopyridine AM in the presence of cangrelor strongly reduces P2Y12 receptor blockade by the AM (clopidogrel AM: 7%, prasugrel AM: 3.2%). The thienopyridine AMs had limited ability to compete with cangrelor for binding to P2Y12 (% P2Y12 receptor blockade after co-incubation with cangrelor 1000 nmol/L: 11.7% for clopidogrel AM 3 µmol/L; 34.1% for prasugrel AM 3 µmol/L). In conclusion, in vitro cangrelor strongly inhibits the binding of clopidogrel and prasugrel AMs to the P2Y12 receptor, consistent with the previous observation of a negative pharmacodynamic interaction. Care may need to be taken to not overlap exposure to thienopyridine AMs and cangrelor in order to reduce the risk of thrombotic complications following PCI.

  4. EVALUATING HYDROLOGICAL RESPONSE TO ...

    EPA Pesticide Factsheets

    Studies of future management and policy options based on different assumptions provide a mechanism to examine possible outcomes and especially their likely benefits or consequences. Planning and assessment in land and water resource management are evolving toward complex, spatially explicit regional assessments. These problems have to be addressed with distributed models that can compute runoff and erosion at different spatial and temporal scales. The extensive data requirements and the difficult task of building input parameter files, however, have long been an obstacle to the timely and cost-effective use of such complex models by resource managers. The U.S. EPA Landscape Ecology Branch in collaboration with the USDA-ARS Southwest Watershed Research Center has developed a geographic information system (GIS) tool to facilitate this process. A GIS provides the framework within which spatially distributed data are collected and used to prepare model input files, and model results are evaluated. The Automated Geospatial Watershed Assessment (AGWA) tool uses widely available standardized spatial datasets that can be obtained via the internet at no cost to the user. The data are used to develop input parameter files for KINEROS2 and SWAT, two watershed runoff and erosion simulation models that operate at different spatial and temporal scales. AGWA automates the process of transforming digital data into simulation model results and provides a visualization tool

  5. Information Science and Responsive Evaluation

    ERIC Educational Resources Information Center

    Stake, Robert E.

    2014-01-01

    Responsive evaluation builds upon the methods of informal evaluation in disciplined ways: getting personally acquainted with the evaluand, observation of activities, interviewing people who are in different ways familiar with the evaluand, searching documents that reveal what happened in the past or somewhere else. It calls for sustained effort to…

  6. Sustained increase in platelet aggregation after the cessation of clopidogrel.

    PubMed

    Djukanovic, Nina; Todorovic, Zoran; Zamaklar-Trifunovic, Danijela; Protic, Dragana; Dzudovic, Boris; Ostojic, Miodrag; Obradovic, Slobodan

    2016-02-01

    This study shows that the abrupt cessation of one-year clopidogrel treatment was not associated with thrombotic events in a prospective, multicentre study that enrolled 200 patients subjected to coronary stent implantation and treated with aspirin + clopidogrel 1 year after the stent placement. The aim of the study was to investigate the causes of a sustained increase of platelet aggregability, considering that the values of platelet aggregation stimulated with ADP + PGE1 (ADPHS values) significantly increased 10-90 days after the cessation of clopidogrel. Values of platelet aggregation induced by thrombin receptor activating peptide (TRAP values) and arachidonic acid (ASPI values) were divided into quartiles on the basis of ADPHS values 10 days after stopping clopidogrel (ADPHS10 ). There was a significant difference between TRAP values divided into quartiles according to ADPHS10 , 10, 45 and 90 days after stopping clopidogrel (P < 0.001, all), and ASPI values across the same quartiles 10 and 45 days after the cessation of clopidogrel (P = 0.028 and 0.003). The results of the study indicate that patients with early pronounced rebound phenomena to clopidogrel termination have a long-term (at least 90 days) increased platelet aggregation to other agonists such as thrombin-related activated protein and arachidonic acid, suggesting the complex mutual relationship of various factors/agonists influencing the function of platelets.

  7. Cytochrome allelic variants and clopidogrel metabolism in cardiovascular diseases therapy.

    PubMed

    Jarrar, Mohammed; Behl, Shalini; Manyam, Ganiraju; Ganah, Hany; Nazir, Mohammed; Nasab, Reem; Moustafa, Khaled

    2016-06-01

    Clopidogrel and aspirin are among the most prescribed dual antiplatelet therapies to treat the acute coronary syndrome and heart attacks. However, their potential clinical impacts are a subject of intense debates. The therapeutic efficiency of clopidogrel is controlled by the actions of hepatic cytochrome P450 (CYPs) enzymes and impacted by individual genetic variations. Inter-individual polymorphisms in CYPs enzymes affect the metabolism of clopidogrel into its active metabolites and, therefore, modify its turnover and clinical outcome. So far, clinical trials fail to confirm higher or lower adverse cardiovascular effects in patients treated with combinations of clopidogrel and proton pump inhibitors, compared with clopidogrel alone. Such inconclusive findings may be due to genetic variations in the cytochromes CYP2C19 and CYP3A4/5. To investigate potential interactions/effects of these cytochromes and their allele variants on the treatment of acute coronary syndrome with clopidogrel alone or in combination with proton pump inhibitors, we analyze recent literature and discuss the potential impact of the cytochrome allelic variants on cardiovascular events and stent thrombosis treated with clopidogrel. The diversity of CYP2C19 polymorphisms and prevalence span within various ethnic groups, subpopulations and demographic areas are also debated.

  8. Antiplatelet effects of clopidogrel and aspirin after interventional patent foramen ovale/ atrium septum defect closure.

    PubMed

    Polzin, Amin; Dannenberg, Lisa; Sophia Popp, Valérie-; Kelm, Malte; Zeus, Tobias

    2016-06-01

    The optimal antiplatelet therapy after patent foramen ovale (PFO)/ atrium septum defect (ASD) closure is a matter of discussion. It is challenging as inter-individual responses to antiplatelet medication vary significantly and common complications are bleeding and ischemic events. In this study, we aimed to analyze the incidence of high on-treatment platelet reactivity (HTPR) to antiplatelet medication in patients undergoing PFO/ASD closure as well as clinical complications and thrombus formation on the occluder during six-month follow-up. This hypothesis generating pilot study was observed, which included 140 patients undergoing PFO/ASD closure. The primary endpoint was pharmacodynamic response to antiplatelet medication. A composite of death, myocardial infarction, bleeding, stroke and thrombus formation on the occluder during six-month follow-up was the secondary endpoint. HTPR to clopidogrel was analyzed using the vasodilator-stimulated protein phosphorylation (VASP), HTPR to aspirin by light-transmission aggregometry (LTA). In 71% of patients HTPR to clopidogrel was detected, HTPR to aspirin in only 4%. We observed 12 complications, 9 bleeding events (including 3 major bleeding events) and 3 transient ischemic attacks. No stroke and no thrombus formation on the occluder occurred. The primary endpoint was not associated with the secondary endpoint. The incidence of HTPR to clopidogrel in PFO/ASD closure patients is very high. Despite this high incidence, no stroke or thrombus formation on the occluder occurred at all. This leads to the hypothesis, that the benefit of additional clopidogrel medication is questionable and has to be investigated in large-scale clinical trials.

  9. Purpuric herpes zoster in patients in therapy with clopidogrel.

    PubMed

    Veraldi, S; Vaira, F; Nazzaro, G

    2015-08-01

    Clopidogrel is an adenosine diphosphate receptor antagonist used for the prevention of vascular events in patients with atherothrombotic diseases manifested by recent myocardial infarction, ischemic stroke or peripheral arterial disease. Diarrhoea, rash and pruritus are rather common side effects of clopidogrel. Other side effects include epistaxis, nausea, abdominal pain, vomiting, gastritis, gastric and duodenal ulcer. Thrombocytopenia is the most common laboratory abnormality. Leucopenia and neutropenia are rare. We report three cases of purpuric herpes zoster in patients in therapy with clopidogrel. To our knowledge, only one case of haemorrhagic herpes zoster has been published in a patient in therapy with this drug.

  10. Antiplatelet Agents in Cardiology: A Report on Aspirin, Clopidogrel, Prasugrel, and Ticagrelor.

    PubMed

    Dobesh, Paul P; Varnado, Sara; Doyle, Meagan

    2016-01-01

    Antiplatelet drugs are the cornerstone of therapy in many cardiovascular conditions. With the current success and increased use of transcatheter aortic valve implantation (TAVI), the use of antiplatelet therapy is considered part of the medical therapy for these patients. Clinicians caring for these patients need to have a thorough understanding of the pharmacology, pharmacokinetics, pharmacodynamic, and clinical efficacy and safety of commonly used antiplatelet therapy. While aspirin therapy is widely used, dual antiplatelet therapy with clopidogrel has become part of standard of care. Despite the extensive experience with clopidogrel, there are limitations such as drug interactions, metabolism genetic polymorphisms, and variability in the antiplatelet response. More predictable and more potent antiplatelet agents, prasugrel and ticagrelor, have demonstrated superior reductions in ischemic endpoints as part of dual antiplatelet therapy compared to clopidogrel, but at the cost of more major bleeding in patients with an acute coronary syndrome. Significant research needs to be conducted in the setting of TAVI to help define the optimal antiplatelet regimen.

  11. Clopidogrel Within Few Hours of Coronary Artery Bypass Grafting Does Significantly Increase the Risk of Bleeding

    PubMed Central

    Hijazi, Emad M.; Musleh, Ghassan S

    2012-01-01

    Background Postoperative bleeding after coronary artery surgery is partly related to platelet dysfunction. The aim of this study was to evaluate the effects of a single loading dose of clopidogrel (300 mg) before coronary angiography on bleeding and use of blood and blood products after emergency coronary artery bypass surgery (CABG). Methods This is a nonrandomized observational prospective study between January, 2006 till December 2009, at a university hospital, we compare the results of a cohort of 65 patients who received 300 mg clopidogrel during coronary angiography that was followed by emergency CABG (group A or study group) to a cohort of 206 patients who underwent elective coronary artery bypass surgery during the same period by the same surgeons in whom clopidogrel was stopped 7 days before surgery (Group B or control group). Emergency surgery was done because of critical coronary anatomy or because of ongoing chest pain. All patients in the two groups were kept on 100 mg of aspirin until the day of surgery. Outcome data used to compare the two groups, Chest tube drainage in first 12 hours (12 h), need for re-exploration and use of blood and blood product transfusion were prospectively collected. Results Postoperative bleeding, reoperation rates for bleeding and use of blood products are significantly more in those who received a loading dose of clopedogril within few hours of CABG (group A) compared to those who stopped clopedogril for a week before CABG. Conclusions Preoperative 300 mg of clopidogrel is associated with significant increase in post operative bleeding, need for surgical exploration and use of blood and blood product transfusion after CABG.

  12. Temporal variability in the antiplatelet effects of clopidogrel and aspirin after elective drug-eluting stent implantation. An ADAPT-DES substudy.

    PubMed

    Nührenberg, Thomas G; Stratz, Christian; Leggewie, Stefan; Hochholzer, Willibald; Valina, Christian M; Gick, Michael; Kirtane, Ajay J; Stone, Gregg W; Neumann, Franz-Josef; Trenk, Dietmar

    2015-11-01

    Given conflicting data on temporal variability in pharmacodynamic platelet responses to clopidogrel, we investigated platelet reactivity on clopidogrel and aspirin for up to six months after elective percutaneous coronary intervention (PCI) with drug-eluting stents. Platelet reactivity was determined in 102 patients before loading with clopidogrel and aspirin, and on maintenance therapy after PCI on day 1, at one month and six months by VerifyNow™ P2Y12 and Aspirin assays and by residual platelet aggregation (RPA) on light transmission aggregometry using adenosine diphosphate and arachidonic acid. By VerifyNow testing, median (interquartile range) P2Y12 reaction units (PRU) on clopidogrel were 166 (90-234), 195 (124-257), and 198 (141-252) on day 1, one month and six months after PCI, respectively (p=0.005 day 1 to 1 month, and p=0.86 1 month to 6 months). Using a cut-off of > 208 PRU, 35 % of patients had high platelet reactivity (HPR) to clopidogrel on day 1, 43 % at one month, and 46 % at six months after PCI. Between day 1 and six months after PCI, 38.2 % of patients changed clopidogrel responder status at least once. Other cut-offs and RPA yielded similar results. Platelet inhibition by aspirin was consistent over time with only five patients being characterised as having HPR. Considerable variation in individual on-clopidogrel platelet reactivity was present during both the subacute and the late phases of maintenance therapy after elective PCI. Hence, the utility of contemporary platelet function testing to guide antiplatelet therapy may be limited.

  13. Synergistic Effects of Clopidogrel and Fufang Danshen Dripping Pills by Modulation of the Metabolism Target and Pharmacokinetics

    PubMed Central

    Ma, Shitang; Ju, Wenzheng; Dai, Guoliang; Zhao, Wenzhu; Cheng, Xiaogui; Fang, Zhuyuan; Tan, Hengshan; Wang, Xiaoxiao

    2014-01-01

    Background and Objective. The aim was to evaluate the synergistic effects of clopidogrel and FDDP by modulating the metabolism target and the pharmacokinetics. Methods. The inhibition effect of FDDP on the CES1 was first investigated by the molecular simulation method, and the synergistic effects on the pharmacokinetics of CPGS were studied as follows: SD rats were treated with oral clopidogrel alone at a dosage of 30 mg/kg or the combination of clopidogrel and FDDP at dosages of 30 mg/kg and 324 mg/kg, respectively, for 21 days. The concentrations of CPGS in the blood plasma samples were determined and the calculated concentrations were used to determine the pharmacokinetic parameters. Results. 20 compounds in FDDP potentially interacted with CES1 target. The CPGS showed a two-compartment model pharmacokinetic profile. The concentration-time course of CPGS was not changed by FDDP, but FDDP decreased the peak plasma concentration and area under the curve of CPGS. Conclusion. The CES1's activity could be partly inhibited by FDDP through the molecular simulation investigation. The concentration-time course of CPGS was altered slightly by FDDP. The results demonstrated the synergistic effects of clopidogrel and FDDP by modulating both the pharmacokinetics and the target metabolism. PMID:25530790

  14. The Pharmacogenetic Control of Antiplatelet Response: Candidate Genes and CYP2C19

    PubMed Central

    Yang, Yao; Lewis, Joshua P.; Hulot, Jean-Sébastien; Scott, Stuart A.

    2016-01-01

    Introduction Aspirin, clopidogrel, prasugrel and ticagrelor are antiplatelet agents for the prevention of ischemic events in patients with acute coronary syndromes (ACS), percutaneous coronary intervention (PCI), and other indications. Variability in response is observed to different degrees with these agents, which can translate to increased risks for adverse cardiovascular events. As such, potential pharmacogenetic determinants of antiplatelet pharmacokinetics, pharmacodynamics and clinical outcomes have been actively studied. Areas covered This article provides an overview of the available antiplatelet pharmacogenetics literature. Evidence supporting the significance of candidate genes and their potential influence on antiplatelet response and clinical outcomes are summarized and evaluated. Additional focus is directed at CYP2C19 and clopidogrel response, including the availability of clinical testing and genotype-directed antiplatelet therapy. Expert opinion The reported aspirin response candidate genes have not been adequately replicated and few candidate genes have thus far been implicated in prasugrel or ticagrelor response. However, abundant data supports the clinical validity of CYP2C19 and clopidogrel response variability among ACS/PCI patients. Although limited prospective trial data are available to support the utility of routine CYP2C19 testing, the increased risks for reduced clopidogrel efficacy among ACS/PCI patients that carry CYP2C19 loss-of-function alleles should be considered when genotype results are available. PMID:26173871

  15. Role of phenotypic and genetic testing in managing clopidogrel therapy.

    PubMed

    Chan, Noel C; Eikelboom, John W; Ginsberg, Jeffrey S; Lauw, Mandy N; Vanassche, Thomas; Weitz, Jeffrey I; Hirsh, Jack

    2014-07-31

    The P2Y12 inhibitors, clopidogrel, prasugrel, and ticagrelor, are administered in fixed doses without laboratory monitoring. Randomized trials in acute coronary syndrome have shown that prasugrel and ticagrelor are more effective than standard-dose clopidogrel. Nonetheless, standard-dose clopidogrel remains widely used because it causes less bleeding and is less expensive. Patients treated with standard-dose clopidogrel have substantial variability in platelet inhibition, which is partly explained by genetic polymorphisms encoding CYP2C19, the hepatic enzyme involved in biotransformation of clopidogrel to its active metabolite. Some advocate tailoring P2Y12 inhibitor therapy according to the results of routine laboratory testing. Although there is good evidence for analytic, biological, and clinical validity of several phenotypic and genotypic biomarkers, the benefit of a management strategy that incorporates routine biomarker testing over standard of care without such testing remains unproven. Appropriately designed, adequately powered trials are needed but face the challenges of feasibility, cost, and the progressive switch from clopidogrel to prasugrel or ticagrelor.

  16. Variability of platelet aggregation in patients with clopidogrel treatment and hip fracture: A retrospective case-control study on 112 patients

    PubMed Central

    Clareus, Anna; Fredriksson, Inga; Wallén, Håkan; Gordon, Max; Stark, André; Sköldenberg, Olof

    2015-01-01

    AIM: To identify the rate of non-responders to clopidogrel treatment in hip fracture patients and study how non-responders differ from controls. METHODS: In a retrospective case-control study we included 28 cases of acute proximal femoral fracture with clopidogrel treatment 2011 to 2013. Eighty-four controls from the same time period were included. Data collected included response to clopidogrel measured with multiple electrode aggregometry (MEA), intraoperative bleeding, erythrocyte transfusion, time to surgery and the incidence of adverse events up to 3 mo after surgery. RESULTS: Eight (29%) of the 28 cases were non-responders. The median intraoperative bleeding was 300 mL (range, 0-1500), and was lower for non-responders (50 mL) but did not reach statistical significance. Erythrocyte transfusions did not differ between responders, non-responders and controls. Forty-five (40%) of 112 patients had adverse events postoperatively but the rate did not differ between patients with and without clopidogrel treatment. CONCLUSION: Almost one-third of patients with clopidogrel treatment and an acute proximal femoral fracture are non-responders to antiplatelet therapy and can be operated without delay. PMID:26085986

  17. Using Responsive Evaluation To Evaluate a Professional Conference.

    ERIC Educational Resources Information Center

    Speigel, Amy N.; Bruning, Roger H.; Giddings, Lisa

    1999-01-01

    Incorporated responsive evaluation methods into the structure of a professional conference and illustrated the usefulness of these techniques in evaluating conferences. Discusses the implications of this pilot study of responsive evaluation. (SLD)

  18. The extent of P2Y12 inhibition by clopidogrel in diabetes mellitus patients with acute coronary syndrome is not related to glycaemic control: roles of white blood cell count and body weight.

    PubMed

    Morel, Olivier; El Ghannudi, Soraya; Hess, Sebastien; Reydel, Antje; Crimizade, Ulun; Jesel, Laurence; Radulescu, Bogdan; Wiesel, Marie L; Gachet, Christian; Ohlmann, Patrick

    2012-08-01

    It was the study objective to determine whether glycaemic control affects the extent of platelet inhibition by thienopyridines as assessed by vasodilator-stimulated phosphoprotein flow cytometry (VASP-FCT) in patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention (PCI) during acute coronary syndrome (ACS). Although the proportion of high on-treatment residual platelet reactivity is higher in DM, the contributions of glycaemic control and other factors associated with DM, such as excess body weight and inflammation, to this impaired platelet inhibition by thienopyridines have not yet been fully characterised. In this study, the extent of P2Y12 ADP receptor pathway inhibition was evaluated by the VASP-FCT. Platelet activation was expressed as the platelet reactivity index (PRI). Low response to clopidogrel (LR) was defined as a PRI of >61%. Four hundred forty-five consecutive ACS patients (DM = 160, NDM = 285) were enrolled. The proportion of LR was higher in DM patients (50 vs. 37.5%). In DM, PRI was not correlated with glycosylated haemoglobin (HbA1c) or glycaemia. In a univariate analysis, LR was associated with age, male sex, overweight, and white blood cell count (WBC). In a multivariate analysis, WBC >10,000 and body weight >80 kg were the sole independent predictors of LR to clopidogrel (hazard ratio (HR) 3.02 [1.36-6.68], p=0.006 and HR 2.47 [1.14-5.35], p = 0.021, respectively). Conversely, in non-DM patients, ST-elevation myocardial infarction was the sole independent predictor of LR. In conclusion, in ACS DM patients undergoing PCI, the extent of P2Y12 inhibition by clopidogrel is not related to glycaemic control but is related to body weight and inflammatory status as assessed by the WBC.

  19. Counterintuitive compaction behavior of clopidogrel bisulfate polymorphs.

    PubMed

    Khomane, Kailas S; More, Parth K; Bansal, Arvind K

    2012-07-01

    Being a density violator, clopidogrel bisulfate (CLP) polymorphic system (forms I and II) allows us to study individually the impact of molecular packing (true density) and thermodynamic properties such as heat of fusion on the compaction behavior. These two polymorphs of CLP were investigated for in-die and out-of-die compaction behavior using CTC profile, Heckel, and Walker equations. Compaction studies were performed on a fully instrumented rotary tabletting machine. Detailed examinations of the molecular packing of each form revealed that arrangement of the sulfate anion differs significantly in both crystal forms, thus conferring different compaction behavior to two forms. Close cluster packing of molecules in form I offers a rigid structure, which has poor compressibility and hence resists deformation under compaction pressure. This results into lower densification, higher yield strength, and mean yield pressure, as compared with form II at a given pressure. However, by virtue of higher bonding strength, form I showed superior tabletability, despite its poor compressibility and deformation behavior. Form I, having higher true density and lower heat of fusion showed higher bonding strength. Hence, true density and not heat of fusion can be considered predictor of bonding strength of the pharmaceutical powders.

  20. Changing CS Features Alters Evaluative Responses in Evaluative Conditioning

    ERIC Educational Resources Information Center

    Unkelbach, Christian; Stahl, Christoph; Forderer, Sabine

    2012-01-01

    Evaluative conditioning (EC) refers to changes in people's evaluative responses toward initially neutral stimuli (CSs) by mere spatial and temporal contiguity with other positive or negative stimuli (USs). We investigate whether changing CS features from conditioning to evaluation also changes people's evaluative response toward these CSs. We used…

  1. [Efficacy of clopidogrel as ADP-dependent platelet aggregation inhibitor. Study on individuals with coronary artery disease].

    PubMed

    Izaguirre Avila, R; de la Peña, A; González Pacheco, H; Ramírez Gutiérrez, A; González Valdez, H; Quiroz, A; Cortina, E; Huerta, M; Lupi, E

    2000-01-01

    Acetyl-salicylic acid inhibits thromboxane A2 production and reduces the risk of vascular occlusive events by 20 to 25%. Ticlopidine inhibits ADP-dependent platelet aggregation and reduces the same risk by 30 to 35%, but produces some adverse effects. Clopidogrel is a ticlopidin-derived antiplatelet-drug, with the same mechanism of action; reduces the expression of the glycoprotein IIb/IIIa, the fibrinogen receptor on the platelet surface. Clopidogrel has the same clinical efficacy of ticlopidin and lowers the incidence of adverse effects. In this study, we evaluated the effects of one daily dosis of 75 mg of clopidogrel on platelet function in 33 subjects with coronary artery disease. Before treatment and after the 6th and 12th week, the following parameters were evaluated: 5 microM-ADP and 20 micrograms/mL collagen-induced platelet aggregation, bleeding time and fibrinogen concentration. In basal and in the 6th and 12th week samples, ADP-induced platelet aggregation was 90.7% +/- 13.2, 54.6% +/- 23.2 and 49.2% +/- 23.7 respectively, that represents a significant reduction of 38.6% and 44.4%. Reduction of collagen-induced platelet aggregation was not significative. Plasmatic fibrinogen did not suffer variation during treatment. Bleeding time was significant prolonged from 4.1 minutes to 15.4 and 14.6 minutes (3.7-3.5 times compared with the test before treatment). There were no haemorrhagic complications, only digestive discomfort in fewer than 3% of patients. We concluded that clopidogrel is a safe and efficacious drug for patients, it efficiently reduces ADP-induced platelet aggregation and prolongs bleeding time.

  2. Clopidogrel Enhances Mesenchymal Stem Cell Proliferation Following Periodontitis

    PubMed Central

    Coimbra, L.S.; Steffens, J.P.; Alsadun, S.; Albiero, M.L.; Rossa, C.; Pignolo, R.J.; Spolidorio, L.C.; Graves, D.T.

    2015-01-01

    Bone formation is dependent on the differentiation of osteoblasts from mesenchymal stem cells (MSCs). In addition to serving as progenitors, MSCs reduce inflammation and produce factors that stimulate tissue formation. Upon injury, MSCs migrate to the periodontium, where they contribute to regeneration. We examined the effect of clopidogrel and aspirin on MSCs following induction of periodontitis in rats by placement of ligatures. We showed that after the removal of ligatures, which induces resolution of periodontal inflammation, clopidogrel had a significant effect on reducing the inflammatory infiltrate. It also increased the number of osteoblasts and MSCs. Mechanistically, the latter was linked to increased proliferation of MSCs in vivo and in vitro. When given prior to inducing periodontitis, clopidogrel had little effect on MSC or osteoblasts numbers. Applying aspirin before or after induction of periodontitis did not have a significant effect on the parameters measured. These results suggest that clopidogrel may have a positive effect on MSCs in conditions where a reparative process has been initiated. PMID:26220958

  3. Actively using clopidogrel correlates with an increased risk of acute pancreatitis in Taiwan.

    PubMed

    Lai, Shih-Wei; Lin, Cheng-Li; Liao, Kuan-Fu

    2015-03-15

    The aim of this study is to assess whether there is an association between clopidogrel use and risk of acute pancreatitis in Taiwan. We conducted a case-control study using the database of the Taiwan National Health Insurance Program from 2000 to 2011. There were 5644 subjects aged 20-84 years with a first-time attack of acute pancreatitis as the case group and 22,576 randomly selected sex-matched and age-matched subjects without acute pancreatitis as the control group. We defined clopidogrel use as "actively using" if the final clopidogrel prescription was filled between 0 and 7 days before the date of diagnosing acute pancreatitis, or "not actively using" if the final clopidogrel prescription was filled ≧ 8 days before the date of diagnosing acute pancreatitis. Subjects who never used clopidogrel were defined as never used. The multivariable logistic regression model was used to calculate the odds ratio (OR) and 95% confidence interval (CI) of acute pancreatitis associated with clopidogrel use. Comparing the subjects actively using clopidogrel to those who never used clopidogrel, the adjusted OR of acute pancreatitis was 8.46 (95%CI 5.25, 13.7). The adjusted OR decreased to 1.16 among subjects not actively using clopidogrel (95%CI 0.95, 1.43). Persons actively using clopidogrel are at an increased risk of acute pancreatitis. Further studies are necessary to prove the causal relationship.

  4. Improving Beta Test Evaluation Response Rates: A Meta-Evaluation

    ERIC Educational Resources Information Center

    Russ-Eft, Darlene; Preskill, Hallie

    2005-01-01

    This study presents a meta-evaluation of a beta-test of a customer service training program. The initial evaluation showed a low response rate. Therefore, the meta-evaluation focused on issues related to the conduct of the initial evaluation and reasons for nonresponse. The meta-evaluation identified solutions to the nonresponse problem as related…

  5. The Practice and Politics of Responsive Evaluation

    ERIC Educational Resources Information Center

    Abma, Tineke

    2006-01-01

    Responsive evaluation offers a perspective in which evaluation is reframed from the assessment of program interventions on the basis of policy makers' goals to an engagement with and among all stakeholders about the value and meaning of their practice. Responsive evaluators have to be extra sensitive to power relations given the deliberate…

  6. Comparison of high-resolution melting analysis, TaqMan Allelic discrimination assay, and sanger sequencing for Clopidogrel efficacy genotyping in routine molecular diagnostics.

    PubMed

    Zhang, Lina; Cui, Guanglin; Li, Zongzhe; Wang, Haoran; Ding, Hu; Wang, Dao Wen

    2013-09-01

    Clopidogrel, as a routine antiplatelet drug, is widely used in patients to reduce cardiovascular events following percutaneous coronary intervention. Because of genetic variation, patients undergoing percutaneous coronary intervention show differing responses to clopidogrel therapy. Recently, five single nucleotide polymorphisms (SNPs) within CYP2C19 (rs4244285, rs4986893, rs12248560), ABCB1 (rs1045642), and ITGB3 (rs5918) were identified that contribute prominently to variability in response to clopidogrel. Given that Sanger sequencing is labor intensive and time consuming, rapid genotyping methods for SNP detection are urgently required before clopidogrel therapy. Accordingly, we developed a high-resolution melting analysis (HRMA) and TaqMan allelic discrimination assay (TaqMan) to genotype those five SNPs, and compared these two assays with Sanger sequencing on accuracy of genotyping as well as operational characteristics. These two assays showed high accuracy (0.995, 95% CI 0.991 to 0.998 for HRMA; 0.997, 95% CI 0.994 to 0.999 for TaqMan, respectively), sensitivity (0.996, 95% CI 0.989 to 1.002 for HRMA; 0.998, 95% CI 0.993 to 1.002 for TaqMan, respectively), and specificity (0.995, 95% CI 0.991 to 0.999 for HRMA; 0.996, 95% CI 0.993 to 1.000 for TaqMan, respectively). Our study indicates that HRMA and TaqMan are easier to operate and obviously faster than Sanger sequencing. In conclusion, HRMA and TaqMan are rapid, convenient, and reliable assays for clopidogrel efficacy genotyping.

  7. Prior chronic clopidogrel therapy is associated with increased adverse events and early stent thrombosis.

    PubMed

    Asher, Elad; Fefer, Paul; Sabbag, Avi; Herscovici, Romana; Regev, Ehud; Mazin, Israel; Shlomo, Nir; Zahger, Doron; Atar, Shaul; Hammerman, Haim; Polak, Arthur; Beigel, Roy; Matetzky, Shlomi

    2016-01-01

    Despite the growing use of clopidogrel, limited data exist regarding the prognostic significance of chronic clopidogrel therapy in patients sustaining acute coronary syndrome (ACS). Our aim was to determine whether patients sustaining ACS while on chronic clopidogrel therapy have a worse prognosis than clopidogrel-naïve patients. A total of 5,386 consecutive ACS patients were prospectively characterised and followed-up for 30 days. Of them, 680 (13%) were treated with clopidogrel prior to the index ACS. Major adverse cardiovascular events (MACE) were defined as death, recurrent ACS, stroke and/or stent thrombosis. Compared with clopidogrel-naïve, chronic clopidogrel-treated patients were older (66 ± 12 vs 63 ± 13, respectively; p<0.01), suffered more from diabetes mellitus, hypertension, dyslipidaemia, prior cardiovascular history, including prior myocardial infarction, revascularisation, coronary artery bypass graft and stroke (p<0.01 for all), and were less likely to present with ST-elevation myocardial infarction (21% vs 45%; respectively; p < 0.001). Prior clopidogrel therapy was associated with a two-fold increase in in-hospital (1.6% vs 0.6%, respectively; p =0.006) as well as 30-day stent thrombosis (2.2% vs 1.0%, respectively; p=0.007). MACE at 30 days was also higher among chronic clopidogrel-treated compared with clopidogrel-naïve patients [12.3% vs 9.4%, respectively; p<0.01]. In multivariate log regression analysis chronic clopidogrel treatment was an independent predictor of stent thrombosis [OR=2.6 (95%CI 1.2-5.6), p=0.001]. Patients sustaining ACS while on chronic clopidogrel treatment are at higher risk for in-hospital and 30-day adverse outcomes, including stent thrombosis.

  8. Response Bias in Hospice Evaluation.

    ERIC Educational Resources Information Center

    Hayslip, Bert, Jr.; And Others

    1991-01-01

    Analyzed response bias among 34 recipients of care in hospice. Found nonrespondents to have better bereavement prognoses and tended to care for patients who were younger, male, and in program for shorter time. Nonrespondents were in contact with staff less than were respondents. Data are consistent with earlier research showing significant…

  9. A Ranking Method for Evaluating Constructed Responses

    ERIC Educational Resources Information Center

    Attali, Yigal

    2014-01-01

    This article presents a comparative judgment approach for holistically scored constructed response tasks. In this approach, the grader rank orders (rather than rate) the quality of a small set of responses. A prior automated evaluation of responses guides both set formation and scaling of rankings. Sets are formed to have similar prior scores and…

  10. Cost-effectiveness of clopidogrel, prasugrel and ticagrelor for dual antiplatelet therapy after acute coronary syndrome: a decision-analytic model

    PubMed Central

    Abdel-Qadir, Husam; Roifman, Idan; Wijeysundera, Harindra C.

    2015-01-01

    Background: The use of prasugrel or ticagrelor as part of dual antiplatelet therapy with acetylsalicylic acid after acute coronary syndrome (ACS) improves clinical outcomes relative to clopidogrel. The relative cost-effectiveness of these agents are unknown. We conducted an economic analysis evaluating 12 months of treatment with clopidogrel, prasugrel or ticagrelor after ACS. Methods: We developed a fully probabilistic Markov cohort decision-analytic model using a lifetime horizon, from the perspective of the Ontario Ministry of Health and Long-Term Care. The model incorporated risks of death, recurrent ACS, heart failure, major bleeding and other adverse effects of treatment. Data on probabilities and utilities were obtained from the published literature where available. The primary outcome was quality-adjusted life-years (QALYs). Results: Treatment with clopidogrel was associated with the lowest effectiveness (7.41 QALYs, 95% confidence interval [CI] 1.05-14.79) and the lowest cost ($39 601, 95% CI $8434-$111 186). Ticagrelor treatment had an effectiveness of 7.50 QALYs (95% CI 1.13-14.84) at a cost of $40 649 (95% CI $9327-$111 881). The incremental cost-effectiveness ratio (ICER) for ticagrelor relative to clopidogrel was $12 205 per QALY gained. Prasugrel had an ICER of $57 630 per QALY gained relative to clopidogrel. Ticagrelor was the preferred option in 90% of simulations at a willingness-to-pay threshold of $50 000 per QALY gained. Interpretation: Ticagrelor was the most cost-effective agent when used as part of dual antiplatelet therapy after ACS. This conclusion was robust to wide variations in model parameters. PMID:26770967

  11. Culturally Responsive Evaluation Meets Systems-Oriented Evaluation

    ERIC Educational Resources Information Center

    Thomas, Veronica G.; Parsons, Beverly A.

    2017-01-01

    The authors of this article each bring a different theoretical background to their evaluation practice. The first author has a background of attention to culturally responsive evaluation (CRE), while the second author has a background of attention to systems theories and their application to evaluation. Both have had their own evolution of…

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

    PubMed Central

    Wang, Zhi-Yu; Chen, Meng; Zhu, Ling-Ling; Yu, Lu-Shan; Zeng, Su; Xiang, Mei-Xiang; Zhou, Quan

    2015-01-01

    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 inhibitors on clopidogrel (omeprazole, esomeprazole versus pantoprazole, rabeprazole), the effects of rifampicin on clopidogrel versus ticagrelor and prasugrel, and the effects of calcium channel blockers on clopidogrel (amlodipine versus P-glycoprotein-inhibiting calcium channel blockers). The mechanism of the DDIs with clopidogrel involves modulating CYP enzymes (eg, CYP2B6, CYP2C8, CYP2C19, and CYP3A4), paraoxonase-1, hepatic carboxylesterase 1, P-glycoprotein, and organic anion

  13. Variation in thromboxane B2 concentrations in serum and plasma in patients taking regular aspirin before and after clopidogrel therapy.

    PubMed

    Good, Richard I S; McGarrity, Anne; Sheehan, Rory; James, Tina E; Miller, Helen; Stephens, Jonathan; Watkins, Stuart; McConnachie, Alex; Goodall, Alison H; Oldroyd, Keith G

    2015-01-01

    Dual antiplatelet therapy with aspirin and a P2Y12 antagonist is widely prescribed for the prevention of thrombotic events in patients with an acute coronary syndrome or undergoing percutaneous coronary intervention (PCI). It is recognised that there is inter-individual variation in the antiplatelet effects of both drugs. Recent data also suggest that P2Y12 antagonists can affect the response to aspirin. A direct indicator of the effect of aspirin on platelets is their ability to generate thromboxane, which if measured as the difference between the level of thromboxane B2 in serum and plasma ([TxB2]S-P) avoids the confounding effect of endogenous TxB2 production from other cells. We therefore analysed [TxB2]S-P as a measure of aspirin response in a group of 123 patients undergoing elective PCI before and after the introduction of clopidogrel. In a subgroup of 40 patients taking aspirin alone, we compared [TxB2]S-P and VerifyNow Aspirin for the assessment of aspirin response. There was a wide variation in plasma and serum TxB2 concentrations both before and after clopidogrel therapy but only 3.5% of patients had residual serum concentration of TxB2 > 10 ng/ml. There was a strong correlation between the pre and post clopidogrel levels of TxB2 (r ≥ 0.78; p = 0.001) and no significant difference in [TxB2]S-P. There was no correlation between the magnitude of response to clopidogrel response and the generation of thromboxane B2. Correlation between [TxB2]S-P and VerifyNow Aspirin was poor. We conclude that the use of a P2Y12 antagonist does not influence the effect of aspirin on the ability of platelets to generate thromboxane. Therefore, measurement of TxB2 levels in serum, after subtracting the contribution from plasma, provides a measure of the response to aspirin in patients taking dual antiplatelet therapy.

  14. Ticagrelor versus Clopidogrel in Symptomatic Peripheral Artery Disease.

    PubMed

    Hiatt, William R; Fowkes, F Gerry R; Heizer, Gretchen; Berger, Jeffrey S; Baumgartner, Iris; Held, Peter; Katona, Brian G; Mahaffey, Kenneth W; Norgren, Lars; Jones, W Schuyler; Blomster, Juuso; Millegård, Marcus; Reist, Craig; Patel, Manesh R

    2017-01-05

    Background Peripheral artery disease is considered to be a manifestation of systemic atherosclerosis with associated adverse cardiovascular and limb events. Data from previous trials have suggested that patients receiving clopidogrel monotherapy had a lower risk of cardiovascular events than those receiving aspirin. We wanted to compare clopidogrel with ticagrelor, a potent antiplatelet agent, in patients with peripheral artery disease. Methods In this double-blind, event-driven trial, we randomly assigned 13,885 patients with symptomatic peripheral artery disease to receive monotherapy with ticagrelor (90 mg twice daily) or clopidogrel (75 mg once daily). Patients were eligible if they had an ankle-brachial index (ABI) of 0.80 or less or had undergone previous revascularization of the lower limbs. The primary efficacy end point was a composite of adjudicated cardiovascular death, myocardial infarction, or ischemic stroke. The primary safety end point was major bleeding. The median follow-up was 30 months. Results The median age of the patients was 66 years, and 72% were men; 43% were enrolled on the basis of the ABI and 57% on the basis of previous revascularization. The mean baseline ABI in all patients was 0.71, 76.6% of the patients had claudication, and 4.6% had critical limb ischemia. The primary efficacy end point occurred in 751 of 6930 patients (10.8%) receiving ticagrelor and in 740 of 6955 (10.6%) receiving clopidogrel (hazard ratio, 1.02; 95% confidence interval [CI], 0.92 to 1.13; P=0.65). In each group, acute limb ischemia occurred in 1.7% of the patients (hazard ratio, 1.03; 95% CI, 0.79 to 1.33; P=0.85) and major bleeding in 1.6% (hazard ratio, 1.10; 95% CI, 0.84 to 1.43; P=0.49). Conclusions In patients with symptomatic peripheral artery disease, ticagrelor was not shown to be superior to clopidogrel for the reduction of cardiovascular events. Major bleeding occurred at similar rates among the patients in the two trial groups. (Funded by Astra

  15. Effect of Ginkgo Biloba Extract on the Pharmacokinetics and Metabolism of Clopidogrel in Rats.

    PubMed

    Deng, Ying; Mo, Yu-Fei; Chen, Xin-Meng; Zhang, Lv-Zhao; Liao, Chao-Feng; Song, Yu; Xu, Chenshu

    2016-11-01

    Ginkgo biloba extract (GBE), a traditional herbal product used worldwide as both medicine and supplement, is often supplied with clopidogrel for the treatment of cerebrovascular diseases. The aim of the current study was to explore the effect of GBE on the metabolism and pharmacokinetics of clopidogrel. The in vitro study using rat liver microsomes revealed that GBE significantly induced the conversion of clopidogrel into its active metabolite. The effect of GBE on the pharmacokinetics of clopidogrel was also investigated in vivo. Compared to rats without GBE pretreatment, administration of 4 mg/kg, 20 mg/kg, and 100 mg/kg of GBE significantly decreased the Cmax and the AUC0-∞ of clopidogrel in a dose-dependent manner. As expected, pretreatment of high dose GBE significantly increased the Cmax and AUC0-∞ of the clopidogrel active metabolite. However, no marked change was observed following medium and low dose of GBE, suggesting that the biotransformation of clopidogrel was altered differently by high dose of GBE. Our study suggested that the awareness of the potential herb-drug interactions between GBE and clopidogrel should be increased in clinical practice. Copyright © 2016 John Wiley & Sons, Ltd.

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

    PubMed Central

    2012-01-01

    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. PMID:22236361

  17. Behavioral Response Research Evaluation Workshop (BRREW)

    DTIC Science & Technology

    2015-09-30

    1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Behavioral Response Research Evaluation Workshop (BRREW...N000141512664 http://www.creem.st-and.ac.uk LONG-TERM GOALS The behavioral response of marine mammals to Navy sonar exposure has been a research...The overall objective is to review the status and future of research into behavioral responses of marine mammals to naval sonar exposure in order to

  18. Clopidogrel Therapy Discontinuation Following Drug Eluting Stent Implantation in Real World Practice in Israel

    PubMed Central

    Blich, Miry; Shwiri, Tawfiq Zeidan; Petcherski, Sirouch; Osherov, Azriel B; Hammerman, Haim

    2012-01-01

    Background Incidence and predictors of clopidogrel discontinuation after drug eluting stent (DES) implantation, in real world practice, are poorly known. Methods Prospective study included all patients who underwent implantation of at least one DES between February 2006 and January 2007. Predictors of clopidogrel discontinuation were assessed by a multivariable analysis. Results In 269 patients, mean period for clopidogrel therapy was 13.2 ± 7.2 month. Twenty eight patients (10.4%) discontinued clolopidogrel prematurely (< 3 months). Early clopidogrel discontinuation was a predictor of late stent thrombosis (P = 0.005) and urgent target vessel revascularization (P = 0.05). There was a trend for higher cardiac mortality among that group (P = 0.07). By 12 months, 173 patients (64.3%) have discontinued clopidogrel therapy. The most frequent circumstance to stop clopidogrel before 12 months was recommendation of family physician. Patients that were followed by cardiologist were more encouraged to longer clopidogrel therapy. In multivariable analysis being non Jew (OR 19.2, 95% CI 2.4 to 142, P = 0.005), not followed by cardiologist (OR 4.7, 95% CI 1 to 23.1, P = 0.05) and lack of information regarding the importance of clopidogrel maintenance at discharge from hospital (OR 10.8, 95% CI 2.7 to 42.9, P = 0.001) were independent predictors of early clopidogrel discontinuation. Conclusions Clopidogrel discontinuation, in real world practice is not unusual and related to poor outcome. Education for general physicians, clear instructions about the importance of antiplatelet maintenance at discharge and follow up by an expert cardiologist are opportunities to improve adherence do antiplatelet therapy following DES implantation.

  19. Use of Responsive Evaluation in Statewide Program Evaluation

    ERIC Educational Resources Information Center

    Kalman, Marjorie

    1976-01-01

    A summer school program stressing basic skills for migrant children in a rural Illinois community was assessed according to Stake's responsive evaluation model. Informal communication, program activities, audience needs, and participant values were emphasized in this case study. This evaluation method provided useful information for the state's…

  20. Use of Responsive Evaluation in Statewide Program Evaluation.

    ERIC Educational Resources Information Center

    Kalman, Marjorie

    The objective of this paper is to discuss the utilization of Stake's theory of responsive evaluation by a unit in state government charged with the evaluation of the Illinois Migrant Program. Through interviews with state and local Title I staff, we were able to discover program purposes and concerns and to later conceptualize these concerns into…

  1. Aspirin and clopidogrel: a sweeping combination in cardiology.

    PubMed

    Manolis, Antonis S; Tzeis, Stylianos; Andrikopoulos, George; Koulouris, Spyros; Melita, Helen

    2005-07-01

    Platelets play a pivotal role in the pathogenesis of atherothrombosis, believed to be integrally involved in both the development and progression of atherosclerotic heart disease, as well as in its acute thrombotic complications. Antiplatelet therapy constitutes the cornerstone in the management of patients with acute coronary syndromes and generally high-risk patients with atherothrombosis. Until recently, long-term antiplatelet therapy for the treatment and prevention of the complications of atherothrombotic disease was traditionally limited to aspirin. The availability of the thienopyridines, in particular clopidogrel, represents an important addition to the physician's armamentarium. Clopidogrel is currently one of the most widely prescribed drugs for the treatment of symptomatic coronary artery disease. Aspirin and clopidogrel interfere with platelet activation in complementary, but separate pathways. Aspirin irreversibly inhibits cyclooxygenase, thus preventing the production of thromboxane A(2), which is a prothrombotic and vasoconstrictive substance. Clopidogrel, a newer thienopyridine which has largely supplanted ticlopidine due to a more favorable safety profile, irreversibly prevents platelet activation by blocking one of the three known adenosine 5'-diphosphate (ADP) receptors (the P2Y(12) receptor) on the platelet surface, thus interfering with platelet activation, degranulation and aggregation. Both these antiplatelet agents have a potent protective effect against adverse vascular events, but the combination of these two agents has an even stronger antiplatelet effect translating into superior antithrombotic protection in coronary, cerebral or peripheral arterial disease, without an inordinate increase in bleeding complications. A number of seminal clinical trials have demonstrated and confirmed the incremental benefit and efficacy of the combination of clopidogrel and aspirin therapy above and beyond that of aspirin alone, with multiple other

  2. Impact of CYP2C19 Variants on Clinical Efficacy of Clopidogrel and 1-Year Clinical Outcomes in Coronary Heart Patients Undergoing Percutaneous Coronary Intervention

    PubMed Central

    Sun, Hong; Qu, Qiang; Chen, Zhen-Fan; Tan, Sheng-Lan; Zhou, Hai-Jun; Qu, Jian; Chen, Hui

    2016-01-01

    The impact of pharmacogenetic variants of cytochrome P450 2C19 (CYP2C19) on clopidogrel-mediated effects on platelet inhibition, inflammatory response and endothelial function, as well as risk of major adverse cardiovascular events (MACE), in coronary heart patients undergoing percutaneous coronary intervention (PCI) was investigated. To this end, we assessed the residual platelet aggregation rate (RPA), maximal aggregation rate (MAR) and plasma levels of sCD40L, sP-selectin, MMP-9, sVCAM-1 and sE-selectin after 24 h of PCI in 559 patients treated with clopidogrel and followed up for 1 year for evidence of MACE. CYP2C19 *2 and *3 variants were identified using a clopidogrel-sensitive gene detection kit. Our results showed higher RPA and MAR as well as increased sE-selectin, sCD40L, sP-selectin, MMP-9, and sVCAM-1 levels in CYP2C19 intermediate metabolizer (IM, CYP2C19*1/*2, or *1/*3), poor metabolizer (PM, CYP2C19*2/*2, *2/*3, or *3/*3) and combined IM+PM groups, relative to those in extensive metabolizers (EM, CYP2C19*1/*1). In total, 519 patients completed 1 year of follow-up, among which 69 (13.3%) experienced MACE. The risk of MACE in CYP2C19 IM+PM patients was 2.664 times higher than that in CYP2C19 EM patients (OR = 2.664 (1.397–5.193), P = 0.004). The data suggest that CYP2C19*2 and *3 variants modulate the drug efficacy of clopidogrel in coronary heart patients undergoing PCI and further enhance the risk of MACE. Accordingly, CYP2C19 pharmacogenetic profiling may be beneficial for coronary heart patients undergoing PCI to predict the efficacy of treatment with clopidogrel. We propose that IM and PM patients should benefit from treatment with higher clopidogrel doses to improve efficacy and reduce the incidence of MACE. PMID:27932982

  3. Postoperative Bleeding Risk for Oral Surgery under Continued Clopidogrel Antiplatelet Therapy

    PubMed Central

    Zeuch, Jürgen; Haase, Martina; Semmusch, Jan; Eichhorn, Wolfgang

    2015-01-01

    Object. To determine the incidence of postoperative bleeding for oral osteotomy carried out under continued monoantiplatelet therapy with clopidogrel and dual therapy with clopidogrel/aspirin. Design. Retrospective single center observatory study of two study groups and a control group. Methods. A total of 64 and 60 oral osteotomy procedures carried out under continued monoclopidogrel therapy and dual clopidogrel/aspirin therapy, respectively, were followed for two weeks for postoperative bleeding. Another 281 similar procedures were also followed as a control group. All oral osteotomy procedures were carried out on an outpatient basis. Results. We observed postoperative bleeding in 2/281 (0.7%) cases in the control group, in 1/64 (1.6%) cases in the clopidogrel group, and in 2/60 (3.3%) cases in the dual clopidogrel/aspirin group. The corresponding 95% confidence intervals are 0–1.7%, 0–4.7%, and 0–7.8%, respectively, and the incidences did not differ significantly among the three groups (P > 0.09). Postoperative hemorrhage was treated successfully in all cases with local measures. No changes of antiplatelet medication, transfusion, nor hospitalisation were necessary. No major cardiovascular events were recorded. Conclusions. Our results indicate that minor oral surgery can be performed safely under continued monoantiplatelet medication with clopidogrel or dual antiplatelet medication with clopidogrel/aspirin. PMID:25632402

  4. Combination of clopidogrel and everolimus dramatically reduced the development of transplant arteriosclerosis in murine aortic allografts.

    PubMed

    Eckl, Sebastian; Heim, Christian; Abele-Ohl, Silke; Hoffmann, Julia; Ramsperger-Gleixner, Martina; Weyand, Michael; Ensminger, Stephan M

    2010-09-01

    Our group has shown that platelet inhibition with clopidogrel, an antagonist of the P2Y12 adenosine diphosphate receptor on platelets, reduced the formation of transplant arteriosclerosis. The aim of this study was to investigate whether a combination of cyclosporin or everolimus with clopidogrel has a beneficial effect on the development of transplant arteriosclerosis. Fully MHC mismatched C57Bl/6 (H2(b)) donor aortas were transplanted into CBA.J (H2(k)) recipients and mice received either clopidogrel alone (1 mg/kg/day) or in combination with cyclosporin (2 mg/kg/day) or everolimus (0.05 mg/kg/day). Grafts were analysed by histology and morphometry on day 30 after transplantation. In mice treated with clopidogrel alone, transplant arteriosclerosis was significantly reduced [intima proliferation 56 +/- 11% vs. 81 +/- 7% (control)/n = 7]. Daily application of everolimus reduced the development of transplant arteriosclerosis compared with untreated controls [intima proliferation of 29 +/- 9% vs. 81 +/- 7% (control)/n = 7]. Strikingly, combination of clopidogrel and everolimus almost abolished the formation of transplant arteriosclerosis [intima proliferation: 11 +/- 8% vs. 81 +/- 7% (control)/n = 7]. By contrast, combination of cyclosporin and clopidogrel compared with clopidogrel alone showed no additive effect. These results demonstrate that combination of platelet- and mammalian target of Rapamycin-inhibition can dramatically reduce the development of transplant arteriosclerosis.

  5. Clopidogrel significantly lowers the development of atherosclerosis in ApoE-deficient mice in vivo.

    PubMed

    Heim, Christian; Gebhardt, Julia; Ramsperger-Gleixner, Martina; Jacobi, Johannes; Weyand, Michael; Ensminger, Stephan M

    2016-05-01

    The anti-platelet drug clopidogrel has been shown to modulate adhesion molecule and cytokine expression, both playing an important role in the pathogenesis of atherosclerosis. The aim of this study was to investigate the impact of clopidogrel on the development and progression of atherosclerosis. ApoE(-/-) mice fed an atherogenic diet (cholesterol: 1 %) for 6 months received a daily dose of clopidogrel (1 mg/kg) by i.p. injection. Anti-platelet treatment was started immediately in one experimental group, and in another group clopidogrel was started 2 month after beginning of the atherogenic diet. Blood was analysed at days 30, 60 and 120 to monitor the lipid profile. After 6 months the aortic arch and brachiocephalic artery were analysed by Sudan IV staining for plaque size and by morphometry for luminal occlusion. Serum levels of various adhesion molecules were investigated by ELISA and the cellular infiltrate was analysed by immunofluorescence. After daily treatment with 1 mg/kg clopidogrel mice showed a significant reduction of atherosclerotic lesions in the thoracic aorta and within cross sections of the aortic arch [plaque formation 55.2 % (clopidogrel/start) vs. 76.5 % (untreated control) n = 8, P < 0.05]. After treatment with clopidogrel P-/E-selectin levels and cytokine levels of MCP-1 and PDGFβ were significantly reduced as compared to controls. The cellular infiltrate showed significantly reduced macrophage and T-cell infiltration in clopidogrel-treated animals. These results show that clopidogrel can effectively delay the development and progression of 'de-novo' atherosclerosis. However, once atherosclerotic lesions were already present, anti-platelet treatment alone did not result in reverse remodelling of these lesions.

  6. [Clopidogrel--proton pump inhibitors drug interaction: implications to clinical practice].

    PubMed

    Fontes-Carvalho, Ricardo; Albuquerque, Aníbal

    2010-10-01

    Recent studies have raised the concern that proton pump inhibitors (PPIs) could potentially interfere with clopidogrel antiplatelet effect. This association is frequent in clinical practice and is recommended by recent consensus guidelines in patients taking dual antiplatelet therapy to prevent gastrointestinal (GI) bleeding. Clopidogrel is a pro-drug which needs to be metabolized into its active metabolite, by cytochrome P450, especially by CYP2C19 isoenzyme. Various PPIs can inhibit CYP2C19, which could possibly decrease clopidogrel bioactivation process and, therefore, its antiplatelet effect. Various platelet function studies have shown that omeprazol can significantly decrease clopidogrel inhibitory effect on platelet P2Y12 receptor, leading to an increase in the number of patients who are "nonresponders" to clopidogrel. These pharmacokinetic studies also shown that this is not probably a class effect of PPIs, because they are metabolized to varying degrees by CYP2C19. The clinical impact of these observations remains uncertain, because various observational studies have shown conflicting results, and remains to demonstrate if PPIs can really increase the risk of cardiovascular events in patients taking clopidogrel. In this review we will discuss the pharmacokinetic basis underlying this drug interaction, the effect of different PPIs on platelet function tests and we will analyze in detail the potential clinical implications of using this association, both on cardiovascular and gastrointestinal events. Until further data is available, some clinical strategies can be recommended: (1) individual gastrointestinal risk assessment, with PPIs administration only to patients on dual anti-platelet therapy with additional GI risk factors; (2) preferential use of PPIs that have shown less interference with clopidogrel efficacy; (3) wide separation of PPI and clopidogrel dosing to minimize the risk of interaction (PPI may be given before breakfast and clopidogrel at

  7. Impact of clopidogrel on bleeding complications and survival in off-pump coronary artery bypass grafting.

    PubMed

    Bittner, Hartmuth B; Lehmann, Sven; Rastan, Ardawan; Mohr, Friedrich W

    2012-03-01

    This study investigated the impact of preoperative clopidogrel on bleeding complications and survival during and after off-pump coronary artery bypass grafting (OPCABG) and assessed the possible role of the antifibrinolytic agent aprotinin for attenuating blood loss after clopidogrel exposure. Prospectively collected data of 753 consecutive adult patients undergoing OPCABG were retrospectively reviewed; 139 (18.5%) patients received clopidogrel preoperatively. Statistical methods used were student paired t-test, Mann-Whitney U, Kruskal-Wallis, chi-square analysis and Kaplan-Meier with log-rank analysis. Clopidogrel was associated with a significant increase in perioperative blood loss (P = 0.003) and more excessive postoperative haemorrhage (P = 0.04). Overall transfusion rates (P = 0.02) and the amount of administered blood products (P = 0.01) were also higher after clopidogrel exposure. Intraoperative aprotinin reduced postoperative bleeding significantly in patients administered clopidogrel [18.7% after 24 h (P = 0.006) and 15.2% after 48 h (P = 0.03)] and attenuated excessive postoperative haemorrhaging. Five-year survival was markedly improved in clopidogrel-treated patients. Preoperative clopidogrel exposure does increase perioperative blood loss and blood transfusion requirements in patients undergoing OPCABG but has an otherwise excellent safety profile with a 94% 5-year survival rate. Aprotinin attenuated this blood loss. Based on these results a recommendation to discontinue clopidogrel prior to coronary artery bypass grafting cannot be maintained, if OPCABG strategies are considered.

  8. Safety and efficacy of minimal biliary sphincterotomy with papillary balloon dilation (m-EBS+EPBD) in patients using clopidogrel or anticoagulation

    PubMed Central

    Mok, Shaffer R. S.; Arif, Murtaza; Diehl, David L; Khara, Harshit S; Ho, Henry C; Elfant, Adam B

    2017-01-01

    Background and study aims Endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic biliary sphincterotomy (EBS) or endoscopic papillary balloon dilation (EPBD) are common techniques of biliary decompression. Potential risks include gastrointestinal hemorrhage, which can be increased by antiplatelet agents, anticoagulants (AC) and/or novel oral anticoagulants (NOACs) (ie. apixaban, dabigatran and rivaroxaban). The study aim is to evaluate the safety/efficacy of an alternative technique, minimal-EBS plus EPBD (m-EBS + EPBD), in individuals for whom clopidogrel, AC, and/or NOACs cannot be interrupted due to high cardiovascular or thromboembolic risk. Patients and methods Patients undergoing m-EBS + EPBD while taking clopidogrel and/or AC were retrospectively evaluated at two United States tertiary care centers for efficacy, GIB and procedure-related, cardiovascular and thromboembolic adverse events (AE). Results Ninety-five patients were identified [55 = clopidogrel and 45 = AC (31.1 % NOACs)]. The main indication for ERCP was choledocholithiasis (34 %). 100 % clinical improvement and 97.9 % endoscopic success were found. The incidence of AE was 5.3 %. There was a 4.2 % incidence of gastrointestinal hemorrhage (2 cases requiring endoscopic intervention). Both severe gastrointestinal hemorrhages also experienced the cases of post-ERCP pancreatitis, and 2 /3 of cholangitis (all aspirin + AC). There was 1cardiovascular event (non-ST elevation myocardial infarction), and no thromboembolic events. Conclusions Minimal-EBS + EPBD is an effective and safe therapy with an incidence of gastrointestinal hemorrhage of 4.2 %, (2.1 % requiring endoscopic intervention), for patients on clopidogrel and/or AC, with a high risk for cardiovascular/thromboembolic events. PMID:28337485

  9. Clopidogrel-Associated Thrombotic Thrombocytopenic Purpura following Endovascular Treatment of Spontaneous Carotid Artery Dissection

    PubMed Central

    Rubano, Jerry A.; Chen, Kwan; Sullivan, Brianne; Vosswinkel, James A.; Jawa, Randeep S.

    2015-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening multisystem disease secondary to platelet aggregation. We present a patient who developed profound thrombocytopenia and anemia 8 days following initiation of therapy with clopidogrel after stent placement for carotid artery dissection. She did not have a disintegrin and metalloproteinase with thrombospondin domain 13 (ADAMTS 13) deficiency. Management included steroids and therapeutic plasma exchange. Clopidogrel has rarely been associated with TTP. Unlike other causes of acquired TTP, the diagnosis of early clopidogrel-associated TTP is largely clinical given the infrequent reduction in ADAMTS 13 activity. PMID:26623244

  10. Platelet factor XIIIa release during platelet aggregation and plasma clot strength measured by thrombelastography in patients with coronary artery disease treated with clopidogrel.

    PubMed

    Kreutz, Rolf P; Owens, Janelle; Lu, Deshun; Nystrom, Perry; Jin, Yan; Kreutz, Yvonne; Desta, Zeruesenay; Flockhart, David A

    2015-01-01

    It has been estimated that up to half of circulating factor XIIIa (FXIIIa) is stored in platelets. The release of FXIIIa from platelets upon stimulation with adenosine diphosphate (ADP) in patients with coronary artery disease treated with dual antiplatelet therapy has not been previously examined. Samples from 96 patients with established coronary artery disease treated with aspirin and clopidogrel were examined. Platelet aggregation was performed by light transmittance aggregometry in platelet-rich plasma (PRP), with platelet-poor plasma (PPP) as reference, and ADP 5 µM as agonist. Kaolin-activated thrombelastography (TEG) was performed in citrate PPP. PRP after aggregation was centrifuged and plasma supernatant (PSN) collected. FXIIIa was measured in PPP and PSN. Platelet aggregation after stimulation with ADP 5 µM resulted in 24% additional FXIIIa release in PSN as compared to PPP (99.3 ± 27 vs. 80.3 ± 24%, p < 0.0001). FXIIIa concentration in PSN correlated with maximal plasma clot strength (TEG-G) (r = 0.48, p < 0.0001), but not in PPP (r = 0.15, p = 0.14). Increasing quartiles of platelet-derived FXIIIa were associated with incrementally higher TEG-G (p = 0.012). FXIIIa release was similar between clopidogrel responders and non-responders (p = 0.18). In summary, platelets treated with aspirin and clopidogrel release a significant amount of FXIIIa upon aggregation by ADP. Platelet-derived FXIIIa may contribute to differences in plasma TEG-G, and thus, in part, provide a mechanistic explanation for high clot strength observed as a consequence of platelet activation. Variability in clopidogrel response does not significantly influence FXIIIa release from platelets.

  11. VerifyNow and VASP phosphorylation assays give similar results for patients receiving clopidogrel, but they do not always correlate with platelet aggregation.

    PubMed

    Bidet, Audrey; Jais, Catherine; Puymirat, Etienne; Coste, Pierre; Nurden, Alan; Jakubowski, Joseph; Nurden, Paquita

    2010-01-01

    Point-of-care testing permits an evaluation of the efficacy of drugs used in the treatment of acute coronary syndromes (ACS). An increased risk of thrombosis after coronary stenting for ACS patients treated with aspirin and clopidogrel has been linked to high platelet reactivity and, for certain patients, poor drug response. The objective of our study was to compare the VerifyNow-P2Y12 device with the VASP (vasodilator-stimulated phosphoprotein) phosphorylation assay and ADP-induced platelet aggregation as assessed by light transmission aggregometry in a group of 81 ACS patients (100 tests) treated in our hospital. There was a good correlation between VerifyNow-P2Y12 and VASP especially during the chronic phase of one month or more after the ischemic event, whereas discordance was sometimes seen with platelet aggregometry. The rapidity and ease of use of the VerifyNow device suggests that it has a valuable place in point-of-care testing of ACS patients.

  12. Implementation of Cell Samples as Controls in National Proficiency Testing for Clopidogrel Therapy-Related CYP2C19 Genotyping in China: A Novel Approach

    PubMed Central

    Zhang, Kuo; Wang, Lunan; Zhang, Rui; Xie, Jiehong; Li, Jinming

    2015-01-01

    Laboratories are increasingly requested to perform CYP2C19 genetic testing when managing clopidogrel therapy, especially in patients with acute coronary syndrome undergoing percutaneous coronary intervention. To ensure high quality molecular testing and ascertain that the referring clinician has the correct information for CYP2C19 genotype–directed antiplatelet therapy, a proficiency testing scheme was set up to evaluate the laboratory performance for the entire testing process. Proficiency panels of 10 cell samples encompassing the common CYP2C19 genetic polymorphisms were distributed to 62 participating laboratories for routine molecular testing and the responses were analyzed for accuracy of genotyping and the reporting of results. Data including the number of samples tested, the accreditation/certification status, and test methodology of each individual laboratory were also reviewed. Fifty-seven of the 62 participants correctly identified the CYP2C19 variants in all samples. There were six genotyping errors, with a corresponding analytical sensitivity of 98.5% (333/338 challenges; 95% confidence interval: 96.5–99.5%) and an analytic specificity of 99.6% (281/282; 95% confidence interval: 98.0–99.9%). Reports of the CYP2C19 genotyping results often lacked essential information. In conclusion, clinical laboratories demonstrated good analytical sensitivity and specificity; however, the pharmacogenetic testing community requires additional education regarding the correct reporting of CYP2C19 genetic test results. PMID:26218263

  13. [Comparative assessment of antiaggregant efficacy of acetylsalicylic acid and clopidogrel in peripheral atherosclerosis].

    PubMed

    Kuznetsov, M R; Sergeeva, N A; Koshkin, V M; Boldin, B V; Rodionov, S V; Virganskiĭ, A O; Kosykh, I V; Lisenkov, O P; Kuznetsova, V F

    2014-01-01

    Presented in the article are the results of studying antiaggregate activity of acetylsalicylic acid and clopidogrel in a total of 36 patients suffering from various-severity chronic arterial insufficiency of lower limbs on the background of atherosclerosis obliterans. The study was conducted prior to treatment for correct selection of a particular antiplatelet agent. The obtained results showed that clopidogrel was not always more efficient than acetylsalicylic acid, since there is individual sensitivity of each patients to a particular antiplatelet agent. Therefore, an individual approach is necessary to conservative therapy of arterial insufficiency of lower limbs. For some patients it is preferable to administer clopidogrel, for others - acetylsalicylic acid. In a series of cases combined treatment is justified, while some patients having low sensitivity to both acetylsalicylic acid and clopidogrel require careful selection of alternative agents influencing other thrombocyte receptors.

  14. Trends in the coprescription of proton pump inhibitors with clopidogrel: an ecological analysis

    PubMed Central

    Juurlink, David N.; Gomes, Tara; Paterson, J. Michael; Hellings, Chelsea; Mamdani, Muhammad M.

    2015-01-01

    Background: In early 2009, 2 observational studies and a US Food and Drug Administration (FDA) advisory addressed the drug interaction between proton pump inhibitors (PPIs) and clopidogrel. One study suggested that pantoprazole could be used safely in this setting, whereas the other study and the FDA advisory did not distinguish among PPIs. We examined trends in PPI prescribing among clopidogrel recipients in the period following these events. Methods: We conducted a population-based time series analysis of Ontario residents aged 66 years or older for whom clopidogrel was prescribed between Apr. 1, 1999, and Sept. 30, 2013. We determined the proportion of clopidogrel recipients dispensed a PPI during each quarter and the proportions who received pantoprazole or other PPIs. The outcome of interest was change in the use of pantoprazole. Results: In the final quarter of 2008, pantoprazole represented 23.7% of all PPI prescriptions dispensed to patients receiving clopidogrel. Following the publications and FDA advisory in early 2009, pantoprazole use increased substantially. By the end of 2009, this medication accounted for 52.5% of all PPI prescriptions issued to patients receiving clopidogrel; by the end of the study period, it accounted for 71.0% of all PPI prescriptions dispensed to such patients (p < 0. 001). We also observed a modest drop in overall PPI use among clopidogrel recipients beginning in early 2009. Interpretation: In 2009, the prescribing of PPIs with clopidogrel changed substantially in Ontario, with pantoprazole rapidly becoming the most commonly prescribed agent in its class. However, a modest decline in overall PPI use also occurred that may reflect suboptimal translation of emerging drug safety information to clinical practice. PMID:26770965

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

    PubMed

    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.

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

    PubMed

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

    2010-03-01

    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 pH, respectively. The samples without and with stressors were subjected for 3 months to (1) 0% RH, 25% RH, 75% RH, and 85% RH at 40 degrees C and also to (2) 60 degrees C, 80 degrees C, and 100 degrees C at 0% RH. In case of solid samples without stressors, the mixture of polymorphic and amorphous forms showed 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 salt to free base. Thermal studies indicated that polymorphic forms of clopidogrel bisulfate and also its glassy amorphous form were highly resistant to temperature, whereas the rubbery state of the drug degraded significantly at temperatures of > or =80 degrees C.

  17. Comparative risk of ischemic stroke among users of clopidogrel together with individual proton pump inhibitors

    PubMed Central

    Bilker, Warren B.; Brensinger, Colleen M.; Flockhart, David A.; Freeman, Cristin P.; Kasner, Scott E.; Kimmel, Stephen E.; Hennessy, Sean

    2015-01-01

    Background and Purpose There is controversy and little information concerning whether individual proton pump inhibitors (PPIs) differentially alter the effectiveness of clopidogrel in reducing ischemic stroke risk. We therefore aimed to elucidate the risk of ischemic stroke among concomitant users of clopidogrel and individual PPIs. Methods We conducted a propensity score-adjusted cohort study of adult new users of clopidogrel, using 1999–2009 Medicaid claims from 5 large states. Exposures were defined by prescriptions for esomeprazole, lansoprazole, omeprazole, rabeprazole and pantoprazole—with pantoprazole serving as the referent. The endpoint was hospitalization for acute ischemic stroke, defined by International Classification of Diseases 9th Revision Clinical Modification codes in the principal position on inpatient claims, within 180 days of concomitant therapy initiation. Results Among 325,559 concomitant users of clopidogrel and a PPI, we identified 1,667 ischemic strokes for an annual incidence of 2.4% (95% confidence interval: 2.3–2.5). Adjusted hazard ratios for ischemic stroke vs. pantoprazole were: 0.98 (0.82–1.17) for esomeprazole; 1.06 (0.92–1.21) for lansoprazole; 0.98 (0.85–1.15) for omeprazole; and 0.85 (0.63–1.13) for rabeprazole. Conclusions PPIs of interest did not increase the rate of ischemic stroke among clopidogrel users when compared to pantoprazole, a PPI thought to be devoid of the potential to interact with clopidogrel. PMID:25657176

  18. [ASA and clopidogrel for urological operations. Perioperative management].

    PubMed

    Fischer, C; Lümmen, G

    2013-11-01

    In a systematic overview and meta-analysis among more than 50,000 patients at risk for coronary artery disease, not adhering to or discontinuing aspirin (acetylsalicylic acid, ASA) was associated with a significantly increased risk of non-fatal myocardial infarction or death. Withdrawal of low dose aspirin was correlated with a threefold increase in the risk of adverse cardiovascular events. This risk is present irrespective of the length of time patients had been taking low dose aspirin. Therefore, in patients on chronic low dose aspirin for secondary prevention of cardiovascular disease, aspirin should never be discontinued. In the few available studies in urological surgery the increase in bleeding does not translate into a significant increase in specific morbidity. This seems to be also true for the additional administration of clopidogrel to aspirin. Nevertheless, in patients with drug-eluting stents and dual antiplatelet therapy, urologists should ensure a multidisciplinary management of the perioperative course.

  19. How to test the effect of aspirin and clopidogrel in patients on dual antiplatelet therapy?

    PubMed

    Bagoly, Zsuzsa; Homoródi, Nóra; Kovács, Emese Gyöngyvér; Sarkady, Ferenc; Csiba, László; Édes, István; Muszbek, László

    2016-01-01

    Dual antiplatelet therapy with clopidogrel and aspirin is frequently used for the prevention of recurrent ischemic events. Various laboratory methods are used to detect the effect of these drugs administered in monotherapy, however their value in dual therapy has not been explored. Here, we determined which methods used for testing the effect of clopidogrel or aspirin are influenced by the other antiplatelet agent. One arm of the study included 53 ischemic stroke patients being on clopidogrel monotherapy showing effective inhibition of the P2Y12 ADP receptor. Laboratory tests routinely used for the detection of aspirin resistance (arachidonic acid (AA)-induced platelet aggregation/secretion, AA-induced thromboxane B2 (TXB2) production in platelet-rich plasma and VerifyNow Aspirin assay) were carried out on samples obtained from these patients. The other arm of the study involved 52 patients with coronary artery disease being on aspirin monotherapy. Methods used for testing the effect of clopidogrel (ADP-induced platelet aggregation and secretion, flow cytometric analysis of vasodilator-stimulated phosphoprotein (VASP) phosphorylation and a newly developed P2Y12-specific platelet aggregation (ADP[PGE1] test)) were performed on samples obtained from these patients. Clopidogrel monotherapy significantly inhibited AA-induced platelet aggregation and secretion, moreover, AA-induced TXB2 production was also significantly decreased. VASP phosphorylation and AA-induced platelet aggregation showed fair correlation in patients taking clopidogrel only. Clopidogrel did not inhibit the VerifyNow Aspirin test significantly. Aspirin monotherapy influenced ADP-induced platelet aggregation and secretion, but did not have an effect on VASP phosphorylation and on the ADP[PGE1] platelet aggregation test.

  20. Changes in Practice Patterns of Clopidogrel in Combination with Proton Pump Inhibitors after an FDA Safety Communication

    PubMed Central

    Guérin, Annie; Mody, Reema; Carter, Valerie; Ayas, Charles; Patel, Haridarshan; Lasch, Karen; Wu, Eric

    2016-01-01

    Objectives In 2009, the FDA issued a warning that omeprazole–a proton pump inhibitor (PPI)–reduces the antithrombotic effect of clopidogrel by almost half when taken concomitantly. This study aims to analyze the impact of the FDA Safety Communications on prescribing clopidogrel together with PPIs. Methods This retrospective study identified clopidogrel users from the Truven Health Analytics MarketScan Databases (01/2006–12/2012). Rates of clopidogrel-PPI combination therapy were estimated in 6-month intervals for patients with ≥1 clopidogrel prescription fill, then were analyzed pre- and post-safety communication (11/17/2009). Analyses were also conducted by grouping PPIs into CYP2C19 inhibitors (omeprazole and esomeprazole) and CYP2C19 non-inhibitors (pantoprazole, lansoprazole, dexlansoprazole, and rabeprazole). Results Overall, 483,074 patients met the selection criteria; of these, 157,248 used a clopidogrel-PPI combination. On average, 30.5% of patients in the pre- and 19.9% in the post-communication period used a clopidogrel-PPI combination therapy. Among clopidogrel users, the probability of using clopidogrel-PPI combinations fell by over 40% in the post-communication period (OR = 0.57; p<0.001); the proportion of patients using esomeprazole fell from 12.9% to 5.3%, and the proportion using omeprazole fell from 10.1% to 6.3%. Among combination therapy users, the probability of patients using a combination with a CYP2C19 inhibitor decreased by 53% (OR = 0.47; p<0.001); however, 31.5% of patients were still prescribed a clopidogrel-PPI combination therapy. Trends were similar for all and newly treated patients, regardless of clopidogrel indication and physician specialty. Conclusions The FDA Safety Communication resulted in a reduction in the number of patients undergoing combination therapy; however approximately one-third of patients still used combination therapy post-communication. PMID:26727382

  1. Evaluation of allergic response using dynamic thermography

    NASA Astrophysics Data System (ADS)

    Rokita, E.; Rok, T.; Tatoń, G.

    2015-03-01

    Skin dynamic termography supplemented by a mathematical model is presented as an objective and sensitive indicator of the skin prick test result. Termographic measurements were performed simultaneously with routine skin prick tests. The IR images were acquired every 70 s up to 910 s after skin prick. In the model histamine is treated as the principal mediator of the allergic reaction. Histamine produces vasolidation and the engorged vessels are responsible for an increase in skin temperature. The model parameters were determined by fitting the analytical solutions to the spatio-temporal distributions of the differences between measured and baseline temperatures. The model reproduces experimental data very well (coefficient of determination = 0.805÷0.995). The method offers a set of parameters to describe separately skin allergic reaction and skin reactivity. The release of histamine after allergen injection is the best indicator of allergic response. The diagnostic parameter better correlates with the standard evaluation of a skin prick test (correlation coefficient = 0.98) than the result of the thermographic planimetric method based on temperature and heated area determination (0.81). The high sensitivity of the method allows for determination of the allergic response in patients with the reduced skin reactivity.

  2. [Identification of the polymorphs of clopidogrel bisulfate based on the steric morphology parameters of crystals].

    PubMed

    Chen, Long; Wang, Liu-yi; Yin, Xian-zhen; Wang, Jin-can; Liu, Rui-hao; Wang, Dan; Li, Hai-yan; Zhu, Wei-feng; Zhang, Ji-wen

    2013-09-01

    The crystal form of solid substance had intrinsic correlation with its three dimensional crystal morphology. Based on the characterization of the three dimensional crystal morphology of clopidogrel bisulfate, this research is to establish a model based on the three dimensional morphological parameters. The granular samples composed of polymorphs of clopidogrel bisulfate and microcrystalline cellulose (MCC) were scanned by synchrotron radiation X-ray microscopic CT technology (SR-microCT) and the three dimensional structural models for which were constructed. Seven groups of three dimensional morphological parameters were calculated. Finally, the mathematical model was established with the multi-layer perception (MLP) artificial neutral network methods to identify and predict the polymorphs of clopidogrel bisulfate. The success rate of the model prediction for the polymorphs of clopidogrel bisulfate was 92.7% and the area under the ROC curve was 96.2%. The polymorphs of drugs could be identified and predicted through the numerical description of the three dimensional morphology. The volume, number of the vertices and the surface area were the major determinants for the identification of the polymorphs of clopidogrel bisulfate.

  3. Prevalence of CYP2C19 alleles, pharmacokinetic and pharmacodynamic variation of clopidogrel and prasugrel in Bangladeshi population.

    PubMed

    Bin Sayeed, Muhammad Shahdaat; Hasan Apu, Mohd Nazmul; Munir, Maliha Tabassum; Ahmed, Maizbha Uddin; Islam, Mohammad Safiqul; Haq, M Maksumul; Ahsan, Chowdhury H; Rashid, M A; Shin, Jae Gook; Hasnat, Abul

    2015-05-01

    The extent to which cytochrome P450 (CYP) 2C19 genotype influences the effectiveness of clopidogrel remains uncertain due to considerable heterogeneity between studies. We used the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method for genotyping loss of function (LOF) allele, CYP2C19*2 and gain of function (GOF) allele, CYP2C19*17 in 163 patients undergoing PCI and 165 healthy volunteers from an ethnically distinctive Bangladeshi population. Thirty-eight patients took prasugrel and 125 patients took clopidogrel among whom 30 patients had their clopidogrel active metabolites (CAM) determined by LC-MS/MS 1-1.5 h after clopidogrel intake. All patients who underwent PCI had their P2Y12 per cent inhibition (PRI) measured by VerifyNow System. The impact of different genotypes on CAM and PRI were also determined. We did not find significant variation of CYP2C19*2 (P > 0.05) and CYP2C9*17 (P > 0.05) alleles among healthy volunteers and patients. CAM concentration as well as PRI by clopidogrel varied significantly (P < 0.05) based on genotypic variation of CYP2C19*2 and CYP2C19*17 individually. Such influence was not observed in case of prasugrel. Genotypic variation did not impact PRI but as a whole PRI by prasugrel was better than that of clopidogrel (P < 0.05). Due to presence of both of alleles the effect on PRI by clopidogrel could not be predicted, effectively indicating possible involvement of other factors. Genotype guided clopidogrel dose adjustment would be beneficial and therefore we propose mandatory genotyping before clopidogrel dosing. Prasugrel proved to be less affected by genotypic variability, but due to lack of sufficient long-term toxicity data, caution would be adopted before substituting clopidogrel.

  4. Influence of low-dose proton pump inhibitors administered concomitantly or separately on the anti-platelet function of clopidogrel.

    PubMed

    Furuta, Takahisa; Sugimoto, Mitsushige; Kodaira, Chise; Nishino, Masafumi; Yamade, Mihoko; Uotani, Takahiro; Sahara, Shu; Ichikawa, Hitomi; Kagami, Takuma; Iwaizumi, Moriya; Hamaya, Yasushi; Osawa, Satoshi; Sugimoto, Ken; Umemura, Kazuo

    2017-04-01

    Proton pump inhibitors (PPIs) at low doses can effectively prevent gastrointestinal bleeding due to aspirin and are widely used in Japan for gastroprotection in patients taking anti-platelet agents. We examined the influence of different PPIs at low doses administered concomitantly or separately on anti-platelet functions of clopidogrel. In 41 healthy Japanese volunteers with different CYP2C19 genotypes who took clopidogrel 75 mg in the morning alone, or with omeprazole 10 mg, esomeprazole 10 mg, lansoprazole 15 mg, or rabeprazole 10 mg, either concomitantly in the morning or separately in the evening, we measured the inhibition of platelet aggregation (IPA, %) using VerifyNow P2Y12 assay at 4 h after the last clopidogrel dose on Day 7 of each regimen. IPA by clopidogrel with rabeprazole administered at lunchtime, approximately 4 h after clopidogrel, was also measured. Mean IPAs in those concomitantly receiving omeprazole, esomeprazole, lansoprazole or rabeprazole (47.2 ± 21.1%, 43.2 ± 20.2%, 46.4 ± 18.8%, and 47.3 ± 19.2%, respectively) were significantly decreased compared with those receiving clopidogrel alone (56.0%) (all ps < 0.001). This decrease was observed when PPIs were administered separately in the evening. However, IPA by clopidogrel with rabeprazole administered at lunchtime was 51.6%, which was markedly similar to that of clopidogrel alone (p = 0.114). All tested PPIs reduce the efficacy of clopidogrel when administered concomitantly. Our preliminary data suggest that administration of rabeprazole 4 h following clopidogrel may minimize potential drug-drug interactions.

  5. High Platelet Reactivity in Patients with Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: Randomised Controlled Trial Comparing Prasugrel and Clopidogrel

    PubMed Central

    Geisler, Tobias; Booth, Jean; Tavlaki, Elli; Karathanos, Athanasios; Müller, Karin; Droppa, Michal; Gawaz, Meinrad; Yanez-Lopez, Monica; Davidson, Simon J.; Stables, Rod H.; Banya, Winston; Zaman, Azfar; Flather, Marcus; Dalby, Miles

    2015-01-01

    Background Prasugrel is more effective than clopidogrel in reducing platelet aggregation in acute coronary syndromes. Data available on prasugrel reloading in clopidogrel treated patients with high residual platelet reactivity (HRPR) i.e. poor responders, is limited. Objectives To determine the effects of prasugrel loading on platelet function in patients on clopidogrel and high platelet reactivity undergoing percutaneous coronary intervention for acute coronary syndrome (ACS). Patients Patients with ACS on clopidogrel who were scheduled for PCI found to have a platelet reactivity ≥40 AUC with the Multiplate Analyzer, i.e. “poor responders” were randomised to prasugrel (60 mg loading and 10 mg maintenance dose) or clopidogrel (600 mg reloading and 150 mg maintenance dose). The primary outcome measure was proportion of patients with platelet reactivity <40 AUC 4 hours after loading with study medication, and also at one hour (secondary outcome). 44 patients were enrolled and the study was terminated early as clopidogrel use decreased sharply due to introduction of newer P2Y12 inhibitors. Results At 4 hours after study medication 100% of patients treated with prasugrel compared to 91% of those treated with clopidogrel had platelet reactivity <40 AUC (p = 0.49), while at 1 hour the proportions were 95% and 64% respectively (p = 0.02). Mean platelet reactivity at 4 and 1 hours after study medication in prasugrel and clopidogrel groups respectively were 12 versus 22 (p = 0.005) and 19 versus 34 (p = 0.01) respectively. Conclusions Routine platelet function testing identifies patients with high residual platelet reactivity (“poor responders”) on clopidogrel. A strategy of prasugrel rather than clopidogrel reloading results in earlier and more sustained suppression of platelet reactivity. Future trials need to identify if this translates into clinical benefit. Trial Registration ClinicalTrials.gov NCT01339026 PMID:26317618

  6. CYP2C19 polymorphisms in acute coronary syndrome patients undergoing clopidogrel therapy in Zhengzhou population.

    PubMed

    Guo, Y M; Zhao, Z C; Zhang, L; Li, H Z; Li, Z; Sun, H L

    2016-05-25

    The goal of this study was to explore the polymorphisms of CYP2C19 (CYP2C19*2, CYP2C19*3) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) on clopidogrel therapy in Zhengzhou city for guidance on clinical medication and reduction in the incidence of thromboembolic events. Two hundred and thirty-four ACS patients undergoing PCI were included in the study, including 171 males (average age = 64.13 ± 12 years) and 63 females (average age = 67.86 ± 10.20 years). Pyrosequencing analysis detected CYP2C19*2/*3 genotypes, which were divided into wild-type homozygous C/C, mutant heterozygous C/T, and mutant homozygous T/T. This study further explored the relationship between CYP2C19 polymorphisms and clopidogrel resistance in ACS patients. Gene frequencies of C/C, C/T, and T/T for CYP2C19*2 were 39.74, 50, and 10.26%, respectively, while the frequencies of C/C, C/T, and T/T for CYP2C19*3 were 94.02, 5.55, and 0.43%, respectively. According to platelet aggregation analysis, 203 cases normally responded to clopidogrel (86.8%) and 31 cases were clopidogrel resistant (13.2%). There was a correlation between gender and genotype distribution but none between age and genotype. In addition, patients with clopidogrel resistance were treated with ticagrelor antiplatelet therapy instead of clopidogrel, and only 1 case in all patients suffered thrombotic events during a 3-12 month follow-up. In conclusion, CYP2C19*2/*3 polymorphisms may be associated with clopidogrel resistance. Wild-type homozygote and single mutant heterozygote of CYP2C19*2/*3 can be given a normal dose of clopidogrel, while carriers with single mutant homozygote or double mutant heterozygote require ticagrelor antiplatelet therapy as an alternative.

  7. Clopidogrel enhances periodontal repair in rats through decreased inflammation

    PubMed Central

    Coimbra, Leila S; Steffens, Joao Paulo; Rossa, Carlos; Graves, Dana T; Spolidorio, Luis C.

    2014-01-01

    Aim We hypothesized that platelet inactivation induced by drugs might interfere with periodontal repair in experimental periodontitis by suppressing the release of biological mediators from platelets at the site of injury. Material and Methods 60 rats were randomly assigned to 6 groups (n=10) and ligatures were placed around lower first molars of three groups. The other three groups were used as negative controls. Ligatures were removed after 10 days of periodontitis induction and all groups were submitted to treatment with aspirin (Asp) (30 mg/kg), clopidogrel (Clop) (75 mg/kg) or NaCl 0.9% intragastrically once daily for 3 days. Periodontal tissue was assessed by the measurement of CXCL12, CXCL4, CCL5 and PDGF by ELISA; histomorphometric analysis of PMN infiltration, attachment loss, bone loss and osteoclast numbers and quantification of blood vessels by imunnohistochemistry. Results During periodontal repair and treatment with NaCl 0.9%, CCL5 was decreased and CXCL12 increased when compared to negative control groups. Asp and Clop did not affect CCL5 expression, decreased CXCL12 but only Clop decreased CXCL4 and PDGF content compared to saline-treated animals. Clop increased blood vessel number, reduced PMN count, and decreased attachment and bone loss, also decreased osteoclast number in animals submitted or not to periodontal repair. Conclusion Systemic administration of Clop during 3 days improved the repair process associated with experimental periodontal disease, suggesting that it may have therapeutic value under situations where tissues undergo a transition from inflammation to repair. PMID:24433307

  8. Ascertainment, classification, and impact of neoplasm detection during prolonged treatment with dual antiplatelet therapy with prasugrel vs. clopidogrel following acute coronary syndrome

    PubMed Central

    Roe, Matthew T.; Cyr, Derek D.; Eckart, Debra; Schulte, Phillip J.; Morse, Michael A.; Blackwell, Kimberly L.; Ready, Neal E.; Zafar, S. Yousuf; Beaven, Anne W.; Strickler, John H.; Onken, Jane E.; Winters, Kenneth J.; Houterloot, Lisa; Zamoryakhin, Dmitry; Wiviott, Stephen D.; White, Harvey D.; Prabhakaran, Dorairaj; Fox, Keith A. A.; Armstrong, Paul W.; Ohman, E. Magnus

    2016-01-01

    Aims Studies have suggested increased cancer incidence associated with long-term dual antiplatelet therapy (DAPT) for acute coronary syndrome (ACS). We evaluated cancer incidence and treatment-related differences in an analysis of DAPT for ACS. Methods and results The Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes trial enrolled 9326 participants with ACS, who received aspirin plus clopidogrel or prasugrel. Median treatment exposure was 15 months. Cancer history and screening procedures were collected. Suspected non-benign neoplasm events were reported and adjudicated. The primary outcome was detection of new, non-benign neoplasm. Factors associated with neoplasm events, the relationship of these events to cardiovascular and bleeding endpoints, and treatment-related differences in neoplasm detection were studied. Among 9240 participants who received ≥1 dose of study drug, 1.8% had a confirmed neoplasm event. The efficacy composite of cardiovascular death, myocardial infarction, or stroke occurred more frequently among those with a neoplasm event vs. those without (18.2 vs. 13.5%) as did Global Use of Strategies to Open Occluded Coronary Arteries severe/moderate bleeding (11.2 vs. 1.5%). Screening rates were substantially higher in North America and Western Europe/Scandinavia vs. other regions. Factors most strongly associated with detection of neoplasm events were older age, region, male sex, and current/recent smoking. Among the pre-specified population without a history of neoplasm or previous curative treatment for neoplasm (n = 9105), the incidence of neoplasm events was similar with prasugrel vs. clopidogrel (1.8 vs. 1.7%; HR = 1.04; 95% CI 0.77–1.42; P = 0.79). Conclusions Neoplasm events were infrequent during long-term DAPT after ACS, were associated with differential cancer-screening practices across regions, and the frequency of neoplasm detection was similar with prasugrel vs. clopidogrel

  9. Regional Anesthesia in Patients of Aged 99 Years in Clopidogrel Use

    PubMed Central

    Brasileiro, Bruno; Imbelloni, Luiz Eduardo

    2017-01-01

    The risk of neuraxial block in patients treated with antiplatelet drugs are uncertain. Elderly patients often have low physiological reserve, delaying surgery can lead to a high rate of morbidity and mortality. The aim of this paper is to present a case of a patient with 99 years using clopidogrel undergoing regional anesthesia for surgical treatment of hip fracture without complications. PMID:28298798

  10. Clopidogrel in the management of acute coronary syndromes: indications, results, obstacles.

    PubMed

    Amsterdam, Ezra A

    2009-06-01

    Atherothrombosis is the underlying pathology of the acute coronary syndromes (ACS), in which platelet activation plays a key role. Therefore, antiplatelet therapy is an essential component of guideline-recommended ACS management. Considerable evidence clearly demonstrates the benefits of the antiplatelet agent clopidogrel in reducing mortality, decreasing recurrent cardiovascular events, and increasing arterial patency in ACS patients. Despite this evidence, data from patient registries and clinical initiatives such as CRUSADE (Can Rapid stratification of Unstable angina Suppress ADverse outcomes with Early implementation of the American College of Cardiology/American Heart Association guidelines) and GRACE (Global Registry of Acute Coronary Events) indicate that clopidogrel is underused in patients with ACS. This is especially true for patients receiving conservative medical management, many of whom have significant risk for recurrent ischemic events. The purpose of this review is to compare "real-life" clopidogrel therapy with evidence-based guidelines, and to highlight clinical factors that drive clopidogrel implementation or provide barriers to its use in ACS patients.

  11. Politics in evaluation: Politically responsive evaluation in high stakes environments.

    PubMed

    Azzam, Tarek; Levine, Bret

    2015-12-01

    The role of politics has often been discussed in evaluation theory and practice. The political influence of the situation can have major effects on the evaluation design, approach and methods. Politics also has the potential to influence the decisions made from the evaluation findings. The current study focuses on the influence of the political context on stakeholder decision making. Utilizing a simulation scenario, this study compares stakeholder decision making in high and low stakes evaluation contexts. Findings suggest that high stakes political environments are more likely than low stakes environments to lead to reduced reliance on technically appropriate measures and increased dependence on measures better reflect the broader political environment.

  12. Response Style Contamination of Student Evaluation Data

    ERIC Educational Resources Information Center

    Dolnicar, Sara; Grun, Bettina

    2009-01-01

    Student evaluation surveys provide instructors with feedback regarding development opportunities and they form the basis of promotion and tenure decisions. Student evaluations have been extensively studied, but one dimension hitherto neglected is the actual measurement aspect: which questions to ask, how to ask them, and what answer options to…

  13. Measurement and evaluation techniques for automated demand response demonstration

    SciTech Connect

    Motegi, Naoya; Piette, Mary Ann; Watson, David S.; Sezgen, Osman; ten Hope, Laurie

    2004-08-01

    The recent electricity crisis in California and elsewhere has prompted new research to evaluate demand response strategies in large facilities. This paper describes an evaluation of fully automated demand response technologies (Auto-DR) in five large facilities. Auto-DR does not involve human intervention, but is initiated at a facility through receipt of an external communications signal. This paper summarizes the measurement and evaluation of the performance of demand response technologies and strategies in five large facilities. All the sites have data trending systems such as energy management and control systems (EMCS) and/or energy information systems (EIS). Additional sub-metering was applied where necessary to evaluate the facility's demand response performance. This paper reviews the control responses during the test period, and analyzes demand savings achieved at each site. Occupant comfort issues are investigated where data are available. This paper discusses methods to estimate demand savings and results from demand response strategies at five large facilities.

  14. St. John's Wort in patients non-responders to clopidogrel undergoing percutaneous coronary intervention: a single-center randomized open-label trial (St. John's Trial).

    PubMed

    Trana, Catalina; Toth, Gabor; Wijns, William; Barbato, Emanuele

    2013-06-01

    We assessed if St. John's Wort (SJW) improves platelet response in patients (pts) resistant to clopidogrel after percutaneous coronary intervention (PCI). Stable angina pts non-responders to 600 mg clopidogrel (P2Y12 reaction units (PRU) >240) were randomized (2:1) to SJW (n = 15) or placebo (n = 8). SJW (300 mg × 3/day) was administrated for 2 weeks after PCI. Platelet reactivity was assessed by VerifyNowTM before (BL), 2 (T1), and 4 weeks (T2) after PCI. PRU significantly changed during protocol in SJW (BL (316 ± 60) vs. T1 (170 ± 87) vs. T2 (220 ± 96), p < 0.0001) and placebo group (BL (288 ± 36) vs. T1 (236 ± 31) vs. T2 (236 ± 62), p = 0.046). Yet, PRU changes from BL were higher at T1 in SJW than in placebo group (Δ%, -47 ± 24 vs. -16 ± 15, p = 0.0033), with no differences at T2 between the groups (Δ%, -30 ± 29 vs. -17 ± 24, p = 0.30). Residual platelet reactivity improved with SJW during the first month post-PCI.

  15. Use of prasugrel in the setting of clopidogrel hypersensitivity: Case report and systematic review of the literature.

    PubMed

    Siu, Henry; Kaliyadan, Antony; Fischman, David L; Nardone, Evan; Poll, David; Savage, Michael P

    2016-12-01

    Allergic reactions to clopidogrel soon after coronary stent implantation pose an important and challenging clinical problem. We describe a 44-year-old man who developed a diffuse maculopapular rash four days after initiation of clopidogrel with drug-eluting coronary stent placement. An initial treat-through strategy was unsuccessful due to patient intolerance to corticosteroids. Because of persistent hypersensitivity, clopidogrel was substituted with prasugrel which was continued successfully for one year without reaction. A systematic review of the literature was performed which identified 10 prior case reports of patients with clopidogrel hypersensitivity who were subsequently treated with prasugrel. Patient characteristics and clinical outcomes of these patients plus the current case were reviewed. There were 9 men and 2 women with ages from 44 to 76 years. All patients had undergone coronary stent procedures. Prasugrel was successfully used without cross-reactivity in 9 of the 11 patients (82%). Cross-reactivity was reported in two patients who developed hypersensitivity reactions to prasugrel similar to those experienced on clopidogrel. In conclusion, prasugrel can be used successfully in most patients with a history of clopidogrel hypersensitivity. However, potential cross-reactivity between these two thienopyridines may occur in some patients.

  16. Transient receptor potential ankyrin 1 (TRPA1) channel activation by the thienopyridine-type drugs ticlopidine, clopidogrel, and prasugrel.

    PubMed

    Schulze, Anja; Hartung, Philipp; Schaefer, Michael; Hill, Kerstin

    2014-04-01

    Transient receptor potential A1 (TRPA1) is widely expressed throughout the human and animal organism, including the dorsal root ganglia as well as the bladder, stomach and small intestine. Here, we examined the effect of three platelet aggregation inhibitors on TRPA1: ticlopidine, clopidogrel and prasugrel. Utilising fluorometric Ca(2+) influx analysis and electrophysiological whole cell measurements in TRPA1-expressing HEK293 and in human enterochromaffin-like QGP-1 cells, we found that ticlopidine, clopidogrel and prasugrel are direct activators of TRPA1. Although this polymodal channel commonly contributes to the perception of pain, temperature and chemical irritants, recent studies provide evidence for its involvement in the release of serotonin (5-HT) from enterochromaffin cells. Therefore, we further investigated the ability of ticlopidine, clopidogrel and prasugrel to stimulate 5-HT release from QGP-1 cells. We could determine 5-HT in supernatants from cultured QGP-1 cells upon treatment with ticlopidine and clopidogrel but not with prasugrel. These findings indicate that a robust TRPA1 activation by ticlopidine and clopidogrel correlates with the stimulatory effect on the secretion of 5-HT. As recipients of ticlopidine and clopidogrel frequently complain about gastrointestinal adverse events such as nausea, vomiting and diarrhoea, an activation of TRPA1 may contribute to adverse effects of such drugs in the digestive system.

  17. Children's Responses to the Medical Evaluation for Child Sexual Abuse.

    ERIC Educational Resources Information Center

    Dubowitz, Howard

    1998-01-01

    Addresses three issues: (1) how children respond to the medical evaluation for sexual abuse; (2) how the trauma of the evaluation experienced by some children can be minimized and the benefits maximized; and (3) how children's responses to the medical evaluation for sexual abuse can be interpreted. (DB)

  18. Aspirin and Extended-Release Dipyridamole versus Clopidogrel for Recurrent Stroke

    PubMed Central

    Sacco, Ralph L.; Diener, Hans-Christoph; Yusuf, Salim; Cotton, Daniel; Ôunpuu, Stephanie; Lawton, William A.; Palesch, Yuko; Martin, Reneé H.; Albers, Gregory W.; Bath, Philip; Bornstein, Natan; Chan, Bernard P.L.; Chen, Sien-Tsong; Cunha, Luis; Dahlöf, Björn; De Keyser, Jacques; Donnan, Geoffrey A.; Estol, Conrado; Gorelick, Philip; Gu, Vivian; Hermansson, Karin; Hilbrich, Lutz; Kaste, Markku; Lu, Chuanzhen; Machnig, Thomas; Pais, Prem; Roberts, Robin; Skvortsova, Veronika; Teal, Philip; Toni, Danilo; VanderMaelen, Cam; Voigt, Thor; Weber, Michael; Yoon, Byung-Woo

    2009-01-01

    BACKGROUND Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens — aspirin plus extendedrelease dipyridamole (ASA–ERDP) versus clopidogrel. METHODS In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned. RESULTS A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA–ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA–ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA–ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA–ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11). CONCLUSIONS The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA–ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke. PMID:18753638

  19. Sharing stories: narrative and dialogue in responsive nursing evaluation.

    PubMed

    Abma, T A; Widdershoven, G A M

    2005-03-01

    Responsive evaluation is an emerging vision and rationale for nursing evaluation. In this vision, evaluation is redefined as an engagement with all stakeholders about the value and meaning of their practice as a vehicle for learning, understanding, and improvement. In this article, the authors aim to illustrate the utility of a particular version of responsive evaluation, one that is connected with recent ideas about narrative and dialogue. They concentrate on methodological issues and use a case example to illustrate these issues. The case concerns a responsive evaluation of the quality of palliative care for cancer patients in a Dutch region. Methodological issues include the collection of stories through the use of conversational interviews. Stories can reveal the meaning and ambiguity of everyday situations. If evaluators listen to different stories and facilitate a dialogue about stories, this will enhance mutual understandings and promote respect, inclusiveness, and social equity.

  20. Imaging in evaluation of response to neoadjuvant breast cancer treatment

    PubMed Central

    Ollivier, L; Balu-Maestro, C; Leclère, J

    2005-01-01

    The role of imaging for patients treated with neoadjuvant therapy for breast cancer is not only to evaluate the therapeutic response in terms of tumour shrinkage, but also to predict the histological response to chemotherapy, which is correlated to survival. Surgery and histopathological analysis after neoadjuvant therapy allow for an objective assessment of the accuracy of imaging techniques in evaluating response. The aim of this study is to compare the value of the different conventional and functional imaging techniques for determining response to neoadjuvant chemotherapy in breast cancer treatment. PMID:16154816

  1. Measurement of platelet P-selectin for remote testing of platelet function during treatment with clopidogrel and/or aspirin.

    PubMed

    Fox, S C; May, J A; Shah, A; Neubert, U; Heptinstall, S

    2009-06-01

    There is great interest in assessing the efficacy of treatment with clopidogrel and aspirin in patients with cardiovascular disease using procedures that can be used in a remote setting. Here we have established methods to assess the effects of clopidogrel and aspirin on platelets based on measurements of platelet P-selectin. Platelets were stimulated in whole blood by adding the combination of adenosine diphosphate and the TXA(2) mimetic U46619 (ADP/U4, designed to assess P2Y(12) inhibition) or the combination of arachidonic acid and epinephrine (AA/Epi, designed to assess COX-1 inhibition). The stimulated samples were then fixed using a fixative solution that provides stability for at least 9 days, and sent to a central laboratory for analysis of P-selectin by flow cytometry. Measurements were performed in blood from healthy volunteers and patients with cardiovascular disease. The inhibitory effects of clopidogrel and aspirin were assessed ex vivo and the effects of the direct acting P2Y(12) antagonist cangrelor and aspirin were assessed in vitro. Measurements of platelet aggregation were also performed for comparison. In healthy volunteers clopidogrel ex vivo and cangrelor in vitro markedly inhibited P-selectin expression induced by ADP/U4. Aspirin did not inhibit and did not interfere with the effects of clopidogrel or cangrelor using this test. There was very little overlap of results obtained in the absence and presence of clopidogrel or cangrelor. In contrast, over half of 42 patients with cardiovascular disease did not respond well to clopidogrel treatment, although cangrelor was still effective. Aspirin markedly inhibited P-selectin expression induced by AA/Epi. Clopidogrel had much less effect and did not interfere with the effects of aspirin. There was no overlap of results obtained in the absence and presence of aspirin. Aspirin provided near-complete inhibition in 29 of 30 patients with cardiovascular disease. Aggregometry measurements agreed well with

  2. Randomised, double-blind trial on the value of tapered discontinuation of clopidogrel maintenance therapy after drug-eluting stent implantation. Intracoronary Stenting and Antithrombotic Regimen: CAUTION in Discontinuing Clopidogrel Therapy--ISAR-CAUTION.

    PubMed

    Fiedler, K Anette; Mehilli, Julinda; Kufner, Sebastian; Schlichting, Anna; Ibrahim, Tareq; Sibbing, Dirk; Ott, Ilka; Schunkert, Heribert; Laugwitz, Karl-Ludwig; Kastrati, Adnan; Schulz, Stefanie

    2014-06-01

    There is little evidence on the optimal mode of clopidogrel discontinuation. Epidemiological studies observed clustering of thrombotic events after cessation of chronic clopidogrel therapy. The underlying mechanism has been ascribed to transient platelet hyper-reactivity. Gradual tapering of clopidogrel may have the potential to attenuate this phenomenon. The objective of the present study was to assess whether in patients with drug-eluting stents (DES) gradual discontinuation of clopidogrel maintenance therapy is superior to conventional, abrupt discontinuation. Patients with planned discontinuation of chronic clopidogrel therapy after DES implantation were randomised in a double-blinded fashion to either gradual discontinuation (according to a tapering schema over four weeks) or abrupt discontinuation (after continued clopidogrel therapy for additional four weeks). The primary endpoint was the composite of cardiac death, myocardial infarction, stroke, stent thrombosis, major bleeding or rehospitalisation due to an acute coronary syndrome at 90 days. Enrollment of 3,000 patients was planned. The study was stopped prematurely due to slow recruitment after enrollment of 782 patients. At 90 days, nine of 392 patients (2.3%) with tapered cessation reached the primary endpoint compared to five of 390 patients (1.3%) with abrupt cessation (p=0.284). The composite of death or myocardial infarction occurred in three patients with tapered and three patients with abrupt discontinuation (p=0.764). In conclusion, tapered discontinuation of chronic clopidogrel therapy is not superior to abrupt discontinuation regarding the primary endpoint in this study. However, the results must be interpreted in view of the premature termination of the trial and low event rates.

  3. Combination of aspirin and clopidogrel for the prevention of thrombosis: implications for the dental practitioner.

    PubMed

    Shah, Paulomi R; Yepes, Juan F; Valenza, John A

    2007-01-01

    The use of aspirin and clopidogrel as effective antiplatelet therapy in preventing secondary thromboembolic events is well-established. However, there is controversy among dentists and physicians regarding the appropriate dental management of patients receiving dual antiplatelet therapy due to the lack of clinical studies about hemorrhagic risk in these patients. Indications for modifying dual antiplatelet therapy--whether it is done by altering doses, switching to monotherapy, or discontinuing it completely--occur infrequently, as most patients can be treated in a dental office setting. In all cases, patients must be managed jointly by the dentist and physician, taking into account the patient's medical and dental history. This article reviews the current use of aspirin and clopidogrel as combination therapy, examining their effect on platelet function, the associated hemorrhagic risk during dental procedures for patients using this therapy, and how oral health care providers can manage these patients safely and effectively.

  4. Overcoming Aspirin Resistance with Loading Clopidogrel Earlier in Elective Percutaneous Coronary Intervention

    PubMed Central

    Ozcan, Ozgur Ulas; Tutar, Eralp; Candemir, Basar; Ustun, Elif Ezgi; Erol, Cetin

    2015-01-01

    We aimed to analyze the clinical effect of clopidogrel loading time on adverse cardiovascular events among patients with aspirin resistance. Recurrent adverse events may still occur despite dual antiplatelet therapy after coronary stenting. Aspirin resistance is one of the possible reasons of this trouble. Optimal antiplatelet strategy for coronary stenting is unknown among patients with aspirin resistance. A total of 980 patients scheduled for elective coronary stenting were enrolled and allocated into two groups according to the loading time of clopidogrel more or less than 6 hours before coronary intervention (early- or late-loaded groups, respectively). Aspirin resistance was determined according to the urinary levels of 11-dehydrothromboxane B2. Overall 240 patients who were allocated to early- and late-loaded groups were identified as aspirin resistant according to the urinary levels of 11-dehydrothromboxane B2. After a follow-up period of 12 months major adverse cardiac events were observed among 16 patients (13.9%) in the early-loaded group and 30 patients (25.8%) in the late-loaded group (p = 0.02). Early loading of clopidogrel was an independent predictor of lower rate of cardiac events (hazard ratio = 0.46 [0.32–0.76, 95% confidence interval], p = 0.001). The rates of bleeding events and periprocedural myocardial infarction were similar in early- and late-loaded groups. The current study demonstrated that loading of clopidogrel earlier than 6 hours before elective coronary stenting among aspirin-resistant patients was associated with increased benefits for ischemic events with similar bleeding rates. PMID:25780324

  5. Species Comparison of Pre-systemic Bioactivation of Vicagrel, a New Acetate Derivative of Clopidogrel

    PubMed Central

    Qiu, Zhi-xia; Gao, Wen-chao; Dai, Yu; Zhou, Su-feng; Zhao, Jie; Lu, Yang; Chen, Xi-jing; Li, Ning

    2016-01-01

    Previously we have found vicagrel, a new acetate derivative of clopidogrel, underwent hydrolysis to 2-oxo-clopidogrel and subsequent conversions to its pharmacological active metabolite (AM) and inactive carboxylic acid metabolite (CAM). This study demonstrated the interspecies differences of the vicagrel bioactivation by comparing the critical vicagrel metabolites formation in rats, dogs and human. The pharmacokinetic studies with rats and dogs were conducted after intragastric administration of vicagrel, followed by in vitro metabolism investigation in venous system, intestinal/hepatic microsomes from rats, dogs and human. An obvious disparity was observed in system exposure to AM (99.0 vs. 635.1 μg⋅h/L, p < 0.05) and CAM (10119 vs. 2634 μg⋅h/L, p < 0.05) in rats and dogs. It was shown that the cleavage of vicagrel was almost completed in intestine with great different clearance (53.28 vs. 3.643 L⋅h-1⋅kg-1, p < 0.05) in rats and dogs. With no further hydrolysis to CAM, the greatest clearance of AM (3.26 mL⋅h-1⋅kg-1) was found in dog intestine. In rat plasma, 2-oxo-clopidogrel was much more extensively hydrolyzed to CAM than in dog and human. Albeit similar hydrolysis clearance and AM production was observed among hepatic microsomes of the three species, the production velocity of CAM ranked highest in dogs (7.55 pmol/min/mg protein). Therefore, the unconformity of AM and CAM exposure cross species mainly came from the metabolism of 2-oxo-clopidogrel associated largely with tissue specificity and interspecies differences of esterases. In human, the pharmacokinetics of vicagrel might be more optimistic due to less inactivation hydrolysis before reaching liver. PMID:27774067

  6. Development and validation of an HPLC–MS/MS method to determine clopidogrel in human plasma

    PubMed Central

    Liu, Gangyi; Dong, Chunxia; Shen, Weiwei; Lu, Xiaopei; Zhang, Mengqi; Gui, Yuzhou; Zhou, Qinyi; Yu, Chen

    2015-01-01

    A quantitative method for clopidogrel using online-SPE tandem LC–MS/MS was developed and fully validated according to the well-established FDA guidelines. The method achieves adequate sensitivity for pharmacokinetic studies, with lower limit of quantifications (LLOQs) as low as 10 pg/mL. Chromatographic separations were performed on reversed phase columns Kromasil Eternity-2.5-C18-UHPLC for both methods. Positive electrospray ionization in multiple reaction monitoring (MRM) mode was employed for signal detection and a deuterated analogue (clopidogrel-d4) was used as internal standard (IS). Adjustments in sample preparation, including introduction of an online-SPE system proved to be the most effective method to solve the analyte back-conversion in clinical samples. Pooled clinical samples (two levels) were prepared and successfully used as real-sample quality control (QC) in the validation of back-conversion testing under different conditions. The result showed that the real samples were stable in room temperature for 24 h. Linearity, precision, extraction recovery, matrix effect on spiked QC samples and stability tests on both spiked QCs and real sample QCs stored in different conditions met the acceptance criteria. This online-SPE method was successfully applied to a bioequivalence study of 75 mg single dose clopidogrel tablets in 48 healthy male subjects. PMID:26904399

  7. Non-antiplatelet effect of clopidogrel: improving endothelial function in Chinese healthy subjects with different CYP2C19 genotype.

    PubMed

    Zhang, Yin-Zhuang; Chen, Bi-Lian; Zhang, Wei; Cao, Xin

    2015-01-01

    Clopidogrel has been shown to improve endothelial function in vitro and in patients with coronary artery disease. However, it remains unclear whether such an effect of clopidogrel is associated with CYP2C19 polymorphisms that determine the antiplatelet effect of clopidogrel. After genotyping, 12 healthy participants were enrolled in the study. Among them, six participants were CYP2C19*1/*1 (extensive metabolizers; EM) and the other six participants were CYP2C19*2/*2 or *3 (poor metabolizers; PM). All participants received 300 mg clopidogel orally. Endothelial function was assessed by measurement of flow-mediated dilation of the brachial artery, and adenosine diphosphate-induced platelet aggregation was determined by using optical aggregometry at 0, 4 and 24 h after administration of 300 mg clopidogrel. Flow-mediated dilation was significantly higher at 4 and 24 h after a loading-dose administration of clopidogrel in both the CYP2C19 EM and PM groups, but showed no significant difference between the two groups. Adenosine diphosphate-induced platelet aggregation was significantly inhibited at 4 and 24 h after administration of clopidogrel in the CYP2C19 EM group. However, there was no statistical correlation between the change in flow-mediated dilation and adenosine diphosphate-induced platelet aggregation in the two CYP2C19 groups. This is the first study to report that clopidogrel improves endothelial function in healthy Chinese subjects, which is unrelated with the CYP2C19 genotype and independent of antiplatelet action.

  8. Comparative Efficacy and Safety of Prasugrel, Ticagrelor, and Standard-Dose and High-Dose Clopidogrel in Patients Undergoing Percutaneous Coronary Intervention: A Network Meta-analysis.

    PubMed

    Singh, Sukhchain; Singh, Mukesh; Grewal, Navsheen; Khosla, Sandeep

    2016-01-01

    Authors aimed to compare efficacy and safety of prasugrel, ticagrelor, and standard-dose (SD) and high-dose (HD) clopidogrel in patients undergoing percutaneous coronary intervention (PCI). PubMed, EMBASE, CENTRAL, and clinicaltrials.gov were searched for studies comparing prasugrel, ticagrelor, SD and HD clopidogrel in patients undergoing PCI. Frequentist and Bayesian network meta-analyses were performed besides direct pairwise comparisons. Thirty trials, comprising 34,563 person-year data, were included. Prasugrel emerged as a best drug to prevent definite or probable stent thrombosis, followed by HD clopidogrel and ticagrelor, with SD clopidogrel being the worst. Myocardial infarction was least likely to be prevented by SD clopidogrel after PCI, and remaining 3 were superior to it with little difference among them. SD clopidogrel was least effective in preventing cardiovascular deaths after PCI. Prasugrel was most effective in preventing cardiovascular deaths, although having only small advantage over ticagrelor and HD clopidogrel. Ticagrelor reduced all-cause mortality by a small margin compared with rest of treatments. SD clopidogrel, followed by ticagrelor, resulted in significantly lower thrombolysis in myocardial infarction major bleeding complications compared with prasugrel. Analysis of any bleeding revealed similar trend. HD clopidogrel performed better than prasugrel in terms of bleeding complications. In conclusion, Prasugrel is likely most effective drug to prevent post-PCI ischemic events but at the expense of higher bleeding. Ticagrelor followed by HD clopidogrel seems to strike the right balance between efficacy and safety. HD clopidogrel can be considered as an alternative to newer P2Y12 inhibitors.

  9. 40 CFR 265.93 - Preparation, evaluation, and response.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 26 2014-07-01 2014-07-01 false Preparation, evaluation, and response. 265.93 Section 265.93 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID..., STORAGE, AND DISPOSAL FACILITIES Ground-Water Monitoring § 265.93 Preparation, evaluation, and...

  10. 40 CFR 265.93 - Preparation, evaluation, and response.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 26 2011-07-01 2011-07-01 false Preparation, evaluation, and response. 265.93 Section 265.93 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID..., STORAGE, AND DISPOSAL FACILITIES Ground-Water Monitoring § 265.93 Preparation, evaluation, and...

  11. 40 CFR 265.93 - Preparation, evaluation, and response.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 27 2013-07-01 2013-07-01 false Preparation, evaluation, and response. 265.93 Section 265.93 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID..., STORAGE, AND DISPOSAL FACILITIES Ground-Water Monitoring § 265.93 Preparation, evaluation, and...

  12. Evaluation Responsibility and Leadership in the Face of Failing Democracies

    ERIC Educational Resources Information Center

    McKegg, Kate

    2013-01-01

    In a world faced with unprecedented rising levels of inequality and injustice, is there a responsibility for our evaluation organizations to take on a leadership role in promoting inclusive, evaluative dialog and deliberation about the state of our democracies in relation to key democratic principles and ideals? In this forum, I question whether…

  13. Clinical bioequivalence of a dose of clopidogrel Leti Cravid tablets 75 mg versus clopidogrel Sanofi Plavix tablets 75 mg administered on a daily dose for 7 days on healthy volunteers: a clinical trial.

    PubMed

    Müller, Aixa; Octavio, José; González, María Y; Contreras, Jesús; Méndez, Gisela; Portillo, Milagros; Valero, Zuleima

    2010-01-01

    Patients undergoing percutaneous coronary intervention procedures, as in patients with coronary disease, should receive treatment indefinitely with acetylsalicylic acid and clopidogrel. New brands of clopidogrel have been developed at lower costs, for helping to avoid premature suspension of antiplatelet therapy, as Cravid Leti Laboratories clopidogrel. Its effectiveness and safety must be compared with Plavix international standard. A prospective, comparative, cross-over, and randomized study was conducted in healthy volunteers. Each group received 1 tablet of Clopidogrel Leti or Clopidogrel Sanofi, 75 mg in a single dose daily for 7 days, followed by 7-day washout period before administration of second treatment. Platelet aggregation was measured at the start of each period and at 7 days of treatment through optical aggregometry, using an optical aggregometer 490-2D Chrono-Log, with a self-calibration system working with platelet-rich plasma with readings 0%-100% of light transmission. An important decrease of platelet aggregation was observed in both groups at 7 days of treatment of more than 50%, independent of adenosine diphosphate reactive (Helena and Chrono-Log) used for aggregation (P < 0.05). The relationship between the mean and 90% confidence interval ratio obtained with the 2 different adenosine diphosphate brands were between 80% and 125%, therefore, it can be considered that both brands are bioequivalent and perfectly exchangeable.

  14. Cytochrome P450 Gene Variants, Race, and Mortality Among Clopidogrel Treated Patients Following Acute Myocardial Infarction

    PubMed Central

    Cresci, Sharon; Depta, Jeremiah P.; Lenzini, Petra A.; Li, Allie Y.; Lanfear, David E.; Province, Michael A.; Spertus, John A.; Bach, Richard G.

    2014-01-01

    Background Clopidogrel is recommended after acute myocardial infarction (AMI) but has variable efficacy and safety, in part related to the effect of cytochrome P450 (CYP) polymorphisms on its metabolism. The effect of CYP polymorphisms on cardiovascular events among clopidogrel-treated patients after AMI remains controversial, and no studies to date have investigated the association of CYP variants with outcomes in African American patients. Methods and Results 2732 subjects (2062 Caucasians; 670 African Americans) hospitalized with AMI enrolled in the prospective, multicenter TRIUMPH study were genotyped for CYP polymorphisms. The majority of Caucasians (79%) and African Americans (64.4%) were discharged on clopidogrel. Among Caucasians, carriers of the loss-of-function CYP2C19*2 allele had significantly increased 1-year mortality (adjusted HR: 1.70; CI: 1.01 to 2.86; p=0.046), and a trend toward increased rate of recurrent MI (adjusted HR: 2.10; CI 0.95 to 4.63; p= 0.066). Among African Americans, increased 1-year mortality was associated with the gain of function CYP2C19*17 allele (adjusted HR for *1/*17 vs. *1/*1: 2.02; CI: 0.92 to 4.44; *17/*17 vs. *1/*1: 8.97; CI: 3.34 to 24.10; p< 0.0001) and the CYP1A2*1C allele (adjusted HR for *1/*1C vs. *1/*1: 1.89; CI: 0.85 to 4.22; *1C/*1C vs. *1/*1: 4.96; CI: 1.69 to 14.56; p= 0.014). Bleeding events were significantly more common among African American carriers of CYP2C19*17 or CYP1A2*1C. Conclusions Both loss of function and gain of function CYP polymorphisms affecting clopidogrel metabolism are associated with increased mortality among clopidogrel treated patients following AMI; the specific polymorphism and the putative mechanism vary according to race. PMID:24762860

  15. Physician Perspectives of CYP2C19 and Clopidogrel Drug-Gene Interaction Active Clinical Decision Support Alerts

    PubMed Central

    Nishimura, Adam A.; Shirts, Brian H.; Salama, Joseph; Smith, Joe W.; Devine, Beth; Tarczy-Hornoch, Peter

    2015-01-01

    Objective To determine if physicians find clinical decision support alerts for pharmacogenomic drug-gene interactions useful and assess their perceptions of usability aspects that impact usefulness. Materials and Methods 52 physicians participated in an online simulation and questionnaire involving a prototype alert for the clopidogrel and CYP2C19 drug-gene interaction. Results Only 4% of participants stated they would override the alert. 92% agreed that the alerts were useful. 87% found the visual interface appropriate, 91% felt the timing of the alert was appropriate and 75% were unfamiliar with the specific drug-gene interaction. 80% of providers preferred the ability to order the recommended medication within the alert. Qualitative responses suggested that supplementary information is important, but should be provided as external links, and that the utility of pharmacogenomic alerts depends on the broader ecosystem of alerts. Principal Conclusions Pharmacogenomic alerts would be welcomed by many physicians, can be built with minimalist design principles, and are appropriately placed at the end of the prescribing process. Since many physicians lack familiarity with pharmacogenomics but have limited time, information and educational resources within the alert should be carefully selected and presented in concise ways. PMID:26642939

  16. The risk of clopidogrel resistance is associated with ABCB1 polymorphisms but not promoter methylation in a Chinese Han population

    PubMed Central

    Su, Jia; Yu, Qinglin; Zhu, Hao; Li, Xiaojing; Cui, Hanbin; Du, Weiping; Ji, Lindan; Tong, Maoqing; Zheng, Yibo; Xu, Hongyu; Zhang, Jianjiang; Zhu, Yunyun; Xia, Yezi; Liu, Ting; Yao, Qi; Yang, Jun; Chen, Xiaomin; Yu, Jingbo

    2017-01-01

    The goal of our study was to investigate the contribution of ABCB1 expression to the risk of clopidogrel resistance (CR). Platelets functions were measured using the Verify-Now P2Y12 assay. Applying Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR-RFLP), the single-nucleotide polymorphisms (SNPs) was tested. Using bisulphite pyrosequencing assay, we investigated the association of the ABCB1 DNA methylation levels and CR. It was shown that female, hypertension, and lower albumin levels increased the risk of CR (P<0.05). If patients did not have hypoproteinaemia or had hypertension, the SNP in rs1045642 was associated with CR (CC vs. TT: albumin ≥35, P = 0.042; hypertension, P = 0.045; C vs. T: albumin ≥35, P = 0.033; hypertension, P = 0.040). Additionally, the platelet inhibition of the CT+TT genotype in rs1128503 was larger than that of the CC genotype (P = 0.021). Multivariate logistic regression analysis showed that male, higher albumin and hsCRP decreased the risk of CR, and the stent size maybe positively correlated with CR. The SNP in rs1045642 was related to all-cause mortality (P = 0.024). We did not find any relationship between the methylation levels of the ABCB1 promoter and CR. In conclusions, our study indicated that ABCB1 polymorphisms might be useful in further evaluating the pathogenesis of CR. PMID:28358842

  17. Non-Hodgkin lymphoma response evaluation with MRI texture classification

    PubMed Central

    Harrison, Lara CV; Luukkaala, Tiina; Pertovaara, Hannu; Saarinen, Tuomas O; Heinonen, Tomi T; Järvenpää, Ritva; Soimakallio, Seppo; Kellokumpu-Lehtinen, Pirkko-Liisa I; Eskola, Hannu J; Dastidar, Prasun

    2009-01-01

    Background To show magnetic resonance imaging (MRI) texture appearance change in non-Hodgkin lymphoma (NHL) during treatment with response controlled by quantitative volume analysis. Methods A total of 19 patients having NHL with an evaluable lymphoma lesion were scanned at three imaging timepoints with 1.5T device during clinical treatment evaluation. Texture characteristics of images were analyzed and classified with MaZda application and statistical tests. Results NHL tissue MRI texture imaged before treatment and under chemotherapy was classified within several subgroups, showing best discrimination with 96% correct classification in non-linear discriminant analysis of T2-weighted images. Texture parameters of MRI data were successfully tested with statistical tests to assess the impact of the separability of the parameters in evaluating chemotherapy response in lymphoma tissue. Conclusion Texture characteristics of MRI data were classified successfully; this proved texture analysis to be potential quantitative means of representing lymphoma tissue changes during chemotherapy response monitoring. PMID:19545438

  18. Pharmacodynamic effects of a new fixed-dose clopidogrel-aspirin combination compared with separate administration of clopidogrel and aspirin in patients treated with coronary stents: The ACCEL-COMBO trial.

    PubMed

    Koh, Jin-Sin; Park, Yongwhi; Tantry, Udaya S; Ahn, Jong-Hwa; Kang, Min Gyu; Kim, Kyehwan; Jang, Jeong Yoon; Park, Hyun Woong; Park, Jeong Rang; Hwang, Seok-Jae; Kwak, Choong Hwan; Hwang, Jin-Yong; Gurbel, Paul A; Jeong, Young-Hoon

    2017-03-01

    Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is a widely prescribed regimen to prevent ischemic events in patients undergoing percutaneous coronary intervention (PCI). A fixed-dose combination (FDC) capsule (HCP0911) has been developed to provide dosing convenience and improve adherence. We compared the antiplatelet effects of single daily dose HCP0911 with separate treatment with daily 75 mg clopidogrel plus 100 mg aspirin. This was a randomized, open-label, two-period, crossover, non-inferiority study conducted in stented patients who had been treated for at least 6 months with clopidogrel and aspirin. Thirty patients were randomly assigned to receive either daily 75 mg clopidogrel plus 100 mg aspirin treatment or HCP0911 for 2 weeks and then were crossed over to the other treatment for 2 weeks. Pharmacodynamic effects were measured with VerifyNow, light transmittance aggregometry (LTA), and thromboelastography (TEG(®)). The primary endpoint was P2Y12 Reaction Units (PRU) measured by VerifyNow. PRUs during treatment with HCP0911 were not inferior to those during separate treatment (202 ± 52 vs. 207 ± 60 PRU; mean difference, -5 PRU; 90% confidence interval of difference, -23 to 13 PRU; P for non-inferiority = 0.015 for predetermined limit). "BASE" and Aspirin Reaction Units by VerifyNow did not differ between the two treatments. During each treatment, there were no differences in maximal and final platelet aggregations by LTA (all P values ≥0.822) and TEG(®) measurements. In conclusion, in stented patients, the antiplatelet effect of a fixed-dose clopidogrel-aspirin combination, HCP0911, was not inferior to separate administration of clopidogrel and aspirin.

  19. Pharmacokinetics and relative bioavailability of fixed-dose combination of clopidogrel and aspirin versus coadministration of individual formulations in healthy Korean men

    PubMed Central

    Choi, Hyang-Ki; Ghim, Jong-Lyul; Shon, Jihong; Choi, Young-Kyung; Jung, Jin Ah

    2016-01-01

    Background Simultaneous prescription of clopidogrel and low-dose aspirin is recommended for the treatment of acute coronary syndrome because of improvements in efficacy and patient compliance. In this study, the pharmacokinetics of a fixed-dose combination (FDC) of clopidogrel and aspirin was compared with coadministration of individual formulations to clarify the equivalence of the FDC. Methods This was a randomized, open-label, two-period, two-treatment, crossover study in healthy Korean men aged 20–55 years. Subjects received two FDC capsules of clopidogrel/aspirin 75/100 mg (test) or two tablets of clopidogrel 75 mg and two capsules of aspirin 100 mg (reference) with a 14-day washout period. Plasma concentrations of clopidogrel, aspirin, and salicylic acid were measured using validated ultraperformance liquid chromatography–tandem mass spectrometry. Bioequivalence was assessed by analysis of variance and calculation of the 90% confidence intervals (CIs) of the ratios of the geometric means (GMRs) for AUClast and Cmax for clopidogrel and aspirin. Results Sixty healthy subjects were enrolled, and 53 completed the study. Clopidogrel, aspirin, and salicylic acid showed similar absorption profiles and no significant differences in Cmax, AUClast, and Tmax between FDC administration and coadministration of individual formulations. The GMRs (90% CI) for the Cmax and AUClast of clopidogrel were 1.08 (0.95, 1.23) and 0.93 (0.84, 1.03), respectively. The GMRs (90% CI) for the Cmax and AUClast of aspirin were 0.98 (0.84, 1.13) and 0.98 (0.93, 1.04), respectively. Both treatments were well tolerated in the study subjects. Conclusion The FDC of clopidogrel and aspirin was bioequivalent to coadministration of each individual formulation. The FDC capsule exhibited similar safety and tolerability profiles to the individual formulations. Therefore, clopidogrel/aspirin 75 mg/100 mg FDC capsules can be prescribed to improve patient compliance. PMID:27822013

  20. Evaluation of the Emergency Response Dose Assessment System(ERDAS)

    NASA Technical Reports Server (NTRS)

    Evans, Randolph J.; Lambert, Winifred C.; Manobianco, John T.; Taylor, Gregory E.; Wheeler, Mark M.; Yersavich, Ann M.

    1996-01-01

    The emergency response dose assessment system (ERDAS) is a protype software and hardware system configured to produce routine mesoscale meteorological forecasts and enhanced dispersion estimates on an operational basis for the Kennedy Space Center (KSC)/Cape Canaveral Air Station (CCAS) region. ERDAS provides emergency response guidance to operations at KSC/CCAS in the case of an accidental hazardous material release or an aborted vehicle launch. This report describes the evaluation of ERDAS including: evaluation of sea breeze predictions, comparison of launch plume location and concentration predictions, case study of a toxic release, evaluation of model sensitivity to varying input parameters, evaluation of the user interface, assessment of ERDA's operational capabilities, and a comparison of ERDAS models to the ocean breeze dry gultch diffusion model.

  1. Simultaneous Two-Vessel Subacute Stent Thrombosis Caused by Clopidogrel Resistance from CYP2C19 Polymorphism

    PubMed Central

    Patel, Bimal; Patel, Neel; Sattur, Sudhakar; Patel, Vinod

    2016-01-01

    Clopidogrel resistance from CYP2C19 polymorphism has been associated with stent thrombosis in patients undergoing percutaneous coronary intervention with drug-eluting stents. We present a case of a 76-year-old male who received drug-eluting stents to the right coronary artery and left anterior descending artery for non-ST elevation myocardial infarction and was discharged on dual antiplatelet therapy with aspirin and clopidogrel. He subsequently presented with chest pain from anterior, anteroseptal, and inferior ST segment elevation myocardial infarction. An emergent coronary angiogram revealed acute stent thrombosis with 100% occlusion of RCA and LAD that was successfully treated with thrombus aspiration and angioplasty. Although he was compliant with his dual antiplatelet therapy, he developed stent thrombosis, which was confirmed as clopidogrel resistance from homozygous CYP2C19 polymorphism. PMID:27555873

  2. Lower mortality following pulmonary adverse events and sepsis with ticagrelor compared to clopidogrel in the PLATO study.

    PubMed

    Storey, Robert F; James, Stefan K; Siegbahn, Agneta; Varenhorst, Christoph; Held, Claes; Ycas, Joseph; Husted, Steen E; Cannon, Christopher P; Becker, Richard C; Steg, Ph Gabriel; Åsenblad, Nils; Wallentin, Lars

    2014-01-01

    In the PLATelet inhibition and patient Outcomes (PLATO) study of patients with acute coronary syndromes, ticagrelor reduced mortality compared to clopidogrel but the mechanisms for this mortality reduction remain uncertain. We analysed adverse events (AEs) consistent with either pulmonary infection or sepsis, and subsequent mortality, in 18,421 PLATO patients treated with ticagrelor or clopidogrel. AEs occurring within 7 days of last dose of study medication were defined as "on-treatment". Serial measurements of blood leukocyte counts, C-reactive protein and interleukin-6 were performed. Fewer on-treatment pulmonary AEs occurred in the ticagrelor compared to the clopidogrel group (275 vs. 331 respectively; p = 0.019), with fewer deaths following these AEs (33 vs. 71; p < 0.001), particularly in those who remained on study medication three days after AE onset (10 vs. 43; p < 0.001). There were fewer deaths attributed to sepsis in the ticagrelor group (7 vs. 23; p = 0.003). Leukocyte counts were lower in the clopidogrel group during treatment (p < 0.0001 at 1, 3 and 6 months) but not at 1 month post-discontinuation. C-reactive protein increased more at discharge in the ticagrelor group (28.0 ± 38.0 vs. 26.1 ± 36.6 mg/l; p < 0.001) and interleukin-6 remained higher during the first month of treatment with ticagrelor. We conclude that the mortality risk following pulmonary AEs and sepsis in acute coronary syndrome patients appears to be lower during ticagrelor compared to clopidogrel therapy. Further work should assess whether ticagrelor and clopidogrel have differential effects on immune signalling.

  3. Cytochromes P450 catalyze both steps of the major pathway of clopidogrel bioactivation, whereas paraoxonase catalyzes the formation of a minor thiol metabolite isomer.

    PubMed

    Dansette, Patrick M; Rosi, Julien; Bertho, Gildas; Mansuy, Daniel

    2012-02-20

    The mechanism generally admitted for the bioactivation of the antithrombotic prodrug, clopidogrel, is its two-step enzymatic conversion into a biologically active thiol metabolite. The first step is a classical cytochrome P450 (P450)-dependent monooxygenation of its thiophene ring leading to 2-oxo-clopidogrel, a thiolactone metabolite. The second step was described as a P450-dependent oxidative opening of the thiolactone ring of 2-oxo-clopidogrel, with intermediate formation of a reactive sulfenic acid metabolite that is eventually reduced to the corresponding thiol 4b. A very recent paper published in Nat. Med. (Bouman et al., (2011) 17, 110) reported that the second step of clopidogrel bioactivation was not catalyzed by P450 enzymes but by paraoxonase-1(PON-1) and that PON-1 was a major determinant of clopidogrel efficacy. The results described in the present article show that there are two metabolic pathways for the opening of the thiolactone ring of 2-oxo-clopidogrel. The major one, that was previously described, results from a P450-dependent redox bioactivation of 2-oxo-clopidogrel and leads to 4b cis, two previously reported thiol diastereomers bearing an exocyclic double bond. The second, minor one, results from a hydrolysis of 2-oxo-clopidogrel, which seems to be dependent on PON-1, and leads to an isomer of 4b cis, 4b "endo", in which the double bond has migrated from an exocyclic to an endocyclic position in the piperidine ring. These results were obtained from a detailed study of the metabolism of 2-oxo-clopidogrel by human liver microsomes and human sera and analysis by HPLC-MS under conditions allowing a complete separation of the thiol metabolite isomers, either as such or after derivatization with 3'-methoxy phenacyl bromide or N-ethyl maleimide (NEM). These results also show that the major bioactive thiol isomer found in the plasma of clopidogrel-treated patients derives from 2-oxo-clopidogrel by the P450-dependent pathway. Finally, chemical

  4. Student Evaluation of Audience Response Technology in Large Lecture Classes

    ERIC Educational Resources Information Center

    MacGeorge, Erina L.; Homan, Scott R.; Dunning, John B., Jr.; Elmore, David; Bodie, Graham D.; Evans, Ed; Khichadia, Sangeetha; Lichti, Steven M.; Feng, Bo; Geddes, Brian

    2008-01-01

    In the past few years, audience response technology (ART) has been widely adopted on college campuses, and is especially popular among instructors of large lecture classes. Claims regarding ART's benefits to students have received only limited empirical evaluation, and prior studies exhibit methodological limitations. The current study provides a…

  5. Notification: OIG Evaluation of EPA's Response to Erroneous Laboratory Data

    EPA Pesticide Factsheets

    Project #OPE-FY12-0023, August 14, 2012. The purpose of this memorandum is to notify you that the Office of Inspector General (OIG) plans to begin preliminary.research on an evaluation of EPA's response to erroneous laboratory data.

  6. An Evaluation of Response Prompts for Teaching Behavior Chains

    ERIC Educational Resources Information Center

    Seaver, Jessica L.; Bourret, Jason C.

    2014-01-01

    Individuals who have been diagnosed with autism spectrum disorders can have difficulty acquiring new skills, and teaching procedures found to be efficient with 1 individual may not be efficient with others. However, relatively little research has evaluated methods to identify efficient, individualized response-prompt and prompt-fading procedures.…

  7. Evaluating Item Fit for Multidimensional Item Response Models

    ERIC Educational Resources Information Center

    Zhang, Bo; Stone, Clement A.

    2008-01-01

    This research examines the utility of the s-x[superscript 2] statistic proposed by Orlando and Thissen (2000) in evaluating item fit for multidimensional item response models. Monte Carlo simulation was conducted to investigate both the Type I error and statistical power of this fit statistic in analyzing two kinds of multidimensional test…

  8. Evaluating the Response of the Terrestrial Biosphere to Significant Drought

    NASA Astrophysics Data System (ADS)

    Shiach, I.; Baker, I. T.; Denning, A.

    2011-12-01

    The response of terrestrial fluxes of energy, water, and carbon to drought is evaluated. Major droughts should be clearly evident in reanalyzed precipitation data, although this is not always the case. With reduced precipitation we can expect a suppression in Gross Primary Photosynthesis (GPP) if physiological stress is sufficient, with atttendant changes in energy partitioning due to stomatal closure. There may also be a response in respiratory release of CO2 with temperature increase. This study aimed to investigate the behavior of the terrestrial biosphere using the Simple Biosphere Model (SiB3) during and following times of drought and to identify any model responses inconsistent with observational relationships. The Standardized Precipitation Index (SPI) was evaluated from 1983 to 2006 in order to evaluate historical drought maps, and to facilitate a qualitative analysis of modeled drought behavior. Standardized and raw anomaly maps were produced for modeled physiological variables (GPP, transpiration, respiration, heat fluxes, carbon flux, and stress factors) in order to determine general response patterns for comparison with observations. The SiB model was determined to be generally accurate in its representation of significant drought, with regard to perturbations in Bowen ratio, GPP, and CO2 respiration. However, model response was heterogeneous, and did not always respond in a manner consistent with published descriptions of drought.

  9. Cost-effectiveness of ticagrelor versus clopidogrel in patients with acute coronary syndromes in Canada

    PubMed Central

    Grima, Daniel T; Brown, Stephen T; Kamboj, Laveena; Bainey, Kevin R; Goeree, Ron; Oh, Paul; Ramanathan, Krishnan; Goodman, Shaun G

    2014-01-01

    Background Ticagrelor demonstrated a significant reduction in major cardiac events in patients with acute coronary syndrome (ACS) compared with clopidogrel in the Platelet Inhibition and Patient Outcomes (PLATO) trial. The objective of this study was to assess the cost-effectiveness of ticagrelor compared with clopidogrel in ACS patients from the perspective of the Canadian publicly funded health care system. Methods A two-part model was developed consisting of a 1-year decision tree and a lifetime Markov model. Within the decision tree, patients remained event-free, experienced a nonfatal myocardial infarction, a nonfatal stroke, or death due to vascular or nonvascular related causes based on data from the PLATO trial. The lifetime Markov model followed these patients and allowed for subsequent myocardial infarction, stroke, and death. Patient utility and resource use were derived from the PLATO trial. Transition probabilities and specific Canadian unit costs were derived from published sources. Univariate and probabilistic sensitivity analyses were conducted. Results In the base case lifetime analysis, treatment with ticagrelor resulted in more years of life per person (0.097), more quality-adjusted life years per person (QALYs, 0.084), and an incremental cost per QALY gained of $9,745 (Canadian$), assuming a generic cost for clopidogrel. A probabilistic sensitivity analysis demonstrated the robustness of the base case analysis, with a 93% probability of being below $20,000 per QALY gained and a 99% probability of being below $30,000 per QALY gained. Conclusion Ticagrelor is a clinically superior and cost-effective option for the prevention of thrombotic events among ACS patients in Canada. PMID:24493930

  10. Moral Knowledge and Responsibilities in Evaluation Implementation: When Critical Theory and Responsive Evaluation Collide

    ERIC Educational Resources Information Center

    Freeman, Melissa; Preissle, Judith; Havick, Steven

    2010-01-01

    An external evaluation documented what occurred in an inaugural summer camp to teach high school students how to preserve religious freedom by learning about and acting on the history and current state of church-state separation and other first amendment issues. Camp designers hoped to promote religious diversity values and civic engagement in…

  11. Comparison of modified Thrombelastograph and Plateletworks whole blood assays to optical platelet aggregation for monitoring reversal of clopidogrel inhibition in elective surgery patients.

    PubMed

    Craft, Robert M; Chavez, Jack J; Snider, Carolyn C; Muenchen, Robert A; Carroll, Roger C

    2005-06-01

    Clinically monitoring recovery from clopidogrel and nonsteroidal anti-inflammatory drug (NSAID) inhibition requires whole blood assays corresponding to a standard methodology such as platelet-rich plasma aggregation monitored optically (OPA). We compared OPA, using an ED 50 dose of adenosine diphosphate activation, with 2 whole blood assays, Plateletworks (PWA) and modified Thrombelastograph (TEG). Two sets of assays were performed on 43 surgery patients while on clopidogrel and off clopidogrel to determine the reversal of absolute and relative inhibition. The modified TEG had Spearman correlations with OPA for absolute (rho = .424; P = .006) and relative inhibition (rho = .742; P < .0001). PWA correlations with OPA gave absolute (rho = .28; P = .08) and relative inhibition (rho = .46; P = .004) values. Bland-Altman analysis indicated agreement of both tests with OPA, showing constant biases of about 18% and some dependency on mean magnitude error. Cohen effect size thresholds defined nonresponders as < 7.7% clopidogrel inhibition relative to baseline recovery of full platelet function. Apparent nonresponse to clopidogrel or lack of platelet recovery did not correlate with statin or NSAID therapies. These PWA and modified TEG whole blood assays could prove useful for monitoring the reversal of clopidogrel and NSAID inhibition before surgery. More important, these assays done at baseline and after beginning clopidogrel therapy could monitor the effectiveness for the individual patients with cardiovascular disease and help identify the need for alternative therapies.

  12. Evaluation of Piloted Inputs for Onboard Frequency Response Estimation

    NASA Technical Reports Server (NTRS)

    Grauer, Jared A.; Martos, Borja

    2013-01-01

    Frequency response estimation results are presented using piloted inputs and a real-time estimation method recently developed for multisine inputs. A nonlinear simulation of the F-16 and a Piper Saratoga research aircraft were subjected to different piloted test inputs while the short period stabilator/elevator to pitch rate frequency response was estimated. Results show that the method can produce accurate results using wide-band piloted inputs instead of multisines. A new metric is introduced for evaluating which data points to include in the analysis and recommendations are provided for applying this method with piloted inputs.

  13. Effects of the short-term application of pantoprazole combined with aspirin and clopidogrel in the treatment of acute STEMI

    PubMed Central

    Wei, Peng; Zhang, Yi-Gang; Ling, Lin; Tao, Zi-Qi; Ji, Li-Ya; Bai, Jie; Zong, Bin; Jiang, Chun-Ying; Zhang, Qian; Fu, Qiang; Yang, Xiang-Jun

    2016-01-01

    The aim of the present study was to determine the effects of the short-term application of pantoprazole on the co-treatment of acute ST-segment elevation myocardial infarction (STEMI) with aspirin and clopidogrel. A total of 207 acute patients showing primary symptoms of STEMI, who received successful emergent percutaneous coronary intervention treatment during hospitalization were randomly divided into two groups. In the test group proton pump inhibitors (PPIs), the patients were treated with a combination of aspirin and clopidogrel and pantoprazole, while those in the control group were treated only with aspirin and clopidogrel. Gastrointestinal bleeding events and major adverse cardiac events (MACEs) were observed in the two groups. Gastrointestinal bleeding events of the two groups mostly occurred within the first week of hospitalization, although the incidence in the PPIs group was significantly higher than that in the control group (p<0.05). However, no significant difference was observed for the incidence of MACEs between the two groups (p>0.05). In conclusion, the results of the present study have shown that the short-term application of pantoprazole combined with aspirin and clopidogrel does not increase the incidence of MACEs in patients with acute STEMI, reduces the risk of gastrointestinal bleeding, and is thus worth promoting clinically, particularly for high-risk groups. PMID:27882086

  14. Routine Screening for CYP2C19 Polymorphisms for Patients being Treated with Clopidogrel is not Recommended

    PubMed Central

    Hong, Robert A; Khan, Zia R; Valentin, Mona R; Badawi, Ramy A

    2015-01-01

    Recent efforts directed at potential litigation in Hawai‘i have resulted in a renewed interest for genetic screening for cytochrome P450 2C19 (CYP2C19) polymorphisms in patients treated with clopidogrel. Clopidogrel is an antiplatelet agent, frequently used in combination with aspirin, for the prevention of thrombotic complications with acute coronary syndrome and in patients undergoing percutaneous coronary interventions. Cytochrome P-450 (CYP) 2C19 is an enzyme involved in the bioactivation of clopidogrel from a pro-drug to an active inhibitor of platelet action. Patients of Asian and Pacific Island background have been reported to have an increase in CYP2C19 polymorphisms associated with loss-of-function of this enzyme when compared to other ethnicities. This has created an interest in genetic testing for CYP2C19 polymorphisms in Hawai‘i. Based upon our review of the current literature, we do not feel that there is support for the routine screening for CYP2C19 polymorphisms in patients being treated with clopidogrel; furthermore, the results of genetic testing may not be helpful in guiding therapeutic decisions. We recommend that decisions on the type of antiplatelet treatment be made based upon clinical evidence of potential differential outcomes associated with the use of these agents rather than on the basis of genetic testing. PMID:25628978

  15. Therapy response evaluation with positron emission tomography-computed tomography.

    PubMed

    Segall, George M

    2010-12-01

    Positron emission tomography-computed tomography with F-18-fluorodeoxyglucose is widely used for evaluation of therapy response in patients with solid tumors but has not been as readily adopted in clinical trials because of the variability of acquisition and processing protocols and the absence of universal response criteria. Criteria proposed for clinical trials are difficult to apply in clinical practice, and gestalt impression is probably accurate in individual patients, especially with respect to the presence of progressive disease and complete response. Semiquantitative methods of determining tissue glucose metabolism, such as standard uptake value, can be a useful descriptor for levels of tissue glucose metabolism and changes in response to therapy if technical quality control measures are carefully maintained. The terms partial response, complete response, and progressive disease are best used in clinical trials in which the terms have specific meanings and precise definitions. In clinical practice, it may be better to use descriptive terminology agreed upon by imaging physicians and clinicians in their own practice.

  16. Development of Metrics to Evaluate Effectiveness of Emergency Response Operations

    DTIC Science & Technology

    2005-06-01

    00-00-2005 4. TITLE AND SUBTITLE Development of Metrics to Evaluate Efectiveness of Emergency Response Operations 5a. CONTRACT NUMBER 5b. GRANT...population and/or property. Furthermore, the disaster will be characterized as being large enough that the resources the community has to mitigate the...disaster are stretched beyond the limits of their capacity. Such events that a community can readily cope with, such as small fires, individual

  17. Building an Evaluation Scale using Item Response Theory

    PubMed Central

    Lalor, John P.; Wu, Hao; Yu, Hong

    2016-01-01

    Evaluation of NLP methods requires testing against a previously vetted gold-standard test set and reporting standard metrics (accuracy/precision/recall/F1). The current assumption is that all items in a given test set are equal with regards to difficulty and discriminating power. We propose Item Response Theory (IRT) from psychometrics as an alternative means for gold-standard test-set generation and NLP system evaluation. IRT is able to describe characteristics of individual items - their difficulty and discriminating power - and can account for these characteristics in its estimation of human intelligence or ability for an NLP task. In this paper, we demonstrate IRT by generating a gold-standard test set for Recognizing Textual Entailment. By collecting a large number of human responses and fitting our IRT model, we show that our IRT model compares NLP systems with the performance in a human population and is able to provide more insight into system performance than standard evaluation metrics. We show that a high accuracy score does not always imply a high IRT score, which depends on the item characteristics and the response pattern.1 PMID:28004039

  18. Characterization of dyspnoea in PLATO study patients treated with ticagrelor or clopidogrel and its association with clinical outcomes.

    PubMed

    Storey, Robert F; Becker, Richard C; Harrington, Robert A; Husted, Steen; James, Stefan K; Cools, Frank; Steg, Philippe Gabriel; Khurmi, Nardev S; Emanuelsson, Håkan; Cooper, Anna; Cairns, Richard; Cannon, Christopher P; Wallentin, Lars

    2011-12-01

    AIMS To describe the incidence of dyspnoea and its associations with demographic characteristics and clinical outcomes in patients with acute coronary syndromes (ACS) treated with ticagrelor or clopidogrel in the PLATelet inhibition and patient Outcomes (PLATO) study. METHODS AND RESULTS In the PLATO study, 18 624 patients were randomized to receive either clopidogrel [300-600 mg loading dose (LD), 75 mg daily] or ticagrelor (180 mg LD, 90 mg b.i.d.). The occurrence of reported dyspnoea adverse events (AEs) was analysed in the 18 421 patients who received at least one dose of study medication in relation to demographic characteristics, clinical outcomes and other associations of patients with and without dyspnoea. A total of 1339 ticagrelor-treated patients (14.5%) and 798 clopidogrel-treated patients (8.7%) had a dyspnoea AE following randomization, with respectively 39 (0.4%) and 24 (0.3%) classified as severe in intensity. Excluding dyspnoea AEs occurring after the secondary endpoint of myocardial infarction (MI), the yearly rates of the efficacy endpoints in dyspnoea AE patients in the ticagrelor and clopidogrel groups were: for the primary composite of CV death, MI, and stroke, 8.8 and 10.4% (unadjusted P = 0.25; adjusted P = 0.54); for CV death, 3.1 and 4.8% (unadjusted P = 0.024; adjusted P = 0.18); and for total death 3.7 and 6.2% (unadjusted P = 0.004; adjusted P = 0.06), respectively. CONCLUSIONS Ticagrelor-related dyspnoea is usually mild or moderate in intensity and does not appear to be associated with differences concerning any efficacy or safety outcomes with ticagrelor compared with clopidogrel therapy in ACS patients.

  19. Cancer Education Program Evaluation: A Responsive Approach to Planning an Evaluation and Initial Results.

    ERIC Educational Resources Information Center

    Pearsol, James A.

    This paper describes evaluation planning for the Cancer Education Program (CEP) at Ohio State University (OSU). The three-year OSU CEP project was designed as a multidisciplinary cancer education program. A responsive method, which trades off some measurement precision in order to increase the usefulness of the findings, was employed in the…

  20. Clopidogrel, prasugrel, ticagrelor or vorapaxar in patients with renal impairment: do we have a winner?

    PubMed

    Serebruany, Victor L; Tomek, Ales; Pokov, Alex N; Kim, Moo Hyun

    2015-12-01

    The optimal utilization of antiplatelet therapy in patients with renal impairment (RI) following acute coronary syndromes (ACS) represents an urgent, unmet and yet unsolved need with regards to the choice of agents, duration of treatment and potential dose/regimen adjustment. The lack of any large randomized trials designed and powered specifically in such high-risk patients, absence of the uniformed efficacy and safety data reporting policy to the FDA and endless overoptimistic publications based on post hoc analyses of primary trials sometimes exaggerating benefits and hiding risks, clouds reality. In addition, triaging RI patients is problematic due to ongoing kidney deterioration and the fact that such patients are prone to both vascular occlusions and bleeding. The authors summarize available FDA-confirmed evidence from the latest trials with approved antiplatelet agents, namely clopidogrel (CAPRIE, CURE, CREDO, CLARITY, CHARISMA); prasugrel (TRITON, TRILOGY); ticagrelor (PLATO, and PEGASUS); and vorapaxar (TRACER and TRA2P) in RI patient cohorts on top of aspirin as part of dual antiplatelet therapy (DAPT). We deliberately avoided any results unless they were verified by the FDA, with the exception of the recent PEGASUS, since Agency reviews are not yet available. Despite differences among the trials and DAPT choices, RI patients universally experience much higher (HR = 1.3-3.1) rates of primary endpoint events, and bleeding risks (HR = 1.7-3.6). However, only ticagrelor increases creatinine and uric acid levels above that of clopidogrel; has the worst incidence of serious adverse events, more adverse events, and inferior outcomes in patients with severe (eGFR <30 ml/min), especially in the lowest (eGFR <15 ml/min) RI subsets. Clopidogrel, prasugrel and vorapaxar appear safer. Moreover, less aggressive half dose (5 mg/daily) prasugrel and strict DAPT, are well justified in RI, but not predominantly triple strategies with vorapaxar as tested in TRA2P and

  1. Incidence of cardiovascular events and gastrointestinal bleeding in patients receiving clopidogrel with and without proton pump inhibitors: an updated meta-analysis

    PubMed Central

    Cardoso, Rhanderson N; Benjo, Alexandre M; DiNicolantonio, James J; Garcia, Daniel C; Macedo, Francisco Y B; El-Hayek, Georges; Nadkarni, Girish N; Gili, Sebastiano; Iannaccone, Mario; Konstantinidis, Ioannis; Reilly, John P

    2015-01-01

    Background Dual antiplatelet therapy is the standard of care after coronary stent placement but increases the bleeding risk. The effects of proton pump inhibitors (PPIs) on clopidogrel metabolism have been described, but the clinical significance is not yet definitive. We aimed to do an updated meta-analysis comparing outcomes in patients receiving clopidogrel with and without PPIs. Methods We systematically searched PubMed, Scopus and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCTs) and controlled observational studies in patients taking clopidogrel stratified by concomitant PPI use. Heterogeneity was examined with the Cochran Q test and I2 statistics; p values inferior to 0.10 and I2 >25% were considered significant for heterogeneity. Results We included 39 studies with a total of 214 851 patients, of whom 73 731 (34.3%) received the combination of clopidogrel and a PPI. In pooled analysis, all-cause mortality, myocardial infarction, stent thrombosis and cerebrovascular accidents were more common in patients receiving both drugs. However, among 23 552 patients from eight RCTs and propensity-matched studies, there were no significant differences in mortality or ischaemic events between groups. The use of PPIs in patients taking clopidogrel was associated with a significant reduction in the risk of gastrointestinal bleeding. Conclusions The results of our meta-analysis suggest that PPIs are a marker of increased cardiovascular risk in patients taking clopidogrel, rather than a direct cause of worse outcomes. The pharmacodynamic interaction between PPIs and clopidogrel most likely has no clinical significance. Furthermore, PPIs have the potential to decrease gastrointestinal bleeding in clopidogrel users. PMID:26196021

  2. Probability effects on stimulus evaluation and response processes

    NASA Technical Reports Server (NTRS)

    Gehring, W. J.; Gratton, G.; Coles, M. G.; Donchin, E.

    1992-01-01

    This study investigated the effects of probability information on response preparation and stimulus evaluation. Eight subjects responded with one hand to the target letter H and with the other to the target letter S. The target letter was surrounded by noise letters that were either the same as or different from the target letter. In 2 conditions, the targets were preceded by a warning stimulus unrelated to the target letter. In 2 other conditions, a warning letter predicted that the same letter or the opposite letter would appear as the imperative stimulus with .80 probability. Correct reaction times were faster and error rates were lower when imperative stimuli confirmed the predictions of the warning stimulus. Probability information affected (a) the preparation of motor responses during the foreperiod, (b) the development of expectancies for a particular target letter, and (c) a process sensitive to the identities of letter stimuli but not to their locations.

  3. Occurrence, causes, and outcome after switching from ticagrelor to clopidogrel in a real-life scenario: data from a prospective registry.

    PubMed

    Biscaglia, Simone; Campo, Gianluca; Pavasini, Rita; Tebaldi, Matteo; Tumscitz, Carlo; Ferrari, Roberto

    2016-07-01

    In randomized clinical trials, ticagrelor has been substituted in roughly one-third of the patients during follow-up. To date, there are no studies addressing safety and modalities of switching from ticagrelor to clopidogrel. The aim of our study is to describe the occurrence, causes, and outcome of the switch from ticagrelor to clopidogrel in a real-life scenario. From June 2013 to March 2015, 586 patients were treated with ticagrelor in our centre. Overall, 101 (17%) patients were switched to clopidogrel through a standardized protocol, and they were followed-up for 12 months. Ischemic and bleeding events were prospectively recorded. The switch from ticagrelor to clopidogrel occurred mostly after discharge (69 ± 40 days), and the most frequent cause was the need of oral anticoagulation treatment, followed by bleeding events. Patients requiring ticagrelor discontinuation were older, more frequently female, with lower body mass index and creatinine clearance if compared to the "non-switched" group. In the 10 days after the switch, we did not observe ischemic adverse events. No definite/probable stent thrombosis was recorded. Before the switch, there was a significant higher occurrence of BARC bleedings in the "switched" group, particularly BARC 1 and 2. Our data confirm that the switch from ticagrelor to clopidogrel is common, and it occurs for several reasons. Our analysis did not demonstrate a significant increase in adverse cardiovascular events in the days following the switch from ticagrelor to clopidogrel, although larger studies are needed to validate our findings.

  4. Six Versus Twelve Months Clopidogrel Therapy After Drug-Eluting Stenting in Patients With Acute Coronary Syndrome: An ISAR-SAFE Study Subgroup Analysis.

    PubMed

    Lohaus, Raphaela; Michel, Jonathan; Mayer, Katharina; Lahmann, Anna Lena; Byrne, Robert A; Wolk, Annabelle; Ten Berg, Jurrien M; Neumann, Franz-Josef; Han, Yaling; Adriaenssens, Tom; Tölg, Ralph; Seyfarth, Melchior; Maeng, Michael; Zrenner, Bernhard; Jacobshagen, Claudius; Wöhrle, Jochen; Kufner, Sebastian; Morath, Tanja; Ibrahim, Tareq; Bernlochner, Isabell; Fischer, Marcus; Schunkert, Heribert; Laugwitz, Karl-Ludwig; Mehilli, Julinda; Kastrati, Adnan; Schulz-Schüpke, Stefanie

    2016-09-14

    In patients presenting with acute coronary syndrome (ACS) the optimal duration of dual-antiplatelet therapy after drug-eluting stent (DES) implantation remains unclear. At 6 months after intervention, patients receiving clopidogrel were randomly assigned to either a further 6-month period of placebo or clopidogrel. The primary composite endpoint was death, myocardial infarction, stent thrombosis, stroke, or major bleeding 9 months after randomization. The ISAR-SAFE trial was terminated early due to low event rates and slow recruitment. 1601/4000 (40.0%) patients presented with ACS and were randomized to 6 (n = 794) or 12 months (n = 807) clopidogrel. The primary endpoint occurred in 14 patients (1.8%) receiving 6 months of clopidogrel and 17 patients (2.2%) receiving 12 months; hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.41-1.68, P = 0.60. There were 2 (0.3%) cases of stent thrombosis in each group; HR 1.00, 95% CI 0.14-7.09, P = >0.99. Major bleeding occurred in 3 patients (0.4%) receiving 6 months clopidogrel and 5 (0.6%) receiving 12 months; HR 0.60, 95% CI 0.15-2.49, P = 0.49. There was no significant difference in net clinical outcomes after DES implantation in ACS patients treated with 6 versus 12 months clopidogrel. Ischaemic and bleeding events were low beyond 6-months.

  5. Clopidogrel Resistance by P2Y12 Platelet Function Testing in Patients Undergoing Neuroendovascular Procedures

    PubMed Central

    Nordeen, Jerah D.; Patel, Alden V.; Darracott, Robert M.; Johns, Gretchen S.; Taussky, Philipp; Tawk, Rabih G.; Miller, David A.; Freeman, William D.; Hanel, Ricardo A.

    2013-01-01

    Purpose: The purpose of the study was to assess clopidogrel resistance and whether “intensified” antiplatelet therapy guided by platelet inhibition tests during neuroendovascular procedures would reduce ischemic complications. Methods: We conducted a retrospective review of patients at Mayo Clinic in Jacksonville, Florida, who underwent neuroendovascular (NV) procedures and had P2Y12 platelet function testing from October 1, 2009, to September 30, 2010. The primary end-point was to determine P2Y12 resistance to antiplatelet therapy in patients who underwent NV procedures. Secondary objectives included incidence of hemorrhagic and ischemic events and a correlation between resistance and genetic CYP2C19 testing. Results: 160 patients underwent P2Y12 platelet function tests. Eighty-one patients (81/160, 50.6%) met inclusion criteria. Platelet function tests identified 64 patients (79%) as non-resistant (≥20% P2Y12 inhibition) and 17 (21%) as resistant (<20% inhibition) after initial clopidogrel loading. There was an increased rate of death when a complication occurred in the resistant group by 30 day (17% versus 3%; p=0.059) and 90 day follow-up (23% versus 4%; p=0.032). There was no significant association found between complication and loading dose (p=0.0721). Conclusions: 21% of patients undergoing NV procedures were resistant to clopidogrel. Intensifying antiplatelet therapy to achieve ≥20% inhibition on platelet function testing did not result in higher numbers of ischemic or hemorrhagic events, but there was a trend toward more death in the resistant group by 30 and 90 days of those experiencing complication(s). Author Justifications: Jerah D. Nordeen, Pharm.D.: Primary author Alden V. Patel, Pharm.D.: Contributor of professional content, study design Robert M. Darracott, Pharm.D.: Contributor of professional content, study design Gretchen S. Johns, M.D.: Contributor of professional content, study design Philipp Taussky, M.D.: Contributor of professional

  6. Clopidogrel-induced refractory thrombotic thrombocytopenic purpura successfully treated with rituximab.

    PubMed

    Khodor, Sara; Castro, Miguel; McNamara, Colin; Chaulagain, Chakra P

    2016-06-01

    Thrombotic thrombocytopenic purpura (TTP) is a multisystem disorder characterized by microvascular aggregation of platelets and fibrin strands causing thrombocytopenia, microangiopathic hemolytic anemia, and organ dysfunction. TTP can develop as a result of a deficiency in ADAMTS13 enzyme activity due to either a genetic defect or, more commonly, the development of anti-ADAMTS13 autoantibodies. TTP can also be associated with pregnancy, organ transplant, lupus, infections, and drugs. Here, we present a case of TTP that developed shortly after the start of clopidogrel treatment for acute ischemic stroke and acute myocardial infarction, and describe the clinical presentation, refractory course of the disease, and successful induction of remission through the use of rituximab in a setting of pre-existing autoimmune diseases.

  7. Neural attention and evaluative responses to gay and lesbian couples.

    PubMed

    Dickter, Cheryl L; Forestell, Catherine A; Mulder, Blakely E

    2015-01-01

    The goal of the current study was to examine whether differential neural attentional capture and evaluative responses for out-group homosexual relative to in-group heterosexual targets occur during social categorization. To this end, 36 heterosexual participants were presented with pictures of heterosexual and homosexual couples in a picture-viewing task that was designed to assess implicit levels of discomfort toward homosexuality and explicit evaluations of pleasantness toward the images. Neural activity in the form of electroencephalogram was recorded during the presentation of the pictures, and event-related potentials resulting from these stimuli were examined. Participants also completed questionnaires that assessed the degree to which they socialized with gays and lesbians. Results demonstrated that relative to straight couples, larger P2 amplitude was observed in response to gay but not to lesbian couples. However, both gay and lesbian couples yielded a larger late positive potential than straight couples. Moreover, the degree to which participants differentially directed early neural attention to out-group lesbian versus in-group straight couples was related to their familiarity with homosexual individuals. This work, which provides an initial understanding of the neural underpinnings of attention toward homosexual couples, suggests that differences in the processing of sexual orientation can occur as early as 200 ms and may be moderated by familiarity.

  8. Effects of omeprazole and genetic polymorphism of CYP2C19 on the clopidogrel active metabolite.

    PubMed

    Boulenc, Xavier; Djebli, Nassim; Shi, Juan; Perrin, Laurent; Brian, William; Van Horn, Robert; Hurbin, Fabrice

    2012-01-01

    Clopidogrel is an antiplatelet agent widely used in cardiovascular diseases and an inactive prodrug that needs to be converted to an active metabolite in two sequential metabolic steps. Several CYP450 isoforms involved in these two steps have been described, although the relative contribution in vivo of each enzyme is still under debate. CYP2C19 is considered to be the major contributor to active metabolite formation. In the current study, net CYP2C19 contribution to the active metabolite formation was determined from exposure of the active metabolite in two clinical studies (one phase I study with well balanced genetic polymorphic populations and a meta-analysis with a total of 396 healthy volunteers) at different clopidogrel doses. CYP2C19 involvements were estimated to be from 58 to 67% in intermediate metabolizers (IMs), from 58 to 72% in extensive metabolizers (EMs), and from 56 to 74% in ultrarapid metabolizers (UMs), depending on the study and the dose. For this purpose, a static model was proposed to estimate the net contribution of a given enzyme to the secondary metabolite formation. This static model was compared with a dynamic approach (Simcyp model) and showed good consistency. In parallel, in vitro investigations showed that omeprazole is a mechanism-based inhibitor of CYP2C19 with K(I) of 8.56 μM and K(inact) of 0.156 min(-1). These values were combined with the net CYP2C19 contribution to the active metabolite formation, through a static approach, to predict the inhibitory effect at 80-mg omeprazole doses in EM, IM, and UM CYP2C19 populations, with good consistency, compared with observed clinical values.

  9. Recombinant activated factor VII does not reduce bleeding in rabbits treated with aspirin and clopidogrel.

    PubMed

    Hindy-François, Clemence; Bachelot-Loza, Christilla; Le Bonniec, Bernard; Grelac, Francoise; Dizier, Blandine; Godier, Anne; Emmerich, Joseph; Gaussem, Pascale; Samama, Charles-Marc

    2010-10-01

    Combined antiplatelet agents (cAPA), aspirin plus clopidogrel, increase the risk of bleeding. We hypothesised that recombinant activated FVIIa (rFVIIa), which normalises thrombin generation in platelet-rich plasma from patients treated with cAPA, could limit this bleeding risk. It was the objective of this study to investigate the efficacy and safety of rFVIIa compared to placebo, in a bleeding and thrombosis model in rabbits treated with aspirin and clopidogrel. New-Zealand rabbits, randomised into two groups (Placebo1, n=36 ; cAPA, n=34), were anaesthetised, ventilated and monitored for blood pressure, temperature and carotid blood flow. The Folts model was applied to a carotid artery. Cyclic flow reductions (CFR) were recorded over a first 20-min period (Obs1). Each rabbit was then randomly assigned into one of three subgroups (Placebo2, 40μg/kg rFVIIa, 160 μg/kg rFVIIa) and CFR were monitored for a second 20-min period (Obs2). Ear bleeding time (BT) was measured at the end of each period. Hepatosplenic (HS) section was performed at the end of the experiment and HS blood loss defines the primary endpoint. Secondary endpoints were thrombosis (CFR), prothrombin time, platelet aggregation, and thrombin generation. Non- parametric statistical tests were used (p<0.05). cAPA significantly increased HS blood loss, BT and suppressed CFR compared to Placebo1 (p<0.05). rFVIIa injection did not modify HS blood loss, BT or CFR rate in Placebo1 rabbits nor in cAPA animals. These effects were unaffected by either rFVIIa dose. rFVIIa accelerated thrombin generation but had no effect on platelet aggregation in citrated platelet-rich plasma. rFVIIa did not modify HS blood loss associated with cAPA in rabbits.

  10. Evaluating Satiated Copepod Behavioral Responses to Thin Layer Flow Structure

    NASA Astrophysics Data System (ADS)

    True, Aaron C.; Webster, Donald R.; Weissburg, Marc J.; Yen, Jeannette

    2011-11-01

    Zooplankton exploit a variety of chemical and fluid mechanical cues in foraging, mate-seeking, and habitat partitioning contexts. To examine the influence of environmental cues on zooplankton aggregations in coastal marine thin layers, a laboratory thin layer mimic was built. The apparatus uses a laminar, planar jet (the Bickley jet) to produce ecologically-relevant layers of chemical (beneficial and harmful phytoplankton) and fluid mechanical (shear strain rate) cues for zooplankton behavioral assays. Particle image velocimetry (PIV) and laser-induced fluorescence (LIF) were employed to fully quantify the spatial structure of the chemical and fluid mechanical cues, ensuring a close match to in situ conditions and allowing for investigations into threshold cue levels responsible for inducing behavioral responses. Evaluating the effect of hunger level on behavioral responses is particularly important for producing accurate individual-based simulations of zooplankton population dynamics. Behavioral assays with the calanoid copepod Temora longicornis have produced digitized trajectories and, subsequently, path kinematics. Observed behaviors include increased turn frequency and decreased relative swimming speed, which result in increased residence time in the free jet shear layer. Cue-induced individual behaviors have the potential to produce population-scale aggregations.

  11. Critical Evaluation of Ayurvedic Plants for Stimulating Intrinsic Antioxidant Response

    PubMed Central

    Shukla, Sunil Dutt; Bhatnagar, Maheep; Khurana, Sukant

    2012-01-01

    Oxidative damage caused by free radicals plays an important role in the causation and progression of many diseases, including aging. Free-radical damage is countered by many mechanisms, including both active antioxidant enzymatic activity in our body and passive antioxidants. Antioxidant response of our body can accommodate increased oxidative damage in diseased states to a level but beyond that level, additional antioxidants are required to combat the increased stress. Apart from the regular dietary sources of antioxidants, many traditional herbal medicines demonstrate a potential to boost antioxidant activity. Rasayana chikitsa that deals with rejuvenation and revitalization is a branch of the Indian traditional medical system of ayurveda. We review some select herbs described in rasayana chikitsa that have been assessed by modern means for stimulating intrinsic antioxidant responses in humans. A critical evaluation of rasayana chikitsa will likely provide urgently needed, actual stimulants of our physiological antioxidant responses and not just more passive antioxidants to add to an already large catalog. PMID:22855669

  12. Clopidogrel (Plavix)

    MedlinePlus

    ... low dose aspirin along with one of these drugs. Side Effects Side effects of this medicine may include: Diarrhea Itching Nausea Skin rash Stomach ... There are a number of other possible side effects, depending on which drug you are prescribed. For example: Ticlopidine may lead ...

  13. Fear of negative evaluation modulates electrocortical and behavioral responses when anticipating social evaluative feedback

    PubMed Central

    Van der Molen, Melle J. W.; Poppelaars, Eefje S.; Van Hartingsveldt, Caroline T. A.; Harrewijn, Anita; Gunther Moor, Bregtje; Westenberg, P. Michiel

    2014-01-01

    Cognitive models posit that the fear of negative evaluation (FNE) is a hallmark feature of social anxiety. As such, individuals with high FNE may show biased information processing when faced with social evaluation. The aim of the current study was to examine the neural underpinnings of anticipating and processing social-evaluative feedback, and its correlates with FNE. We used a social judgment paradigm in which female participants (N = 31) were asked to indicate whether they believed to be socially accepted or rejected by their peers. Anticipatory attention was indexed by the stimulus preceding negativity (SPN), while the feedback-related negativity and P3 were used to index the processing of social-evaluative feedback. Results provided evidence of an optimism bias in social peer evaluation, as participants more often predicted to be socially accepted than rejected. Participants with high levels of FNE needed more time to provide their judgments about the social-evaluative outcome. While anticipating social-evaluative feedback, SPN amplitudes were larger for anticipated social acceptance than for social rejection feedback. Interestingly, the SPN during anticipated social acceptance was larger in participants with high levels of FNE. None of the feedback-related brain potentials correlated with the FNE. Together, the results provided evidence of biased information processing in individuals with high levels of FNE when anticipating (rather than processing) social-evaluative feedback. The delayed response times in high FNE individuals were interpreted to reflect augmented vigilance imposed by the upcoming social-evaluative threat. Possibly, the SPN constitutes a neural marker of this vigilance in females with higher FNE levels, particularly when anticipating social acceptance feedback. PMID:24478667

  14. Spectral response of the Viking lander camera: Preliminary evaluation

    NASA Technical Reports Server (NTRS)

    Kelly, W. L., IV; Huck, F. O.; Arvidson, R. E.

    1975-01-01

    One of the objectives of the Viking lander imaging investigation is to obtain color and near-infrared multispectral panoramas of the Martian surface using six spectral channels in the 0.4 to 1.1 microns wavelength range. This data can be compared with data obtained by imaging a reference test chart to construct approximate spectral reflectance curves that can then be matched to laboratory standards to aid in identifying surface materials. Some channels exhibit appreciable out-of-band spectral responses, making data reduction and interpretation difficult. A preliminary evaluation of predicted multispectral data for eight geological materials reveals that fairly good reflectance estimates can be made for those materials which have monotonically increasing or decreasing reflectances. Reflectance estimates for materials with more complex reflectances often do not reveal important spectral features and sometimes provide misleading results.

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

    PubMed Central

    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

    2017-01-01

    Objective: 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). Methods: 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. Results: 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 H0 to H5) according to the linkage disequilibrium R square (except for rs2046934). Haplotype H1 showed a significantly lower incidence of HTPR than the reference haplotype (H0) in the total study population while haplotypes H1 and H2 showed significantly lower incidences of HTPR than H0 in the nonsmoker subgroup after adjusting for CYP2C19 effects and demographic characteristics. rs2046934 (T744C) did not show any significant association with HTPR. Conclusions: 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. PMID:28070995

  16. Acute Coronary Syndromes, Gastrointestinal Protection, and Recommendations Regarding Concomitant Administration of Proton-Pump Inhibitors (Omeprazol/Esomeprazole) and Clopidogrel.

    PubMed

    Lozano, Iñigo; Sanchez-Insa, Esther; de Leiras, Sergio Rodríguez; Carrillo, Pilar; Ruiz-Quevedo, Valeriano; Pinar, Eduardo; Gopar-Gopar, Silvia; Bayon, Jeremías; Mañas, Pilar; Lasa, Garikoitz; CruzGonzalez, Ignacio; Hernandez, Felipe; Fernandez-Portales, Javier; Fernandez-Fernandez, Javier; Pérez-Serradilla, Ana; de la Torre Hernandez, José M; Gomez-Jaume, Alfredo

    2016-02-01

    The Food and Drug Administration and the European Medicines Agency sent a warning in 2010 discouraging the concomitant use of clopidogrel with omeprazole or esomeprazole. The purpose is to know the gastroprotective approach in patients with acute coronary syndrome (ACS) and the level of follow-up of the alert. In 17 hospitals with catheterization laboratory in Spain, 1 per region, we studied 25 consecutive patients per hospital whose diagnosis of discharge since October 1, 2013, had been any type of ACS. We analyzed their baseline clinical profile, the gatroprotective agents at admission and discharge and the antiplatelet therapy at discharge. The number of patients included was 425: age 67.2 ± 12.5 years, women 29.8%, diabetes 36.5%. The patients presented unstable angina in 21.6%, non-ST-elevation myocardial infarction in 35.3% and ST-elevation myocardial infarction in 43.1%. Conservative approach was chosen in 17.9%, bare-metal stents 32.2%, ≥ 1 drug-eluting stent 48.5%, and surgery 1.4%. Aspirin was indicated in 1.9%, aspirin + clopidogrel 73.6%, aspirin + prasugrel 17.6%, and aspririn + ticagrelor 6.8%. Gastroprotective agents were present in 40.2% patients at admission and this percentage increased to 93.7% at discharge. Of the 313 (73.6%) on clopidogrel in 96 (30.6%) was combined with omeprazole and 3 (0.95%) with esomeprazole, whereas the most commonly used was pantoprazole with 190 patients (44.7%). In conclusion, almost the totality of the patients with an ACS receive gastroprotective agents at the moment of discharge, most of them with proton-pump inhibitors. In one every 3 cases of the patients who are on clopidogrel, the recommendation of the Food and Drug Administration and the European Medicines Agency is not followed.

  17. Visible hyperspectral imaging evaluating the cutaneous response to ultraviolet radiation

    NASA Astrophysics Data System (ADS)

    Ilias, Michail A.; Häggblad, Erik; Anderson, Chris; Salerud, E. Göran

    2007-02-01

    In vivo diagnostics of skin diseases as well as understanding of the skin biology constitute a field demanding characterization of physiological and anatomical parameters. Biomedical optics has been successfully used, to qualitatively and quantitatively estimate the microcirculatory conditions of superficial skin. Capillaroscopy, laser Doppler techniques and spectroscopy, all elucidate different aspects of microcirculation, e.g. capillary anatomy and distribution, tissue perfusion and hemoglobin oxygenation. We demonstrate the use of a diffuse reflectance hyperspectral imaging system for spatial and temporal characterization of tissue oxygenation, important to skin viability. The system comprises: light source, liquid crystal tunable filter, camera objective, CCD camera, and the decomposition of the spectral signature into relative amounts of oxy- and deoxygenized hemoglobin as well as melanin in every pixel resulting in tissue chromophore images. To validate the system, we used a phototesting model, creating a graded inflammatory response of a known geometry, in order to evaluate the ability to register spatially resolved reflectance spectra. The obtained results demonstrate the possibility to describe the UV inflammatory response by calculating the change in tissue oxygen level, intimately connected to a tissue's metabolism. Preliminary results on the estimation of melanin content are also presented.

  18. Blue gum gaming machine: an evaluation of responsible gambling features.

    PubMed

    Blaszczynski, Alexander; Gainsbury, Sally; Karlov, Lisa

    2014-09-01

    Structural characteristics of gaming machines contribute to persistence in play and excessive losses. The purpose of this study was to evaluate the effectiveness of five proposed responsible gaming features: responsible gaming messages; a bank meter quarantining winnings until termination of play; alarm clock facilitating setting time-reminders; demo mode allowing play without money; and a charity donation feature where residual amounts can be donated rather than played to zero credits. A series of ten modified gaming machines were located in five Australian gambling venues. The sample comprised 300 patrons attending the venue and who played the gaming machines. Participants completed a structured interview eliciting gambling and socio-demographic data and information on their perceptions and experience of play on the index machines. Results showed that one-quarter of participants considered that these features would contribute to preventing recreational gamblers from developing problems. Just under half of the participants rated these effects to be at least moderate or significant. The promising results suggest that further refinements to several of these features could represent a modest but effective approach to minimising excessive gambling on gaming machines.

  19. Evaluating Melanoma Drug Response and Therapeutic Escape with Quantitative Proteomics*

    PubMed Central

    Rebecca, Vito W.; Wood, Elizabeth; Fedorenko, Inna V.; Paraiso, Kim H. T.; Haarberg, H. Eirik; Chen, Yi; Xiang, Yun; Sarnaik, Amod; Gibney, Geoffrey T.; Sondak, Vernon K.; Koomen, John M.; Smalley, Keiran S. M.

    2014-01-01

    The evolution of cancer therapy into complex regimens with multiple drugs requires novel approaches for the development and evaluation of companion biomarkers. Liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM) is a versatile platform for biomarker measurement. In this study, we describe the development and use of the LC-MRM platform to study the adaptive signaling responses of melanoma cells to inhibitors of HSP90 (XL888) and MEK (AZD6244). XL888 had good anti-tumor activity against NRAS mutant melanoma cell lines as well as BRAF mutant cells with acquired resistance to BRAF inhibitors both in vitro and in vivo. LC-MRM analysis showed HSP90 inhibition to be associated with decreased expression of multiple receptor tyrosine kinases, modules in the PI3K/AKT/mammalian target of rapamycin pathway, and the MAPK/CDK4 signaling axis in NRAS mutant melanoma cell lines and the inhibition of PI3K/AKT signaling in BRAF mutant melanoma xenografts with acquired vemurafenib resistance. The LC-MRM approach targeting more than 80 cancer signaling proteins was highly sensitive and could be applied to fine needle aspirates from xenografts and clinical melanoma specimens (using 50 μg of total protein). We further showed MEK inhibition to be associated with signaling through the NFκB and WNT signaling pathways, as well as increased receptor tyrosine kinase expression and activation. Validation studies identified PDGF receptor β signaling as a potential escape mechanism from MEK inhibition, which could be overcome through combined use of AZD6244 and the PDGF receptor inhibitor, crenolanib. Together, our studies show LC-MRM to have unique value as a platform for the systems level understanding of the molecular mechanisms of drug response and therapeutic escape. This work provides the proof-of-principle for the future development of LC-MRM assays for monitoring drug responses in the clinic. PMID:24760959

  20. Simultaneous quantitation of acetylsalicylic acid and clopidogrel along with their metabolites in human plasma using liquid chromatography tandem mass spectrometry.

    PubMed

    Chhonker, Yashpal S; Pandey, Chandra P; Chandasana, Hardik; Laxman, Tulsankar Sachin; Prasad, Yarra Durga; Narain, V S; Dikshit, Madhu; Bhatta, Rabi S

    2016-03-01

    The interest in therapeutic drug monitoring has increased over the last few years. Inter- and intra-patient variability in pharmacokinetics, plasma concentration related toxicity and success of therapy have stressed the need of frequent therapeutic drug monitoring of the drugs. A sensitive, selective and rapid liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous quantification of acetylsalicylic acid (aspirin), salicylic acid, clopidogrel and carboxylic acid metabolite of clopidogrel in human plasma. The chromatographic separations were achieved on Waters Symmetry Shield(TM) C18 column (150 × 4.6 mm, 5 µm) using 3.5 mm ammonium acetate (pH 3.5)-acetonitrile (10:90, v/v) as mobile phase at a flow rate of 0.75 mL/min. The present method was successfully applied for therapeutic drug monitoring of aspirin and clopidogrel in 67 patients with coronary artery disease.

  1. Clopidogrel pretreatment of patients with ST-elevation myocardial infarction does not affect platelet reactivity after subsequent prasugrel-loading: platelet reactivity in an observational study.

    PubMed

    Nührenberg, Thomas G; Trenk, Dietmar; Leggewie, Stefan; Ristau, Inga; Amann, Michael; Stratz, Christian; Hochholzer, Willibald; Valina, Christian M; Neumann, Franz-Josef

    2013-01-01

    Current guidelines recommend prasugrel or ticagrelor for patients undergoing percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI). Whereas available data support ticagrelor independent of pretreatment with clopidogrel, corresponding data for prasugrel are missing. Here, we investigated platelet reactivity after loading with prasugrel in clopidogrel-naïve vs. clopidogrel-pretreated patients. Forty-seven consecutive patients with STEMI referred for primary PCI were enrolled. Use of GPIIb/IIIa inhibitors and known contraindications to prasugrel served as exclusion criteria. A total of 31 patients were already treated with a loading dose of clopidogrel 600 mg by the emergency medical system before admission, while 16 patients were P2Y12 antagonist naïve. All patients received a loading dose of prasugrel 60 mg immediately before PCI. Adenosine diphosphate (ADP) induced platelet reactivity was determined by VerifyNow™ P2Y12 assay, by light transmission aggregometry (LTA) and by multiple electrode impedance aggregometry (MEIA; Multiplate™ analyser). No differences in platelet reactivity were observed at day 1 after PCI between the bolus-on-bolus treatment regimen and single prasugrel loading. Platelet reactivity was profoundly decreased to 10 [8-31] platelet reactivity unit (PRU; median [interquartile range]) in patients on clopidogrel + prasugrel vs. 9 [6-60] PRU in patients on prasugrel only (p = 0.916). Consistent results were obtained by LTA and MEIA. The proportion of patients reaching a MEIA associated with increased risk bleeding (<188 AU*min) was also similar between the two study groups. The level of platelet reactivity at day 1 after the 60 mg loading dose of prasugrel was independent of pretreatment with clopidogrel. Our results do not support withholding prasugrel in patients pretreated with clopidogrel who undergo PCI for STEMI.

  2. Impact of concomitant use of proton pump inhibitors and clopidogrel or ticagrelor on clinical outcomes in patients with acute coronary syndrome

    PubMed Central

    Yan, Yan; Wang, Xiao; Fan, Jing-Yao; Nie, Shao-Ping; Raposeiras-Roubín, Sergio; Abu-Assi, Emad; Henriques, Jose P Simao; D'Ascenzo, Fabrizio; Saucedo, Jorge; González-Juanatey, José R; Wilton, Stephen B; Kikkert, Wouter J; Nuñez-Gil, Iván; Ariza-Sole, Albert; Song, Xian-Tao; Alexopoulos, Dimitrios; Liebetrau, Christoph; Kawaji, Tetsuma; Moretti, Claudio; Huczek, Zenon; Fujii, Toshiharu; Correia, Luis C; Kawashiri, Masa-aki; Kedev, Sasko

    2016-01-01

    Background There is great debate on the possible adverse interaction between proton pump inhibitors (PPIs) and clopidogrel. In addition, whether the use of PPIs affects the clinical efficacy of ticagrelor remains less known. We aimed to determine the impact of concomitant administration of PPIs and clopidogrel or ticagrelor on clinical outcomes in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Methods We retrospectively analyzed data from a “real world”, international, multi-center registry between 2003 and 2014 (n = 15,401) and assessed the impact of concomitant administration of PPIs and clopidogrel or ticagrelor on 1-year composite primary endpoint (all-cause death, re-infarction, or severe bleeding) in patients with ACS after PCI. Results Of 9429 patients in the final cohort, 54.8% (n = 5165) was prescribed a PPI at discharge. Patients receiving a PPI were older, more often female, and were more likely to have comorbidities. No association was observed between PPI use and the primary endpoint for patients receiving clopidogrel (adjusted HR: 1.036; 95% CI: 0.903–1.189) or ticagrelor (adjusted HR: 2.320; 95% CI: 0.875–6.151) (Pinteraction = 0.2004). Similarly, use of a PPI was not associated with increased risk of all-cause death, re-infarction, or a decreased risk of severe bleeding for patients treated with either clopidogrel or ticagrelor. Conclusions In patients with ACS following PCI, concomitant use of PPIs was not associated with increased risk of adverse outcomes in patients receiving either clopidogrel or ticagrelor. Our findings indicate it is reasonable to use a PPI in combination with clopidogrel or ticagrelor, especially in patients with a higher risk of gastrointestinal bleeding. PMID:27103915

  3. What Do We Do Now That the Evaluation Is Over? Methods for Transitioning the Responsibility of Evaluation to Program Staff.

    ERIC Educational Resources Information Center

    Cassata, Jennifer Coyne; Siddens, Stephanie K.

    This paper describes the methods engaged in by an internal evaluation unit within a large school district to transition program staff from participating in a formal program evaluation to continuing the responsibility of program monitoring once an evaluation ends. Formal multiyear program evaluations can provide program managers and staff with…

  4. CYP2C19 loss-of-function alleles are not associated with clinical outcome of clopidogrel therapy in patients treated with newer-generation drug-eluting stents

    PubMed Central

    Choi, Ik Jun; Koh, Yoon-Seok; Park, Mahn-Won; Her, Sung Ho; Choi, Yun-Seok; Park, Chul-Soo; Park, Hun-Jun; Kim, Pum-Joon; Chung, Wook-Sung; Kim, Ho-Sook; Shin, Jae-Gook; Seung, Ki-Bae; Chang, Kiyuk

    2016-01-01

    Abstract CYP2C19 loss-of-function (LOF) alleles adversely affect clinical outcome of clopidogrel therapy. Recent introduction of a newer-generation drug-eluting stent (DES) has significantly reduced the occurrence of stent thrombosis. The aim of this study was to evaluate the impact of CYP2C19 LOF alleles on clinical outcome in patients treated with the newer-generation DES. The effects of CYP2C19 genotypes were evaluated on clinical outcome of clopidogrel therapy in 2062 patients treated with percutaneous coronary intervention using either first-generation DES (sirolimus- and paclitaxel-eluting stent, n = 1349) or newer-generation DES (everolimus- and zotarolimus-eluting stent, n = 713). The primary clinical outcome was major cardiac and cerebrovascular event (MACCE) including cardiac death, nonfatal myocardial infarction, stroke, and stent thrombosis during 1 year of follow-up. CYP2C19 LOF alleles were significantly associated with a higher risk of MACCE in patients treated with first-generation DES (hazard ratio [HR] 2.599, 95% confidence interval [CI] 1.047–6.453; P = 0.034). In contrast, CYP2C19 LOF alleles were not associated with primary outcome in newer-generation DES (HR 0.716, 95% CI 0.316–1.622; P = 0.522). In the further multivariate analysis, CYP2C19 LOF alleles were not associated with MACCE in patients receiving newer-generation DES (adjusted HR 0.540, 95% CI 0.226–1.291; P = 0.166), whereas they were demonstrated to be an independent risk factor for MACCE in those implanted with first-generation DES (adjusted HR 3.501, 95% CI 1.194–10.262; P = 0.022). In contradiction to their clinical impact in first-generation DES era, CYP2C19 LOF alleles may not affect clinical outcome of clopidogrel therapy in patients treated with newer-generation DES. PMID:27368038

  5. Defining hormesis: evaluation of a complex concentration response phenomenon.

    PubMed

    Kendig, Eric L; Le, Hoa H; Belcher, Scott M

    2010-01-01

    Hormesis describes dose-response relationships characterized by a reversal of response between low and high doses of chemicals, biological molecules, physical stressors, or other initiators of a response. Acceptance of hormesis as a viable dose-response theory has been limited until recently, in part, because of poor conceptual understanding, ad hoc and inappropriate use, and lack of a defined mechanism. By examining the history of this dose-response theory, it is clear that both pharmacological and toxicological studies provide evidence for hormetic dose responses, but retrospective examination of studies can be problematic at best. Limited scientific evidence and lack of a common lexicon with which to describe these responses have left hormesis open to inappropriate application to unrelated dose-response relationships. Future studies should examine low-dose effects using unbiased, descriptive criteria to further the scientific understanding of this dose response. A clear, concise definition is required to further the limited scientific evidence for hormetic dose responses.

  6. Development and validation of a liquid chromatographic method for purity control of clopidogrel-acetylsalicylic acid in combined oral dosage forms.

    PubMed

    Kahsay, Getu; Van Schepdael, Ann; Adams, Erwin

    2012-03-05

    A reversed phase liquid chromatographic method with UV detection for the simultaneous determination of clopidogrel and acetylsalicylic acid and their related substances in combined oral formulations was developed and validated. Good separation was achieved on a Luna C18 column (150 mm × 4.6 mm, 3 μm) using gradient elution at a flow rate of 1 mL/min and a column temperature of 35 °C. UV detection was performed at 220 nm. The validation was performed according to the ICH guidelines. The method proved to be specific, sensitive (LOQ=0.975 μg/mL and 0.0384 μg/mL for clopidogrel and acetylsalicylic acid, respectively), linear in the concentration range from LOQ to 325 μg/mL for clopidogrel and from LOQ to 650 μg/mL for acetylsalicylic acid, precise (RSD values for intermediate precision <1%) and accurate with mean recovery values of 100.7% and 100.2% for clopidogrel and acetylsalicylic acid, respectively. Moreover, the solution stability and method robustness were examined. The method gives satisfactory separation of impurities of clopidogrel and acetylsalicylic acid and so it is suitable for quantification of the related substances as well as for the assay of the actives.

  7. Molecular structure and vibrational spectroscopic analysis of an antiplatelet drug; clopidogrel hydrogen sulphate (form 2) - A combined experimental and quantum chemical approach

    NASA Astrophysics Data System (ADS)

    Srivastava, Anubha; Mishra, Soni; Tandon, Poonam; Patel, Sarasvatkumar; Ayala, A. P.; Bansal, A. K.; Siesler, H. W.

    2010-02-01

    Clopidogrel hydrogen sulphate which belongs to a class of medicine called antiplatelet drugs. Chemically it is methyl (+)-(S)-α-(2-chlorophenyl)-4,5,6,7-tetrahydrothieno [3,2- c] pyridine-5-acetate hydrogen sulphate having the empirical formula C 16H 17ClNO 2S.HSO 4 and molecular mass 321.82 g/mol. The present study is confined to vibrational spectroscopy of the polymorph identified as form 2 of the clopidogrel hydrogen sulphate. The vibrational analysis of clopidogrel hydrogen sulphate salt (form 2) considering separately the two counterions has been performed. We also report a theoretical and experimental study of the molecular conformation and vibrational dynamics of the independent moieties of the clopidogrel hydrogen sulphate salt. The equilibrium geometry, harmonic vibrational frequencies, infrared intensities and activities of Raman scattering were calculated by ab initio Hartree-Fock and density functional theory employing B3LYP with complete relaxation in the potential energy surface using 6-311++G(d,p) basis set. The calculated wavenumbers after a proper scaling show a very good agreement with the observed values. A complete vibrational assignment is provided for the observed Raman and infrared spectra of clopidogrel hydrogen sulphate form 2.

  8. Platelet-to-lymphocyte ratio but not neutrophil-to-lymphocyte ratio predicts high on-treatment platelet reactivity in clopidogrel-treated patients with acute coronary syndrome

    PubMed Central

    Efe, Edem; Kocayiğit, Ibrahim; Türker, Pabuccu Mustafa; Murat, Küçükukur; Erkan, Alpaslan; Sedat, Taş; Alper, Çil; Necati, Aksoy Murat; Gökhan, Vural Mustafa; Bahri, Akdeniz

    2016-01-01

    Objectives: Dual antiplatelet therapy (DAPT), consisting of clopidogrel and aspirin, is the main-stay treatment of acute coronary syndromes (ACS). However, major adverse cardiovascular events may occur even in patients undergoing DAPT, and this has been related to the variable pharmacodynamic efficacy of these drugs, especially clopidogrel. Platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) are novel inflammatory markers for cardiovascular risk stratification, which may reflect an inflammatory state and thus high on-treatment platelet reactivity (HPR). Methods: We investigated the usefulness of PLR and NLR in predicting HPR in clopidogrel-treated patients with ACS. A total of 244 patients were enrolled in this study, and 43 of them were nonresponsive to clopidogrel. Results: Logistic regression analysis indicated that PLR was significantly associated with HPR (P < 0.001). Using a cutoff level of 331, PLR predicted HPR with a sensitivity of 73% and a specificity of 69% (odds ratio: 376.15, 95% confidence interval = 37.813–3741.728 P < 0.001, receiver operating characteristic curve: 0.885). Conclusions: We suggest that more attention should be paid to the PLR values of these patients on admission to identify individuals who may not benefit from clopidogrel during the course of ACS. PMID:27756943

  9. A definition and ethical evaluation of overdiagnosis: response to commentaries.

    PubMed

    Carter, Stacy M; Doust, Jenny; Degeling, Chris; Barratt, Alexandra

    2016-08-29

    It is a privilege to have respected colleagues engage with our definition and ethical evaluation of overdiagnosis. In our response to the commentaries, we first deal with paradigmatic issues: the place of realism, the relationship between diagnostic standards and correctness and the distinction between overdiagnosis and both false-positives and medicalisation. We then discuss issues arising across the commentaries in turn. Our definition captures the range of different types of overdiagnosis, unlike a definition limited to diagnosis of harmless disease. Certain implications do flow from our definition, as noted by commentators, but we do not view them as problematic: overdiagnoses can become beneficial diagnoses as medical knowledge and practice changes over time; inadequate systems of healthcare can produce tragic overdiagnosis, and the effectiveness of treatment partly determines whether overdiagnosis occurs. Complexity and uncertainty in balancing benefits and harms is unfortunate, but not a reason to avoid making a judgement (ideally one that reflects multiple perspectives). We reaffirm that overdiagnosis, for the foreseeable future, must be estimated at a population level and defend the importance of good-quality risk communication for individuals. We acknowledge that a lot turns on the relevance of professional communities in our definition and expand our reasoning in this regard then conclude with a note on the difference between intentions and goals. We expect that it will be some time before these matters are settled and we look forward to continue debating these matters with our colleagues.

  10. Evaluations of indoor noise criteria systems based on human response

    NASA Astrophysics Data System (ADS)

    Bowden, Erica E.; Wang, Lily M.

    2005-09-01

    The goal of this research is to examine human response to background noise, and relate results to indoor noise criteria. In previous work by the authors, subjects completed perception surveys, typing tasks, and proofreading tasks under typical heating, ventilating, and air-conditioning (HVAC) noise conditions. Results were correlated with commonly used indoor noise criteria systems including noise criteria (NC), room criteria (RC) and others. The findings suggested that the types of tasks used and the length of exposure can impact the results. To examine these two issues, the authors conducted a new study in which each test subject completed 38 total hours of testing over multiple days. Subjects were exposed to several background noise exposures over 20, 40, 80, and 240 minute trials. During the trials, subjects completed a variety of performance tasks and answered questions about their perception of the noise, the thermal environment, and various other factors. Findings from this study were used to determine optimum testing conditions for on-going research examining the effects of tonal or fluctuating background noise on performance, annoyance, and spectral perception. Results are being used to evaluate the effectiveness of commonly used indoor noise criteria systems. [Work supported by INCE and ASHRAE.

  11. Evaluating Educational Programmes: The Need and the Response.

    ERIC Educational Resources Information Center

    Stake, Robert E.

    This survey of recent developments in educational program evaluation is intended for persons who commission, implement, direct, or carry out evaluation studies. The attitudes of government officials, educators, and researchers toward assessment and their own evaluation needs are discussed. Various approaches to evaluation are briefly described;…

  12. Will They Like Me? Adolescents' Emotional Responses to Peer Evaluation

    ERIC Educational Resources Information Center

    Guyer, Amanda E.; Caouette, Justin D.; Lee, Clinton C.; Ruiz, Sarah K.

    2014-01-01

    Relative to children and adults, adolescents are highly focused on being evaluated by peers. This increased attention to peer evaluation has implications for emotion regulation in adolescence, but little is known about the characteristics of the evaluatee and evaluator that influence emotional reactions to evaluative outcomes. The present study…

  13. Visualization and quantification of deformation behavior of clopidogrel bisulfate polymorphs during tableting

    NASA Astrophysics Data System (ADS)

    Yin, Xian-Zhen; Wu, Li; Li, Ying; Guo, Tao; Li, Hai-Yan; Xiao, Ti-Qiao; York, Peter; Nangia, Ashwini; Gui, Shuang-Ying; Zhang, Ji-Wen

    2016-02-01

    The deformation behavior of particles under pressure dominates the mechanical properties of solid dosage forms. In this study, the in situ 3D deformation of two polymorphs (I and II) of clopidogrel bisulfate (CLP) was determined to illustrate pressure distribution profiles within the tablet by the deformation of the crystalline particles for the first time. Synchrotron radiation X-ray computed microtomography (SR-μCT) was utilized to visualize and quantify the morphology of thousands crystalline particles of CLP I and CLP II before and after compression. As a result, the deformation was examined across scale dimensions from microns to the size of the final dosage form. Three dimensional parameters such as volume, sphericity, oblate and prolate of individual particle and distributions were computed and analyzed for quantitative comparison to CLP I and CLP II. The different degrees of deformation under the same compression conditions of CLP I and CLP II were observed and characterized quantitatively. The map of deformation degrees within the tablet illustrated the heterogeneous pressure distribution in various regions of the compacted tablet. In conclusion, the polymorph deformation behaviors demonstrated by SR-μCT quantitative structure analysis deepen understanding of tableting across dimensions from microns to millimeters for the macrostrcuture of tablet.

  14. Visualization and quantification of deformation behavior of clopidogrel bisulfate polymorphs during tableting

    PubMed Central

    Yin, Xian-Zhen; Wu, Li; Li, Ying; Guo, Tao; Li, Hai-Yan; Xiao, Ti-Qiao; York, Peter; Nangia, Ashwini; Gui, Shuang-Ying; Zhang, Ji-Wen

    2016-01-01

    The deformation behavior of particles under pressure dominates the mechanical properties of solid dosage forms. In this study, the in situ 3D deformation of two polymorphs (I and II) of clopidogrel bisulfate (CLP) was determined to illustrate pressure distribution profiles within the tablet by the deformation of the crystalline particles for the first time. Synchrotron radiation X-ray computed microtomography (SR-μCT) was utilized to visualize and quantify the morphology of thousands crystalline particles of CLP I and CLP II before and after compression. As a result, the deformation was examined across scale dimensions from microns to the size of the final dosage form. Three dimensional parameters such as volume, sphericity, oblate and prolate of individual particle and distributions were computed and analyzed for quantitative comparison to CLP I and CLP II. The different degrees of deformation under the same compression conditions of CLP I and CLP II were observed and characterized quantitatively. The map of deformation degrees within the tablet illustrated the heterogeneous pressure distribution in various regions of the compacted tablet. In conclusion, the polymorph deformation behaviors demonstrated by SR-μCT quantitative structure analysis deepen understanding of tableting across dimensions from microns to millimeters for the macrostrcuture of tablet. PMID:26911359

  15. Design and Development of Clopidogrel Bisulfate Gastroretentive Osmotic Formulation Using Quality by Design Tools.

    PubMed

    Desai, Nilesh; Purohit, Ravindra

    2017-02-28

    Clopidogrel bisulfate (CBS) is antiplatelet drug and it is becoming a drug of choice in the treatment and management of prevention of heart attacks and strokes. CBS is stable and soluble in acidic pH; therefore, retention in stomach for prolonged period appears to be beneficial for controlling the bioavailability. The gastroretentive osmotic system (GROS) facilitates prolonged retention of drug in stomach and provides zero-order drug release. A complex formulation like GROS poses many challenges, and QbD tools can help in designing robust formulation which takes all aspects of product and process development in order to deliver a robust product. The GROS was formulated in three steps: core tablet, osmotic tablet, and gastroretentive osmotic tablet. The design of experiment was used for screening and optimization of formulation and process-related parameters. The dissolution study was carried out to analyze the release pattern of tablet. The optimized batch O-4 showed cumulative drug release of 19.43, 30.49, 64.41, and 85.11% at 2, 4, 8, and 12 h which is in the range of QTPP predictions. The novel technique of GROS was implemented successfully which demonstrates robust design giving consistent and desired results.

  16. Visualization and quantification of deformation behavior of clopidogrel bisulfate polymorphs during tableting.

    PubMed

    Yin, Xian-Zhen; Wu, Li; Li, Ying; Guo, Tao; Li, Hai-Yan; Xiao, Ti-Qiao; York, Peter; Nangia, Ashwini; Gui, Shuang-Ying; Zhang, Ji-Wen

    2016-02-25

    The deformation behavior of particles under pressure dominates the mechanical properties of solid dosage forms. In this study, the in situ 3D deformation of two polymorphs (I and II) of clopidogrel bisulfate (CLP) was determined to illustrate pressure distribution profiles within the tablet by the deformation of the crystalline particles for the first time. Synchrotron radiation X-ray computed microtomography (SR-μCT) was utilized to visualize and quantify the morphology of thousands crystalline particles of CLP I and CLP II before and after compression. As a result, the deformation was examined across scale dimensions from microns to the size of the final dosage form. Three dimensional parameters such as volume, sphericity, oblate and prolate of individual particle and distributions were computed and analyzed for quantitative comparison to CLP I and CLP II. The different degrees of deformation under the same compression conditions of CLP I and CLP II were observed and characterized quantitatively. The map of deformation degrees within the tablet illustrated the heterogeneous pressure distribution in various regions of the compacted tablet. In conclusion, the polymorph deformation behaviors demonstrated by SR-μCT quantitative structure analysis deepen understanding of tableting across dimensions from microns to millimeters for the macrostrcuture of tablet.

  17. Monoclinic form I of clopidogrel hydrogen sulfate from powder diffraction data

    PubMed Central

    Chernyshev, Vladimir V.; Pirogov, Sergey V.; Shishkina, Irina N.; Velikodny, Yurii A.

    2010-01-01

    The asymmetric unit of the title compound, C16H17ClNO2S+·HSO4 −, (I) [systematic name: (+)-(S)-5-[(2-chloro­phen­yl)(meth­oxy­carbon­yl)meth­yl]-4,5,6,7-tetra­hydro­thieno[3,2-c]pyridin-5-ium hydrogen sulfate], contains two independent cations of clopidogrel and two independent hydrogensulfate anions. The two independent cations are of similar conformation; however, this differs from that observed in ortho­rhom­bic form (II) [Bousquet et al. (2003 ▶). US Patent No. 6 504 030]. The H—N—Cchiral—H fragment shows a trans conformation in both independent cations in (I) and a gauche conformation in (II). In (I), classical inter­molecular N—H⋯O and O—H⋯O hydrogen bonds link two independent cations and two independent anions into an isolated cluster, in which two cations inter­act with one anion only via N—H⋯O hydrogen bonds. Weak inter­molecular C—H⋯O hydrogen bonds further consolidate the crystal packing. PMID:21588394

  18. Diagnosis, risk stratification, and response evaluation in classical myeloproliferative neoplasms

    PubMed Central

    2017-01-01

    Philadelphia-negative classical myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The 2016 revision of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues includes new criteria for the diagnosis of these disorders. Somatic mutations in the 3 driver genes, that is, JAK2, CALR, and MPL, represent major diagnostic criteria in combination with hematologic and morphological abnormalities. PV is characterized by erythrocytosis with suppressed endogenous erythropoietin production, bone marrow panmyelosis, and JAK2 mutation. Thrombocytosis, bone marrow megakaryocytic proliferation, and presence of JAK2, CALR, or MPL mutation are the main diagnostic criteria for ET. PMF is characterized by bone marrow megakaryocytic proliferation, reticulin and/or collagen fibrosis, and presence of JAK2, CALR, or MPL mutation. Prefibrotic myelofibrosis represents an early phase of myelofibrosis, and is characterized by granulocytic/megakaryocytic proliferation and lack of reticulin fibrosis in the bone marrow. The genomic landscape of MPNs is more complex than initially thought and involves several mutant genes beyond the 3 drivers. Comutated, myeloid tumor-suppressor genes contribute to phenotypic variability, phenotypic shifts, and progression to more aggressive disorders. Patients with myeloid neoplasms are at variable risk of vascular complications, including arterial or venous thrombosis and bleeding. Current prognostic models are mainly based on clinical and hematologic parameters, but innovative models that include genetic data are being developed for both clinical and trial settings. In perspective, molecular profiling of MPNs might also allow for accurate evaluation and monitoring of response to innovative drugs that target the mutant clone. PMID:28028026

  19. Diagnosis, risk stratification, and response evaluation in classical myeloproliferative neoplasms.

    PubMed

    Rumi, Elisa; Cazzola, Mario

    2017-02-09

    Philadelphia-negative classical myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The 2016 revision of the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues includes new criteria for the diagnosis of these disorders. Somatic mutations in the 3 driver genes, that is, JAK2, CALR, and MPL, represent major diagnostic criteria in combination with hematologic and morphological abnormalities. PV is characterized by erythrocytosis with suppressed endogenous erythropoietin production, bone marrow panmyelosis, and JAK2 mutation. Thrombocytosis, bone marrow megakaryocytic proliferation, and presence of JAK2, CALR, or MPL mutation are the main diagnostic criteria for ET. PMF is characterized by bone marrow megakaryocytic proliferation, reticulin and/or collagen fibrosis, and presence of JAK2, CALR, or MPL mutation. Prefibrotic myelofibrosis represents an early phase of myelofibrosis, and is characterized by granulocytic/megakaryocytic proliferation and lack of reticulin fibrosis in the bone marrow. The genomic landscape of MPNs is more complex than initially thought and involves several mutant genes beyond the 3 drivers. Comutated, myeloid tumor-suppressor genes contribute to phenotypic variability, phenotypic shifts, and progression to more aggressive disorders. Patients with myeloid neoplasms are at variable risk of vascular complications, including arterial or venous thrombosis and bleeding. Current prognostic models are mainly based on clinical and hematologic parameters, but innovative models that include genetic data are being developed for both clinical and trial settings. In perspective, molecular profiling of MPNs might also allow for accurate evaluation and monitoring of response to innovative drugs that target the mutant clone.

  20. Content-Responsive Program Evaluation: An Integrated Preservice Example.

    ERIC Educational Resources Information Center

    Costner, Kelly M.; Wagner, Sigrid; Owens, Douglas T.

    This paper discusses the lack of and the need for program evaluation models for mathematics education and points out generic approaches to program evaluation. This project attempts to develop a mathematical approach to program evaluation that can be applied to an integrated preservice program for mathematics, science, and technology education…

  1. On Messes, Systems Thinking, and Evaluation: A Response to Patton

    ERIC Educational Resources Information Center

    Miller, Robin Lin

    2016-01-01

    To help evaluation professionals better understand what an authentic attempt at Developmental Evaluation (DE) ought to look like and when it is appropriate to use, Michael Patton's provocative essay (this issue) offers evaluators eight sensitizing concepts to call on as guides. Patton states these concepts succinctly define DE and persuasively…

  2. Accreditation Stimuli and Evaluation Responses in a Clinical Training Program.

    ERIC Educational Resources Information Center

    Wood, David; And Others

    Assessment and evaluation skills are significant goals of clinical training, yet many clinical and counseling students lack personal experiences with applied program evaluation. Clinical psychology graduate students responded to successive impending accreditation visits by conducting in-house evaluations. Students in 1977 (N=38) and 1980 (N=35)…

  3. Prasugrel Results in Higher Decrease in High-Sensitivity C-Reactive Protein Level in Patients Undergoing Percutaneous Coronary Intervention Comparing to Clopidogrel

    PubMed Central

    Hajsadeghi, Shokoufeh; Chitsazan, Mandana; Chitsazan, Mitra; Salehi, Negar; Amin, Ahmad; Bidokhti, Arash Amin; Babaali, Nima; Bordbar, Armin; Hejrati, Maral; Moghadami, Samar

    2016-01-01

    OBJECTIVES A growing body of clinical and laboratory evidence indicates that inflammation plays a crucial role in atherosclerosis. In the present study, we compared the effects of clopidogrel and prasugrel on high-sensitivity C-reactive protein (hs-CRP) in patients undergoing percutaneous coronary intervention (PCI). METHODS The present randomized, double-blind clinical trial included 120 patients who underwent PCI. Eligible patients were randomly assigned 2:1 to one of the two groups: 80 patients in the first group received clopidogrel (Plavix®; loading dose and maintenance dose of 300 and 75 mg daily, respectively) and 40 patients in the second group received prasugrel (Effient®; loading dose and maintenance dose of 60 and 10 mg, respectively) for 12 weeks. The hs-CRP levels between baseline and 12th week were compared. RESULTS Of the 120 patients, 69 patients (57.5%) were male. Pretreatment hs-CRP level was statistically comparable in clopidogrel (median, 15.10 mg/dL; interquartile range [IQR], 9.62–23.75 mg/dL) and prasugrel groups (median, 18 mg/dL; IQR, 14.25–22 mg/dL; P = 0.06). Patients taking clopidogrel showed a significant reduction in hs-CRP level compared with the baseline values (P < 0.001). Prasugrel administration also resulted in a significant reduction in hs-CRP level (P < 0.001). A significant 73% overall reduction in the hs-CRP level was seen with prasugrel compared with 39% overall reduction in hs-CRP level with clopidogrel (P = 0.002). CONCLUSION Prasugrel seems to be superior to clopidogrel in the reduction of hs-CRP in patients undergoing PCI. PMID:27597810

  4. Six Versus Twelve Months Clopidogrel Therapy After Drug-Eluting Stenting in Patients With Acute Coronary Syndrome: An ISAR-SAFE Study Subgroup Analysis

    PubMed Central

    Lohaus, Raphaela; Michel, Jonathan; Mayer, Katharina; Lahmann, Anna Lena; Byrne, Robert A.; Wolk, Annabelle; ten Berg, Jurrien M.; Neumann, Franz-Josef; Han, Yaling; Adriaenssens, Tom; Tölg, Ralph; Seyfarth, Melchior; Maeng, Michael; Zrenner, Bernhard; Jacobshagen, Claudius; Wöhrle, Jochen; Kufner, Sebastian; Morath, Tanja; Ibrahim, Tareq; Bernlochner, Isabell; Fischer, Marcus; Schunkert, Heribert; Laugwitz, Karl-Ludwig; Mehilli, Julinda; Kastrati, Adnan; Schulz-Schüpke, Stefanie

    2016-01-01

    In patients presenting with acute coronary syndrome (ACS) the optimal duration of dual-antiplatelet therapy after drug-eluting stent (DES) implantation remains unclear. At 6 months after intervention, patients receiving clopidogrel were randomly assigned to either a further 6-month period of placebo or clopidogrel. The primary composite endpoint was death, myocardial infarction, stent thrombosis, stroke, or major bleeding 9 months after randomization. The ISAR-SAFE trial was terminated early due to low event rates and slow recruitment. 1601/4000 (40.0%) patients presented with ACS and were randomized to 6 (n = 794) or 12 months (n = 807) clopidogrel. The primary endpoint occurred in 14 patients (1.8%) receiving 6 months of clopidogrel and 17 patients (2.2%) receiving 12 months; hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.41–1.68, P = 0.60. There were 2 (0.3%) cases of stent thrombosis in each group; HR 1.00, 95% CI 0.14–7.09, P = >0.99. Major bleeding occurred in 3 patients (0.4%) receiving 6 months clopidogrel and 5 (0.6%) receiving 12 months; HR 0.60, 95% CI 0.15–2.49, P = 0.49. There was no significant difference in net clinical outcomes after DES implantation in ACS patients treated with 6 versus 12 months clopidogrel. Ischaemic and bleeding events were low beyond 6-months. PMID:27624287

  5. Crop insurance evaluation in response to extreme events

    NASA Astrophysics Data System (ADS)

    Moriondo, Marco; Ferrise, Roberto; Bindi, Marco

    2013-04-01

    Crop yield insurance has been indicated as a tool to manage the uncertainties of crop yields (Sherrick et al., 2004) but the changes in crop yield variability as expected in the near future should be carefully considered for a better quantitative assessment of farmer's revenue risk and insurance values in a climatic change regime (Moriondo et al., 2011). Under this point of view, mechanistic crop growth models coupled to the output of General/Regional Circulation Models (GCMs, RCMs) offer a valuable tool to evaluate crop responses to climatic change and this approach has been extensively used to describe crop yield distribution in response to climatic change considering changes in both mean climate and variability. In this work, we studied the effect of a warmer climate on crop yield distribution of durum wheat (Triticum turgidum L. subsp durum) in order to assess the economic significance of climatic change in a risk decision context. Specifically, the outputs of 6 RCMs (Tmin, Tmax, Rainfall, Global Radiation) (van der Linden and Mitchell 2009) have been statistically downscaled by a stochastic weather generator over eight sites across the Mediterranean basin and used to feed the crop growth model Sirius Quality. Three time slices were considered i) the present period PP (average of the period 1975-1990, [CO2]=350 ppm), 2020 (average of the period 2010-2030, SRES scenario A1b, [CO2]=415 ppm) and 2040 (average of the period 2030-2050, SRES scenario A1b, [CO2]=480 ppm). The effect of extreme climate events (i.e. heat stress at anthesis stage) was also considered. The outputs of these simulations were used to estimate the expected payout per hectare from insurance triggered when yields fall below a specific threshold defined as "the insured yield". For each site, the threshold was calculated as a fraction (70%) of the median of yield distribution under PP that represents the percentage of median yield above which indemnity payments are triggered. The results

  6. Evaluating immune responses after sipuleucel-T therapy.

    PubMed

    Strauss, Julius; Madan, Ravi A; Figg, William D

    2015-01-01

    Following FDA approval of sipuleucel-T in 2010 for metastatic castration resistant prostate cancer (mCRPC), several studies have described the effect of sipuleucel-T on peripheral immune responses. Retrospective associations have also been made with immune responses and survival. A recently published study by Fong et al. was the first to characterize the immune response of sipuleucel-T in the tumor microenvironment. The findings of this study have been hypothesis generating, yet it remains unclear whether the peri-tumor immune response described is predictive of survival. Increasing evidence suggests that radiographic or PSA progression does not accurately reflect survival with sipuleucel-T and other immunotherapies. Finding an immune biomarker which can accurately reflect clinical benefit and validating it prospectively offers the potential for a predictive indicator of response in an area where none currently exists.

  7. Learning about fishery management: evaluation of a contextualized responsive evaluation approach.

    PubMed

    Kouévi, T A; van Mierlo, B; Leeuwis, C

    2013-12-01

    This article discusses the extent to which a responsive evaluation (RE) approach contributed to learning by stakeholders in a case of high complexity. Fishery management in Grand-Popo, Benin is characterized by ambiguity, that is contrasting views among fishery stakeholders about what should be done, why, how, where, and when to resolve fishery problems like the depletion of fish-stock and absence of income alternatives. It was also characterized by great gaps (mismatches) between interventionists' plans and actions, despite generations of interventions and evaluations of their effectiveness. The RE approach aimed at facilitating interactions between interventionists and fishing people to stimulate learning and hence reduce the ambiguity and mismatches. In this article, we take distance and evaluate the results of this action research approach. We found that in the interaction some learning indeed occurred. The fishing people learned among others that intervention resources are limited and that they should organize themselves to lobby for and monitor interventions to solve their problems. Interventionists learned that they could share knowledge about their roles and limited resources with fishing people so that the latter could lobby for more resources. Fishing people however, did not learn to adopt more sustainable fishing practices. Also, interventionists did not learn to influence politicians and financial partners themselves for sufficient resources. Both categories of stakeholders developed ideas for how to collaborate to improve fishery management. We conclude that although some single-loop, double-loop and social learning occurred, the learning was limited and reflect on the related challenges for RE in natural resource management.

  8. Evaluative Priming of Naming and Semantic Categorization Responses Revisited: A Mutual Facilitation Explanation

    ERIC Educational Resources Information Center

    Schmitz, Melanie; Wentura, Dirk

    2012-01-01

    The evaluative priming effect (i.e., faster target responses following evaluatively congruent compared with evaluatively incongruent primes) in nonevaluative priming tasks (such as naming or semantic categorization tasks) is considered important for the question of how evaluative connotations are represented in memory. However, the empirical…

  9. Bioequivalence and tolerability study of two brands of clopidogrel tablets, using inhibition of platelet aggregation and pharmacodynamic measures☆

    PubMed Central

    Rao, Takallapalli Ramesh Kumar; Usha, P.Rani; Naidu, M.U.R; Gogtay, J.A; Meena, Matthew

    2003-01-01

    Background The role of platelets in acute cardiovascular atherothrombotic events has been well established and attention has focused on platelet inhibition therapy. Clopidogrel is a novel thienopyridine inhibitor of adenosine diphosphate–induced platelet activation. Recent studies have shown that in the setting of coronary angioplasty/stenting, a loading dose of 300 mg followed by 75 mg once daily is required for optimum benefit. Objective This study assessed the bioequivalence and tolerability of 2 oral formulations of clopidogrel 75-mg tablets. Methods This 10-day, open-label, randomized, parallel-group, comparative bioequivalence and tolerability study was carried out in the Department of Clinical Pharmacology and Therapeutics, Nizam's Institute of Medical Sciences (Hyderabad, India). Young healthy male volunteers were enrolled. Subjects were randomized to receive one of two 75-mg tablet formulations of clopidogrel (Clopivas® [test formulation] or Plavix® [reference formulation]). Subjects first received a 300-mg loading dose (four 75-mg tablets) on day 1, followed by 75 mg (1 tablet) at 8:00 AM daily for the next 6 days. Inhibition of platelet aggregation, which is the pharmacologic basis for the therapeutic efficacy of antiplatelet agents, and the effect on bleeding time were used as the pharmacodynamic assessment criteria. Pharmacodynamic variables included mean of maximum activity of percentage of inhibition of platelet aggregation (Emax), mean time to reach Emax (tmax), and mean area under the activity–time curve from time 0 to 168 hours (AUC0–168). Tolerability assessments included blood pressure and heart rate measurements before and at regular intervals (every hour for 12 hours and then at 24 hours) over a 24-hour period after drug administration. Clinical tolerability was assessed using adverse effects, platelet count (assessed on days 3, 6, and 10 after first-dose administration), and neutrophil count (assessed on day 10 after first

  10. Solid-state NMR as an effective method of polymorphic analysis: solid dosage forms of clopidogrel hydrogensulfate.

    PubMed

    Pindelska, Edyta; Szeleszczuk, Lukasz; Pisklak, Dariusz Maciej; Mazurek, Andrzej; Kolodziejski, Waclaw

    2015-01-01

    Clopidogrel hydrogensulfate (HSCL) is an antiplatelet agent, one of top-selling drugs in the world. In this paper, we have described a rapid and convenient method of verification which polymorph of HSCL is present in its final solid dosage form. Our methodology based on solid-state NMR spectroscopy and ab initio gauge-including projector-augmented wave calculations of NMR shielding constants is appropriate for currently available commercial solid dosage forms of HSCL. Furthermore, such structural characterization can assist with the development of new pharmaceutical products containing HSCL and also be useful in the identification of counterfeit drugs.

  11. On the Intentional Control of Conditioned Evaluative Responses

    ERIC Educational Resources Information Center

    Balas, Robert; Gawronski, Bertram

    2012-01-01

    The evaluative conditioning (EC) effect is defined as a change in the evaluation of a conditioned stimulus (CS) due to its pairing with a valenced unconditioned stimulus (US). The current research investigated the controllability of EC effects by asking participants to either promote or prevent the influence of CS-US pairings before they provided…

  12. Federally Mandated Evaluation of Vocational Programs: One College's Response.

    ERIC Educational Resources Information Center

    Stevenson, Mike; Walleri, R. Dan

    The process and findings of the evaluation of seven of the 52 vocational preparatory programs at Mount Hood Community College are described with a focus on demonstrating the feasibility, utility, and problems associated with making program evaluations meet both internal needs and federal requirements. Summaries of data collected are provided in…

  13. Evaluating mechano-transduction and touch responses in plant roots.

    PubMed

    Swanson, Sarah J; Barker, Richard; Ye, Yonggeng; Gilroy, Simon

    2015-01-01

    Mechanical forces can be imposed on plants either from the environment, through factors such as the weather, mechanical properties of the soil and animal movement, or through the internal forces generated by the interplay between turgor-driven growth and the rigid plant cell wall. Such mechanical cues have profound effects on plant growth and development leading to responses ranging from directional growth patterns as seen, e.g., in tendrils coiling around supports, to the reprogramming of entire developmental programs. Thus, assays to assess mechanical sensitivity and response provide important tools for helping understand a wide range of plant physiological and developmental responses. Here, we describe simple assays to monitor mechanical response in the plant root system focusing on the quantification of root skewing, waving and obstacle avoidance.

  14. Differential compaction behaviour of roller compacted granules of clopidogrel bisulphate polymorphs.

    PubMed

    Khomane, Kailas S; Bansal, Arvind K

    2014-09-10

    In the present work, in-die and out-of-die compaction behaviour of dry-granulated powders of clopidogrel bisulphate (CLP) polymorphs, form I and form II, was investigated using a fully instrumented rotary tablet press. Each polymorph was compacted at three different roller pressures [70.3 (S1), 105.5 (S2) and 140.6 (S3)kgf/cm(2)], and obtained granules were characterized for their physico-mechanical properties. Compaction data were analyzed for out-of-die compressibility, tabletability and compactibility profiles, and in-die Heckel, Kawakita and Walker analysis. The roller compacted granules of both forms showed markedly different tabletting behaviour. Roller pressure exhibited a trend on compaction behaviour of form I granules, whereas, in case of form II, the effect was insignificant. Tabletability of the six granule batches follows the order; I_S1>I_S2>I_S3>II_S1≈II_S2≈II_S3. In case of form I, the reduced tabletability of the granules compacted at higher roller pressure was attributed to the decreased compressibility and plastic deformation. This was confirmed by compressibility plot and various mathematical parameters derived from Heckel (Py), Kawakita (1/b) and Walker (W) equations. The reduced tabletability of form I granules was due to 'granule hardening' during roller compaction. On the other hand, insignificant effect of roller compaction on tabletting behaviour of form II granules was attributed to brittle fragmentation. The extensive fragmentation of granules offered new 'clean' surfaces and higher contact points that negated the effect of granule hardening.

  15. Clopidogrel attenuates lithium-induced alterations in renal water and sodium channels/transporters in mice.

    PubMed

    Zhang, Yue; Peti-Peterdi, János; Heiney, Kristina M; Riquier-Brison, Anne; Carlson, Noel G; Müller, Christa E; Ecelbarger, Carolyn M; Kishore, Bellamkonda K

    2015-12-01

    Lithium (Li) administration causes deranged expression and function of renal aquaporins and sodium channels/transporters resulting in nephrogenic diabetes insipidus (NDI). Extracellular nucleotides (ATP/ADP/UTP), via P2 receptors, regulate these transport functions. We tested whether clopidogrel bisulfate (CLPD), an antagonist of ADP-activated P2Y(12) receptor, would affect Li-induced alterations in renal aquaporins and sodium channels/transporters. Adult mice were treated for 14 days with CLPD and/or Li and euthanized. Urine and kidneys were collected for analysis. When administered with Li, CLPD ameliorated polyuria, attenuated the rise in urine prostaglandin E2 (PGE2), and resulted in significantly higher urinary arginine vasopressin (AVP) and aldosterone levels as compared to Li treatment alone. However, urine sodium excretion remained elevated. Semi-quantitative immunoblotting revealed that CLPD alone increased renal aquaporin 2 (AQP2), Na-K-2Cl cotransporter (NKCC2), Na-Cl cotransporter (NCC), and the subunits of the epithelial Na channel (ENaC) in medulla by 25-130 %. When combined with Li, CLPD prevented downregulation of AQP2, Na-K-ATPase, and NKCC2 but was less effective against downregulation of cortical α- or γ-ENaC (70 kDa band). Thus, CLPD primarily attenuated Li-induced downregulation of proteins involved in water conservation (AVP-sensitive), with modest effects on aldosterone-sensitive proteins potentially explaining sustained natriuresis. Confocal immunofluorescence microscopy revealed strong labeling for P2Y(12)-R in proximal tubule brush border and blood vessels in the cortex and less intense labeling in medullary thick ascending limb and the collecting ducts. Therefore, there is the potential for CLPD to be directly acting at the tubule sites to mediate these effects. In conclusion, P2Y(12)-R may represent a novel therapeutic target for Li-induced NDI.

  16. Evaluations that Respond: Prescription, Application, and Implications of Responsive Evaluation Theory for Community College Instructional Support Programs

    ERIC Educational Resources Information Center

    Durdella, Nathan R.

    2010-01-01

    This study examines two community college instructional support programs to explore the effectiveness of an evaluation model--responsive evaluation theory--that may ease the tensions between a concern over programs' processes and reporting requirements for program outcomes. The study uses a comparative qualitative case study design and applies…

  17. Evaluation of Rugged Wireless Mesh Nodes for Use In Emergency Response

    SciTech Connect

    Kevin L Young; Alan M Snyder

    2007-11-01

    During the summer of 2007, engineers at the Idaho National Laboratory (INL) conducted a two-day evaluation of commercially available battery powered, wireless, self-forming mesh nodes for use in emergency response. In this paper, the author describes the fundamentals of this emerging technology, applciations for emergency response and specific results of the technology evaluation conducted at the Idaho National Laboratory.

  18. 34 CFR 403.204 - What are the State's responsibilities for program evaluation and improvement?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... responsibilities for program evaluation and improvement? (a) If, one year after an eligible recipient has... 34 Education 3 2013-07-01 2013-07-01 false What are the State's responsibilities for program evaluation and improvement? 403.204 Section 403.204 Education Regulations of the Offices of the Department...

  19. 34 CFR 403.204 - What are the State's responsibilities for program evaluation and improvement?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... responsibilities for program evaluation and improvement? (a) If, one year after an eligible recipient has... 34 Education 3 2011-07-01 2011-07-01 false What are the State's responsibilities for program evaluation and improvement? 403.204 Section 403.204 Education Regulations of the Offices of the Department...

  20. 34 CFR 403.204 - What are the State's responsibilities for program evaluation and improvement?

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... responsibilities for program evaluation and improvement? (a) If, one year after an eligible recipient has... 34 Education 3 2014-07-01 2014-07-01 false What are the State's responsibilities for program evaluation and improvement? 403.204 Section 403.204 Education Regulations of the Offices of the Department...

  1. 34 CFR 403.204 - What are the State's responsibilities for program evaluation and improvement?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... responsibilities for program evaluation and improvement? (a) If, one year after an eligible recipient has... 34 Education 3 2012-07-01 2012-07-01 false What are the State's responsibilities for program evaluation and improvement? 403.204 Section 403.204 Education Regulations of the Offices of the Department...

  2. Evaluation of Representations and Response Models for Polarizable Force Fields

    PubMed Central

    2016-01-01

    For classical simulations of condensed-phase systems, such as organic liquids and biomolecules, to achieve high accuracy, they will probably need to incorporate an accurate, efficient model of conformation-dependent electronic polarization. Thus, it is of interest to understand what determines the accuracy of a polarizable electrostatics model. This study approaches this problem by breaking polarization models down into two main components: the representation of electronic polarization and the response model used for mapping from an inducing field to the polarization within the chosen representation. Among the most common polarization representations are redistribution of atom-centered charges, such as those used in the fluctuating charge model, and atom-centered point dipoles, such as those used in a number of different polarization models. Each of these representations has been combined with one or more response models. The response model of fluctuating charge, for example, is based on the idea of electronegativity equalization in the context of changing electrostatic potentials (ESPs), whereas point-dipole representations typically use a response model based on point polarizabilities whose induced dipoles are computed based on interaction with other charges and dipoles. Here, we decouple polarization representations from their typical response models to analyze the strengths and weaknesses of various polarization approximations. First, we compare the maximal possible accuracies achievable by the charge redistribution and point-dipole model representations, by testing their ability to replicate quantum mechanical (QM) ESPs around small molecules polarized by external inducing charges. Perhaps not surprisingly, the atom-centered dipole model can yield higher accuracy. Next, we test two of the most commonly used response functions used for the point-dipole representations, self-consistent and direct (or first-order) inducible point polarizabilities, where the

  3. Alcohol: the clinician's role in evaluating legal responsibility.

    PubMed

    Lande, R G

    1993-11-01

    Alcohol-related misconduct poses a challenge for society, the legal system, and the medical profession. The debate is centered on alcohol abuse and the determination of responsibility for misbehavior. In assessing responsibility, the legal system often requests the expertise of the medical professional. The knowledgeable clinician can contribute to the just resolution of complex medico-legal cases. The best contribution considers medical facts in relation to the evolution of legal thinking. This article explores the historical, social, and legal approaches to alcohol-related misconduct. The article concludes with a discussion of a model clinical assessment.

  4. Evaluation of Representative Smart Grid Investment Project Technologies: Demand Response

    SciTech Connect

    Fuller, Jason C.; Prakash Kumar, Nirupama; Bonebrake, Christopher A.

    2012-02-14

    This document is one of a series of reports estimating the benefits of deploying technologies similar to those implemented on the Smart Grid Investment Grant (SGIG) projects. Four technical reports cover the various types of technologies deployed in the SGIG projects, distribution automation, demand response, energy storage, and renewables integration. A fifth report in the series examines the benefits of deploying these technologies on a national level. This technical report examines the impacts of a limited number of demand response technologies and implementations deployed in the SGIG projects.

  5. A Systemic Approach to Culturally Responsive Assessment Practices and Evaluation

    ERIC Educational Resources Information Center

    Slee, June

    2010-01-01

    In an earlier paper, Slee and Keenan demonstrated that it was possible for tertiary education institutions to design culturally responsive assessment procedures that complied with standardised assessment policy. The authors' paper described "Growing Our Own," an initiative between Charles Darwin University and Northern Territory Catholic…

  6. Responsibility-Based Youth Programs Evaluation: Investigating the Investigations.

    ERIC Educational Resources Information Center

    Hellison, Don; Walsh, David

    2002-01-01

    Reviews 26 studies that have investigated the impact of the personal-social responsibility model (RM), a physical activity program model, on underserved and/or at-risk youth since its inception. Results indicate that field research encompasses a wide range of approaches. However, the 26 studies enhance the theoretical and practical potential of RM…

  7. Antiplatelet efficacy of P2Y12 inhibitors (prasugrel, ticagrelor, clopidogrel) in patients treated with mild therapeutic hypothermia after cardiac arrest due to acute myocardial infarction.

    PubMed

    Bednar, Frantisek; Kroupa, Josef; Ondrakova, Martina; Osmancik, Pavel; Kopa, Milos; Motovska, Zuzana

    2016-05-01

    Survivors after cardiac arrest (CA) due to AMI undergo PCI and then receive dual antiplatelet therapy. Mild therapeutic hypothermia (MTH) is recommended for unconscious patients after CA to improve neurological outcomes. MTH can attenuate the effectiveness of P2Y12 inhibitors by reducing gastrointestinal absorption and metabolic activation. The combined effect of these conditions on the efficacy of P2Y12 inhibitors is unknown. We compared the antiplatelet efficacies of new P2Y12 inhibitors in AMI patients after CA treated with MTH. Forty patients after CA for AMI treated with MTH and received one P2Y12 inhibitor (clopidogrel, prasugrel or ticagrelor) were enrolled in a prospective observational single-center study. Platelet inhibition was measured by VASP (PRI) on days 1, 2, and 3 after drug administration. In-hospital clinical data and 1-year survival data were obtained. The proportion of patients with ineffective platelet inhibition (PRI > 50 %, high on-treatment platelet reactivity) for clopidogrel, prasugrel, and ticagrelor was 77 vs. 19 vs. 1 % on day 1; 77 vs. 17 vs. 0 % on day 2; and 85 vs. 6 vs. 0 % on day 3 (P < 0.001). The platelet inhibition was significantly worse in clopidogrel group than in prasugrel or ticagrelor group. Prasugrel and ticagrelor are very effective for platelet inhibition in patients treated with MTH after CA due to AMI, but clopidogrel is not. Using prasugrel or ticagrelor seems to be a more suitable option in this high-risk group of acute patients.

  8. Development and Validation of a Reversed-phase HPLC Method for Simultaneous Determination of Aspirin, Atorvastatin Calcium and Clopidogrel Bisulphate in Capsules.

    PubMed

    Londhe, S V; Deshmukh, R S; Mulgund, S V; Jain, K S

    2011-01-01

    A simple, accurate, rapid and precise isocratic reversed-phase high-performance liquid chromatographic method has been developed and validated for simultaneous determination of aspirin, atorvastatin calcium and clopidogrel bisulphate in capsules. The chromatographic separation was carried out on an Inertsil ODS analytical column (150×4.6 mm; 5 μm) with a mixture of acetonitrile:phosphate buffer pH 3.0 adjusted with o-phosphoric acid (50:50, v/v) as mobile phase; at a flow rate of 1.2 ml/min. UV detection was performed at 235 nm. The retention times were 1.89, 6.6 and 19.8 min. for aspirin, atorvastatin calcium and clopidogrel bisulphate, respectively. Calibration plots were linear (r(2)>0.998) over the concentration range 5-30 μg/ml for atorvastatin calcium and 30-105 μg/ml for aspirin and clopidogrel bisulphate. The method was validated for accuracy, precision, specificity, linearity, and sensitivity. The proposed method was successfully used for quantitative analysis of capsules. No interference from any component of pharmaceutical dosage form was observed. Validation studies revealed that method is specific, rapid, reliable, and reproducible. The high recovery and low relative standard deviation confirm the suitability of the method for routine determination of aspirin, atorvastatin calcium and clopidogrel bisulphate in bulk drug and capsule dosage form.

  9. Electrochemical study of the antiplatelet agent clopidogrel and its determination using differential pulse voltammetry in bulk form and pharmaceutical preparations with a glassy carbon electrode.

    PubMed

    Dermiş, S; Aydoğan, E

    2010-03-01

    In the present study, the electroanalytical behaviour of clopidogrel (CLP) bisulfate, an antithrombotic drug, was investigated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques using a glassy carbon electrode (GCE). The anodic oxidation of clopidogrel bisulfate was investigated with a GCE to determine the oxidation conditions. The voltammograms of solutions having various concentrations of clopidogrel were recorded in order to obtain the optimum oxidation conditions of this drug on a GCE. To determine the effects of the nature of the supporting electrolyte, pH and scan rate on the anodic oxidation reactions, the experiments were performed in 0.2 M sulphuric acid, and in Britton-Robinson (BR) (pH 2-5) and acetate (pH 3.5-5.63) buffers with a 10-400 mVs(-1) scan rate interval. The oxidation of clopidogrel bisulfate was found to be diffusion-controlled over a concentration range of 0.08 mM-1.0 mM in pH 3.7 acetate buffer by an optimized DPV technique. The voltammetric method developed was applied to the tablet form of pharmaceutical preparation of this compound and the accuracy, precision, selectivity, sensitivity, repeatibility within and between days and reproducibility of the proposed method was investigated statistically. The results were compared with the spectrophotometric and HPLC methods developed in our laboratory and found to be in good agreement. No interference was observed from common pharmaceutical adjuvants.

  10. Ticagrelor versus prasugrel in patients with high on-clopidogrel treatment platelet reactivity after PCI: The ISAR-ADAPT-PF study.

    PubMed

    Bernlochner, Isabell; Mayer, Katharina; Orban, Martin; Morath, Tanja; Jaitner, Juliane; Rössner, Lisa; Gross, Lisa; Laugwitz, Karl-Ludwig; Kastrati, Adnan; Sibbing, Dirk

    2016-12-01

    Patients with high on-treatment platelet reactivity (HTPR) on clopidogrel are at high risk for adverse cardiovascular events after percutaneous coronary intervention (PCI). The aim of the ISAR-ADAPT-PF study was to assess the antiplatelet efficacy of ticagrelor versus prasugrel in patients with HTPR on clopidogrel. In a prospective and randomized clinical study, 70 patients with HTPR on clopidogrel loading dose (LD) within 24 h post PCI were assigned to receive either ticagrelor [180 mg LD followed by 90 mg maintenance dose (MD) twice daily] or prasugrel (60 mg LD followed by 10 mg MD once daily). The adenosine diphosphate-induced platelet aggregation assessed on the Multiplate analyzer on day 2 after randomization (primary end point) was as follows: the mean difference between the two treatment groups was 6 aggregation units (AU) × min with an upper 95% confidence interval (CI) of 41 AU × min, which was greater than the predefined noninferiority margin of 18 AU × min (P for noninferiority = 0.29). However, no significant differences in absolute platelet reactivity levels between ticagrelor- versus prasugrel-treated patients at that time point were observed (138 ± 100 AU × min vs. 132 ± 64 AU × min, P for superiority = 0.77). In conclusion, neither drug was statistically more effective for inhibition of platelet aggregation in patients with HTPR on clopidogrel post PCI, although the study could not formally demonstrate the assumed noninferiority of ticagrelor versus prasugrel.

  11. A validated stability-indicating normal phase LC method for clopidogrel bisulfate and its impurities in bulk drug and pharmaceutical dosage form.

    PubMed

    Durga Rao, Dantu; Kalyanaraman, L; Sait, Shakil S; Venkata Rao, P

    2010-05-01

    A novel stability-indicating normal phase liquid chromatographic (NP-LC) method was developed for the determination of purity of clopidogrel drug substance and drug products in bulk samples and pharmaceutical dosage forms in the presence of its impurities and degradation products. This method is capable of separating all the related substances of clopidogrel along with the chiral impurities. This method can be also be used for the estimation of assay of clopidogrel in drug substance as well as in drug product. The method was developed using Chiralcel OJ-H (250mmx4.6mm, 5microm) column. n-Hexane, ethanol and diethyl amine in 95:5:0.05 (v/v/v) ratio was used as a mobile phase. The eluted compounds were monitored at 240nm. Clopidogrel bisulfate was subjected to the stress conditions of oxidative, acid, base, hydrolytic, thermal and photolytic degradation. The degradation products were well resolved from main peak and its impurities, proving the stability-indicating power of the method. The developed method was validated as per International Conference on Harmonization (ICH) guidelines with respect to specificity, limit of detection, limit of quantification, precision, linearity, accuracy, robustness and system suitability.

  12. Evaluation of a high response electrohydraulic digital control valve

    NASA Technical Reports Server (NTRS)

    Anderson, R. L.

    1973-01-01

    The application is described of a digital control valve on an electrohydraulic servo actuator. The digital control problem is discussed in general as well as the design and evaluation of a breadboard actuator. The evaluation revealed a number of problems associated with matching the valve to a hydraulic load. The problems were related to lost motion resulting from bulk modulus and leakage. These problems were effectively minimized in the breadboard actuator by maintaining a 1000 psi back pressure on the valve circuit and thereby improving the effective bulk modulus.

  13. Pharmacodynamic effects of cangrelor and clopidogrel: the platelet function substudy from the cangrelor versus standard therapy to achieve optimal management of platelet inhibition (CHAMPION) trials.

    PubMed

    Angiolillo, Dominick J; Schneider, David J; Bhatt, Deepak L; French, William J; Price, Matthew J; Saucedo, Jorge F; Shaburishvili, Tamaz; Huber, Kurt; Prats, Jayne; Liu, Tiepu; Harrington, Robert A; Becker, Richard C

    2012-07-01

    Cangrelor is an intravenous antagonist of the P2Y(12) receptor characterized by rapid, potent, predictable, and reversible platelet inhibition. However, cangrelor was not superior to clopidogrel in reducing the incidence of ischemic events in the cangrelor versus standard therapy to achieve optimal management of platelet inhibition (CHAMPION) trials. A prospectively designed platelet function substudy was performed in a selected cohort of patients to provide insight into the pharmacodynamic effects of cangrelor, particularly in regard to whether cangrelor therapy may interfere with the inhibitory effects of clopidogrel. This pre-defined substudy was conducted in a subset of patients from the CHAMPION-PCI trial (n = 230) comparing cangrelor with 600 mg of clopidogrel administered before percutaneous coronary intervention (PCI) and from the CHAMPION-PLATFORM trial (n = 4) comparing cangrelor at the time of PCI and 600 mg clopidogrel given after the PCI. Pharmacodynamic measures included P2Y12 reaction units (PRU) assessed by VerifyNow P2Y12 testing (primary endpoint marker), platelet aggregation by light transmittance aggregometry following 5 and 20 μmol/L adenosine diphosphate stimuli, and markers of platelet activation determined by flow cytometry. The primary endpoint was the percentage of patients who achieved <20 % change in PRU between baseline and >10 h after PCI. The main trial was stopped early limiting enrollment in the platelet substudy. A total of 167 patients had valid pharmacodynamic assessments for the primary endpoint. The percent of individuals achieving <20 % change in PRU between baseline and >10 h after PCI was higher with cangrelor + clopidogrel (32/84, 38.1 %) compared with placebo + clopidogrel (21/83, 25.3 %), but this was not statistically significant (difference:12.79 %, 95 % CI: -1.18 %, 26.77 %;p = 0.076). All pharmacodynamic markers as well as the prevalence of patients with high on-treatment platelet reactivity were significantly lower

  14. Platelet reactivity after administration of third generation P2Y12-antagonists does not depend on body weight in contrast to clopidogrel.

    PubMed

    Olivier, Christoph B; Schnabel, Katharina; Weber, Susanne; Zhou, Qian; Bode, Christoph; Moser, Martin; Diehl, Philipp

    2016-07-01

    The current standard of antiplatelet therapy for patients with myocardial infarction (MI) includes the P2Y12-receptor antagonist clopidogrel, prasugrel or ticagrelor. While it has been shown that platelet reactivity after clopidogrel administration depends on factors such as body weight, it is not known if these factors have an effect on the activity of prasugrel or ticagrelor. Thus, this study aimed to analyse factors associated with high residual platelet reactivity after administration of third generation P2Y12-antagonists compared to clopidogrel. In a single centre registry the antiplatelet effect of clopidogrel, prasugrel or ticagrelor was investigated by aggregometry in patients after MI. To assess the overall capacity of platelet aggregation whole blood was induced with thrombin receptor activating peptide (TRAP; 32 µM). To specifically quantify the effect of P2Y12-antagonists, blood was stimulated with 6.4 µM adenosine diphophosphate (ADP). Relative ADP induced aggregation (r-ADP-agg) was defined as the ADP-TRAP-ratio to reflect an individual degree of P2Y12-dependent platelet inhibition. Platelet function of 238 patients was analysed [clopidogrel (n = 58), prasugrel (n = 65), ticagrelor (n = 115)]. It was found that the r-ADP-agg correlated significantly with body weight in patients after clopidogrel administration (r = 0.423; p < 0.001). In contrast, this association was not present in patients after prasugrel (r = -0.117; p = 0.354) or ticagrelor (r = -0.082; p = 0.382) administration. Comparison of the correlation coefficients showed a significant difference (p = 0.003). In contrast to clopidogrel, platelet reactivity after administration of prasugrel or ticagrelor does not depend on body weight in patients after MI. Hence, our mechanistic data support the results of large clinical trials indicating that patients with high body weight do not need to be treated with increased doses of third generation P2Y12-antagonists to achieve

  15. Pharmacodynamic effects of EV-077 in patients with diabetes mellitus and coronary artery disease on aspirin or clopidogrel monotherapy: results of an in vitro pilot investigation.

    PubMed

    Rollini, Fabiana; Tello-Montoliu, Antonio; Patel, Ronakkumar; Darlington, Andrew; Wilson, Ryan E; Franchi, Francesco; Muñiz-Lozano, Ana; Desai, Bhaloo; Bender, Norbert; Sakariassen, Kjell S; Angiolillo, Dominick J

    2014-01-01

    Patients with diabetes mellitus (DM) have increased propensity to generate thromboxane A2 (TXA2) and other eicosanoids which can contribute to their heightened platelet reactivity. EV-077 is a potent thromboxane receptor antagonist and thromboxane synthase inhibitor and thus represents an attractive therapy in patients with DM. However, the effects of EV-077 on pharmacodynamic (PD) profiles in patients with DM and coronary artery disease (CAD) while on antiplatelet therapy is poorly explored and represented the aim of this in vitro pilot investigation. Patients with DM and stable CAD (n = 10) on low-dose aspirin (81 mg/day) were enrolled and then switched to clopidogrel (75 mg/day) monotherapy for 7-10 days. PD assessments were conducted while on aspirin and on clopidogrel using light transmittance aggregometry following stimuli with U-46619 [TXA2 stable analogue (7 μM)], arachidonic acid [AA (1 mM)], collagen (3 μg/mL) and adenosine diphosphate [ADP (5 μM and 20 μM)] with and without in vitro EV-077. EV-077 completely inhibited U-46619-stimulated platelet aggregation (p = 0.005 for both aspirin and clopidogrel) and also showed a significant reduction of collagen-induced aggregation (aspirin p = 0.008; clopidogrel p = 0.005). EV-077 significantly reduced AA-induced platelet aggregation in clopidogrel (p = 0.009), but not aspirin (p = 0.667) treated patients. Ultimately, EV-077 significantly reduced ADP-mediated platelet aggregation in both aspirin (ADP 5 μM p = 0.012; ADP 20 μM p = 0.032) and clopidogrel (ADP 5 μM p = 0.007; ADP 20 μM p = 0.008) treated patients. In conclusion, in DM patients with CAD on aspirin or clopidogrel monotherapy, in vitro EV-077 exerts potent platelet inhibitory effects on multiple platelet signaling pathways. These data support that EV-077 has only additive platelet inhibiting effects on top of standard antiplatelet therapies. These findings warrant further investigation in ex vivo settings.

  16. Test-Based Teacher Evaluations: Accountability vs. Responsibility

    ERIC Educational Resources Information Center

    Bolyard, Chloé

    2015-01-01

    Gert Biesta contends that managerial accountability, which focuses on efficiency and competition, dominates the current political arena in education. Such accountability has influenced states' developments of test-based teacher evaluations in an attempt to quantify teachers' efficacy on student learning. With numerous state policies requiring the…

  17. The RFP Challenge: Evaluation of Responses to Requests for Proposals.

    ERIC Educational Resources Information Center

    LeDuc, A. L.

    1993-01-01

    When a college contracts for a product or service, the request for proposal (RFP) may be an appropriate tool. It must clearly define what is needed for fair evaluation. A rating or weighting system for costs and benefits is useful for isolating and quantifying important elements of the decision-making process. (MSE)

  18. Evaluation of the stress response of heifers during transportation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To evaluate the stress associated with transportation; 22 heifers (326 ± 47 kg) were randomly assigned to a control (Con) or transport (Tran) group. On d 0, 12 h prior to the transportation, heifers were weighed and fitted with an indwelling rectal temperature (RT) probe, jugular catheters, and hear...

  19. The Practice of Evaluation in Public Sector Contexts: A Response

    ERIC Educational Resources Information Center

    Chouinard, Jill Anne

    2013-01-01

    In the original paper, it was argued that while there is an array of methods and methodologies available, their use is delimited by the culture of accountability that prevails in public sector institutions, a fact that is particularly problematic given the complexity and diversity of evaluation contexts today. This short rejoinder, to responses…

  20. Evaluate Scintillation Response Over a Continuous Energy Region

    SciTech Connect

    Zhang, Yanwen; Elfman, Mikael; Milbrath, Brian D.; Weber, William J.

    2008-06-26

    A recently developed fast analysis technique utilizing a time of flight (TOF) telescope is demonstrated to obtain relevant quantitative data on material scintillation response to energetic He particles. With superior energy resolution and fast response of the TOF telescope, energy of individual particle before impinging on a scintillating crystal can be determined with a high counting rate, which allows quantitative study of material performance over a continuous energy range in a relatively short time. Scintillation performances in terms of light output, nonlinearity and energy resolution in bismuth germinate (BGO) and europium-doped calcium fluoride (CaF2:Eu) Crystals are demonstrated, and the corresponding energy resolution is compared with gamma-ray tests on the same crystals.

  1. Auditorium acoustics evaluation based on simulated impulse response

    NASA Astrophysics Data System (ADS)

    Wu, Shuoxian; Wang, Hongwei; Zhao, Yuezhe

    2001-05-01

    The impulse responses and other acoustical parameters of Huangpu Teenager Palace in Guangzhou were measured. Meanwhile, the acoustical simulation and auralization based on software ODEON were also made. The comparison between the parameters based on computer simulation and measuring is given. This case study shows that auralization technique based on computer simulation can be used for predicting the acoustical quality of a hall at its design stage.

  2. Responding to Ambiguity, Responding to Change the Value of a Responsive Approach to Evaluation.

    ERIC Educational Resources Information Center

    Abma, T. A.

    2000-01-01

    Evaluated the success of a palliative health care team in a Dutch health region. Results show that it is more appropriate to acknowledge ambiguity and facilitate its handling as part of dynamic learning processes. Discusses the usefulness of a responsive approach to evaluation, evaluation methodology, and learning experiences. (SLD)

  3. 48 CFR 715.303-70 - Responsibilities of USAID evaluation committees.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... written documentation summarizing the results of the evaluation of each proposal, including an assessment... evaluation committees. 715.303-70 Section 715.303-70 Federal Acquisition Regulations System AGENCY FOR....303-70 Responsibilities of USAID evaluation committees. (a) Establishment and composition of...

  4. Evaluating Radiometric Measurements Using a Fixed 45 Degrees Responsivity and Zenith Angle Dependent Responsivities (Poster)

    SciTech Connect

    Dooraghi, M.; Habte, A.; Reda, I.; Sengupta, M.; Gotseff, P.; Andreas, A.; Anderberg, M.

    2014-03-01

    This poster seeks to demonstrate the importance and application of an existing but unused approach that ultimately reduces the uncertainty of radiometric measurements. Current radiometric data is based on a single responsivity value that introduces significant uncertainty to the data, however, through using responsivity as a function of solar zenith angle, the uncertainty could be decreased by 50%.

  5. Effects of pioglitazone on platelet P2Y12-mediated signalling in clopidogrel-treated patients with type 2 diabetes mellitus.

    PubMed

    Suryadevara, Siva; Ueno, Masafumi; Tello-Montoliu, Antonio; Ferreiro, Jose Luis; Desai, Bhaloo; Rollini, Fabiana; Box, Lyndon C; Zenni, Martin; Guzman, Luis A; Bass, Theodore A; Angiolillo, Dominick J

    2012-11-01

    Patients with type 2 diabetes mellitus (T2DM) have impaired clopidogrel-induced antiplatelet effects, which may be in part attributed to their reduced sensitivity to insulin and consequently, results in upregulation of the P2Y12 signalling pathway. It has been hypothesised that insulin sensitising strategies may enhance clopidogrel-mediated P2Y12 inhibitory effects. The aim of this pilot pharmacodynamics (PD) study was to assess the impact of pioglitazone on clopidogrel-mediated P2Y12 inhibitory effects in patients with T2DM. This was a prospective, randomised, double-blind, placebo-controlled, cross-over PD study. Patients with T2DM and stable coronary artery disease on maintenance aspirin and clopidogrel were randomised to receive either pioglitazone 30 mg or matching placebo daily for 14 days. PD assessments were measured at baseline, 14 days after randomisation, at the end of the wash-out period, and 14 days after cross-over. The primary endpoint measure was maximal platelet aggregation (MPA) to 20 μM adenosine diphosphate (ADP) as assessed by light transmittance aggregometry (LTA). Flow cytometric analysis of vasodilator-stimulated phosphoprotein phosphorylation (VASP-PRI), and VerifyNow P2Y12 testing were also performed. A total of 15 randomised patients completed the study. MPA to 20 μM ADP (primary endpoint) was not significantly different with pioglitazone compared with placebo (49.53 ± 4.76 vs. 52.52 ± 3.89%; p = 0.594). Similarly, other PD measures did not differ significantly between the groups. In conclusion, in patients with T2DM on maintenance aspirin and clopidogrel therapy, the adjunctive use of pioglitazone does not result in enhanced inhibition of platelet P2Y12 mediated signalling.

  6. Mortality in primary angioplasty patients starting antiplatelet therapy with prehospital prasugrel or clopidogrel: a 1-year follow-up from the European MULTIPRAC Registry

    PubMed Central

    Goldstein, Patrick; Grieco, Niccolò; Ince, Hüseyin; Danchin, Nicolas; Ramos, Yvonne; Goedicke, Jochen; Clemmensen, Peter

    2016-01-01

    Aim MULTIPRAC was designed to provide insights into the use and outcomes associated with prehospital initiation of antiplatelet therapy with either prasugrel or clopidogrel in the context of primary percutaneous coronary intervention. After a previous report on efficacy and safety outcomes during 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 was associated with a significantly lower risk of CV death than treatment with clopidogrel (odds ratio 0.248; 95% confidence interval 0.06–0.89). Conclusion In STEMI patients from routine practice undergoing primary angioplasty, who were able to start oral antiplatelet therapy prehospital, treatment with prasugrel as compared to clopidogrel was associated with a lower risk of CV death at 1-year follow-up. PMID:27143908

  7. Prasugrel vs clopidogrel in cardiogenic shock patients undergoing primary PCI for acute myocardial infarction. Results of the ISAR-SHOCK registry.

    PubMed

    Orban, M; Mayer, K; Morath, T; Bernlochner, I; Hadamitzky, M; Braun, S; Schulz, S; Hoppmann, P; Hausleiter, J; Tiroch, K; Mehilli, J; Schunkert, H; Massberg, S; Laugwitz, K-L; Sibbing, D; Kastrati, A

    2014-12-01

    There is limited clinical data comparing different P2Y12-receptor inhibitors in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock. The aim of the ISAR-SHOCK registry was to compare the clinical outcome of patients treated with clopidogrel vs prasugrel in this setting. Patients (n=145) with AMI complicated by cardiogenic shock and undergoing primary PCI in two centres (Deutsches Herzzentrum München and Klinikum rechts der Isar, Technical University Munich) between January 2009 and May 2012 were included in this registry. The use of prasugrel for patients within this registry reflected co-morbidities and platelet function testing results during the acute AMI phase. Early outcome at 30-days was reported with regard to all-cause mortality, myocardial infarction (MI), stent thrombosis (ST) and bleeding events. With regard to antiplatelet treatment in the 145 cardiogenic shock patients, 50 patients were initially treated or immediately switched to prasugrel while 95 patients were treated with clopidogrel. All-cause mortality was lower in prasugrel- vs clopidogrel-treated patients (30 % vs 50.5%, HR: 0.51, 95% CI [0.29-0.92], p=0.025). No significant differences in prasugrel- vs clopidogrel-treated patients were observed for the occurrence of MI (p=0.233), ST (p=0.306) or TIMI major bleedings (p=0.571). Results of the ISAR-SHOCK registry suggest that the use of prasugrel in AMI patients complicated by cardiogenic shock might be associated with a lower mortality risk as compared to clopidogrel therapy without increasing the risk of bleeding. These findings, however, need confirmation from specifically designed randomised studies in this high-risk cohort of patients.

  8. Bleeding complications with the P2Y12 receptor antagonists clopidogrel and ticagrelor in the PLATelet inhibition and patient Outcomes (PLATO) trial.

    PubMed

    Becker, Richard C; Bassand, Jean Pierre; Budaj, Andrzej; Wojdyla, Daniel M; James, Stefan K; Cornel, Jan H; French, John; Held, Claes; Horrow, Jay; Husted, Steen; Lopez-Sendon, Jose; Lassila, Riitta; Mahaffey, Kenneth W; Storey, Robert F; Harrington, Robert A; Wallentin, Lars

    2011-12-01

    AIMS More intense platelet-directed therapy for acute coronary syndrome (ACS) may increase bleeding risk. The aim of the current analysis was to determine the rate, clinical impact, and predictors of major and fatal bleeding complications in the PLATO study. METHODS AND RESULTS PLATO was a randomized, double-blind, active control international, phase 3 clinical trial in patients with acute ST elevation and non-ST-segment elevation ACS. A total of 18 624 patients were randomized to either ticagrelor, a non-thienopyridine, reversibly binding platelet P2Y(12) receptor antagonist, or clopidogrel in addition to aspirin. Patients randomized to ticagrelor and clopidogrel had similar rates of PLATO major bleeding (11.6 vs. 11.2%; P = 0.43), TIMI major bleeding (7.9 vs. 7.7%, P = 0.56) and GUSTO severe bleeding (2.9 vs. 3.1%, P = 0.22). Procedure-related bleeding rates were also similar. Non-CABG major bleeding (4.5 vs. 3.8%, P = 0.02) and non-procedure-related major bleeding (3.1 vs. 2.3%, P = 0.05) were more common in ticagrelor-treated patients, primarily after 30 days on treatment. Fatal bleeding and transfusion rates did not differ between groups. There were no significant interactions for major bleeding or combined minor plus major bleeding between treatment groups and age ≥75 years, weight <60 kg, region, chronic kidney disease, creatinine clearance <60 mL/min, aspirin dose >325 mg on the day of randomization, pre-randomization clopidogrel administration, or clopidogrel loading dose. CONCLUSION Ticagrelor compared with clopidogrel was associated with similar total major bleeding but increased non-CABG and non-procedure-related major bleeding, primarily after 30 days on study drug treatment. Fatal bleeding was low and did not differ between groups.

  9. Injuries in the elderly: evaluation and initial response.

    PubMed

    Demarest, G B; Osler, T M; Clevenger, F W

    1990-08-01

    The injured elderly patient presents a special challenge to the treating physician; there tends to be less margin for error than in younger patients and a greater chance that mortality will result. Beyond the general need for rapid assessment of an often complicated situation, there are specific evaluative and therapeutic techniques, system-by-system and organ-by-organ, that can help expedite the patient's recovery. Guidelines for ICU admission and possible withholding of care are also suggested.

  10. Use of field experimental studies to evaluate emergency response models

    SciTech Connect

    Gudiksen, P.H.; Lange, R.; Rodriguez, D.J.; Nasstrom, J.S.

    1985-07-16

    The three-dimensional diagnostic wind field model (MATHEW) and the particle-in-cell atmospheric transport and diffusion model (ADPIC) are used by the Atmospheric Release Advisory Capability to estimate the environmental consequences of accidental releases of radioactivity into the atmosphere. These models have undergone extensive evaluations against field experiments conducted in a variety of environmental settings ranging from relatively flat to very complex terrain areas. Simulations of tracer experiments conducted in a complex mountain valley setting revealed that 35 to 50% of the comparisons between calculated and measured tracer concentrations were within a factor of 5. This may be compared with a factor of 2 for 50% of the comparisons for relatively flat terrain. This degradation of results in complex terrain is due to a variety of factors such as the limited representativeness of measurements in complex terrain, the limited spatial resolution afforded by the models, and the turbulence parameterization based on sigma/sub theta/ measurements to evaluate the eddy diffusivities. Measurements of sigma/sub theta/ in complex terrain exceed those measured over flat terrain by a factor of 2 to 3 leading to eddy diffusivities that are unrealistically high. The results of model evaluations are very sensitive to the quality and the representativeness of the meteorological data. This is particularly true for measurements near the source. The capability of the models to simulate the dispersion of an instantaneously produced cloud of particulates was illustrated to be generally within a factor of 2 over flat terrain. 19 refs., 16 figs.

  11. A quantitative evaluation of the public response to climate engineering

    NASA Astrophysics Data System (ADS)

    Wright, Malcolm J.; Teagle, Damon A. H.; Feetham, Pamela M.

    2014-02-01

    Atmospheric greenhouse gas concentrations continue to increase, with CO2 passing 400 parts per million in May 2013. To avoid severe climate change and the attendant economic and social dislocation, existing energy efficiency and emissions control initiatives may need support from some form of climate engineering. As climate engineering will be controversial, there is a pressing need to inform the public and understand their concerns before policy decisions are taken. So far, engagement has been exploratory, small-scale or technique-specific. We depart from past research to draw on the associative methods used by corporations to evaluate brands. A systematic, quantitative and comparative approach for evaluating public reaction to climate engineering is developed. Its application reveals that the overall public evaluation of climate engineering is negative. Where there are positive associations they favour carbon dioxide removal (CDR) over solar radiation management (SRM) techniques. Therefore, as SRM techniques become more widely known they are more likely to elicit negative reactions. Two climate engineering techniques, enhanced weathering and cloud brightening, have indistinct concept images and so are less likely to draw public attention than other CDR or SRM techniques.

  12. Evaluation of lung tumor response to therapy: Current and emerging techniques.

    PubMed

    Coche, E

    2016-10-01

    Lung tumor response to therapy may be evaluated in most instances by morphological criteria such as RECIST 1.1 on computed tomography (CT) or magnetic resonance imaging (MRI). However, those criteria are limited because they are based on tumoral dimensional changes and do not take into account other morphologic criteria such as density evaluation, functional or metabolic changes that may occur following conventional or targeted chemotherapy. New techniques such as dual-energy CT, PET-CT, MRI including diffusion-weighted MRI has to be considered into the new technical armamentarium for tumor response evaluation. Integration of all informations provided by the different imaging modalities has to be integrated and represents probably the future goal of tumor response evaluation. The aim of the present paper is to review the current and emerging imaging criteria used to evaluate the response of therapy in the field of lung cancer.

  13. Evaluating physiological responses of plants to salinity stress

    PubMed Central

    Negrão, S.; Schmöckel, S. M.; Tester, M.

    2017-01-01

    Background Because soil salinity is a major abiotic constraint affecting crop yield, much research has been conducted to develop plants with improved salinity tolerance. Salinity stress impacts many aspects of a plant’s physiology, making it difficult to study in toto. Instead, it is more tractable to dissect the plant’s response into traits that are hypothesized to be involved in the overall tolerance of the plant to salinity. Scope and conclusions We discuss how to quantify the impact of salinity on different traits, such as relative growth rate, water relations, transpiration, transpiration use efficiency, ionic relations, photosynthesis, senescence, yield and yield components. We also suggest some guidelines to assist with the selection of appropriate experimental systems, imposition of salinity stress, and obtaining and analysing relevant physiological data using appropriate indices. We illustrate how these indices can be used to identify relationships amongst the proposed traits to identify which traits are the most important contributors to salinity tolerance. Salinity tolerance is complex and involves many genes, but progress has been made in studying the mechanisms underlying a plant’s response to salinity. Nevertheless, several previous studies on salinity tolerance could have benefited from improved experimental design. We hope that this paper will provide pertinent information to researchers on performing proficient assays and interpreting results from salinity tolerance experiments. PMID:27707746

  14. Responsive Meta-Evaluation: A Participatory Approach to Enhancing Evaluation Quality

    ERIC Educational Resources Information Center

    Sturges, Keith M.; Howley, Caitlin

    2017-01-01

    In an era of ever-deepening budget cuts and a concomitant demand for substantiated programs, many organizations have elected to conduct internal program evaluations. Internal evaluations offer advantages (e.g., enhanced evaluator program knowledge and ease of data collection) but may confront important challenges, including credibility threats,…

  15. Evaluation of the impact response of textile composites

    NASA Technical Reports Server (NTRS)

    Portanova, M. A.

    1995-01-01

    An evaluation of the impact damage resistance and impact damage tolerance of stitched and unstitched uniweaves, 2-D braids, and 3-D weaves was conducted. Uniweave laminates were tested at four thicknesses to determine the sensitivity of the tests to this parameter. Several braid and weave parameters were also varied to establish their velocity (large mass) impacts and then loaded in tension or compression to measure residual strength. Experimental results indicate that stitching significantly improves the uniweaves' damage resistance. The 2-D braids and 3-D weaves offered less damage resistance than the stitched materials. Stitching also improved the compression after impact (CAI) and tension after impact (TAI) strengths of the uniweave materials.

  16. Computerized PET/CT image analysis in the evaluation of tumour response to therapy

    PubMed Central

    Wang, J; Zhang, H H

    2015-01-01

    Current cancer therapy strategy is mostly population based, however, there are large differences in tumour response among patients. It is therefore important for treating physicians to know individual tumour response. In recent years, many studies proposed the use of computerized positron emission tomography/CT image analysis in the evaluation of tumour response. Results showed that computerized analysis overcame some major limitations of current qualitative and semiquantitative analysis and led to improved accuracy. In this review, we summarize these studies in four steps of the analysis: image registration, tumour segmentation, image feature extraction and response evaluation. Future works are proposed and challenges described. PMID:25723599

  17. Dose-Response Evaluation of Braslet-M Occlusion Cuffs

    NASA Technical Reports Server (NTRS)

    Ebert, Douglas; Garcia, Kathleen; Sargsyan, Ashot E.; Ham, David; Hamilton, Douglas; Dulchavsky, Scott A.

    2010-01-01

    Introduction: Braslet-M is a set of special elasticized thigh cuffs used by the Russian space agency to reduce the effects of the head-ward fluid shift during early adaptation to microgravity by sequestering fluid in the lower extremities. Currently, no imaging modalities are used in the calibration of the device, and the pressure required to produce a predictable physiological response is unknown. This investigation intends to relate the pressure exerted by the cuffs to the extent of fluid redistribution and commensurate physiological effects. Materials and Methods: Ten healthy subjects with standardized fluid intake participated in the study. Data collection included femoral and internal jugular vein imaging in two orthogonal planes, pulsed Doppler of cervical and femoral vessels and middle cerebral artery, optic nerve imaging, and echocardiography. Braslet-M cuff pressure was monitored at the skin interface using pre-calibrated pressure sensors. Using 6 and 30 head-down tilt in two separate sessions, the effect of Braslet-M was assessed while incrementally tightening the cuffs. Cuffs were then simultaneously released to document the resulting hemodynamic change. Results: Preliminary analysis shows correlation between physical pressure exerted by the Braslet-M device and several parameters such as jugular and femoral vein cross-sections, resistivity of the lower extremity vascular bed, and others. A number of parameters reflect blood redistribution and will be used to determine the therapeutic range of the device and to prevent unsafe application. Conclusion: Braslet-M exerts a physical effect that can be measured and correlated with many changes in central and peripheral hemodynamics. Analysis of the full data set will be required to make definitive recommendations regarding the range of safe therapeutic application. Objective data and subjective responses suggest that a safer and equally effective use of Braslet can be achieved when compared with the current

  18. Evaluation of cytocompatibility and cell response to boron nitride nanotubes.

    PubMed

    Ciofani, Gianni; Danti, Serena

    2012-01-01

    While in the last years applications of carbon nanotubes in the field of biotechnology have been largely proposed, so far biomedical applications of boron nitride nanotubes (BNNTs) are still totally unexplored. BNNTs show very interesting physical properties that might be exploited in the nanomedicine field. To fill up the lack of biocompatibility studies on BNNTs, our group has recently begun a rational investigation on interactions between BNNTs and different cell lines. This chapter reports on preliminary cytocompatibility studies carried out on human neuroblastoma (SH-SY5Y) and on mouse myoblast (C2C12) cell lines as model of neural and skeletal muscle cells, respectively, highlighting the methods that allowed us to evaluate the main parameters of interests for cytocompatibility, such as cell viability, metabolism, apoptosis, and differentiation.

  19. Reevaluating assembly evaluations with feature response curves: GAGE and assemblathons.

    PubMed

    Vezzi, Francesco; Narzisi, Giuseppe; Mishra, Bud

    2012-01-01

    In just the last decade, a multitude of bio-technologies and software pipelines have emerged to revolutionize genomics. To further their central goal, they aim to accelerate and improve the quality of de novo whole-genome assembly starting from short DNA sequences/reads. However, the performance of each of these tools is contingent on the length and quality of the sequencing data, the structure and complexity of the genome sequence, and the resolution and quality of long-range information. Furthermore, in the absence of any metric that captures the most fundamental "features" of a high-quality assembly, there is no obvious recipe for users to select the most desirable assembler/assembly. This situation has prompted the scientific community to rely on crowd-sourcing through international competitions, such as Assemblathons or GAGE, with the intention of identifying the best assembler(s) and their features. Somewhat circuitously, the only available approach to gauge de novo assemblies and assemblers relies solely on the availability of a high-quality fully assembled reference genome sequence. Still worse, reference-guided evaluations are often both difficult to analyze, leading to conclusions that are difficult to interpret. In this paper, we circumvent many of these issues by relying upon a tool, dubbed [Formula: see text], which is capable of evaluating de novo assemblies from the read-layouts even when no reference exists. We extend the FRCurve approach to cases where lay-out information may have been obscured, as is true in many deBruijn-graph-based algorithms. As a by-product, FRCurve now expands its applicability to a much wider class of assemblers - thus, identifying higher-quality members of this group, their inter-relations as well as sensitivity to carefully selected features, with or without the support of a reference sequence or layout for the reads. The paper concludes by reevaluating several recently conducted assembly competitions and the datasets that

  20. Relationship between clopidogrel-related polymorphisms and variable platelet reactivity at 1 year: A cohort study from Han Chinese

    PubMed Central

    Wang, Xiaodong; Lai, Yan; Luo, Yu; Zhang, Xumin; Zhou, Hua; Ye, Zi; Tang, Jiani; Liu, Xuebo

    2016-01-01

    Background: This study was designed to investigate the effect of clopidogrel-related gene polymorphisms on platelet reactivity and clinical outcome in Chinese Han patients. Materials and Methods: Three hundred and thirty-six percutaneous coronary intervention - treated patients were recruited and followed for 1 year. Blood samples were collected from all patients for DNA genotyping. The platelet reactivity unit was measured by the VerifyNow technique. The CYP2C19*2, CYP2C19*3, CYP2C19*17, ATP-binding cassette subfamily B member 1, ITGB3, CYP2C9*3, CYP2B6*9, and P2Y12 alleles were assessed. Results: The clinical endpoints were related to previous heart disease history (11.90% vs. 28.57%, P = 0.017), stroke (12.24% vs. 16.67%, P = 0.039), and diabetes (27.55% vs. 52.38%, P = 0.047). High on-treatment platelet reactivity (HTPR) was frequent in advanced age (P = 0.019), male gender (P = 0.016), hypertension (P = 0.033), and chronic renal failure (P = 0.040). There were more endpoints in the CYP2C19*2 and P2Y12 mutant carriers (76.19% vs. 43.20%, P < 0.001; 50.00% vs. 35.71%, P = 0.001, respectively), whereas fewer in the CYP2C19*17 mutant carriers (11.90% vs. 56.46%, P = 0.001). CYP2C19*2 and P2Y12 polymorphism manifested HTPR (194.25 ± 45.91 vs. 151.38 ± 58.14, P < 0.001; 180.33 ± 67.25 vs. 161.89 ± 56.49, P = 0.008, respectively), whereas CYP2C19*17 mutant improved platelet reactivity (97.17 ± 45.38 vs. 169.08 ± 57.15, P = 0.003). However, there were no further cardiovascular deaths in endpoint patients. Conclusion: In Han Chinese people of mainland China, clopidogrel-related gene polymorphisms are related to variable platelet reactivity after clopidogrel maintenance dosing, which influences major adverse cardiovascular events, without an effect on cardiac death. PMID:28255319

  1. Physical dosimetric evaluations in the Apollo 16 microbial response experiment.

    PubMed

    Taylor, G R; Bailey, J V; Benton, E V

    1975-01-01

    Nine biological species, including viruses, bacteria, fungi, and nematodes, were exposed to various combinations of space vacuum, galactic radiation, and solar UV light during the Apollo 16 space flight. No major changes in number of surviving cells occurred, permitting detailed genetic and somatic studies of returned test subjects. To enable dose-response studies, solar UV was employed as a mutagenic source with cells exposed to full sunlight or to components of the UV spectrum at peak wavelengths of 254, 280, and 300 nanometers over a range of energy levels. Proper in-flight UV irradiation monitoring required the development of a potassium ferrioxalate actinometer and an anaerobic photographic emulsion dosimeter which were tested for the first time in space. Studies of the mutagenic activity of cosmic-ray particulate radiation environment required measurement of its components with several lithium fluoride thermoluminescent dosimeters and a package of passive nuclear-track detectors capable of recording high-energy multicharge particles. These detectors included cellulose nitrate, Lexan, Ilford G5, and silver chloride crystals. The nuclear track detectors measured the incident heavy particles with the recorded spherical fluences with LET350,H2O>100 keV x micrometers-1 to be 19.3 +/- 1.8 particles cm-2. This value was found to be lower than that recorded by detectors located in the Biostack and the passive personnel dosimeters worn by the astronauts, suggesting a somewhat greater average shielding.

  2. Evaluation of the impact of neutralizing antibodies on IFNβ response.

    PubMed

    Bertolotto, Antonio

    2015-09-20

    IFNβ therapeutic action depends on a sequence of biological steps: i) the interaction between interferon beta (IFNβ) and its receptor (IFNAR) located at the cell surface of peripheral blood mononuclear cells; ii) activation of second messengers; iii) transcription of several genes containing specific ISRE regions (Interferon Stimulated Response Elements); and iv) synthesis of specific proteins. Although IFNβ therapy has improved treatment options of patients with multiple sclerosis (MS), the long-term efficacy of IFNβs can be compromised due to the development of neutralizing antibodies (NAbs). High titer NAbs develop in about 15% of patients; they abolish IFNβ biological activity and consequently the therapeutic action of IFNβ. Different IFNβ preparations carry different risks of developing NAbs, ranging from 3 to 28%. The risk of inducing NAbs must be considered in the selection of treatment. Guidelines for NAbs testing and the therapeutic decision in case of NAbs positivity have been established. NAbs positivity predicts MRI and clinical activity. Precocious identification of Nabs-positive patients and switch to alternative treatments can improve the percentage of responders and allow a better allocation of relevant economical resources.

  3. Evaluation of ozone exposure indices in exposure-response modeling.

    PubMed

    Lee, E H; Tingey, D T; Hogsett, W E

    1988-01-01

    In exposure-response modeling, a major concern is the numerical definition of exposure in relating crop loss to O3, yet few indices have been considered. This paper addresses research in which plant growth was regressed for soybean, wheat, cotton, corn, and sorghum against 613 numerical exposure indices using the Box-Tidwell model. When the minimum sum of squared errors criterion was used, optimum performance was not attained for any single index; however, near optimum performances were achieved by two censored cumulative indices and from a class of indices called the generalized, phenologically weighted, cumulative impact indices (GPWCIs). The top-performing GPWCIs accumulated concentrations, used sigmoid weighting schemes emphasizing O3 concentrations of 0.06 ppm (118 microg m(-3)) or higher, and had phenological weighting schemes with greatest weight occurring 20 to 40 days prior to crop maturity. These findings indicate that (1) peak concentrations are important, but lower concentrations should be included in the calculations, (2) increased plant sensitivity occurs between flowering and maturity, and (3) plants respond to cumulative exposure impact.

  4. Anger and sadness as adaptive emotion expression strategies in response to negative competence and warmth evaluations.

    PubMed

    Celik, Pinar; Storme, Martin; Myszkowski, Nils

    2016-12-01

    Previous literature suggested that anger and sadness may be necessary to restore social bonds in the face of immediate relationship threat. The present research compared the social effectiveness of expressing anger and sadness in response to a negative personal evaluation. Results indicated that target anger in response to a negative competence evaluation, and target sadness in response to a negative warmth evaluation, had the most positive effects on the evaluators' subjectively perceived persuasiveness of the targets' communication (Study 1) and on the subjectively perceived fluency of the interaction by both interaction partners (Study 2). Results are discussed in light of the social functionality of emotion expression and the importance of interpersonal emotion congruency with evaluation content.

  5. Evaluating Cognitive Theory: A Joint Modeling Approach Using Responses and Response Times

    ERIC Educational Resources Information Center

    Klein Entink, Rinke H.; Kuhn, Jorg-Tobias; Hornke, Lutz F.; Fox, Jean-Paul

    2009-01-01

    In current psychological research, the analysis of data from computer-based assessments or experiments is often confined to accuracy scores. Response times, although being an important source of additional information, are either neglected or analyzed separately. In this article, a new model is developed that allows the simultaneous analysis of…

  6. Evaluation of the community response to HIV and AIDS: learning from a portfolio approach.

    PubMed

    Rodriguez-García, Rosalía; Wilson, David; York, Nick; Low, Corinne; N'Jie, N'Della; Bonnel, Rene

    2013-01-01

    While communities have played a large role in the HIV/AIDS response, their contributions and innovative approaches to HIV prevention, treatment, care and support have not always been the focus of systematic and rigorous evaluations. To address this gap, the World Bank led an evaluation of the impact of the community response to HIV, including country studies in Burkina Faso, India, Kenya, Lesotho, Nigeria, Senegal, South Africa and Zimbabwe over a three-year period. Due to the complexity and varied nature of community responses, the evaluation attempted to determine the results that investments have produced at the community level by applying a mixed method approach: Randomized Controlled Trials, quasi-experimental studies, qualitative studies and analytical studies including financial data. Specifically, the studies examined a typology of community response and the flow of funds to community-based organizations, while investigating the impact of the community responses on (1) knowledge and behavior, (2) use of services, (3) social transformation, and (4) HIV incidence. This editorial summarizes the results of this evaluation portfolio, finding that investments in communities have produced significant results, including, improved knowledge and behavior, and increased use of health services, and even decreased HIV incidence. Evidence on social transformation was more mixed, with community groups found to be effective only in some settings. Each study in the evaluation provides a partial view of how communities shape the local response; however, taken together they corroborate the common wisdom that communities can be a vital part of the global HIV/AIDS response.

  7. Differential effects of motor efference copies and proprioceptive information on response evaluation processes.

    PubMed

    Stock, Ann-Kathrin; Wascher, Edmund; Beste, Christian

    2013-01-01

    It is well-kown that sensory information influences the way we execute motor responses. However, less is known about if and how sensory and motor information are integrated in the subsequent process of response evaluation. We used a modified Simon Task to investigate how these streams of information are integrated in response evaluation processes, applying an in-depth neurophysiological analysis of event-related potentials (ERPs), time-frequency decomposition and sLORETA. The results show that response evaluation processes are differentially modulated by afferent proprioceptive information and efference copies. While the influence of proprioceptive information is mediated via oscillations in different frequency bands, efference copy based information about the motor execution is specifically mediated via oscillations in the theta frequency band. Stages of visual perception and attention were not modulated by the interaction of proprioception and motor efference copies. Brain areas modulated by the interactive effects of proprioceptive and efference copy based information included the middle frontal gyrus and the supplementary motor area (SMA), suggesting that these areas integrate sensory information for the purpose of response evaluation. The results show how motor response evaluation processes are modulated by information about both the execution and the location of a response.

  8. Prediction and Early Evaluation of Anticancer Therapy Response: From Imaging of Drug Efflux Pumps to Targeted Therapy Response.

    PubMed

    Meng, Qingqing; Li, Zheng; Li, Shaoshun

    2016-01-01

    Multidrug resistance (MDR) describes the resistance of tumor cells to chemotherapy and has been ascribed to the overexpression of drug efflux pumps. Molecular imaging of drug efflux pumps is helpful to identify the patients who may be resistant to the chemotherapy and thus will avoid the unnecessary treatment and increase the therapeutic effectiveness. Imaging probes targeting drug efflux pumps can non-invasively evaluate the Pgp function and play an important role in identification of MDR, prediction of response, and monitoring MDR modulation. On the other hand, new anticancer agents based on molecular targets such as epidermal growth factor receptor (EGFR) and angiogenic factor receptor may potentially be combined with chemotherapeutic drugs to overcome the MDR. Imaging of molecular targets visualize treatment response of patients at molecular level vividly and help to select right patients for certain targeted anticancer therapy. Among all the imaging modalities, nuclear imaging including positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging has the greatest promise for rapid translation to the clinic and can realize quantitative visualization of biochemical processes in vivo. In this review, we will summarize the nuclear imaging probes utilized for predicting and evaluating the early anticancer therapy response.99mTc labeled agents and PET based radiopharmaceuticals like 18F-Paclitaxel, 11C-Verapamil for drug efflux pumps imaging will be discussed here. Moreover, molecular imaging probes used for targeted therapy response evaluation like 18F-Tamoxifen,89Zr-Trastuzumab will also be introduced in this review.

  9. The Evaluation and Prediction of Affective Response to Graduate Teaching Assistants' Classroom Communication.

    ERIC Educational Resources Information Center

    O'Hair, H. Dan; Babich, Roger M.

    A study was conducted to determine whether graduate teaching assistants in speech communication were aware of the affective components of their classroom behavior and of the student responses to them, and whether the instructors' awareness of the affective dimensions of instruction related to the student evaluative responses. Subjects were 640…

  10. The Influence of Learning Characteristics on Evaluation of Audience Response Technology

    ERIC Educational Resources Information Center

    MacGeorge, Erina L.; Homan, Scott R.; Dunning, John B.; Elmore, David; Bodie, Graham D.; Evans, Ed; Khichadia, Sangeetha; Lichti, Steven M.

    2008-01-01

    Audience Response Technology (ART) has been widely adopted on college campuses, and prior research indicates that, on average, it receives positive evaluations from students. However, research has not yet examined how characteristics of students as learners influence their responses to ART. The current study examined aptitude for learning,…

  11. 33 CFR 154.1135 - Response plan development and evaluation criteria.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Operating in Prince William Sound, Alaska § 154.1135 Response plan development and evaluation criteria. The following response times must be used in determining the on scene arrival time in Prince William Sound for... William Sound Area 12 24 36...

  12. EVALUATING QUANTITATIVE FORMULAS FOR DOSE-RESPONSE ASSESSMENT OF CHEMICAL MIXTURES

    EPA Science Inventory

    Risk assessment formulas are often distinguished from dose-response models by being rough but necessary. The evaluation of these rough formulas is described here, using the example of mixture risk assessment. Two conditions make the dose-response part of mixture risk assessment d...

  13. Evaluating the Effectiveness of a Personal Response System in the Classroom

    ERIC Educational Resources Information Center

    Shaffer, Dennis M.; Collura, Michael J.

    2009-01-01

    We evaluated the effectiveness of the use of an electronic personal response system (or "clickers") during an introductory psychology lecture on perceptual constancy. We graphed and projected student responses to questions during the lecture onto a large-screen display in Microsoft PowerPoint. The distributions of answers corresponded…

  14. Formative Evaluation in Health Education: An Exploratory Study of the Usefulness of the Cognitive Response Method

    ERIC Educational Resources Information Center

    Schwartz, Jaime; Byrd-Bredbenner, Carol

    2006-01-01

    Purpose: The purpose of this study was to explore the usefulness of a simplified version of cognitive response analysis (CRA) as a formative evaluation tool for health education materials developed for small, unfunded projects. Design/methodology/approach: A group of women (n=15), aged between 25 and 50 years, provided cognitive responses (CRs)…

  15. Effects of Ethnicity and Gender on Teachers' Evaluation of Students' Spoken Responses

    ERIC Educational Resources Information Center

    Shepherd, Michael A.

    2011-01-01

    To update and extend research on teachers' expectations of students of different sociocultural groups, 57 Black, White, Asian, and Hispanic teachers were asked to evaluate responses spoken by Black, White, and Hispanic 2nd- and 3rd-grade boys and girls. The results show that responses perceived as spoken by minority boys, minority girls, and White…

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

    PubMed

    Raijada, Dhara K; Prasad, Bhagwat; Paudel, Amrit; Shah, Ravi P; Singh, Saranjit

    2010-07-08

    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, polymorph I and polymorph II of the drug were exposed to 40 degrees C/75% relative humidity (RH), with and without stressors for 3 months. The samples were analyzed by HPLC, and the relative extent of degradation as well as nature of decomposition was compared among three solid forms. In total, eight degradation products were observed under various stress conditions. The structures of all of them were elucidated using LC-MS/TOF and LC-MS(n) studies. While one matched the known hydrolytic decomposition product of the drug in solution, seven others were new. The postulated degradation pathway and mechanism of decomposition are discussed.

  17. How to Evaluate Your School Instructional Program. Curriculum Is a Board Member Responsibility.

    ERIC Educational Resources Information Center

    California School Boards Association, Sacramento.

    To help California school board members fulfill their duties, this guidebook tells them how to begin evaluating district curriculum and instructional materials. The first chapter reviews school boards' legal responsibilities for educational program evaluation, under California state law, state board of education decrees, and legal interpretations.…

  18. Nobody Knows my Name: In Praise of African American Evaluators Who Were Responsive.

    ERIC Educational Resources Information Center

    Hood, Stafford

    2001-01-01

    Provides a historical accounting of the work of early African American educational evaluators to show the critical place of race and culture in both historical and contemporary visions of responsive evaluation. Discusses reasons their work has so largely been ignored. (SLD)

  19. Evaluating Medication Response in ADHD: Cognitive, Behavioral, and Single-Subject Methodology.

    ERIC Educational Resources Information Center

    Hale, James B.; Hoeppner, Jo-Ann B.; DeWitt, Mary Beth; Coury, Daniel L.; Ritacco, David G.; Trommer, Barbara

    1998-01-01

    A technique is presented for evaluating methylphenidate (MPH) effects on core behavioral symptoms of attention deficit hyperactivity disorder at the single-subject level of analysis. Case-study results and multivariate analyses suggests systematic evaluation of behavior and cognitive MPH dose-response relationships could lead to more accurate MPH…

  20. Evaluation of the Immediate and Subsequent Effects of Response Interruption and Redirection on Vocal Stereotypy

    ERIC Educational Resources Information Center

    Schumacher, Brittany I.; Rapp, John T.

    2011-01-01

    We evaluated 2 3-component multiple-schedule sequences--a response interruption and redirection (RIRD) treatment sequence and a no-interaction control sequence--using a multielement design. With this design, we were able to evaluate the immediate and subsequent effects of RIRD on 2 participants' vocal stereotypy. For both participants, RIRD…

  1. Tumour response evaluation with fluorodeoxyglucose positron emission tomography: research technique or clinical tool?

    PubMed

    Anderson, H; Singh, N; Miles, K

    2010-10-04

    The evaluation of treatment response is an established role for imaging in oncologic research and clinical practice. In early phase trials, imaging response criteria are used to determine the presence and magnitude of the drug effect on tumour to aid decisions concerning progress to late phase trials, and to inform dose selection and scheduling. In late phase trials and clinical practice, the imaging response is used as a surrogate for clinical outcome. Due to the limitations of current anatomic response criteria, there is growing interest in the use of [(18)F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) to assess treatment response. The technique is beginning to be adopted within mainstream approaches for evaluation of response in solid tumours and lymphoma. Difficulties with standardisation across PET centres and tumour types combined with uncertainty concerning the timing of assessment relative to treatment, have limited the use of quantitative measurements of FDG uptake to research applications. However, with a growing body of evidence that qualitative criteria such as the development of new PET lesions or complete metabolic response following treatment can provide surrogates marker for clinical outcome, [(18)F]FDG-PET is becoming established as a clinical technique for assessing tumour response, especially for FDG-avid lymphoma subtypes. Multimodality imaging using perfusion computed tomography/PET is an exciting novel technique with the potential to define treatment response in a new way.

  2. Clinical outcomes associated with proton pump inhibitor use among clopidogrel-treated patients within CYP2C19 genotype groups following acute myocardial infarction

    PubMed Central

    Depta, Jeremiah P.; Lenzini, Petra A.; Lanfear, David E.; Wang, Tracy Y.; Spertus, John A.; Bach, Richard G.; Cresci, Sharon

    2014-01-01

    We examined clinical outcomes with proton pump inhibitors (PPI) use within CYP2C19 genotype groups during clopidogrel treatment following acute myocardial infarction (AMI). 2062 patients were genotyped for CYP2C19*2 and *17 variants in TRIUMPH. 12 month clinical outcomes were analyzed among patients discharged on clopidogrel within CYP2C19*2 carrier, CYP2C19*17 carrier, and CYP2C19*1 homozygote genotype groups. PPI use was not associated with a difference in mortality. Among clopidogrel-treated Caucasians following AMI, PPI use was associated with a significantly higher rate of cardiac rehospitalization (HR 1.62, 95% CI 1.19-2.19; p = 0.002) compared with no PPI use. PPI users who were carriers of the CYP2C19*17 variant experienced significantly higher rates of cardiac rehospitalization (HR 2.05, 95% CI 1.26-3.33; p = 0.003), carriers of the CYP2C19*2 variant had a trend toward increased 1-year cardiac rehospitalization (HR 1.69, 95% CI 0.95-2.99; P=0.07) while no significant differences were observed among CYP2C19*1 homozygotes. These results indicate that the risks associated with PPI use among clopidogrel-treated Caucasian post-MI patients are impacted by CYP2C19 genotype, and suggest knowledge of genotype may be useful for personalizing PPI use among patients following AMI to reduce rehospitalization. PMID:25001880

  3. A randomised trial of the pharmacodynamic and pharmacokinetic effects of ticagrelor compared with clopidogrel in Hispanic patients with stable coronary artery disease.

    PubMed

    Price, Matthew J; Clavijo, Leonardo; Angiolillo, Dominick J; Carlson, Glenn; Caplan, Richard; Teng, Renli; Maya, Juan

    2015-01-01

    The objective was to compare the pharmacodynamic (PD) and pharmacokinetic (PK) effects of ticagrelor with clopidogrel among subjects of Hispanic ethnicity, as the PD and PK effects of antiplatelet agents among Hispanics are not specifically known. This was a randomised, open-label, crossover PD/PK study of 40 Hispanic subjects with stable coronary artery disease (CAD). Subjects were allocated to either ticagrelor 180 mg loading dose (LD)/90 mg twice-daily maintenance dose (MD) followed by clopidogrel 600 mg LD/75 mg once-daily MD with an intervening washout period, or vice versa. The primary endpoint was on-treatment reactivity (OTR) at 2 h post-LD according to the VerifyNow P2Y12 test. OTR was significantly lower at 2 h post-LD with ticagrelor compared with clopidogrel (34 PRU vs. 201 PRU, least square means difference = -167 PRU [95 % CI, -197, -137], P < 0.001). OTR was also lower with ticagrelor at 30 min and 8 h post-LD (P < 0.001). The greater magnitude of antiplatelet effect with ticagrelor persisted after 7 days of MD (52 PRU [95 % CI, 30, 73] vs. 182 PRU [95 % CI, 160, 205], P < 0.001). Mean plasma concentration of ticagrelor and its active metabolite were greatest at 2 h post-LD, with similar levels at 2 h post-MD after 7 days of MD. Among Hispanic subjects with stable CAD, ticagrelor provides a more rapid onset of platelet inhibition and a significantly greater antiplatelet effect compared with clopidogrel during both the loading and maintenance phases of treatment.

  4. A comparative cohort study on personalised antiplatelet therapy in PCI-treated patients with high on-clopidogrel platelet reactivity. Results of the ISAR-HPR registry.

    PubMed

    Mayer, K; Schulz, S; Bernlochner, I; Morath, T; Braun, S; Hausleiter, J; Massberg, S; Schunkert, H; Laugwitz, K-L; Kastrati, A; Sibbing, D

    2014-08-01

    In clopidogrel-treated patients undergoing percutaneous coronary intervention (PCI), high platelet reactivity (HPR) is associated with a higher risk for thrombotic events including stent thrombosis (ST). A personalised therapy with selective intensification of treatment may improve HPR patients´ outcome in this setting although recent randomised trials are against this hypothesis. The aim of the ISAR-HPR registry was to assess whether clopidogrel-treated HPR patients benefit from selective intensification of P2Y12 receptor inhibition. For the registry, outcomes were compared between two cohorts. We identified 428 clopidogrel treated HPR patients (AU x min ≥468 on the Multiplate analyser) between 2007-2008 (historical control cohort) without a change of treatment based on platelet function (PF) testing results. Between 2009-2011, we identified 571 HPR patients (guided therapy cohort) and used this information for guidance and selective intensification of P2Y12 receptor directed treatment (reloading with clopidogrel, switch to prasugrel, re-testing) in a setting of routine PF testing. The primary outcome was the composite of death from any cause or ST after 30 days. Major bleeding according to TIMI criteria was also monitored. The incidence of the primary outcome was significantly lower in the guided vs the control cohort (7 [1.2%] vs 16 [3.7%] events; HR 0.32, 95% CI 0.13-0.79; p=0.009). The incidence of major bleeding was numerically but not statistically higher in the guided vs the control cohort (1.9 vs 0.7%; p=0.10). In conclusion, present findings are in support for a PF testing guided antiplatelet therapy with selective intensification of P2Y12 receptor inhibition. The issue of personalised antiplatelet treatment warrants further investigation in randomized and well-controlled clinical trials.

  5. Pulmonary function in patients with acute coronary syndrome treated with ticagrelor or clopidogrel (from the Platelet Inhibition and Patient Outcomes [PLATO] pulmonary function substudy).

    PubMed

    Storey, Robert F; Becker, Richard C; Harrington, Robert A; Husted, Steen; James, Stefan K; Cools, Frank; Steg, Philippe Gabriel; Khurmi, Nardev S; Emanuelsson, Hakan; Lim, Soo Teik; Cannon, Christopher P; Katus, Hugo A; Wallentin, Lars

    2011-12-01

    The Platelet Inhibition and Patient Outcomes (PLATO) trial showed that ticagrelor reduced the risk for cardiovascular events in patients with acute coronary syndromes compared to clopidogrel but was associated with increased incidence of dyspnea. This substudy assessed whether ticagrelor affects pulmonary function in patients with acute coronary syndromes: 199 patients enrolled in the PLATO trial and receiving randomized treatment with ticagrelor 90 mg twice daily (n = 101) or clopidogrel 75 mg/day (n = 98) took part in the pulmonary function substudy. Patients with advanced lung disease, congestive heart failure, or coronary artery bypass graft surgery after the index event were excluded. Pulse oximetry (blood oxygen saturation), spirometry (forced expiratory volume in 1 second, forced vital capacity, and forced expiratory flow between 25% and 75% of forced vital capacity before and 20 minutes after inhalation of a β(2) agonist), lung volumes (total lung capacity, functional residual capacity, residual volume), and diffusion capacity were performed after patients received study medication for 30 to 40 days. Tests were then repeated <10 days before and approximately 30 days after the discontinuation of study medication. After a mean treatment duration of 31 days, there were no differences between the groups for any of the pulmonary function parameters. At the end of treatment (mean 211 days) and after the discontinuation of study medication (mean 32 days after the last dose), there was also no evidence of a change in pulmonary function in either group. For example, forced expiratory volume in 1 second values before β(2) agonist inhalation in the ticagrelor and clopidogrel groups were 2.81 ± 0.73 and 2.70 ± 0.84 L, respectively, at the first visit and did not change significantly at subsequent visits. In conclusion, no effect of ticagrelor on pulmonary function was seen in this cohort of patients with acute coronary syndromes compared to clopidogrel.

  6. Information Gap Analysis: near real-time evaluation of disaster response

    NASA Astrophysics Data System (ADS)

    Girard, Trevor

    2014-05-01

    Disasters, such as major storm events or earthquakes, trigger an immediate response by the disaster management system of the nation in question. The quality of this response is a large factor in its ability to limit the impacts on the local population. Improving the quality of disaster response therefore reduces disaster impacts. Studying past disasters is a valuable exercise to understand what went wrong, identify measures which could have mitigated these issues, and make recommendations to improve future disaster planning and response. While such ex post evaluations can lead to improvements in the disaster management system, there are limitations. The main limitation that has influenced this research is that ex post evaluations do not have the ability to inform the disaster response being assessed for the obvious reason that they are carried out long after the response phase is over. The result is that lessons learned can only be applied to future disasters. In the field of humanitarian relief, this limitation has led to the development of real time evaluations. The key aspect of real time humanitarian evaluations is that they are completed while the operation is still underway. This results in findings being delivered at a time when they can still make a difference to the humanitarian response. Applying such an approach to the immediate disaster response phase requires an even shorter time-frame, as well as a shift in focus from international actors to the nation in question's government. As such, a pilot study was started and methodology developed, to analyze disaster response in near real-time. The analysis uses the information provided by the disaster management system within the first 0 - 5 days of the response. The data is collected from publicly available sources such as ReliefWeb and sorted under various categories which represent each aspect of disaster response. This process was carried out for 12 disasters. The quantity and timeliness of information

  7. Salivary cortisol and behavioral response to social evaluative threat in adolescents with autism spectrum disorder.

    PubMed

    Edmiston, E Kale; Blain, Scott D; Corbett, Blythe A

    2017-02-01

    Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social behavior. One possible explanation for social communication deficits in ASD could be differences in biological systems that support responses to environmental stimuli. If so, it is unclear if differences in the arousal response to social stimuli in ASD are due to reduced interest in social information, or to an increased stress response. The hypothalamic pituitary adrenal axis facilitates arousal and the stress response to sensory input, including social stimuli. Previous research shows blunted cortisol response to social evaluative threat in children with ASD. The majority of prior work has focused on children with ASD, but adolescents with ASD are understudied. The adolescent period is of interest, as this developmental epoch is associated with increased salience of social evaluative threat in typically developing (TD) populations. In this study, we employed the Trier Social Stress Test (TSST), a laboratory paradigm that involves exposure to social evaluative threat, to study the cortisol and behavioral response to social evaluative threat in ASD and TD adolescents. Salivary cortisol data were collected at six time points before and after the TSST. Behavioral data were collected using video recordings of the TSST, which were then operationalized and coded. Paired sample t-tests were used to calculate within-group cortisol response to the TSST. Cortisol significantly increased in response to the TSST in the TD group but not the ASD group. The TD group showed a trend for more self-soothing behaviors during the stressor than the ASD group. The lack of a cortisol response to the TSST in the ASD group suggests that the TSST is not interpreted as stressful or salient for ASD adolescents. Autism Res 2017, 10: 346-358. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

  8. 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

    PubMed Central

    Croitoru, Octavian; Spiridon, Adela-Maria; Belu, Ionela; Turcu-Ştiolică, Adina; Neamţu, Johny

    2015-01-01

    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. PMID:26839733

  9. Attempting to hide our real thoughts: electrophysiological evidence from truthful and deceptive responses during evaluation.

    PubMed

    Dong, Guangheng; Wu, Haiyan

    2010-07-19

    This study seeks to investigate neural activity during a deceptive evaluation process. Attractive and unattractive facial photos were presented to participants who were then asked to evaluate and respond to these photos according to different cues (truthfulness or deceptiveness). Behavioral and event-related potential (ERP) activities were recorded while participants offered their truthful or deceptive responses based on their evaluations. Consistent with previous results on the old/new paradigm, deceptive responses required greater cognitive endeavor, as indicated by a larger later positive component (LPC). Meanwhile, deceptive responses on attractive items were more easily offered than deceptive replies on unattractive items, as indicated by smaller LPCs. Truthfulness towards attractive items was more easily conveyed than truthfulness towards unattractive items, as indicated by the smaller contingent negative variation (CNV). The potential reasons for these results are discussed.

  10. Evaluation of human response to structural vibrations induced by sonic booms

    NASA Technical Reports Server (NTRS)

    Sutherland, Louis C.; Czech, J.

    1992-01-01

    The topic is addressed of building vibration response to sonic boom and the evaluation of the associated human response to this vibration. An attempt is made to reexamine some of the issues addressed previously and to offer fresh insight that may assist in reassessing the potential impact of sonic boom over populated areas. Human response to vibration is reviewed first and a new human vibration response criterion curve is developed as a function of frequency. The difference between response to steady state versus impulsive vibration is addressed and a 'vibration exposure' or 'vibration energy' descriptor is suggested as one possible way to evaluate duration effects on response to transient vibration from sonic booms. New data on the acoustic signature of rattling objects are presented along with a review of existing data on the occurrence of rattle. Structural response to sonic boom is reviewed and a new descriptor, 'Acceleration Exposure Level' is suggested which can be easily determined from the Fourier Spectrum of a sonic boom. A preliminary assessment of potential impact from sonic booms is provided in terms of human response to vibration and detection of rattle based on a synthesis of the preceding material.

  11. Response of osteosarcoma to preoperative intravenous high-dose methotrexate chemotherapy: CT evaluation

    SciTech Connect

    Mail, J.T.; Cohen, M.D.; Mirkin, L.D.; Provisor, A.J.

    1985-01-01

    The histologic response of an osteosarcoma to preamputation high-dose methotrexate therapy can be used to determine the optimum maintenance chemotherapy regimen to be administered after amputation. This study evaluates computed tomography (CT) as a method of assessing the response of the tumor to the methotrexate therapy. Nine patients with nonmetastatic osteosarcoma of an extremity had a CT scan of the tumor at initial presentation. This was compared with a second CT scan after four courses of high-dose intravenous methotrexate. Each set of scans was evaluated for changes in bony destruction, soft-tissue mass, pattern of calcification, and extent of tumor involvement of the marrow cavity. These findings were correlated with the histologic response of the tumor as measured by the degree of tumor necrosis. The changes seen on CT correlated well with the degree of the histologic response in seven of the nine patients.

  12. A Comprehensive Evaluation System for Military Hospitals' Response Capability to Bio-terrorism.

    PubMed

    Wang, Hui; Jiang, Nan; Shao, Sicong; Zheng, Tao; Sun, Jianzhong

    2015-05-01

    The objective of this study is to establish a comprehensive evaluation system for military hospitals' response capacity to bio-terrorism. Literature research and Delphi method were utilized to establish the comprehensive evaluation system for military hospitals' response capacity to bio-terrorism. Questionnaires were designed and used to survey the status quo of 134 military hospitals' response capability to bio-terrorism. Survey indicated that factor analysis method was suitable to for analyzing the comprehensive evaluation system for military hospitals' response capacity to bio-terrorism. The constructed evaluation system was consisted of five first-class and 16 second-class indexes. Among them, medical response factor was considered as the most important factor with weight coefficient of 0.660, followed in turn by the emergency management factor with weight coefficient of 0.109, emergency management consciousness factor with weight coefficient of 0.093, hardware support factor with weight coefficient of 0.078, and improvement factor with weight coefficient of 0.059. The constructed comprehensive assessment model and system are scientific and practical.

  13. Non-invasive evaluation of therapeutic response in keloid scar using diffuse reflectance spectroscopy.

    PubMed

    Hsu, Chao-Kai; Tzeng, Shih-Yu; Yang, Chao-Chun; Lee, Julia Yu-Yun; Huang, Lynn Ling-Huei; Chen, Wan-Rung; Hughes, Michael; Chen, Yu-Wen; Liao, Yu-Kai; Tseng, Sheng-Hao

    2015-02-01

    The pathogenesis and ideal treatment of keloid are still largely unknown, and it is essential to develop an objective assessment of keloid severity to evaluate the therapeutic response. We previously reported that our diffuse reflectance spectroscopy (DRS) system could assist clinicians in understanding the functional and structural condition of keloid scars. The purpose of this study was to understand clinical applicability of our DRS system on evaluating the scar severity and therapeutic response of keloid. We analyzed 228 spectral data from 71 subjects with keloid scars. The scars were classified into mild (0-3), moderate (4-7) and severe (8-11) according to the Vancouver scar scale. We found that as the severity of the scar increased, collagen concentration and water content increased, and the reduced scattering coefficient at 800 nm and oxygen saturation (SaO2) decreased. Using the DRS system, we found that collagen bundles aligned in a specific direction in keloid scars, but not in normal scars. Water content and SaO2 may be utilized as reliable parameters for evaluating the therapeutic response of keloid. In conclusion, the results obtained here suggest that the DRS has potential as an objective technique with which to evaluate keloid scar severity. In addition, it may be useful as a tool with which to track longitudinal response of scars in response to various therapeutic interventions.

  14. A systematic evaluation of abscopal responses following radiotherapy in patients with metastatic melanoma treated with ipilimumab

    PubMed Central

    Chandra, Ravi A; Wilhite, Tyler J; Balboni, Tracy A; Alexander, Brian M; Spektor, Alexander; Ott, Patrick A; Ng, Andrea K; Hodi, F Stephen; Schoenfeld, Jonathan D

    2015-01-01

    Case reports and preclinical data suggest radiotherapy and immunotherapy may synergize to generate “abscopal” responses outside the radiation field. This phenomenon remains relatively unexplored, prompting our systematic evaluation of metastatic melanoma patients treated with the CTLA-4 inhibitor ipilimumab and palliative radiation therapy. We evaluated 47 consecutive metastatic melanoma patients treated with ipilimumab and 65 courses of radiation. Responses of index lesions outside the radiation field were compared before and after radiotherapy, and parameters associated with favorable response were assessed. Median survival was 28 months, with an estimated 20% 5-y survival. Index lesions shrank in 7 instances prior to radiation therapy (11%), compared with 16 instances (25%) after radiation therapy; in 11 of the latter instances (69%), the index lesion had been increasing in size prior to radiotherapy (P = 0.03). In 68% of cases, radiotherapy was associated with an improved rate of index lesion response (P = 0.006). Radiation fraction size ≤ 3 Gy was the only parameter identified associated with favorable index lesion response (P = 0.014). Our systematic review of melanoma patients treated with radiotherapy and ipilimumab suggests that a subset of patients may have more favorable out-of-field responses following treatment with radiation. Interestingly, we found that multiple fraction radiation regimens were associated with a more favorable response. These results are encouraging regarding potential synergies between radiation and immunotherapy, but suggest that attention and even prospective testing of radiation parameters critical to producing abscopal effects in human patients would be of value. PMID:26451318

  15. The proton pump inhibitor, omeprazole, but not lansoprazole or pantoprazole, is a metabolism-dependent inhibitor of CYP2C19: implications for coadministration with clopidogrel.

    PubMed

    Ogilvie, Brian W; Yerino, Phyllis; Kazmi, Faraz; Buckley, David B; Rostami-Hodjegan, Amin; Paris, Brandy L; Toren, Paul; Parkinson, Andrew

    2011-11-01

    As a direct-acting inhibitor of CYP2C19 in vitro, lansoprazole is more potent than omeprazole and other proton pump inhibitors (PPIs), but lansoprazole does not cause clinically significant inhibition of CYP2C19 whereas omeprazole does. To investigate this apparent paradox, we evaluated omeprazole, esomeprazole, R-omeprazole, lansoprazole, and pantoprazole for their ability to function as direct-acting and metabolism-dependent inhibitors (MDIs) of CYP2C19 in pooled human liver microsomes (HLM) as well as in cryopreserved hepatocytes and recombinant CYP2C19. In HLM, all PPIs were found to be direct-acting inhibitors of CYP2C19 with IC(50) values varying from 1.2 μM [lansoprazole; maximum plasma concentration (C(max)) = 2.2 μM] to 93 μM (pantoprazole; C(max) = 6.5 μM). In addition, we identified omeprazole, esomeprazole, R-omeprazole, and omeprazole sulfone as MDIs of CYP2C19 (they caused IC(50) shifts after a 30-min preincubation with NADPH-fortified HLM of 4.2-, 10-, 2.5-, and 3.2-fold, respectively), whereas lansoprazole and pantoprazole were not MDIs (IC(50) shifts < 1.5-fold). The metabolism-dependent inhibition of CYP2C19 by omeprazole and esomeprazole was not reversed by ultracentrifugation, suggesting that the inhibition was irreversible (or quasi-irreversible), whereas ultracentrifugation largely reversed such effects of R-omeprazole. Under various conditions, omeprazole inactivated CYP2C19 with K(I) (inhibitor concentration that supports half the maximal rate of inactivation) values of 1.7 to 9.1 μM and k(inact) (maximal rate of enzyme inactivation) values of 0.041 to 0.046 min(-1). This study identified omeprazole, and esomeprazole, but not R-omeprazole, lansoprazole, or pantoprazole, as irreversible (or quasi-irreversible) MDIs of CYP2C19. These results have important implications for the mechanism of the clinical interaction reported between omeprazole and clopidogrel, as well as other CYP2C19 substrates.

  16. Toward Diversity-Responsive Medical Education: Taking an Intersectionality-Based Approach to a Curriculum Evaluation

    ERIC Educational Resources Information Center

    Muntinga, M. E.; Krajenbrink, V. Q.; Peerdeman, S. M.; Croiset, G.; Verdonk, P.

    2016-01-01

    Recent years have seen a rise in the efforts to implement diversity topics into medical education, using either a "narrow" or a "broad" definition of culture. These developments urge that outcomes of such efforts are systematically evaluated by mapping the curriculum for diversity-responsive content. This study was aimed at…

  17. Student Response to Faculty Instruction (SRFI): An Empirically Derived Instrument to Measure Student Evaluations of Teaching

    ERIC Educational Resources Information Center

    Beitzel, Brian D.

    2013-01-01

    The Student Response to Faculty Instruction (SRFI) is an instrument designed to measure the student perspective on courses in higher education. The SRFI was derived from decades of empirical studies of student evaluations of teaching. This article describes the development of the SRFI and its psychometric attributes demonstrated in two pilot study…

  18. Weaving New Meanings: Evaluating Children's Written Responses to a Story Telling Resource Package

    ERIC Educational Resources Information Center

    Brady, Josephine; Millard, Elaine

    2012-01-01

    This paper documents an evaluation of children's written responses to a story telling package used in an intervention project set up by the National Association for the Teaching of English as part of the larger "Inspire Rotherham" literacy campaign. The brief was to provide a group of primary teachers with innovative and inspirational approaches…

  19. Preliminary evaluation of the Accident Response Mobile Manipulation System for accident site salvage operations

    SciTech Connect

    Trujillo, J.M.; Morse, W.D.; Jones, D.P.

    1994-10-01

    This paper describes and evaluates operational experiences with the Accident Response Mobile Manipulation System (ARMMS) during simulated accident site salvage operations which might involve nuclear weapons. The ARMMS is based upon a teleoperated mobility platform with two Schilling Titan 7F Manipulators.

  20. An Evaluation of Simultaneous Presentation and Differential Reinforcement with Response Cost to Reduce Packing

    ERIC Educational Resources Information Center

    Buckley, Scott D.; Newchok, Debra K.

    2005-01-01

    We evaluated the effects of multiple treatment procedures, including simultaneous presentation of preferred foods, on the packing behavior of a 9-year-old girl with autism. A reversal design was used to assess the effects of differential reinforcement with response cost alone and with simultaneous presentation. In addition, simultaneous…

  1. Development of Response Evaluation and Decision (Red) and Antisocial Behavior in Childhood and Adolescence

    ERIC Educational Resources Information Center

    Fontaine, Reid Griffith; Yang, Chongming; Dodge, Kenneth A.; Pettit, Gregory S.; Bates, John E.

    2009-01-01

    Using longitudinal data on 585 youths (48% female; 17% African American, 2% other ethnic minority), the authors examined the development of social response evaluation and decision (RED) across childhood (Study 1; kindergarten through Grade 3) and adolescence (Study 2; Grades 8 and 11). Participants completed hypothetical-vignette-based RED…

  2. An Evaluation of Three Methods of Saying "No" to Avoid an Escalating Response Class Hierarchy

    ERIC Educational Resources Information Center

    Mace, F. Charles; Pratt, Jamie L.; Prager, Kevin L.; Pritchard, Duncan

    2011-01-01

    We evaluated the effects of three different methods of denying access to requested high-preference activities on escalating problem behavior. Functional analysis and response class hierarchy (RCH) assessment results indicated that 4 topographies of problem behaviors displayed by a 13-year-old boy with high-functioning autism constituted an RCH…

  3. Appraisal, Coping, Task Performance, and Cardiovascular Responses during the Evaluated Speaking Task.

    ERIC Educational Resources Information Center

    Baggett, H. Lane; And Others

    1996-01-01

    Appraisal, coping, task performance, and cardiovascular responses were examined among men high and low in speech anxiety who prepared and performed a speech under evaluative conditions. Speech-anxious men saw the task as more threatening. They were more stressed, anxious, distracted, and aware of their emotions, focused on the passage of time, and…

  4. Evaluation of noise pollution level based upon community exposure and response data

    NASA Technical Reports Server (NTRS)

    Edmiston, R. D.

    1972-01-01

    The results and procedures are reported from an evaluation of noise pollution level as a predictor of annoyance, based on aircraft noise exposure and community response data. The measures of noise exposure presented include composite noise rating, noise exposure forecast, noise and number index. A proposed measure as a universal noise exposure measure for noise pollution level (L sub NP) is discussed.

  5. Physiological Response to Social Evaluative Threat in Adolescents with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Edmiston, E. Kale; Jones, Robin M.; Corbett, Blythe A.

    2016-01-01

    The Trier Social Stress Test (TSST) was employed to study response to social evaluative threat in male adolescents with Autism Spectrum Disorder (ASD, n = 21) and typical development (n = 13). Participants wore a mobile electrocardiogram to collect heart rate data. There were significant group effects on respiratory sinus arrhythmia (RSA), a…

  6. Further Evaluation of Response Interruption and Redirection as Treatment for Stereotypy

    ERIC Educational Resources Information Center

    Ahrens, Erin N.; Lerman, Dorothea C.; Kodak, Tiffany; Worsdell, April S.; Keegan, Courtney

    2011-01-01

    The effects of 2 forms of response interruption and redirection (RIRD)--motor RIRD and vocal RIRD--were examined with 4 boys with autism to evaluate further the effects of this intervention and its potential underlying mechanisms. In Experiment 1, the effects of motor RIRD and vocal RIRD on vocal stereotypy and appropriate vocalizations were…

  7. EVALUATION OF BIOLOGICALLY BASED DOSE-RESPONSE MODELING FOR DEVELOPMENTAL TOXICITY: A WORKSHOP REPORT

    EPA Science Inventory

    Evaluation of biologically based dose-response modeling for developmental toxicity: a workshop report.

    Lau C, Andersen ME, Crawford-Brown DJ, Kavlock RJ, Kimmel CA, Knudsen TB, Muneoka K, Rogers JM, Setzer RW, Smith G, Tyl R.

    Reproductive Toxicology Division, NHEERL...

  8. Do Social Goals, Ethical Evaluations, and Perceptions of Efficacy Lead Preadolescents to Behave Responsibly?

    ERIC Educational Resources Information Center

    Wood, Deborah N.; Quintanar, Rosalinda

    Based on the social cognitive perspective which assumes that children and teenagers internalize social values, this study focused on the psychological processes involved in the internalization of responsibility by young adolescents. The study examined whether preadolescents experienced social goals, ethical evaluations, and perceptions of efficacy…

  9. Evaluating Timing of Weaning Stress on Response to BVDV2 Vaccinations in Angus Calves

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was designed to evaluate the impact of environmental factors and genetic controls on response to vaccination against bovine viral diarrhea virus type 2 (BVDV2) in Purebred American Angus beef cattle. This study utilized 362 Angus calves born in the spring (n = 211) and fall (n = 151) of ...

  10. Reader-Response Theory and Instructors' Holistic Evaluating in and out of Their Fields.

    ERIC Educational Resources Information Center

    Anderson, Larry; And Others

    1994-01-01

    Claims that holistic scoring for schoolwide assessment of writing proficiency is influenced by the disciplines represented by the faculty readers. Describes in detail the findings of a study designed to measure reader bias in evaluation, a phenomenon suggested by reader-response theory. (HB)

  11. Extra Credit Micro-Incentives and Response Rates for Online Course Evaluations: Two Quasi-Experiments

    ERIC Educational Resources Information Center

    Sundstrom, Eric D.; Hardin, Erin E.; Shaffer, Matthew J.

    2016-01-01

    To extend prior findings on the motivational value of tiny, nonfinancial incentives, we conducted two quasi-experiments on the relationship of extra credit micro-incentives (ECMIs, worth =1% of course grade) and response rates for online course evaluations. Study 1 involved two advanced undergraduate psychology courses taught by the same…

  12. Exact evaluation of the quadratic longitudinal response function for an unmagnetized Maxwellian plasma

    SciTech Connect

    Layden, B.; Cairns, Iver H.; Robinson, P. A.; Percival, D. J.

    2012-07-15

    The quadratic longitudinal response function describes the second-order nonlinear response of a plasma to electrostatic wave fields. An explicit expression for this function in the weak-turbulence regime requires the evaluation of velocity-space integrals involving the velocity distribution function and various resonant denominators. Previous calculations of the quadratic longitudinal response function were performed by approximating the resonant denominators to facilitate the integration. Here, we evaluate these integrals exactly for a non-relativistic collisionless unmagnetized isotropic Maxwellian plasma in terms of generalized plasma dispersion functions, and correct certain aspects of expressions previously derived for these functions. We show that in the appropriate limits the exact expression reduces to the approximate form used for interactions between two fast waves and one slow wave, such as the electrostatic decay of Langmuir waves into Langmuir waves and ion sound waves, and the scattering of Langmuir waves off thermal ions.

  13. Early detection of disease program: Evaluation of the cellular immune response

    NASA Technical Reports Server (NTRS)

    Criswell, B. S.; Knight, V.; Martin, R. R.; Kasel, J. A.

    1974-01-01

    The early cellular responses of specific components of the leukocyte and epithelial cell populations to foreign challenges of both an infectious and noninfectious character were evaluated. Procedures for screening potential flight crews were developed, documented, and tested on a control population. Methods for preparing suitable populations of lymphocytes, polymorphonuclear leukocytes, macrophages, and epithelial cells were first established and evaluated. Epithelial cells from viral infected individuals were screened with a number of anti-viral antisera. This procedure showed the earliest indication of disease as well as providing a specific diagnosis to the physicians. Both macrophages and polymorphonuclear leukocytes were studied from normal individuals, smokers, and patients with viral infections. Newer techniques enabling better definition of lymphocyte subpopulations were then developed, namely the E and EAC rosette procedures for recognition of T (thymus-derived) and B (bone-marrow-derived) lymphocyte subpopulations. Lymphocyte and lymphocyte subpopulation response to multiple mitogens have been evaluated.

  14. Social anxiety and the cortisol response to social evaluation in children and adolescents.

    PubMed

    van den Bos, Esther; Tops, Mattie; Westenberg, P Michiel

    2017-04-01

    Contradictory findings have been reported on the relation between social anxiety and the cortisol response to social evaluation in youth. The present longitudinal study aimed to clarify this relation by taking pubertal development into account. Data were collected in two waves, two years apart, for a community sample of 196 participants, aged 8-17 years at Time 1. Pubertal development and social anxiety were assessed with self-report questionnaires. Salivary cortisol was obtained before and after participants completed the Leiden Public Speaking Task. Data were analyzed using regression analysis with clustered bootstrap. The dependent variable was the cortisol area under the curve. Social anxiety and pubertal development scores were decomposed into between- and within-participants components. Between participants, the relation between social anxiety and the cortisol response to public speaking varied with pubertal development: socially anxious individuals showed higher responses at low levels of pubertal development, but lower responses at high levels of pubertal development. Within participants, an increase in social anxiety over time was associated with a lower cortisol response. The results are in line with the suggestion that the responses of socially anxious individuals change from elevated in childhood to attenuated in adolescence and adulthood. Attenuation of the cortisol response is explained by theories proposing that the stress response changes with the duration of the stressor.

  15. Development and evaluation of fully automated demand response in large facilities

    SciTech Connect

    Piette, Mary Ann; Sezgen, Osman; Watson, David S.; Motegi, Naoya; Shockman, Christine; ten Hope, Laurie

    2004-03-30

    This report describes the results of a research project to develop and evaluate the performance of new Automated Demand Response (Auto-DR) hardware and software technology in large facilities. Demand Response (DR) is a set of activities to reduce or shift electricity use to improve electric grid reliability, manage electricity costs, and ensure that customers receive signals that encourage load reduction during times when the electric grid is near its capacity. The two main drivers for widespread demand responsiveness are the prevention of future electricity crises and the reduction of electricity prices. Additional goals for price responsiveness include equity through cost of service pricing, and customer control of electricity usage and bills. The technology developed and evaluated in this report could be used to support numerous forms of DR programs and tariffs. For the purpose of this report, we have defined three levels of Demand Response automation. Manual Demand Response involves manually turning off lights or equipment; this can be a labor-intensive approach. Semi-Automated Response involves the use of building energy management control systems for load shedding, where a preprogrammed load shedding strategy is initiated by facilities staff. Fully-Automated Demand Response is initiated at a building or facility through receipt of an external communications signal--facility staff set up a pre-programmed load shedding strategy which is automatically initiated by the system without the need for human intervention. We have defined this approach to be Auto-DR. An important concept in Auto-DR is that a facility manager is able to ''opt out'' or ''override'' an individual DR event if it occurs at a time when the reduction in end-use services is not desirable. This project sought to improve the feasibility and nature of Auto-DR strategies in large facilities. The research focused on technology development, testing, characterization, and evaluation relating to Auto

  16. CT versus FDG-PET/CT response evaluation in patients with metastatic colorectal cancer treated with irinotecan and cetuximab

    PubMed Central

    Skougaard, Kristin; Johannesen, Helle Hjorth; Nielsen, Dorte; Schou, Jakob Vasehus; Jensen, Benny Vittrup; Høgdall, Estrid V S; Hendel, Helle Westergren

    2014-01-01

    We compared morphologic computed tomography (CT)-based to metabolic fluoro-deoxy-glucose (FDG) positron emission tomography (PET)/CT-based response evaluation in patients with metastatic colorectal cancer and correlated the findings with survival and KRAS status. From 2006 to 2009, patients were included in a phase II trial and treated with cetuximab and irinotecan every second week. They underwent FDG-PET/CT examination at baseline and after every fourth treatment cycle. Response evaluation was performed prospectively according to Response Evaluation Criteria in Solid Tumors (RECIST 1.0) and retrospectively according to Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST). Best overall responses were registered. Sixty-one patients were eligible for response evaluation. Partial response (PR) rate was 18%, stable disease (SD) rate 64%, and progressive disease (PD) rate 18%. Partial metabolic response (PMR) rate was 56%, stable metabolic disease rate 33%, and progressive metabolic disease (PMD) rate 11%. Response agreement was poor, κ-coefficient 0.19. Hazard ratio for overall survival for responders (PR/PMR) versus nonresponders (PD/PMD) was higher for CT- than for FDG-PET/CT evaluation. Within patients with KRAS mutations, none had PR but 44% had PMR. In conclusion, morphologic and metabolic response agreement was poor primarily because a large part of the patients shifted from SD with CT evaluation to PMR when evaluated with FDG-PET/CT. Furthermore, a larger fraction of the patients with KRAS mutations had a metabolic treatment response. PMID:24941936

  17. Evaluating quantitative formulas for dose-response assessment of chemical mixtures.

    PubMed

    Hertzberg, Richard C; Teuschler, Linda K

    2002-12-01

    Risk assessment formulas are often distinguished from dose-response models by being rough but necessary. The evaluation of these rough formulas is described here, using the example of mixture risk assessment. Two conditions make the dose-response part of mixture risk assessment difficult, lack of data on mixture dose-response relationships, and the need to address risk from combinations of chemicals because of public demands and statutory requirements. Consequently, the U.S. Environmental Protection Agency has developed methods for carrying out quantitative dose-response assessment for chemical mixtures that require information only on the toxicity of single chemicals and of chemical pair interactions. These formulas are based on plausible ideas and default parameters but minimal supporting data on whole mixtures. Because of this lack of mixture data, the usual evaluation of accuracy (predicted vs. observed) cannot be performed. Two approaches to the evaluation of such formulas are to consider fundamental biological concepts that support the quantitative formulas (e.g., toxicologic similarity) and to determine how well the proposed method performs under simplifying constraints (e.g., as the toxicologic interactions disappear). These ideas are illustrated using dose addition and two weight-of-evidence formulas for incorporating toxicologic interactions.

  18. Evaluation of optimum profile modification curves of profile shifted spur gears based on vibration responses

    NASA Astrophysics Data System (ADS)

    Ma, Hui; Pang, Xu; Feng, Ranjiao; Wen, Bangchun

    2016-03-01

    In this paper, a mesh stiffness model is developed for profile shifted gears with addendum modifications and tooth profile modifications (TPMs). The time-varying mesh stiffness (TVMS), load sharing factor (LSF), loaded static transmission error (LSTE) and non-loaded static transmission error (NLSTE) of a profile shifted spur gear pair with TPMs are obtained by the analytical model. The optimum profile modification curve under different amounts of TPM is determined by analyzing the LSTE first. Then, considering the effect of NLSTE, finite element (FE) model of a geared rotor system is established. The system vibration responses under different TPM curves are analyzed and the optimum modification curve is further evaluated by amplitude frequency responses. The results show that the optimum modification curve is related to the amount of TPM and modification coefficients. The comparison of the optimum profile modification curves is evaluated by LSTE and vibration responses, which shows that the optimum modification curve should be determined by evaluating the vibration response of the geared rotor system in the low mesh frequency range.

  19. Dopamine Inactivation Efficacy Related to Functional DAT1 and COMT Variants Influences Motor Response Evaluation

    PubMed Central

    Bender, Stephan; Rellum, Thomas; Freitag, Christine; Resch, Franz; Rietschel, Marcella; Treutlein, Jens; Jennen-Steinmetz, Christine; Brandeis, Daniel; Banaschewski, Tobias; Laucht, Manfred

    2012-01-01

    Background Dopamine plays an important role in orienting, response anticipation and movement evaluation. Thus, we examined the influence of functional variants related to dopamine inactivation in the dopamine transporter (DAT1) and catechol-O-methyltransferase genes (COMT) on the time-course of motor processing in a contingent negative variation (CNV) task. Methods 64-channel EEG recordings were obtained from 195 healthy adolescents of a community-based sample during a continuous performance task (A-X version). Early and late CNV as well as motor postimperative negative variation were assessed. Adolescents were genotyped for the COMT Val158Met and two DAT1 polymorphisms (variable number tandem repeats in the 3′-untranslated region and in intron 8). Results The results revealed a significant interaction between COMT and DAT1, indicating that COMT exerted stronger effects on lateralized motor post-processing (centro-parietal motor postimperative negative variation) in homozygous carriers of a DAT1 haplotype increasing DAT1 expression. Source analysis showed that the time interval 500–1000 ms after the motor response was specifically affected in contrast to preceding movement anticipation and programming stages, which were not altered. Conclusions Motor slow negative waves allow the genomic imaging of dopamine inactivation effects on cortical motor post-processing during response evaluation. This is the first report to point towards epistatic effects in the motor system during response evaluation, i.e. during the post-processing of an already executed movement rather than during movement programming. PMID:22649558

  20. Impact of cytochrome P450 3A4-metabolized statins on the antiplatelet effect of a 600-mg loading dose clopidogrel and on clinical outcome in patients undergoing elective coronary stent placement.

    PubMed

    Trenk, Dietmar; Hochholzer, Willibald; Frundi, Devine; Stratz, Christian; Valina, Christian M; Bestehorn, Hans-Peter; Büttner, Heinz Joachim; Neumann, Franz-Josef

    2008-01-01

    Early studies suggested interactions between statins and clopidogrel. Based on the outcome and platelet data, there is now huge evidence of no interactions between statins and 75 to 300 mg clopidogrel; however, data with 600-mg loading are lacking. In a pre-specified analysis of the EXCELSIOR cohort, we investigated the interaction between statins, especially cytochrome P4503A4-metabolized atorvastatin and simvastatin, and the antiplatelet effects of a 600-mg loading dose of clopidogrel. We analyzed 1,395 patients scheduled for coronary angiography (CA). Patients received clopidogrel 600 mg at least two hours before CA and 75 mg daily thereafter in case of percutaneous coronary intervention (PCI). Statin medication on admission was continued unaltered until discharge. Platelet function was assessed by optical aggregometry and flow cytometry of adenosine diphosphate (ADP)-stimulated surface expression of CD62P, CD63 and PAC-1 before clopidogrel and immediately before CA. Residual platelet aggregation (RPA) after addition of ADP 5 muM was similar irrespective of statin treatment at baseline (p = 0.968). RPA at CA was 46.2 +/- 16.8% in patients without statin (n = 682), 45.5 +/- 17.0% in patients with atorvastatin (n = 255), 45.8 +/- 16.3% with simvastatin (n = 335), 47.3 +/- 14.9% with fluvastatin (n = 42) and 45.9 +/- 16.2% with pravastatin (n = 81; p = 0.962). Consistent results were obtained by flow cytometry. In patients with PCI (n = 553), the one-year incidence of death, myocardial infarction and target lesion reintervention did not differ between cohorts stratified according to statin co-medication (p = 0.645). Thus, peri-interventional atorvastatin and simvastatin had no effect on the antiplatelet activity of a loading dose of clopidogrel 600 mg and did not affect clinical outcome after PCI.

  1. An empirical comparison of effective concentration estimators for evaluating aquatic toxicity test responses

    SciTech Connect

    Bailer, A.J.; Hughes, M.R.; Denton, D.L.; Oris, J.T.

    2000-01-01

    Aquatic toxicity tests are statistically evaluated by either hypothesis testing procedures to derive a no-observed-effect concentration or by inverting regression models to calculate the concentration associated with a specific reduction from the control response. These latter methods can be described as potency estimation methods. Standard US Environmental Protection Agency (USEPA) potency estimation methods are based on two different techniques. For continuous or count response data, a nominally nonparametric method that assumes monotonic decreasing responses and piecewise linear patterns between successive concentration groups is used. For quantal responses, a probit regression model with a linear dose term is fit. These techniques were compared with a recently developed parametric regression-based estimator, the relative inhibition estimator, RIp. This method is based on fitting generalized linear models, followed by estimation of the concentration associated with a particular decrement relative to control responses. These estimators, with levels of inhibition (p) of 25 and 50%, were applied to a series of chronic toxicity tests in a US EPA region 9 database of reference toxicity tests. Biological responses evaluated in these toxicity tests included the number of young produced in three broods by the water flea (Ceriodaphnia dubia) and germination success and tube length data from the giant kelp (Macrocystis pyrifera). The greatest discrepancy between the RIp and standard US EPA estimators was observed for C. dubia. The concentration-response pattern for this biological endpoint exhibited nonmonotonicity more frequently than for any of the other endpoint. Future work should consider optimal experimental designs to estimate these quantities, methods for constructing confidence intervals, and simulation studies to explore the behavior of these estimators under known conditions.

  2. A responsive evaluation of mental health treatment in Cambodia: Intentionally addressing poverty to increase cultural responsiveness in therapy.

    PubMed

    Seponski, Desiree M; Lewis, Denise C; Megginson, Maegan C

    2014-01-01

    Mental health issues are significant contributors to the global burden of disease with the highest incidence in resource poor countries; 90% of those in need of mental health treatment reside in low resource countries but receive only 10% of the world's resources. Cambodia, the eighth least developed country in the world, serves as one example of the need to address mental health concerns in low-income, resource poor countries. The current study utilises responsive evaluation methodology to explore how poverty-stricken Cambodian clients, therapists and supervisors experience Western models of therapy as culturally responsive to their unique needs. Quantitative and qualitative data were triangulated across multiple stakeholders using numerous methods including a focus group, interviews, surveys, case illustrations and live supervision observation and analysed using constant comparative analysis. Emerging findings suggest that poverty, material needs, therapy location and financial situations greatly impact the daily lives and mental health conditions of Cambodians and hinder clients' therapeutic progress. The local community needs and context of poverty greatly hinder clients' therapeutic progress in therapy treatment and when therapy does not directly address the culture of poverty, clients did not experience therapy as valuable despite some temporary decreases in mental health symptoms.

  3. Ambient Pressure Evaluation Through Sub-Harmonic Response of Chirp-Sonicated Microbubbles.

    PubMed

    Liu, Siyu; Wu, Jun; Gu, Yuyang; Guo, Xiasheng; Tu, Juan; Xu, Di; Zhang, Dong

    2017-01-01

    The sub-harmonic response generated by oscillating ultrasound contrast microbubbles has been proven to be a potentially efficient and effective measure for non-invasive blood pressure evaluation. In this work, an improved approach to ambient pressure measurement is proposed, and the general principle underlying this approach is the combination of sub-harmonic responses of microbubbles with a chirp excitation technique. Agreement between theoretical and experimental studies indicates that compared with sinusoidal excitation, the chirp technique is beneficial in that it produces bubble sub-harmonics with higher amplitudes and lower generation thresholds and thus offers better sensitivity for ambient pressure evaluations. Studies that took the chirp parameters (e.g., central frequency, bandwidth and pulse length) into account were also carried out to determine an optimized routine for the proposed method.

  4. The effect of context on responses to racially ambiguous faces: changes in perception and evaluation

    PubMed Central

    2015-01-01

    Reactions to individuals who possess features associated with multiple racial groups may be particularly susceptible to external contextual influences, leading to meaningfully different racial perceptions and judgments in different situations. In the present study, we found that an extrinsic race-label cue not only changed evaluative associations activated by a racially ambiguous face, but also changed quickly occurring neural responses sensitive to racial perception. Behaviorally, prototypical Black faces and racially ambiguous faces labeled as Black activated more negative implicit associations than prototypical White faces and racially ambiguous faces labeled as White. Neurally, prototypical faces and racially ambiguous faces cued with the same race elicited similar responses. Specifically, prototypical Black and racially ambiguous faces labeled as Black elicited larger P200s but smaller N200s than prototypical White and racially ambiguous faces labeled as White. These results show that racial perception can be changed by an external cue and this, in turn, influences subsequent evaluative reactions. PMID:25344946

  5. Evaluating high resolution climate model predictability and skill in response to the Mount Pinatubo eruption

    NASA Astrophysics Data System (ADS)

    Gaddis, A. L.; Evans, K. J.

    2013-12-01

    A central goal of climate research is to determine the perceptible effect of climate change on humans; in other words, the regional and decadal scale effects of carbon dioxide forcing. Identifying the most pronounced and long-lasting responses of climate variables to forcing is important for decadal prediction since forcing terms are one of the sources of predictability on those time scales. Volcanic eruptions provide a powerful, transient forcing on the global climate system by injecting tons of sulfur compounds into the stratosphere that react to form sulfate aerosols. The Community Earth System Model is used to explore predictability in response to the Mount Pinatubo eruption. In this study, the Mount Pinatubo eruption is simulated at very high resolution (T341) using the Community Earth System Model. The predictability of responses to the eruption are calculated and compared with previous studies of the same model at lower resolution for two configurations. All three configurations are compared with observations to evaluate model skill. The Northern Hemisphere winter warming response to the eruption improves in spatial distribution and strength at higher resolution. Stratospheric humidity increases predictably in all model configurations, with spatial analysis showing the that response is centered over the tropical tropopause. The polar night jet response to the eruption is not well replicated for any configuration.

  6. Typicality effects in picture-word interference paradigm: An evaluation of the response exclusion hypothesis.

    PubMed

    Fang, Yanhong; Zhang, Jijia; Yin, Guanhai; Hu, Senqi; Zhang, Entao

    2015-06-01

    The response exclusion hypothesis suggests that the polarity of semantic effects in the picture-word interference paradigm is determined by the response-relevant criteria. Semantic interference effects would be observed when semantically related distractor words satisfy the response-relevant criteria; otherwise, semantic facilitation effects should be found. The purpose of this study was to further evaluate the response exclusion hypothesis by exploring the typicality effects in pictures naming. In two experiments, pictures of objects were named either in the context of verb distractor words with different typicality of passive functions or in the context of adjective distractor words with different typicality of characteristics. Facilitation effects were observed in context of typical verbs and adjectives, while interference effects were observed in the context of atypical verbs and adjectives. Given that neither typical nor atypical distractor words satisfy the response-relevant criteria to produce noun, these findings are problematic for the response exclusion hypothesis. Role of syntagmatic relationships in lexical retrieval was invoked to explain present findings.

  7. Unidimensional Measurement May Evaluate Target Lymph Nodal Response After Induction Chemotherapy for Nasopharyngeal Carcinoma

    PubMed Central

    Chen, Chuanben; Zhang, Mingwei; Xu, Yuanji; Yue, Qiuyuan; Bai, Penggang; Zhou, Lin; Xiao, Youping; Zheng, Dechun; Lin, Kongqi; Qiu, Sufang; Chen, Yunbin; Pan, Jianji

    2016-01-01

    Abstract The aim of the study was to evaluate whether short axis and long axis on axial and coronal magnetic resonance imaging planes would reflect the tumor burden or alteration in size after induction chemotherapy in nasopharyngeal carcinoma. Patients with pathologically confirmed nasopharyngeal carcinoma (n = 37) with at least 1 positive cervical lymph node (axial short axis ≥15 mm) were consecutively enrolled in this prospective study. Lymph nodal measurements were performed along its short axis and long axis in both axial and coronal magnetic resonance imaging planes at diagnosis and after 2 cycles of induction chemotherapy. In addition, lymph nodal volumes were automatically calculated in 3D treatment-planning system, which were used as reference standard. Student's t test or nonparametric Mann–Whitney U test was used to compare the continuous quantitative variables. Meanwhile, the κ statistic and McNemar's test were used to evaluate the degree of agreement and discordance in response categorization among different measurements. Axial short axis was significantly associated with volumes at diagnosis (P < 0.001). A good agreement (κ=0.583) was found between axial short axis and volumetric criteria. However, the inconsistent lymph nodal shrinkage in 4 directions was observed. Axial short-axis shrinking was more rapid than the other 3 parameters. Interestingly, when utilizing the alternative planes for unidimensional measurements to assess tumor response, coronal short-axis showed the best concordance (κ=0.792) to the volumes. Axial short axis may effectively reflect tumor burden or change in tumor size in the assessment of target lymph nodal response after induction chemotherapy for nasopharyngeal carcinoma. However, it should be noted that axial short axis may amplify the therapeutic response. In addition, the role of coronal short axis in the assessment of tumor response needs further evaluation. PMID:26945354

  8. Heart rate responses provide an objective evaluation of human disturbance stimuli in breeding birds.

    PubMed

    Ellenberg, Ursula; Mattern, Thomas; Seddon, Philip J

    2013-01-01

    Intuition is a poor guide for evaluating the effects of human disturbance on wildlife. Using the endangered Yellow-eyed penguin, Megadyptes antipodes, as an example, we show that heart rate responses provide an objective tool to evaluate human disturbance stimuli and encourage the wider use of this simple and low-impact approach. Yellow-eyed penguins are a flagship species for New Zealand's wildlife tourism; however, unregulated visitor access has recently been associated with reduced breeding success and lower first year survival. We measured heart rate responses of Yellow-eyed penguins via artificial eggs to evaluate a range of human stimuli regularly occurring at their breeding sites. We found the duration of a stimulus to be the most important factor, with elevated heart rate being sustained while a person remained within sight. Human activity was the next important component; a simulated wildlife photographer, crawling slowly around during his stay, elicited a significantly higher heart rate response than an entirely motionless human spending the same time at the same distance. Stimuli we subjectively might perceive as low impact, such as the careful approach of a 'wildlife photographer', resulted in a stronger response than a routine nest-check that involved lifting a bird up to view nest contents. A single, slow-moving human spending 20 min within 2 m from the nest may provoke a response comparable to that of 10 min handling a bird for logger deployment. To reduce cumulative impact of disturbance, any human presence in the proximity of Yellow-eyed penguins needs to be kept at a minimum. Our results highlight the need for objective quantification of the effects of human disturbance in order to provide a sound basis for guidelines to manage human activity around breeding birds.

  9. Heart rate responses provide an objective evaluation of human disturbance stimuli in breeding birds

    PubMed Central

    Ellenberg, Ursula; Mattern, Thomas; Seddon, Philip J.

    2013-01-01

    Intuition is a poor guide for evaluating the effects of human disturbance on wildlife. Using the endangered Yellow-eyed penguin, Megadyptes antipodes, as an example, we show that heart rate responses provide an objective tool to evaluate human disturbance stimuli and encourage the wider use of this simple and low-impact approach. Yellow-eyed penguins are a flagship species for New Zealand's wildlife tourism; however, unregulated visitor access has recently been associated with reduced breeding success and lower first year survival. We measured heart rate responses of Yellow-eyed penguins via artificial eggs to evaluate a range of human stimuli regularly occurring at their breeding sites. We found the duration of a stimulus to be the most important factor, with elevated heart rate being sustained while a person remained within sight. Human activity was the next important component; a simulated wildlife photographer, crawling slowly around during his stay, elicited a significantly higher heart rate response than an entirely motionless human spending the same time at the same distance. Stimuli we subjectively might perceive as low impact, such as the careful approach of a ‘wildlife photographer’, resulted in a stronger response than a routine nest-check that involved lifting a bird up to view nest contents. A single, slow-moving human spending 20 min within 2 m from the nest may provoke a response comparable to that of 10 min handling a bird for logger deployment. To reduce cumulative impact of disturbance, any human presence in the proximity of Yellow-eyed penguins needs to be kept at a minimum. Our results highlight the need for objective quantification of the effects of human disturbance in order to provide a sound basis for guidelines to manage human activity around breeding birds. PMID:27293597

  10. Digital Image Analysis for Morphometric Evaluation of Tissue Response after Implanting Alloplastic Vascular Prostheses

    NASA Astrophysics Data System (ADS)

    Zippel, Roland; Hoene, Andreas; Walschus, Uwe; Jarchow, Raymond; Ueberrueck, Torsten; Patrzyk, Maciej; Schlosser, Michael; Wilhelm, Lutz

    2006-07-01

    The aim of this study was to examine the suitability of digital image analysis, using the KS400 software system, for the morphometric evaluation of the tissue response after prosthesis implantation in an animal model. Twenty-four female pigs aged 10 weeks were implanted with infrarenal Dacron® prostheses for 14, 21, 28, and 116 days. Following the explantation and investigation of the neointima region, the expression of beta-1-integrin, the proliferation rate by means of Ki-67 positive cells, and the intima thickness were evaluated as exemplary parameters of the tissue response after implantation. Frozen tissue sections were immunohistochemically stained and subsequently examined using computer-aided image analysis. A maximum expression of 32.9% was observed for beta-1-integrin 14 days after implantation, gradually declining over time to 9.8% after 116 days. The proliferation rate was found to be 19% on day 14, increasing to 39% on day 21 with a subsequent gradual decline to 5% after 116 days. The intima thickness increased from 189.9 [mu]m on day 14 to 1228.0 [mu]m on day 116. In conclusion, digital image analysis was found to be an efficient and reproducible method for the morphometric evaluation of a peri-prosthetic tissue response.

  11. Clopidogrel metaboliser status based on point-of-care CYP2C19 genetic testing in patients with coronary artery disease.

    PubMed

    Erlinge, David; James, Stefan; Duvvuru, Suman; Jakubowski, Joseph A; Wagner, Henrik; Varenhorst, Christoph; Tantry, Udaya S; Brown, Patricia B; Small, David; Moser, Brian A; Sundseth, Scott S; Walker, Joseph R; Winters, Kenneth J; Gurbel, Paul A

    2014-05-05

    We compared results obtained with the Nanosphere Verigene® System, a novel point-of-care (POC) genetic test capable of analysing 11 CYP2C19 variants within 3 hours, to an established, validated genotyping method (Affymetrix™ DMET+; reference assay) for identifying extensive and reduced metabolisers of clopidogrel. Based on genotyping, patients (N=82) with stable coronary artery disease on clopidogrel 75 mg daily were defined as extensive metabolisers (*1/*1, *1/*17, *17/*17), reduced metabolisers (*1/*2, *1/*8, *2/*2, *2/*3), or of indeterminate metaboliser status (*2/*17). Pharmacokinetic exposure to clopidogrel's active metabolite and pharmacodynamic measures with P2Y12 reaction units (PRU) (VerifyNow®P2Y12 assay) and VASP PRI (PRI) were also assessed. There was a 99.9% overall concordance of marker-level data between the Nanosphere Verigene and DMET+ systems in identifying the CYP2C19 variants and 100% agreement in classifying the patients as extensive (n=59) or reduced metabolisers (n=15). Extensive metabolisers had significantly higher active metabolite exposure than reduced metabolisers (LS means 12.6 ng*h/ml vs 7.7 ng*h/ml; p<0.001). Extensive metabolisers also had lower PRU (LS means 158 vs 212; p=0.003) and VASP PRI (LS means 48% vs 63%, p=0.01) compared to reduced metabolisers. Rates of high on-treatment platelet reactivity were higher in reduced metabolisers compared to extensive metabolisers (VASP PRI ≥ 50%: 79% vs 47%; PRU >235: 33% vs 16%). The Nanosphere Verigene CBS system identified 11 CYP2C19 alleles in less than 3 hours with a high degree of accuracy when compared to a conventional method, and was further validated against pharmacokinetic and pharmacodynamic phenotypes.

  12. The 6 "ws" of rapid response systems: best practices for improving development, implementation, and evaluation.

    PubMed

    Lazzara, Elizabeth H; Benishek, Lauren E; Sonesh, Shirley C; Patzer, Brady; Robinson, Patricia; Wallace, Ruth; Salas, Eduardo

    2014-01-01

    Delays in care have been cited as one of the primary contributors of preventable mortality; thus, quality patient safety is often contingent upon the delivery of timely clinical care. Rapid response systems (RRSs) have been touted as one mechanism to improve the ability of suitable staff to respond to deteriorating patients quickly and appropriately. Rapid response systems are defined as highly skilled individual(s) who mobilize quickly to provide medical care in response to clinical deterioration. While there is mounting evidence that RRSs are a valid strategy for managing obstetric emergencies, reducing adverse events, and improving patient safety, there remains limited insight into the practices underlying the development and execution of these systems. Therefore, the purpose of this article was to synthesize the literature and answer the primary questions necessary for successfully developing, implementing, and evaluating RRSs within inpatient settings-the Who, What, When, Where, Why, and How of RRSs.

  13. Analytical ultrasonics for evaluation of composite materials response. Part 2: Generation and detection

    NASA Technical Reports Server (NTRS)

    Duke, J. C., Jr.; Henneke, E. G., II

    1986-01-01

    To evaluate the response of composite materials, it is imperative that the input excitation as well as the observed output be well characterized. This characterization ideally should be in terms of displacements as a function of time with high spatial resolution. Additionally, the ability to prescribe these features for the excitation is highly desirable. Various methods for generating and detecting ultrasound in advanced composite materials are examined. Characterization and tailoring of input excitation is considered for contact and noncontact, mechanical, and electromechanical devices. Type of response as well as temporal and spatial resolution of detection methods are discussed as well. Results of investigations at Virginia Tech in application of these techniques to characterizing the response of advanced composites are presented.

  14. Associations between maternal negative affect and adolescent's neural response to peer evaluation.

    PubMed

    Tan, Patricia Z; Lee, Kyung Hwa; Dahl, Ronald E; Nelson, Eric E; Stroud, Laura J; Siegle, Greg J; Morgan, Judith K; Silk, Jennifer S

    2014-04-01

    Parenting is often implicated as a potential source of individual differences in youths' emotional information processing. The present study examined whether parental affect is related to an important aspect of adolescent emotional development, response to peer evaluation. Specifically, we examined relations between maternal negative affect, observed during parent-adolescent discussion of an adolescent-nominated concern with which s/he wants parental support, and adolescent neural responses to peer evaluation in 40 emotionally healthy and depressed adolescents. We focused on a network of ventral brain regions involved in affective processing of social information: the amygdala, anterior insula, nucleus accumbens, and subgenual anterior cingulate, as well as the ventrolateral prefrontal cortex. Maternal negative affect was not associated with adolescent neural response to peer rejection. However, longer durations of maternal negative affect were associated with decreased responsivity to peer acceptance in the amygdala, left anterior insula, subgenual anterior cingulate, and left nucleus accumbens. These findings provide some of the first evidence that maternal negative affect is associated with adolescents' neural processing of social rewards. Findings also suggest that maternal negative affect could contribute to alterations in affective processing, specifically, dampening the saliency and/or reward of peer interactions during adolescence.

  15. Evaluation of response variables in computer-simulated virtual cataract surgery

    NASA Astrophysics Data System (ADS)

    Söderberg, Per G.; Laurell, Carl-Gustaf; Simawi, Wamidh; Nordqvist, Per; Skarman, Eva; Nordh, Leif

    2006-02-01

    We have developed a virtual reality (VR) simulator for phacoemulsification (phaco) surgery. The current work aimed at evaluating the precision in the estimation of response variables identified for measurement of the performance of VR phaco surgery. We identified 31 response variables measuring; the overall procedure, the foot pedal technique, the phacoemulsification technique, erroneous manipulation, and damage to ocular structures. Totally, 8 medical or optometry students with a good knowledge of ocular anatomy and physiology but naive to cataract surgery performed three sessions each of VR Phaco surgery. For measurement, the surgical procedure was divided into a sculpting phase and an evacuation phase. The 31 response variables were measured for each phase in all three sessions. The variance components for individuals and iterations of sessions within individuals were estimated with an analysis of variance assuming a hierarchal model. The consequences of estimated variabilities for sample size requirements were determined. It was found that generally there was more variability for iterated sessions within individuals for measurements of the sculpting phase than for measurements of the evacuation phase. This resulted in larger required sample sizes for detection of difference between independent groups or change within group, for the sculpting phase as compared to for the evacuation phase. It is concluded that several of the identified response variables can be measured with sufficient precision for evaluation of VR phaco surgery.

  16. [THE EVALUATION OF RESPONSIBILITY CITIZEN FOR ONE'S OWN HEALTH FROM THE POSITIONS OF MEDICAL WORKERS].

    PubMed

    Dauletkalieva, J A; Kulov, D B

    2015-01-01

    The article demonstrates necessity of implementing principle of solidary responsibility of citizenfore one's own health with purpose of health promotion and development of health care in country and all over the world. The analysis of national and international literature proved that human health in many ways depends on life style. Nowadays, population places the responsibility for one's own health to state, employers and medical personnel. The article presents main results of anonymous questionnaire survey carried out among 723 workers of municipal polyclinics. The software Statisitka was applied to determine relative frequency of occurrence of characteristic in different groups (percentage) and confidence range. The comparative analysis according the Student criterion was applied among physicians and paramedical personnel. The purpose of survey was to evaluate degree of responsibility of population for one's own health from point of view of medical personnel. It is established that 69.5% of physicians and 79.6% of paramedical personnel consider their patients responsible for implementation of prescribed recommendations. The opposite point of view have 30.5% of physicians and 20.4% of paramedical personnel. According opinion of 42.9% Of physicians and 48.9% of paramedical personnel human age has no impact on degree of one's own health caring. The physicians of polyclinics evaluate responsibility of citizenfor one's own health quite low. So, only 11. 6% of physicians and 28.6% of paramedical personnel of polyclinics provide positive reply to the asked question. The majority of physicians (37.4%) and medical nurses (34.2%) are convinced that to increase responsibility for one's own health the activities infield of health education are to be implemented. The application of the mechanism of co-payments for medical services is supported by 34.6% of physicians and 27.4% of medical nurses. The given question caused difficulties with answer among 20.2% of physicians and

  17. Adolescents' Increasing Stress Response to Social Evaluation: Pubertal Effects on Cortisol and Alpha-Amylase during Public Speaking

    ERIC Educational Resources Information Center

    van den Bos, Esther; de Rooij, Mark; Miers, Anne C.; Bokhorst, Caroline L.; Westenberg, P. Michiel

    2014-01-01

    Stress responses to social evaluation are thought to increase during adolescence, which may be due to pubertal maturation. However, empirical evidence is scarce. This study is the first to investigate the relation between pubertal development and biological responses to a social-evaluative stressor longitudinally. Participants performed the Leiden…

  18. Novel Oral P2Y12 Inhibitor Prasugrel vs. Clopidogrel in Patients with Acute Coronary Syndrome: Evidence Based on 6 Studies

    PubMed Central

    Jia, Min; Li, Zaibo; Chu, Hongtao; Li, Lin; Chen, Keyong

    2015-01-01

    Background Whether prasugrel can take the place of clopidogrel for patients with acute coronary syndrome (ACS) is not clear. The aim of this study was to perform a meta-analysis for systematically reviewing the evidence on prasugrel in comparison to clopidogrel in patients with ACS. Material/Methods Relevant prospective and retrospective studies were searched in databases. Six studies were finally included. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated to assess all causes of death, myocardial infarction (MI), stroke, major bleeding, major/minor bleeding, and stent thrombosis (for PCI performed). Results Compared with clopidogrel, prasugrel had similar risks of all cause of death (Pooled RR: 0.83; 95% CI: 0.64–1.06, p=0.14, I2=55%), MI (Pooled RR: 0.86; 95% CI: 0.71–1.04, p=0.12) and stroke (pooled RR: 0.88; 95% CI: 0.70–1.10, p=0.25). However, prasugrel was associated with significantly higher risk of both major bleeding (Pooled RR: 1.19; 95% CI: 0.99–1.44, p=0.06, I2=0%) and the risk of total major and minor bleeding (Pooled RR: 1.30; 95% CI: 1.15–1.48, p<0.0001, I2=0%). For the patients who underwent percutaneous coronary intervention (PCI), prasugrel was associated with significantly lower risk of stent thrombosis (Pooled RR: 0.47; 95% CI: 0.34–0.61, p<0.00001, I2=0%). Conclusions Prasugrel has similar effects as clopidogrel in terms of all causes of death, MI, and stroke in ACS patients. For the patients who underwent PCI, prasugrel contributes to lower risk of stent thrombosis. However, prasugrel is associated with significantly higher risk of bleeding. For the patients with active pathological bleeding or a history of stroke and/or TIA, prasugrel should not be recommended. PMID:25893318

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

    PubMed

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

    2013-01-01

    Objetivo: Evaluar a largo plazo el coste-efectividad de 12 meses de tratamiento con prasugrel frente a clopidogrel en pacientes con síndrome coronario agudo (SCA) sometidos a intervención coronaria percutánea (ICP) desde la perspectiva del sistema nacional de salud español. Métodos: Se desarrolló un modelo de Markov de transición entre estados para estimar los resultados en salud, los años de vida ajustados por calidad (AVACs), los años de vida (AV) y los costes a lo largo de la vida de los pacientes. Los datos clínicos fueron obtenidos de un análisis del ensayo clínico TRITON-TIMI 38. Los reingresos hospitalarios registrados durante el ensayo en un subestudio de pacientes provenientes de ocho países, (y las subsiguientes rehospitalizaciones fueron modeladas para acumularse más alla del horizonte temporal del ensayo) fueron asignados a grupos relacionados con el diagnóstico españoles para estimar los costes de hospitalización. Resultados: Los costes medios totales del tratamiento con prasugrel y clopidogrel fueron 11.427 ??y 10.910 ?, respectivamente. El coste medio del fármaco fue 538 ??superior para prasugrel frente a clopidogrel, pero los costes de rehospitalización a los 12 meses fueron 79 ??menores para prasugrel debido a la reducción en las tasas de revascularización. Los costes de hospitalización más allá de los 12 meses fueron 55 ??superiores con prasugrel, debido a la mayor esperanza de vida (+0,071 AV y +0,054 AVACs) asociada a la reducción de la tasa de infartos de miocardio no mortales en el grupo de prasugrel. El coste-efectividad incremental por año de vida y AVAC ganado con prasugrel fue 7.198 ??y 9.489 ?, respectivamente. Conclusión: Considerando el umbral de disponibilidad a pagar de 30.000 ?/ AVAC para España, prasugrel representa una opción coste-efectiva en comparación con clopidogrel en pacientes con SCA sometidos a ICP.

  20. Multiple aspects of the stress response under social evaluative threat: an electrophysiological investigation.

    PubMed

    Cavanagh, James F; Allen, John J B

    2008-01-01

    Affective traits and states may be important moderators of stress reactivity, providing insight into stress-related consequences on cognitive functioning. This study assessed cognitive control processes using response-related brain electrical activities-the error-related negativity (ERN) and error positivity (Pe)-that are sensitive to trait and state affect. To assess the role of cognitive control in affective and cortisol reactivity to social evaluative threat, 55 undergraduates first completed a standard task designed to elicit the ERN in order to index 'baseline' error monitoring. Participants then performed a difficult mathematical task designed to elicit the ERN under conditions of exposed failure and social evaluation. Baseline ERN amplitude predicted future cortisol reactivity to social evaluative threat in highly punishment-sensitive individuals (high self-reported Behavioral Inhibition System: Carver and White [1994. Behavioral inhibition, behavioral activation, and affective responses to impending reward and punishment: the BIS/BAS scales. J. Pers. Soc. Psych. 67, 319-333], although the presence of outliers suggest the need for replication. The math stress ERN amplitude was diminished in direct relationship to trait (punishment sensitivity) and state (fear and shame) negative affect. Individuals high in punishment sensitivity also showed specific deficits in task performance following error feedback under stress. High state affect related to a larger Pe amplitude. Results are interpreted as consequences of different motivational and affective reactivities under social evaluative threat.

  1. Pitfalls and guidelines for the numerical evaluation of moderate-order system frequency response

    NASA Technical Reports Server (NTRS)

    Frisch, H. P.

    1981-01-01

    The design and evaluation of a feedback control system via frequency response methods relies heavily upon numerical methods. In application, one can usually develop low order simulation models which for the most part are devoid of numerical problems. However, when complex feedback interactions, for example, between instrument control systems and their flexible mounting structure, must be evaluated, simulation models become moderate to large order and numerical problems become common. A large body of relevant numerical error analysis literature is summarized in a large language understandable to nonspecialists. The intent is to provide engineers using simulation models with an engineering feel for potential numerical problems without getting intertwined in the complexities of the associated mathematical theory. Guidelines are also provided by suggesting alternate state of the art methods which have good numerical evaluation characteristics.

  2. Study on corporate social responsibility evaluation system based on stakeholder theory

    NASA Astrophysics Data System (ADS)

    Ma, J.; Deng, Liming

    2011-10-01

    The issue of Corporate Social Responsibility (CSR) has been attracting the attention from many disciplines such as economics, management, laws, sociality and philosophy since last century. The purpose of this study is to explore the impact of CSR on performance and develop a CSR evaluation system. Building on the definition of CSR and Stakeholder theory, this article built a path-relationship model of CSR and business operation performance. The paper also constructed CSR evaluation system based on KLD index, GRJ report, CSR accounting account, SA8000, ISO14000 etc. The research provides a basis for future studies about the relationship between CSR and business performance and shed some light on the evaluation of CSR practices.

  3. New tools for detecting latent tuberculosis infection: evaluation of RD1-specific long-term response

    PubMed Central

    2009-01-01

    Background Interferon-gamma (IFN-γ) release assays (IGRAs) were designed to detect latent tuberculosis infection (LTBI). However, discrepancies were found between the tuberculin skin test (TST) and IGRAs results that cannot be attributed to prior Bacille Calmètte Guerin vaccinations. The aim of this study was to evaluate tools for improving LTBI diagnosis by analyzing the IFN-γ response to RD1 proteins in prolonged (long-term response) whole blood tests in those subjects resulting negative to assays such as QuantiFERON-TB Gold In tube (QFT-IT). Methods The study population included 106 healthy TST+ individuals with suspected LTBI (recent contact of smear-positive TB and homeless) consecutively enrolled. As controls, 13 healthy subjects unexposed to M. tuberculosis (TST-, QFT-IT-) and 29 subjects with cured pulmonary TB were enrolled. IFN-γ whole blood response to RD1 proteins and QFT-IT were evaluated at day 1 post-culture. A prolonged test evaluating long-term IFN-γ response (7-day) to RD1 proteins in diluted whole blood was performed. Results Among the enrolled TST+ subjects with suspected LTBI, 70/106 (66.0%) responded to QFT-IT and 64/106 (60.3%) to RD1 proteins at day 1. To evaluate whether a prolonged test could improve the detection of LTBI, we set up the test using cured TB patients (with a microbiologically diagnosed past pulmonary disease) who resulted QFT-IT-negative and healthy controls as comparator groups. Using this assay, a statistically significant difference was found between IFN-γ levels in cured TB patients compared to healthy controls (p < 0.006). Based on these data, we constructed a receiver operating characteristic (ROC) curve and we calculated a cut-off. Based on the cut-off value, we found that among the 36 enrolled TST+ subjects with suspected LTBI not responding to QFT-IT, a long term response to RD1 proteins was detected in 11 subjects (30.6%). Conclusion These results indicate that IFN-γ long-term response to M. tuberculosis RD1

  4. Trend tests for the evaluation of exposure-response relationships in epidemiological exposure studies

    PubMed Central

    Hothorn, Ludwig A; Vaeth, Michael; Hothorn, Torsten

    2009-01-01

    One possibility for the statistical evaluation of trends in epidemiological exposure studies is the use of a trend test for data organized in a 2 × k contingency table. Commonly, the exposure data are naturally grouped or continuous exposure data are appropriately categorized. The trend test should be sensitive to any shape of the exposure-response relationship. Commonly, a global trend test only determines whether there is a trend or not. Once a trend is seen it is important to identify the likely shape of the exposure-response relationship. This paper introduces a best contrast approach and an alternative approach based on order-restricted information criteria for the model selection of a particular exposure-response relationship. For the simple change point alternative H1 : π1 = ...= πq <πq+1 = ... = πk an appropriate approach for the identification of a global trend as well as for the most likely shape of that exposure-response relationship is characterized by simulation and demonstrated for real data examples. Power and simultaneous confidence intervals can be estimated as well. If the conditions are fulfilled to transform the exposure-response data into a 2 × k table, a simple approach for identification of a global trend and its elementary shape is available for epidemiologists. PMID:19265556

  5. International Working Group consensus response evaluation criteria in lymphoma (RECIL 2017).

    PubMed

    Younes, A; Hilden, P; Coiffier, B; Hagenbeek, A; Salles, G; Wilson, W; Seymour, J F; Kelly, K; Gribben, J; Pfreunschuh, M; Morschhauser, F; Schoder, H; Zelenetz, A D; Rademaker, J; Advani, R; Valente, N; Fortpied, C; Witzig, T E; Sehn, L H; Engert, A; Fisher, R I; Zinzani, P-L; Federico, M; Hutchings, M; Bollard, C; Trneny, M; Elsayed, Y A; Tobinai, K; Abramson, J S; Fowler, N; Goy, A; Smith, M; Ansell, S; Kuruvilla, J; Dreyling, M; Thieblemont, C; Little, R F; Aurer, I; Van Oers, M H J; Takeshita, K; Gopal, A; Rule, S; de Vos, S; Kloos, I; Kaminski, M S; Meignan, M; Schwartz, L H; Leonard, J P; Schuster, S J; Seshan, V E

    2017-04-03

    In recent years, the number of approved and investigational agents that can be safely administered for the treatment of lymphoma patients for a prolonged period of time has substantially increased. Many of these novel agents are evaluated in early-phase clinical trials in patients with a wide range of malignancies, including solid tumors and lymphoma. Furthermore, with the advances in genome sequencing, new "basket" clinical trial designs have emerged that select patients based on the presence of specific genetic alterations across different types of solid tumors and lymphoma. The standard response criteria currently in use for lymphoma are the Lugano Criteria which are based on 18-Fluoro-deoxyglucose positron emission tomography (FDG-PET) or bidimensional tumor measurements on computerized tomography (CT) scans. These differ from the RECIST criteria used in solid tumors, which use unidimensional measurements. The RECIL group hypothesized that single dimension measurement could be used to assess response to therapy in lymphoma patients, producing results similar to the standard criteria. We tested this hypothesis by analyzing 47,828 imaging measurements from 2983 individual adult and pediatric lymphoma patients enrolled on 10 multicenter clinical trials, and developed new lymphoma response criteria (RECIL 2017). We demonstrate that assessment of tumor burden in lymphoma clinical trials can use the sum of longest diameters of a maximum of three target lesions. Furthermore, we introduced a new provisional category of a minor response. We also clarified response assessment in patients receiving novel immune therapy and targeted agents that generate unique imaging situations.

  6. Evaluation of ex vivo human immune response against candidate antigens for a visceral leishmaniasis vaccine.

    PubMed

    Kumar, Rajiv; Goto, Yasuyuki; Gidwani, Kamlesh; Cowgill, Karen D; Sundar, Shyam; Reed, Steven G

    2010-05-01

    People cured from visceral leishmaniasis (VL) develop protection mediated by Th1-type cellular responses against new infections. We evaluated cytokine responses against 6 defined candidate vaccine antigens in 15 cured VL subjects and 5 healthy endemic controls with no evidence of previous exposure to Leishmania parasites. Of the 6 cytokines examined, only interferon-gamma (IFN-gamma) differentiated cured VL patients from non-exposed individuals, with cured patients mounting a significantly higher IFN-gamma response to a crude parasite antigen preparation. Among candidate vaccine antigens tested, the largest number of cured subjects recognized cysteine proteinase B, leading to heightened IFN-gamma responses, followed by sterol 24-c-methyltransferase. These two antigens were the most immunogenic and protective antigens in a murine VL model, indicating a relationship between T cell recall responses of humans cured from VL and protective efficacy in an experimental model. Further studies may help prioritize antigens for clinical development of a subunit vaccine against VL.

  7. Brain responses to cardiac electrical stimulation: a new EEG method for evaluating cardiac sensation.

    PubMed

    Suzuki, Hideaki; Hirose, Masanori; Watanabe, Satoshi; Fukuda, Koji; Fukudo, Shin; Shimokawa, Hiroaki

    2012-01-01

    Although cardiac sensation, such as palpitation or chest pain, is common and is sometimes a malignant sign of heart diseases, the mechanism by which the human brain responds to afferent signals from the heart remains unclear. In this study, we investigated whether electrical stimulation of the heart provokes brain responses in humans. We examined 15 patients (age: 65.4 ± 3.1 years old, 11 males and 4 females) implanted with either a cardiac pacemaker or cardiac resynchronization therapy (CRT) device. Electroencephalogram (EEG) was simultaneously recorded from the vertex during right ventricular pacing at 70-100 beats/min at baseline (1.5 V) and intense (6-8 V) stimulation sessions. We evaluated brain responses to cardiac electrical stimulation by measuring cerebral potentials that were obtained by subtracting the average of 100 EEG waves triggered by cardiac pacing during baseline stimulation from those during the intense stimulation. Intense stimulation of the cardiac pacemaker or CRT device reproducibly induced cardiac sensation in 6 out of the 15 patients; namely, the remaining 9 patients showed no reproducible response. Brain responses were evident by averaging cerebral potentials from all of the 15 patients and those from 6 patients with reproducible cardiac sensation. To the best our knowledge, this is the first report that demonstrates the brain responses to cardiac electrical stimulation in humans. This new method should be useful for examining pathophysiology of cardiac diseases with pathological cardiac sensation, including cardiac anxiety and silent myocardial ischemia.

  8. Evaluation of Neoadjuvant Chemotherapy Response with Dynamic Contrast Enhanced Breast Magnetic Resonance Imaging in Locally Advanced Invasive Breast Cancer

    PubMed Central

    Gezer, Naciye Sinem; Orbay, Özge; Balcı, Pınar; Durak, Merih Guray; Demirkan, Binnaz; Saydam, Serdar

    2014-01-01

    Objective The reliability of traditional methods such as physical examination, ultrasonography (US) and mammography is limited in determining the type of treatment response in patients with neoadjuvant chemotherapy (NAC) application for locally advanced breast cancer (LABC). Dynamic contrast-enhanced magnetic resonance imaging (MRI) is gaining popularity in the evaluation of NAC response. This study aimed to compare NAC response as determined by dynamic contrast-enhanced breast MRI in patients with LABC to histopathology that is the gold standard; and evaluate the compatibility of MRI, mammography and US with response types. Materials and Methods The US, mammography and MRI findings of 38 patients who received NAC with a diagnosis of locally advanced breast cancer and surgical treatment were retrospectively analyzed and compared to histopathology results. Type of response to treatment was determined according to the “Criteria in Solid Tumors Response Evolution 1.1” by mammography, US and MRI criteria. The relationship between response types as defined by all three imaging modalities and histopathology were evaluated, and the correlation of response type as detected by MRI and pathological response and histopathological type of breast cancer was further determined. For statistical analysis, the chi-square, paired t test, correlation and kappa tests were used. Results There is a statistical moderate positive correlation between response type according to pathology and MRI (kappa: 0.63). There was a weak correlation between response type according to mammography or US and according to pathology (kappa: 0.2). When the distribution of treatment response by MRI is stratified according to histopathological types, partial response was higher in all histopathological types similar to the type of pathologic response. When compared with pathology MRI detected treatment response accurately in 84.2% of the patients. Conclusion Dynamic contrast-enhanced breast MRI appears to

  9. Evaluation of response to immune checkpoint inhibitors: Is there a role for positron emission tomography?

    PubMed Central

    Bauckneht, Matteo; Piva, Roberta; Sambuceti, Gianmario; Grossi, Francesco; Morbelli, Silvia

    2017-01-01

    Strategies targeting intracellular negative regulators such as immune checkpoint inhibitors (ICPIs) have demonstrated significant antitumor activity across a wide range of solid tumors. In the clinical practice, the radiological effect of immunotherapeutic agents has raised several more relevant and complex challenges for the determination of their imaging-based response at single patient level. Accordingly, it has been suggested that the conventional Response Evaluation Criteria in Solid Tumors assessment alone, based on dimensional evaluation provided by computed tomography (CT), tends to underestimate the benefit of ICPIs at least in a subset of patients, supporting the need of immune-related response criteria. Different from CT, very few data are available for the evaluation of immunotherapy by means of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Moreover, since the antineoplastic activity of ICPIs is highly related to the activation of T cells against cancer cells, FDG accumulation might cause false-positive findings. Yet, discrimination between benign and malignant processes represents a huge challenge for FDG-PET in this clinical setting. Consequently, it might be of high interest to test the complex and variegated response to ICPIs by means of PET and thus it is worthwhile to ask if a similar introduction of immune-related PET-based criteria could be proposed in the future. Finally, PET might offer a new insight into the biology and pathophysiology of ICPIs thanks to a growing number of non-invasive immune-diagnostic approaches based on non-FDG tracers. PMID:28298962

  10. Impact of reticulated platelets on antiplatelet response to thienopyridines is independent of platelet turnover.

    PubMed

    Stratz, Christian; Nührenberg, Thomas; Amann, Michael; Cederqvist, Marco; Kleiner, Pascal; Valina, Christian M; Trenk, Dietmar; Neumann, Franz-Josef; Hochholzer, Willibald

    2016-10-28

    Reticulated platelets are associated with impaired antiplatelet response to thienopyridines. It is uncertain whether this interaction is caused by a decreased drug exposure due to high platelet turnover reflected by elevated levels of reticulated platelets or by intrinsic properties of reticulated platelets. This study sought to investigate if the impact of reticulated platelets on early antiplatelet response to thienopyridines is mainly caused by platelet turnover as previously suggested. Elective patients undergoing coronary intervention were randomised to loading with clopidogrel 600 mg or prasugrel 60 mg (n=200). Adenosine diphosphate (ADP)-induced platelet reactivity was determined by impedance aggregometry before, at 30, 60, 90, and 120 minutes and at day 1 after loading. Immature platelet count was assessed as marker of reticulated platelets by flow cytometry. Platelet reactivity increased with rising levels of immature platelet count in both groups. This effect was more distinctive in patients on clopidogrel as compared to patients on prasugrel. Overall, immature platelet count correlated well with on-treatment platelet reactivity at all time-points (p < 0.001). These correlations did not change over time in the entire cohort as well as in patients treated with clopidogrel or prasugrel indicating an effect independent of platelet turnover (comparison of correlations 120 minutes/day 1: p = 0.64). In conclusion, the association of immature platelet count with impaired antiplatelet response to thienopyridines is similar early and late after loading. This finding suggests as main underlying mechanism another effect of reticulated platelets on thienopyridines than platelet turnover.

  11. Quantitative evaluation of photic driving response for computer-aided diagnosis

    NASA Astrophysics Data System (ADS)

    Fukami, Tadanori; Ishikawa, Fumito; Ishikawa, Bunnoshin; Saito, Yoichi

    2008-12-01

    The aim of our research is the quantification of the photic driving response, a routine electroencephalogram (EEG) examination, for computer-aided diagnosis. It is well known that the EEG responds not only to the fundamental frequency but also to all sub and higher harmonics of a stimulus. In this study, we propose a method for detecting and evaluating responses in screening data for individuals. This method consists of two comparisons based on statistical tests. One is an intraindividual comparison between the EEG at rest and the photic stimulation (PS) response reflecting enhancement and suppression by PS, and the other is a comparison between data from an individual and a distribution of normals reflecting the position of the individual's data in the distribution of normals in the normal database. These tests were evaluated using the Z-value based on the Mann-Whitney U-test. We measured EEGs from 130 normal subjects and 30 patients with any of schizophrenia, dementia and epilepsy. Normal data were divided into two groups, the first consisting of 100 data for database construction and the second of 30 data for test data. Using our method, a prominent statistical peak of the Z-value was recognized even if the harmonics and alpha band overlapped. Moreover, we found a statistical difference between patients and the normal database at diagnostically helpful frequencies such as subharmonics, the fundamental wave, higher harmonics and the alpha frequency band.

  12. Analytical and experimental evaluations of Space Shuttle TPS tile vibration response

    NASA Technical Reports Server (NTRS)

    Piersol, A. G.; Pope, L. D.

    1982-01-01

    Analytical studies and laboratory experiments have been performed to evaluate the vibration response of the Space Shuttle Thermal Protection System (TPS) tiles due to the intense rocket generated acoustic noise during lift-off. The TPS tiles are mounted over the exterior of the Space Shuttle Orbiter structure through Strain Isolation Pads (SIP) which protect the tiles from thermal induced shear loads at their interface. The analytical predictions indicate that the response of a typical tile is governed by the structural vibration inputs through the SIP under the tile at frequencies below 250 Hz, and by the direct acoustic excitation over the exterior surface of the tile at frequencies above 250 Hz. An evaluation of the laboratory test data for this same tile, in which conditioned (partial) coherent output spectral analysis procedures were used, leads to exactly the same conclusion. The results demonstrate the power of conditioned spectral analysis procedures in identifying vibration response mechanisms when two or more of the inputs are highly correlated.

  13. The burden of conscientiousness? Examining brain activation and cortisol response during social evaluative stress.

    PubMed

    Dahm, Anne-Sophie; Schmierer, Phöbe; Veer, Ilya M; Streit, Fabian; Görgen, Anna; Kruschwitz, Johann; Wüst, Stefan; Kirsch, Peter; Walter, Henrik; Erk, Susanne

    2017-04-01

    Although conscientiousness has for a long time been considered generally adaptive, there are findings challenging this view, suggesting that conscientiousness might be less advantageous during uncontrollable stress. We here examined the impact of conscientiousness on brain activation during and the cortisol response following an uncontrollable social evaluative stress task in order to test this hypothesis. Brain activation and cortisol levels were measured during an fMRI stress task, where subjects (n=86) performed cognitive tasks containing preprogrammed failure under time pressure, while being monitored by a panel of experts inducing social-evaluative threat. The degree of conscientiousness was measured using the NEO-FFI. We observed a positive correlation between conscientiousness and salivary cortisol levels in response to the stressful task in male subjects only. In male subjects conscientiousness correlated positively with activation in right amygdala and left insula, and, moreover, mediated the influence of amygdala and insula activation on cortisol output. This pattern of brain activation can be interpreted as a disadvantageous response to uncontrollable stress to which highly conscientious individuals might be predisposed. This is the first study showing the effect of conscientiousness on physiology and brain activation to an uncontrollable psychosocial stressor. Our results provide neurobiological evidence for the hypothesis that conscientiousness should not just be seen as beneficial, but rather as a trait associated with either costs or benefits depending on the extent to which one is in control of the situation.

  14. Evaluation of a sudden brake warning system: effect on the response time of the following driver.

    PubMed

    Isler, Robert B; Starkey, Nicola J

    2010-07-01

    This study used a video-based braking simulation dual task to carry out a preliminary evaluation of the effect of a sudden brake warning system (SBWS) in a leading passenger vehicle on the response time of the following driver. The primary task required the participants (N=25, 16 females, full NZ license holders) to respond to sudden braking manoeuvres of a lead vehicle during day and night driving, wet and dry conditions and in rural and urban traffic, while concurrently performing a secondary tracking task using a computer mouse. The SBWS in the lead vehicle consisted of g-force controlled activation of the rear hazard lights (the rear indicators flashed), in addition to the standard brake lights. Overall, the results revealed that responses to the braking manoeuvres of the leading vehicles when the hazard lights were activated by the warning system were 0.34 s (19%) faster compared to the standard brake lights. The SBWS was particularly effective when the simulated braking scenario of the leading vehicle did not require an immediate and abrupt braking response. Given this, the SBWS may also be beneficial for allowing smoother deceleration, thus reducing fuel consumption. These preliminary findings justify a larger, more ecologically valid laboratory evaluation which may lead to a naturalistic study in order to test this new technology in 'real world' braking situations.

  15. The Multidimensional Character of Teaching Effectiveness: A Comparative Analysis of Student Evaluation Responses of Full and Part-Time Faculty.

    ERIC Educational Resources Information Center

    Obiekwe, Jerry C.

    This study compared college students' responses on their evaluations of the effectiveness of full- and part-time college faculty. A group of 1,101 students completed evaluation instruments for all courses taught by full-time faculty, and 2,067 students completed evaluations for all courses taught by part-time faculty in spring 1998. In fall 1998,…

  16. 33 CFR 155.5050 - Response plan development and evaluation criteria for nontank vessels carrying groups I through...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... evaluation criteria for nontank vessels carrying groups I through IV petroleum oil. 155.5050 Section 155.5050... petroleum oil. (a) Criteria for evaluating operability of response resources. The criteria used to evaluate... or operator of a nontank vessel that carries groups I through IV petroleum oil as cargo must...

  17. Toward diversity-responsive medical education: taking an intersectionality-based approach to a curriculum evaluation.

    PubMed

    Muntinga, M E; Krajenbrink, V Q E; Peerdeman, S M; Croiset, G; Verdonk, P

    2016-08-01

    Recent years have seen a rise in the efforts to implement diversity topics into medical education, using either a 'narrow' or a 'broad' definition of culture. These developments urge that outcomes of such efforts are systematically evaluated by mapping the curriculum for diversity-responsive content. This study was aimed at using an intersectionality-based approach to define diversity-related learning objectives and to evaluate how biomedical and sociocultural aspects of diversity were integrated into a medical curriculum in the Netherlands. We took a three-phase mixed methods approach. In phase one and two, we defined essential learning objectives based on qualitative interviews with school stakeholders and diversity literature. In phase three, we screened the written curriculum for diversity content (culture, sex/gender and class) and related the results to learning objectives defined in phase two. We identified learning objectives in three areas of education (medical knowledge and skills, patient-physician communication, and reflexivity). Most diversity content pertained to biomedical knowledge and skills. Limited attention was paid to sociocultural issues as determinants of health and healthcare use. Intersections of culture, sex/gender and class remained mostly unaddressed. The curriculum's diversity-responsiveness could be improved by an operationalization of diversity that goes beyond biomedical traits of assumed homogeneous social groups. Future efforts to take an intersectionality-based approach to curriculum evaluations should include categories of difference other than culture, sex/gender and class as separate, equally important patient identities or groups.

  18. Evaluating the dynamic response of in-flight thrust calculation techniques during throttle transients

    NASA Technical Reports Server (NTRS)

    Ray, Ronald J.

    1994-01-01

    New flight test maneuvers and analysis techniques for evaluating the dynamic response of in-flight thrust models during throttle transients have been developed and validated. The approach is based on the aircraft and engine performance relationship between thrust and drag. Two flight test maneuvers, a throttle step and a throttle frequency sweep, were developed and used in the study. Graphical analysis techniques, including a frequency domain analysis method, were also developed and evaluated. They provide quantitative and qualitative results. Four thrust calculation methods were used to demonstrate and validate the test technique. Flight test applications on two high-performance aircraft confirmed the test methods as valid and accurate. These maneuvers and analysis techniques were easy to implement and use. Flight test results indicate the analysis techniques can identify the combined effects of model error and instrumentation response limitations on the calculated thrust value. The methods developed in this report provide an accurate approach for evaluating, validating, or comparing thrust calculation methods for dynamic flight applications.

  19. Evaluation of age-dependent response to NMDA receptor antagonism in zebrafish.

    PubMed

    Menezes, Fabiano Peres; Kist, Luiza Wilges; Bogo, Maurício Reis; Bonan, Carla Denise; Da Silva, Rosane Souza

    2015-04-01

    Imbalances in glutamatergic signaling have been proposed as the cause of several neurological disturbances. The use of MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, to mimic features of these neurological disorders is effective both in mammals and in fish. However, the variability of the subunits comprising the NMDA receptor during development alters the pharmacokinetic properties of the receptor and leads to different responses to this drug. Here, we evaluated the locomotor response of zebrafish to MK-801 (1, 5, and 20 μM) through the development (30 days postfertilization [dpf] to 2 years postfertilization [ypf]). The NMDA receptor subunit gene expression was also analyzed through the development (7 dpf to 2 ypf). Zebrafish displayed an age-related response to MK-801 with a higher response at 60 and 120 dpf. The magnitude of hyperlocomotion promoted by MK-801 seems to be less powerful for zebrafish in relation to rodents. The verification of expression levels in zebrafish NMDA receptor subunits shows that NR1.1 had a slight reduction throughout the development, while the NR2 subunits, especially NR2A.2 and NR2C.1, vary their expression levels according to the stage of development. The time-specific locomotor response to MK-801 through the development could be a consequence of differential NMDA receptor subunit expression. This result of developmental response to MK-801 is a crucial component in the consolidation of zebrafish as a suitable model to study glutamatergic neurotransmission in early phases.

  20. Beating the heat: development and evaluation of a Canadian hot weather health-response plan.

    PubMed Central

    Smoyer-Tomic, K E; Rainham, D G

    2001-01-01

    An increasing number of cities subject to hazardous summer weather in the United States and Canada have begun to develop and implement hot weather response plans to prevent heat-related illnesses and deaths. In this study we focus on heat-mortality relationships in Toronto, Ontario, between 1980 and 1996 and evaluate the potential effectiveness of the city's interim hot weather-health response plan. Using two heat stress indexes--humidex and apparent temperature--we identified excess mortality associated with hot and humid weather and then estimated excess deaths for hot and cool summers. Mortality rates for all ages and for > 64 years age groups rose with increasing humidex and apparent temperature, with no significant increase for the population < 65 years. Excess mortality occurred as low as the 30-35 degrees C humidex range, which is below the 40 degrees C humidex used to issue a heat warning under Toronto's interim hot weather response plan. During a hot summer (such as 1988 or 1995), 32 excess deaths would be expected, whereas 34 fewer deaths than baseline levels would be expected during a cool summer like 1982 or 1992. Days with high humidex levels occur infrequently in Toronto, and thus exposure is limited under current climatic conditions. In the event of a warming climate, more days with dangerously high humidex levels are likely to occur, and summer deaths are expected to increase. Toronto's hot weather health-response plan is an important early step for adaptation to climate change. PMID:11748031

  1. Beating the heat: development and evaluation of a Canadian hot weather health-response plan.

    PubMed

    Smoyer-Tomic, K E; Rainham, D G

    2001-12-01

    An increasing number of cities subject to hazardous summer weather in the United States and Canada have begun to develop and implement hot weather response plans to prevent heat-related illnesses and deaths. In this study we focus on heat-mortality relationships in Toronto, Ontario, between 1980 and 1996 and evaluate the potential effectiveness of the city's interim hot weather-health response plan. Using two heat stress indexes--humidex and apparent temperature--we identified excess mortality associated with hot and humid weather and then estimated excess deaths for hot and cool summers. Mortality rates for all ages and for > 64 years age groups rose with increasing humidex and apparent temperature, with no significant increase for the population < 65 years. Excess mortality occurred as low as the 30-35 degrees C humidex range, which is below the 40 degrees C humidex used to issue a heat warning under Toronto's interim hot weather response plan. During a hot summer (such as 1988 or 1995), 32 excess deaths would be expected, whereas 34 fewer deaths than baseline levels would be expected during a cool summer like 1982 or 1992. Days with high humidex levels occur infrequently in Toronto, and thus exposure is limited under current climatic conditions. In the event of a warming climate, more days with dangerously high humidex levels are likely to occur, and summer deaths are expected to increase. Toronto's hot weather health-response plan is an important early step for adaptation to climate change.

  2. Evaluation of the Hair Cell Regeneration in Zebrafish Larvae by Measuring and Quantifying the Startle Responses

    PubMed Central

    Wang, Changquan; Zhong, Zhenmin; Sun, Peng

    2017-01-01

    The zebrafish has become an established model organism for the study of hearing and balance systems in the past two decades. The classical approach to examine hair cells is to use dye to conduct selective staining, which shows the number and morphology of hair cells but does not reveal their function. Startle response is a behavior closely related to the auditory function of hair cells; therefore it can be used to measure the function of hair cells. In this study, we developed a device to measure the startle response of zebrafish larvae. By applying various levels of stimulus, it showed that the system can discern a 10 dB difference. The hair cell in zebrafish can regenerate after damage due to noise exposure or drug treatment. With this device, we measured the startle response of zebrafish larvae during and after drug treatment. The results show a similar trend to the classical hair cell staining method. The startle response was reduced with drug treatment and recovered after removal of the drug. Together it demonstrated the capability of this behavioral assay in evaluating the hair cell functions of fish larvae and its potential as a high-throughput screening tool for auditory-related gene and drug discovery. PMID:28250994

  3. Evaluating the responses of a territorial solitary carnivore to potential mates and competitors

    PubMed Central

    Allen, Maximilian L.; Yovovich, Veronica; Wilmers, Christopher C.

    2016-01-01

    Successful communication is critical to the fitness of individuals and maintenance of populations, but less is known regarding the social contexts and reactions to scent marking by other individuals in solitary carnivores, including pumas. We evaluated the responses of resident male pumas to visitation and scent marking by potential competitors (other male pumas) and potential mates (female pumas) by capturing and marking 46 pumas (Puma concolor), and documenting scent marking behaviours using motion-triggered video cameras. By comparing resident male puma visitation rates and communication behaviours in response to either male or female visitors, we found that their visitation and communication behaviours were best explained by the combination of visitation by both competitors and potential mates. Resident males returned to scent marking sites more quickly and increased their rate of flehmen response after visitation by a females, while they increased their rate of visitation and duration of visits in response to other males. Male pumas also visited less frequently in summer and autumn when female visitation rates were lower, but males created nearly twice as many scrapes during these visits. This study suggests that advertising for mates when scent marking may sometimes overshadow the importance of deterring competitors and claiming territory. PMID:27251230

  4. Clinical evaluation of the vector algorithm for neonatal hearing screening using automated auditory brainstem response.

    PubMed

    Keohane, Bernie M; Mason, Steve M; Baguley, David M

    2004-02-01

    A novel auditory brainstem response (ABR) detection and scoring algorithm, entitled the Vector algorithm is described. An independent clinical evaluation of the algorithm using 464 tests (120 non-stimulated and 344 stimulated tests) on 60 infants, with a mean age of approximately 6.5 weeks, estimated test sensitivity greater than 0.99 and test specificity at 0.87 for one test. Specificity was estimated to be greater than 0.95 for a two stage screen. Test times were of the order of 1.5 minutes per ear for detection of an ABR and 4.5 minutes per ear in the absence of a clear response. The Vector algorithm is commercially available for both automated screening and threshold estimation in hearing screening devices.

  5. Effects of glyphosate on hepatic tissue evaluating melanomacrophages and erythrocytes responses in neotropical anuran Leptodactylus latinasus.

    PubMed

    Pérez-Iglesias, Juan Manuel; Franco-Belussi, Lilian; Moreno, Liliana; Tripole, Susana; de Oliveira, Classius; Natale, Guillermo Sebastián

    2016-05-01

    Glyphosate (GLY) is the most used herbicide worldwide and its effects on anurans are well known. Pollutants can cause physiological and morphological effects. Therefore, this study evaluated the effects of GLY on hepatic melanomacrophages as a response to environmental stressors. Three treatments were exposed to different concentrations of pure GLY (100, 1000, and 10,000 μg g(-1), respectively), and there was also a control group. After the experimental time, liver and blood were analyzed. Melanomacrophages (MMCs) were located between the hepatocyte cordons, close to sinusoids. GLY increased the melanin area in MMCs of Leptodactylus latinasus exposed since lowest concentration until highest concentration. GLY also changed the occurrence of hepatic catabolism pigments into melanomacrophages and erythrocyte nuclear abnormalities; therefore, it can interfere with the hepatic metabolism. In conclusion, GLY promotes alterations in the hepatic tissue and erythrocyte nuclear abnormalities. Furthermore, MMCs may be useful as morphological responses of GLY effects.

  6. Multivariate data analysis to evaluate the fingerprint peaks responsible for the cytotoxic activity of Mallotus species.

    PubMed

    Tistaert, C; Chataigné, G; Dejaegher, B; Rivière, C; Nguyen Hoai, N; Chau Van, M; Quetin-Leclercq, J; Vander Heyden, Y

    2012-12-01

    The Mallotus genus comprises numerous species used as traditional medicines in oriental countries and provides scientists a broad basis in the search for pharmacologically active constituents. In this paper, the cytotoxicity of 39 Mallotus extracts, different in species, part of the plant used, origin, and harvest season, is evaluated combining cytotoxicity assays with fingerprint technology and data handling tools. At first, the antiproliferative activity of the plant extracts is analyzed both on a non-cancerous cell line (WI-38--human lung fibroblast) and on a cancerous cell line (HeLa human cervix carcinoma). The results are linked to a data set of high-performance liquid chromatographic fingerprint profiles of the samples using multivariate calibration techniques. The regression coefficients of the multivariate model are then evaluated to indicate those peaks potentially responsible for the cytotoxic activity of the Mallotus extracts. In a final step, the cytotoxic extracts are analyzed by HPLC-MS and the indicated peaks identified.

  7. Evaluating the international humanitarian system: rationale, process and management of the joint evaluation of the international response to the Rwanda genocide.

    PubMed

    Dabelstein, N

    1996-12-01

    The Rwanda evaluation has been termed a landmark in evaluation, not only because of its quality and the insights it has produced. It was also an unprecedented international collaboration to learn the lessons from the immense tragedy that was the genocide in Rwanda and its aftermath. This paper reports on the rationale, process and management of the joint evaluation of the international response to the Great Lakes crisis of 1994-5.

  8. Evaluation of lamb and calf responses to Rift Valley fever MP-12 vaccination.

    PubMed

    Wilson, William C; Bawa, Bhupinder; Drolet, Barbara S; Lehiy, Chris; Faburay, Bonto; Jasperson, Dane C; Reister, Lindsey; Gaudreault, Natasha N; Carlson, Jolene; Ma, Wenjun; Morozov, Igor; McVey, D Scott; Richt, Jürgen A

    2014-08-06

    Rift Valley fever (RVF) is an important viral disease of animals and humans in Africa and the Middle East that is transmitted by mosquitoes. The disease is of concern to international agricultural and public health communities. The RVFV MP-12 strain has been the most safety tested attenuated vaccine strain; thus it is being considered as a potential vaccine for the US national veterinary stockpile. This study was designed to establish safety protocols for large animal research with virulent RVF viruses, establish a target host immune response baseline using RVF MP-12 strain, and independently evaluate this strain as a potential US emergency response vaccine. Ten, approximately four month-old lambs and calves were vaccinated with RVF MP-12 strain; two additional animals per species provided negative control specimens. The animals were monitored for clinical and immune response, fever, and viremia. Two animals per species were sacrificed on 2, 3, 4, 10 and 28 days post infection and full necropsies were performed for histopathological examination. No clinical or febrile responses were observed in this study. The onset and titer of the immune response is discussed. There was no significant histopathology in the lambs; however, 6 out of 10 vaccinated calves had multifocal, random areas of hepatocellular degeneration and necrosis. RVF MP12 antigen was detected in these areas of necrosis by immunohistochemistry in one calf. This study provides independent and baseline information on the RVF MP-12 attenuated vaccination in vaccine relevant age target species and indicates the importance of performing safety testing on vaccine relevant aged target animals.

  9. Are Auditory Steady-State Responses Useful to Evaluate Severe-to-Profound Hearing Loss in Children?

    PubMed Central

    Grasel, Signe Schuster; de Almeida, Edigar Rezende; Beck, Roberto Miquelino de Oliveira; Goffi-Gomez, Maria Valéria Schmidt; Ramos, Henrique Faria; Rossi, Amanda Costa; Koji Tsuji, Robinson; Bento, Ricardo Ferreira; de Brito, Rubens

    2015-01-01

    Objective. To evaluate Auditory Steady-State Responses (ASSR) at high intensities in pediatric cochlear implant candidates and to compare the results to behavioral tests responses. Methods. This prospective study evaluated 42 children with suspected severe-to-profound hearing loss, aged from 3 to 72 months. All had absent ABR and OAE responses. ASSR were evoked using binaural single frequency stimuli at 110 dB HL with a 10 dB down-seeking procedure. ASSR and behavioral test results were compared. Results. Forty-two subjects completed both ASSR and behavioral evaluation. Eleven children (26.2%) had bilateral responses. Four (9.5%) showed unilateral responses in at least two frequencies, all confirmed by behavioral results. Overall 61 ASSR responses were obtained, most (37.7%) in 500 Hz. Mean thresholds were between 101.3 and 104.2 dB HL. Among 27 subjects with absent ASSR, fifteen had no behavioral responses. Seven subjects showed behavioral responses with absent ASSR responses. No spurious ASSR responses were observed at 100 or 110 dB HL. Conclusion. ASSR is a valuable tool to detect residual hearing. No false-positive ASSR results were observed among 42 children, but in seven cases with absent ASSR, the test underestimated residual hearing as compared to the behavioral responses. PMID:26557677

  10. Development of a scale to evaluate young children's responses to uncertainty and low environmental structure.

    PubMed

    Sanchez, Amanda L; Cornacchio, Danielle; Chou, Tommy; Leyfer, Ovsanna; Coxe, Stefany; Pincus, Donna; Comer, Jonathan S

    2017-01-01

    Intolerance of Uncertainty (IU), defined as the dispositional interpretation of uncertain or ambiguous events as stressful and problematic, has been linked to excessive worry and other anxiety-related problems in adults and youth. IU has been conceptualized as a vulnerability factor for excessive worry and anxiety, but the historical absence of a supported measure of IU in young children has hampered longitudinal research needed to evaluate temporal relationships between IU and anxiety and the differential developmental pathways of IU leading to different anxiety disorders and depression. The present study evaluated the psychometric properties of a newly developed 17-item parent-report measure of younger children's Responses to Uncertainty and Low Environmental Structure (i.e., the RULES questionnaire). We examined the preliminary structure, reliability, and validity of the RULES within a treatment-seeking sample of children aged 3-10 (N=160) with anxiety. Findings from an exploratory factor analysis supported a one-factor model that retained all 17 items. The RULES demonstrated strong internal consistency, and predictive, convergent, and divergent validity. In this early childhood sample, the RULES also showed stronger associations with anxiety than did a previously supported measure of IU developed for older youth, and showed preliminary sensitivity to treatment-related change. Findings provide preliminary psychometric support for the RULES as a parent-report measure of children's responses to uncertainty and low environmental structure that may inform etiologic models of anxiety.

  11. Laboratory and field evaluation of brown dog tick behavioral responses to potential semiochemicals.

    PubMed

    Carnohan, Lucas P; Kaufman, Phillip E; Allan, Sandra A; Gezan, Salvador A; Weeks, Emma N I

    2017-02-01

    The brown dog tick, Rhipicephalus sanguineus sensu lato (Parasitiformis: Ixodidae), is an ectoparasite of dogs that can be found worldwide. This tick poses unique difficulties in management because it can complete its entire life cycle indoors and has demonstrated acaricide resistance. The ability to monitor for tick presence and abundance is necessary for developing effective control programs. As such, an evaluation of adult brown dog tick behavioral responses to 16 potential semiochemicals was undertaken using Y-tube and straight-tube olfactometers. Both sexes of ticks were activated by nine of the 16 semiochemicals tested, including 300μg of 1-octen-3-ol, benzaldehyde, benzyl alcohol, hexanoic acid, nonanoic acid, methyl salicylate, o-nitrophenol, 2,6-dichlorophenol and salicylaldehyde. Rhipicephalus sanguineus s.l. behaviors including movement speed, direction and duration, as well as turning, were quantified following exposure to the same nine chemicals in a straight-tube olfactometer, individually at 300μg and as mixtures. Three individual chemicals, 1-octen-3-ol, hexanoic acid, and methyl salicylate induced strong responses. These three chemicals were evaluated in a semi-field setting using a modified bed bug trap but were found to provide no significant increase in attraction compared with CO2 alone. The results of these studies provide a foundation for future research regarding semiochemicals of R. sanguineus s.l.

  12. Development of a micro cell compression stimulator for evaluating real-time cellular responses

    NASA Astrophysics Data System (ADS)

    Nakashima, Y.; Yang, Y.; Minami, K.

    2012-05-01

    This paper presents a micro cell compression stimulator for evaluating real-time cellular responses to compression stimuli. The device was produced by a micro three-dimensional structure fabrication process using multiple exposures to the photoresist. The device consists of a pressure inlet port, cell inlet ports, a gasket, microchannels, cell culture chambers, and a diaphragm on the culture chamber for applying compressive pressure to cells. Compression stimuli applied to the cells can be controlled by regulating the expansion of the diaphragm via a pressure control. The device permits the observation of cellular responses to compressive pressure in real time because it is made of transparent materials and stimulates the cells without deforming the cell culture surface, when observed by optical microscopy. We demonstrated the validity of the fabrication process, evaluated the performance of the fabricated device, and compared the experimental results with the FEM structural analysis results. We found through operational testing that the diaphragm was deformed quickly by applying negative/positive pressure and that the diaphragm displacement became larger with increasing applied pressure. These results indicate that this device can be used to control the intensity and the cell stimulus profile by regulating the applied pressure. In all cases, the cellular deformation during compression stimulus was successfully observed in real time using an optical microscope. The device is expected to facilitate the control of stem cell differentiation and the clarification of cellular mechanoreceptor mechanisms and signal transduction pathways.

  13. Evaluation of an operational malaria outbreak identification and response system in Mpumalanga Province, South Africa

    PubMed Central

    Coleman, Marlize; Coleman, Michael; Mabuza, Aaron M; Kok, Gerdalize; Coetzee, Maureen; Durrheim, David N

    2008-01-01

    Background and objective To evaluate the performance of a novel malaria outbreak identification system in the epidemic prone rural area of Mpumalanga Province, South Africa, for timely identification of malaria outbreaks and guiding integrated public health responses. Methods Using five years of historical notification data, two binomial thresholds were determined for each primary health care facility in the highest malaria risk area of Mpumalanga province. Whenever the thresholds were exceeded at health facility level (tier 1), primary health care staff notified the malaria control programme, which then confirmed adequate stocks of malaria treatment to manage potential increased cases. The cases were followed up at household level to verify the likely source of infection. The binomial thresholds were reviewed at village/town level (tier 2) to determine whether additional response measures were required. In addition, an automated electronic outbreak identification system at town/village level (tier 2) was integrated into the case notification database (tier 3) to ensure that unexpected increases in case notification were not missed. The performance of these binomial outbreak thresholds was evaluated against other currently recommended thresholds using retrospective data. The acceptability of the system at primary health care level was evaluated through structured interviews with health facility staff. Results Eighty four percent of health facilities reported outbreaks within 24 hours (n = 95), 92% (n = 104) within 48 hours and 100% (n = 113) within 72 hours. Appropriate response to all malaria outbreaks (n = 113, tier 1, n = 46, tier 2) were achieved within 24 hours. The system was positively viewed by all health facility staff. When compared to other epidemiological systems for a specified 12 month outbreak season (June 2003 to July 2004) the binomial exact thresholds produced one false weekly outbreak, the C-sum 12 weekly outbreaks and the mean + 2 SD nine false

  14. Watershed Evaluation and Habitat Response to Recent Storms : Annual Report for 1999.

    SciTech Connect

    Rhodes, Jonathan J.; Huntington, Charles W.

    2000-02-01

    evaluated and the methods used to evaluate them. Watershed responses and attributes evaluated include mass failures, historic soil loss, the integration of roads with the drainage network, estimated flood recurrence intervals, and headwater channel morphology. Habitat attributes evaluated include large woody debris, pool frequency and depth, substrate conditions, and bank stability. Multiple analyses of habitat data in the Tucannon and Wenaha subbasins remain to be completed due to difficulties stemming from data characteristics that indicated that some of the pre-existing data may have be of questionable accuracy. Diagnostic attributes of the questionable data included a change in monitoring protocols during the pre- to post-flood analysis period, physically implausible temporal trends in some habitat attributes at some sites, and conflicting results for the same attribute at the same locations from different data sources. Since unreliable data can lead to spurious results, criteria were developed to screen the data for analysis, as described in this report. It is anticipated that while the data screening will prevent spurious results, it will also truncate some of the planned analysis in the Tucannon and Wenaha systems.

  15. Using the /phi/resund experimental data to evaluate the ARAC emergency response models

    SciTech Connect

    Gudiksen, P.H.; Gryning, S.E.

    1988-07-01

    A series of meteorological and tracer experiments, was conducted during May and June 1984 over the 20-km wide /O/resund strait between Denmark and Sweden for the purpose of studying atmospheric dispersion processes over cold water and warm land surfaces and providing the data needed to evaluate meso-scale models in a coastal environment. In concert with these objectives the data from these experiments have been used as part of a continuing effort to evaluate the capability of the three-dimensional MATHEW/ADPIC (M/A) atmospheric dispersion models to simulate pollutant transport and diffusion characteristics of the atmospheric during a wide variety of meteorological conditions. Since previous studies have focused primarily on M/A model evaluations over rolling and complex terrain at inland sites, the /O/resund experiments provide a unique opportunity to evaluate the models in a coastal environment. The M/A models are used by the Atmospheric Release Advisory Capability (ARAC), developed by the Lawrence Livermore National Laboratory, for performing real-time assessments of the environmental consequences of potential or actual releases of radioactivity into the atmosphere. These assessments include estimation of radiation doses to nearby population centers and of the extent of surface contamination. Model evaluations, using field experimental data such as those generated by the /O/resund experiments, serve as a basis for providing emergency response managers with estimated of the uncertainties associated with accident consequence assessments. This report provides a brief description of the /O/resund experiments, the current understanding of the meteorological processes governing pollutant dispersion over the /O/resund strait, and the results of the M/A model simulations of these experiments. 11 refs., 7 figs., 1 tab.

  16. SU-E-J-148: Evaluating Tumor Response with a Commercially Available Deformable Registration System

    SciTech Connect

    Bowling, J; Ramsey, C

    2014-06-01

    Purpose: The purpose of this study is to present a method for evaluating the response to treatment using a commercially available deformable image registration software package (Velocity Medical Systems) and repeat PET/CT imaging. This technique can be used to identify volumes that are risk for tumor recurrence. Methods: Response to treatment was evaluated using PET/CT images acquired prior-to and post-treatment for radiation therapy patients treated with concurrent chemotherapy. Velocity (Version 3.0.1) was used to deform the initial PET/CT to the post treatment PET/CT. The post-treatment PET images were then subtracted from the pre-treatment PET images. The resulting re-sampled image is a three-dimensional SUV difference map that shows pixels with increasing SUV values. SUV values increases greater than 2.5 in the post treatment images were identified for additional follow-up. Results: A total of 5 Lung patients were analyzed as part of this study. One lung patient in the cohort had an SUV increase of +3.28 that was identified using the SUV difference map. This volume of increased uptake was located outside the treatment field and adjacent to the 35 Gy isodose line. The remaining four patients all had SUV decreases inside the planning target volume, and no unexpected areas of increase outside the irradiated volumes. All five patients were analyzed using standard tools inside the Velocity application. Conclusion: The response to treatment can easily be measured using serial PET/CT images and a commercially available deformable image registration. This provides both the radiation oncologists and medical oncologists with a quantitative assessment of their treatment to use in patient follow-up.

  17. Endocytosis as a biological response in receptor pharmacology: evaluation by fluorescence microscopy.

    PubMed

    Campa, Víctor M; Capilla, Almudena; Varela, María J; de la Rocha, Arlet M Acanda; Fernandez-Troyano, Juan C; Barreiro, R Belén; Lopez-Gimenez, Juan F

    2015-01-01

    The activation of G-protein coupled receptors by agonist compounds results in diverse biological responses in cells, such as the endocytosis process consisting in the translocation of receptors from the plasma membrane to the cytoplasm within internalizing vesicles or endosomes. In order to functionally evaluate endocytosis events resulted from pharmacological responses, we have developed an image analysis method -the Q-Endosomes algorithm- that specifically discriminates the fluorescent signal originated at endosomes from that one observed at the plasma membrane in images obtained from living cells by fluorescence microscopy. Mu opioid (MOP) receptor tagged at the carboxy-terminus with yellow fluorescent protein (YFP) and permanently expressed in HEK293 cells was used as experimental model to validate this methodology. Time-course experiments performed with several agonists resulted in different sigmoid curves depending on the drug used to initiate MOP receptor endocytosis. Thus, endocytosis resulting from the simultaneous activation of co-expressed MOP and serotonin 5-HT2C receptors by morphine plus serotonin was significantly different, in kinetics as well as in maximal response parameters, from the one caused by DAMGO, sufentanyl or methadone. Therefore, this analytical tool permits the pharmacological characterization of receptor endocytosis in living cells with functional and temporal resolution.

  18. Comparing Visible and Invisible Social Support: Non-evaluative Support Buffers Cardiovascular Responses to Stress.

    PubMed

    Kirsch, Julie A; Lehman, Barbara J

    2015-12-01

    Previous research suggests that in contrast to invisible social support, visible social support produces exaggerated negative emotional responses. Drawing on work by Bolger and colleagues, this study disentangled social support visibility from negative social evaluation in an examination of the effects of social support on negative emotions and cardiovascular responses. As part of an anticipatory speech task, 73 female participants were randomly assigned to receive no social support, invisible social support, non-confounded visible social support or visible social support as delivered in a 2007 study by Bolger and Amarel. Twelve readings, each for systolic blood pressure, diastolic blood pressure and heart rate were taken at 5-min intervals throughout the periods of baseline, reactivity and recovery. Cardiovascular outcomes were tested by incorporating a series of theoretically driven planned contrasts into tests of stress reactivity conducted through piecewise growth curve modelling. Linear and quadratic trends established cardiovascular reactivity to the task. Further, in comparison to the control and replication conditions, the non-confounded visible and invisible social support conditions attenuated cardiovascular reactivity over time. Pre- and post-speech negative emotional responses were not affected by the social support manipulations. These results suggest that appropriately delivered visible social support may be as beneficial as invisible social support.

  19. Evaluation of drug-induced changes in myocardial repolarisation using the paced evoked response.

    PubMed Central

    Donaldson, R M; Rickards, A F

    1982-01-01

    The use of the pace evoked response system in the assessment of drug-induced changes in myocardial repolarisation is reported. Using a conventional pacing electrode lead for both pacing and sensing, this system records the dominantly local repolarisation which follows a controlled (paced) depolarisation from the same site. Measurements of the latency of the ventricular evoked response at matched heart rates before and after drug administration permit the accurate direct comparison of the effects of drugs with class 3 mode of action on cardiac muscle repolarisation. Using this method we have evaluated the effect on the timing of the evoked T wave of two drugs which are known to prolong phase 2 of the action potential. Intravenous amiodarone (5 mg/kg) prolonged the stimulus-peak evoked T wave interval by an average of 39-4 ms (15% of control values); three hours after oral bethanidine (2 mg/kg) this interval increased by an average of 25.8 ms (10% of control values). The effect of therapeutic interventions on the latency of the local paced evoked response provides a simple, accurate assessment of their effect on the cellular action potential duration and constitutes a new tool in electrophysiological investigations. PMID:7126390

  20. Evaluation of the accuracy of BOTDA systems based on the phase spectral response.

    PubMed

    Lopez-Gil, Alexia; Soto, Marcelo A; Angulo-Vinuesa, Xabier; Dominguez-Lopez, Alejandro; Martin-Lopez, Sonia; Thévenaz, Luc; Gonzalez-Herraez, Miguel

    2016-07-25

    We evaluate the Brillouin frequency shift (BFS) determination error when utilizing the Brillouin phase spectrum (BPS) instead of the Brillouin gain spectrum (BGS) in BOTDA systems. Systems based on the BPS perform the determination of the BFS through a linear fit around the zero de-phase frequency region. An analytical expression of the error obtained in the BFS determination as a function of the different experimental parameters is provided and experimentally validated. The experimental results show a good agreement with the theoretical predictions as a function of the number of sampling points, signal-to-noise ratio (SNR) and Brillouin spectral linewidth. For an equal SNR and linewidth, the phase response only provides a better BFS estimation than the gain response when the fit is performed over a restricted frequency range around the center of the spectral profile. This may reduce the measurement time of specific BOTDA systems requiring a narrow frequency scanning. When the frequency scan covers most of the Brillouin spectral profile, gain and phase responses give very similar estimations of the BFS and the BPS offers no crucial benefit.

  1. Adolescents' increasing stress response to social evaluation: pubertal effects on cortisol and alpha-amylase during public speaking.

    PubMed

    van den Bos, Esther; de Rooij, Mark; Miers, Anne C; Bokhorst, Caroline L; Westenberg, P Michiel

    2014-01-01

    Stress responses to social evaluation are thought to increase during adolescence, which may be due to pubertal maturation. However, empirical evidence is scarce. This study is the first to investigate the relation between pubertal development and biological responses to a social-evaluative stressor longitudinally. Participants performed the Leiden Public Speaking Task twice, with a 2-year interval (N = 217; age at Time 1: 8-17 years). The results support an increase in sensitivity to social evaluation during adolescence. The overall cortisol and alpha-amylase responses increased-both between and within participants-and were more strongly related to self-reported pubertal development than to age. The cortisol response shifted from speech delivery toward anticipation. The alpha-amylase response increased in both phases.

  2. How does not responding to appetitive stimuli cause devaluation: Evaluative conditioning or response inhibition?

    PubMed

    Chen, Zhang; Veling, Harm; Dijksterhuis, Ap; Holland, Rob W

    2016-12-01

    In a series of 6 experiments (5 preregistered), we examined how not responding to appetitive stimuli causes devaluation. To examine this question, a go/no-go task was employed in which appetitive stimuli were consistently associated with cues to respond (go stimuli), or with cues to not respond (either no-go cues or the absence of cues; no-go stimuli). Change in evaluations of no-go stimuli was compared to change in evaluations of both go stimuli and of stimuli not presented in the task (untrained stimuli). Experiments 1 to 3 show that not responding to appetitive stimuli in a go/no-go task causes devaluation of these stimuli regardless of the presence of an explicit no-go cue. Experiments 4a and 4b show that the devaluation effect of appetitive stimuli is contingent on the percentage of no-go trials; devaluation appears when no-go trials are rare, but disappears when no-go trials are frequent. Experiment 5 shows that simply observing the go/no-go task does not lead to devaluation. Experiment 6 shows that not responding to neutral stimuli does not cause devaluation. Together, these results suggest that devaluation of appetitive stimuli by not responding to them is the result of response inhibition. By employing both go stimuli and untrained stimuli as baselines, alternative explanations are ruled out, and apparent inconsistencies in the literature are resolved. These experiments provide new theoretical insight into the relation between not responding and evaluation, and can be applied to design motor response training procedures aimed at changing people's behavior toward appetitive stimuli. (PsycINFO Database Record

  3. Staging Evaluation and Response Criteria Harmonization (SEARCH) for Childhood, Adolescent and Young Adult Hodgkin Lymphoma (CAYAHL): Methodology statement.

    PubMed

    Flerlage, Jamie E; Kelly, Kara M; Beishuizen, Auke; Cho, Steve; De Alarcon, Pedro A; Dieckmann, Ute; Drachtman, Richard A; Hoppe, Bradford S; Howard, Scott C; Kaste, Sue C; Kluge, Regine; Kurch, Lars; Landman-Parker, Judith; Lewis, Jocelyn; Link, Michael P; McCarten, Kathleen; Punnett, Angela; Stoevesandt, Dietrich; Voss, Stephan D; Wallace, William Hamish; Mauz-Körholz, Christine; Metzger, Monika L

    2017-01-18

    International harmonization of staging evaluation and response criteria is needed for childhood, adolescence, and young adulthood Hodgkin lymphoma. Two Hodgkin lymphoma protocols from cooperative trials in Europe and North America were compared for areas in need of harmonization, and an evidence-based approach is currently underway to harmonize staging and response evaluations with a goal to enhance comparisons, expedite identification of effective therapies, and aid in the approval process for new agents by regulatory agencies.

  4. Evaluation of human antibody responses to diphtheria toxin subunits A and B in various age groups.

    PubMed

    Karakus, R; Caglar, K; Aybay, C

    2007-11-01

    This study aimed to evaluate human antibody responses to diphtheria toxin subunits in various age groups. Antibodies against the intact diphtheria toxin and the diphtheria toxin subunits A and B were evaluated in 1319 individuals using a double-antigen ELISA. Although high levels of protection (83.6%, 95% CI 79.2-87.4) were found in children and adolescents, the middle-aged adult population was less protected (28.8%, 95% CI 24.3-33.6). An increase in age was associated with a decrease in the frequency of protected individuals in the 0-39-year age group (p <0.001). Anti-subunit B levels correlated well (p <0.01) with levels of antibodies against the intact toxin. In children aged < or =16 years, the intervals at which the peaks in geometric mean titres of anti-subunit B antibodies were observed were found to correlate with the ages at which booster doses are administered. Overall, males appeared to be more protected than females (OR 1.67, 95% CI 1.34-2.08, p <0.001). A small group of individuals had antibody levels of > or =0.1 IU/mL against the intact toxin, but did not have protective antibody against subunit B. Determination of anti-subunit B antibody levels should help in evaluating the effectiveness of diphtheria boosters and other aspects of diphtheria immunity.

  5. Liquid biopsy and therapeutic response: Circulating tumor cell cultures for evaluation of anticancer treatment.

    PubMed

    Khoo, Bee Luan; Grenci, Gianluca; Jing, Tengyang; Lim, Ying Bena; Lee, Soo Chin; Thiery, Jean Paul; Han, Jongyoon; Lim, Chwee Teck

    2016-07-01

    The lack of a robust anticancer drug screening system to monitor patients during treatment delays realization of personalized treatment. We demonstrate an efficient approach to evaluate drug response using patient-derived circulating tumor cell (CTC) cultures obtained from liquid biopsy. Custom microfabricated tapered microwells were integrated with microfluidics to allow robust formation of CTC clusters without pre-enrichment and subsequent drug screening in situ. Rapid feedback after 2 weeks promotes immediate intervention upon detection of drug resistance or tolerance. The procedure was clinically validated with blood samples (n = 73) from 55 patients with early-stage, newly diagnosed, locally advanced, or refractory metastatic breast cancer. Twenty-four of these samples were used for drug evaluation. Cluster formation potential correlated inversely with increased drug concentration and therapeutic treatment. This new and robust liquid biopsy technique can potentially evaluate patient prognosis with CTC clusters during treatment and provide a noninvasive and inexpensive assessment that can guide drug discovery development or therapeutic choices for personalized treatment.

  6. Liquid biopsy and therapeutic response: Circulating tumor cell cultures for evaluation of anticancer treatment

    PubMed Central

    Khoo, Bee Luan; Grenci, Gianluca; Jing, Tengyang; Lim, Ying Bena; Lee, Soo Chin; Thiery, Jean Paul; Han, Jongyoon; Lim, Chwee Teck

    2016-01-01

    The lack of a robust anticancer drug screening system to monitor patients during treatment delays realization of personalized treatment. We demonstrate an efficient approach to evaluate drug response using patient-derived circulating tumor cell (CTC) cultures obtained from liquid biopsy. Custom microfabricated tapered microwells were integrated with microfluidics to allow robust formation of CTC clusters without pre-enrichment and subsequent drug screening in situ. Rapid feedback after 2 weeks promotes immediate intervention upon detection of drug resistance or tolerance. The procedure was clinically validated with blood samples (n = 73) from 55 patients with early-stage, newly diagnosed, locally advanced, or refractory metastatic breast cancer. Twenty-four of these samples were used for drug evaluation. Cluster formation potential correlated inversely with increased drug concentration and therapeutic treatment. This new and robust liquid biopsy technique can potentially evaluate patient prognosis with CTC clusters during treatment and provide a noninvasive and inexpensive assessment that can guide drug discovery development or therapeutic choices for personalized treatment. PMID:27453941

  7. Laboratory study of the response of select insecticides to toxicity identification evaluation procedures

    USGS Publications Warehouse

    Kuivila, Kathryn; Crepeau, Kathryn L.

    1999-01-01

    A laboratory study was used to evaluate the response of select insecticides to toxicity identification evaluation procedures. Fourteen insecticides, one degradation product, and one synergist were spiked into organic-grade water and carried through toxicity identification evaluation procedures. Concentrations of each compound were analyzed by gas chromatography/mass spectrometry. During Phase I, the water sample was pumped through a C-8 solid-phase extraction cartridge and then eluted with methanol. Dimethoate was not removed by the extraction, but remained in the rinsate. In contrast, permethrin was removed by the extraction, but was not recovered by the methanol elution, and 80 percent of the permethrin remained on the cartridge, teflon tubing, and glassware. Chlorpyrifos also was not recovered completely with the methanol elution (only 62 percent was recovered). The other insecticides were extracted by C-8 solid-phase extraction cartridge and recovered by elution with methanol (80 percent or greater). During Phase II, a new spiked water sample was extracted by C-8 solid-phase extraction cartridge and then eluted with varying concentrations of methanol and water into different fractions. Each methanol:water fraction was analyzed for the added compounds. Most of the insecticides eluted in two fractions, with concentrations of 10 percent or greater. The largest number of insecticides eluted in the 75 percent methanol:water fraction.

  8. Generation of a reference transcriptome for evaluating rainbow trout responses to various stressors

    PubMed Central

    2011-01-01

    Background Fish under intensive culture conditions are exposed to a variety of acute and chronic stressors, including high rearing densities, sub-optimal water quality, and severe thermal fluctuations. Such stressors are inherent in aquaculture production and can induce physiological responses with adverse effects on traits important to producers and consumers, including those associated with growth, nutrition, reproduction, immune response, and fillet quality. Understanding and monitoring the biological mechanisms underlying stress responses will facilitate alleviating their negative effects through selective breeding and changes in management practices, resulting in improved animal welfare and production efficiency. Results Physiological responses to five treatments associated with stress were characterized by measuring plasma lysozyme activity, glucose, lactate, chloride, and cortisol concentrations, in addition to stress-associated transcripts by quantitative PCR. Results indicate that the fish had significant stressor-specific changes in their physiological conditions. Sequencing of a pooled normalized transcriptome library created from gill, brain, liver, spleen, kidney and muscle RNA of control and stressed fish produced 3,160,306 expressed sequence tags which were assembled and annotated. SNP discovery resulted in identification of ~58,000 putative single nucleotide polymorphisms including 24,479 which were predicted to fall within exons. Of these, 4907 were predicted to occupy the first position of a codon and 4110 the second, increasing the probability to impact amino acid sequence variation and potentially gene function. Conclusion We have generated and characterized a reference transcriptome for rainbow trout that represents multiple tissues responding to multiple stressors common to aquaculture production environments. This resource compliments existing public transcriptome data and will facilitate approaches aiming to evaluate gene expression

  9. California state Mosquito-Borne Virus Surveillance and Response Plan: a retrospective evaluation using conditional simulations.

    PubMed

    Barker, Christopher M; Reisen, William K; Kramer, Vicki L

    2003-05-01

    The California Mosquito-Borne Virus Surveillance and Response Plan recently was developed to provide a semi-quantitative means for assessing risk for western equine encephalomyelitis (WEE) or St. Louis encephalitis (SLE) viruses and to provide intervention guidelines for mosquito control and public health agencies during periods of heightened risk for human infection. West Nile virus recently has arrived in California, and the response plan also will provide a baseline for assessing the risk for human and equine infection with this virus. In the response plan, overall risk is calculated by averaging risk due to 1) environmental conditions, 2) adult mosquito vector abundance, 3) vector infection rates, 4) sentinel chicken seroconversion rates, 5) equine cases (for WEE), 6) human cases, and 7) the proximity of virus activity to populated areas. Overall risk is categorized into three levels: normal season, emergency planning, or epidemic conditions. We evaluated this response plan using historical data from years with no, enzootic, and epidemic activity of WEE and SLE in several areas of California to determine whether calculated risk levels approximated actual conditions. Multiple methods of risk calculation were considered for both viruses. Assessed risk based on cumulative temperature, rainfall, and runoff levels over the entire season provided more or equally accurate assessments than biweekly assessments based solely on the previous half-month. For WEE, during years with enzootic activity or early-season periods of years with WEE epidemic activity, combining horse and human cases as a single risk factor improved the model's ability to forecast pending WEE activity, but separating the two factors allowed a better indication of WEE activity during epidemics and periods with no activity. For SLE, assignment of higher risk to drier conditions as measured by rainfall and runoff yielded the most accurate representation of actual virus activity during all recent study

  10. Evaluation of the Phase-Dependent Rhythm Control of Human Walking Using Phase Response Curves

    PubMed Central

    Yamamoto, Yuki; Aoi, Shinya; Imai, Takashi; Aoyagi, Toshio; Tomita, Nozomi; Tsuchiya, Kazuo

    2016-01-01

    Humans and animals control their walking rhythms to maintain motion in a variable environment. The neural mechanism for controlling rhythm has been investigated in many studies using mechanical and electrical stimulation. However, quantitative evaluation of rhythm variation in response to perturbation at various timings has rarely been investigated. Such a characteristic of rhythm is described by the phase response curve (PRC). Dynamical simulations of human skeletal models with changing walking rhythms (phase reset) described a relation between the effective phase reset on stability and PRC, and phase reset around touch-down was shown to improve stability. A PRC of human walking was estimated by pulling the swing leg, but such perturbations hardly influenced the stance leg, so the relation between the PRC and walking events was difficult to discuss. This research thus examines human response to variations in floor velocity. Such perturbation yields another problem, in that the swing leg is indirectly (and weakly) perturbed, so the precision of PRC decreases. To solve this problem, this research adopts the weighted spike-triggered average (WSTA) method. In the WSTA method, a sequential pulsed perturbation is used for stimulation. This is in contrast with the conventional impulse method, which applies an intermittent impulsive perturbation. The WSTA method can be used to analyze responses to a large number of perturbations for each sequence. In the experiment, perturbations are applied to walking subjects by rapidly accelerating and decelerating a treadmill belt, and measured data are analyzed by the WSTA and impulse methods. The PRC obtained by the WSTA method had clear and stable waveforms with a higher temporal resolution than those obtained by the impulse method. By investigation of the rhythm transition for each phase of walking using the obtained PRC, a rhythm change that extends the touch-down and mid-single support phases is found to occur. PMID:27203839

  11. Evaluation of pleth variability index as a predictor of fluid responsiveness during orthotopic liver transplantation.

    PubMed

    Konur, Huseyin; Erdogan Kayhan, Gulay; Toprak, Huseyin Ilksen; Bucak, Nizamettin; Aydogan, Mustafa Said; Yologlu, Saim; Durmus, Mahmut; Yılmaz, Sezai

    2016-07-01

    Fluid management is challenging and still remains controversial in orthotopic liver transplantation (OLT). The pleth variability index (PVI) has been shown to be a reliable predictor of fluid responsiveness of perioperative and critically ill patients; however, it has not been evaluated in OLT. This study was designed to examine whether the PVI can reliably predict fluid responsiveness in OLT and to compare PVI with other hemodynamic indexes that are measured using the PiCCO2 monitoring system. Twenty-five patients were enrolled in this study. Each patient was monitored using the noninvasive Masimo and PiCCO2 monitoring system. PVI was obtained with a Masimo pulse oximeter. Cardiac index was obtained using a transpulmonary thermodilution technique (CITPTD). Stroke volume variation (SVV), pulse pressure variation, and systemic vascular resistance index were measured using the PiCCO2 system. Fluid loading (10 mL/kg colloid) was performed at two different phases during the operation, and fluid responsiveness was defined as an increase in CITPTD ≥ 15%. During the dissection phase and the anhepatic phase, respectively, 14 patients (56%) and 18 patients (75%) were classified as responders. There were no differences between the baseline values of the PVI of responders and nonresponders. Area under the curve for PVI was 0.56 (sensitivity 35%, specificity 90%, p = 0.58) at dissection phase, and was 0.55 (sensitivity 55%, specificity 66%, p = 0.58) at anhepatic phase. Of the parameters, a higher area under the curve value was found for SVV. We conclude that PVI was unable to predict fluid responsiveness with sufficient accuracy in patients undergoing OLT, but the SVV parameter was reliable.

  12. Evaluation of simulated photolysis rates and their response to solar irradiance variability

    NASA Astrophysics Data System (ADS)

    Sukhodolov, Timofei; Rozanov, Eugene; Ball, William T.; Bais, Alkiviadis; Tourpali, Kleareti; Shapiro, Alexander I.; Telford, Paul; Smyshlyaev, Sergey; Fomin, Boris; Sander, Rolf; Bossay, Sébastien; Bekki, Slimane; Marchand, Marion; Chipperfield, Martyn P.; Dhomse, Sandip; Haigh, Joanna D.; Peter, Thomas; Schmutz, Werner

    2016-05-01

    The state of the stratospheric ozone layer and the temperature structure of the atmosphere are largely controlled by the solar spectral irradiance (SSI) through its influence on heating and photolysis rates. This study focuses on the uncertainties in the photolysis rate response to solar irradiance variability related to the choice of SSI data set and to the performance of the photolysis codes used in global chemistry-climate models. To estimate the impact of SSI uncertainties, we compared several photolysis rates calculated with the radiative transfer model libRadtran, using SSI calculated with two models and observed during the Solar Radiation and Climate Experiment (SORCE) satellite mission. The importance of the calculated differences in the photolysis rate response for ozone and temperature changes has been estimated using 1-D a radiative-convective-photochemical model. We demonstrate that the main photolysis reactions, responsible for the solar signal in the stratosphere, are highly sensitive to the spectral distribution of SSI variations. Accordingly, the ozone changes and related ozone-temperature feedback are shown to depend substantially on the SSI data set being used, which highlights the necessity of obtaining accurate SSI variations. To evaluate the performance of photolysis codes, we compared the results of eight, widely used, photolysis codes against two reference schemes. We show that, in most cases, absolute values of the photolysis rates and their response to applied SSI changes agree within 30%. However, larger errors may appear in specific atmospheric regions because of differences, for instance, in the treatment of Rayleigh scattering, quantum yields, or absorption cross sections.

  13. DISSOCIATED RESPONSES IN THE AMYGDALA AND ORBITOFRONTAL CORTEX TO BOTTOM-UP AND TOP-DOWN COMPONENTS OF EMOTIONAL EVALUATION

    PubMed Central

    Wright, Paul; Albarracin, Dolores; Brown, Rick D.; Li, Hong; He, Guojun; Liu, Yijun

    2008-01-01

    Although emotional responses to stimuli may be automatic, explicit evaluation of emotion is a voluntary act. These bottom-up and top-down processes may be supported by distinct neural systems. Previous studies reported bottom-up responses in the amygdala, top-down responses in the orbital and ventromedial prefrontal cortices, and top-down modulation of the amygdalar response. The current study used event-related fMRI on fifteen healthy males to examine these responses in the absence of stimulus anticipation or task repetition. Factorial analysis distinguished bottom-up responses in the amygdala from top-down responses in the orbitofrontal cortex. Activation of ventromedial prefrontal cortex and modulation of amygdalar response were not observed, and future studies may investigate whether these effects are contingent upon anticipation or cognitive set. PMID:17950625

  14. Assessing Beaked Whale Reproduction and Stress Response Relative to Sonar Activity at the Atlantic Undersea Test and Evaluation Center

    DTIC Science & Technology

    2014-09-30

    1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Assessing Beaked Whale Reproduction and Stress Response...both groups of animals to investigate whether there is a relationship between sonar activity, stress measures, and reproductive rates, to assess... Reproduction and Stress Response Relative to Sonar Activity at the Atlantic Undersea Test and Evaluation Center (AUTEC) 5a. CONTRACT NUMBER 5b. GRANT

  15. Using the Nominal Response Model to Evaluate Response Category Discrimination in the PROMIS Emotional Distress Item Pools

    ERIC Educational Resources Information Center

    Preston, Kathleen; Reise, Steven; Cai, Li; Hays, Ron D.

    2011-01-01

    The authors used a nominal response item response theory model to estimate category boundary discrimination (CBD) parameters for items drawn from the Emotional Distress item pools (Depression, Anxiety, and Anger) developed in the Patient-Reported Outcomes Measurement Information Systems (PROMIS) project. For polytomous items with ordered response…

  16. Evaluation of Hearing Aid Frequency Response Fittings in Pediatric and Young Adult Bimodal Recipients

    PubMed Central

    Davidson, Lisa S.; Firszt, Jill B.; Brenner, Chris; Cadieux, Jamie H.

    2015-01-01

    Background A coordinated fitting of a cochlear implant (CI) and contralateral hearing aid (HA) for bimodal device use should emphasize balanced audibility and loudness across devices. However, guidelines for allocating frequency information to the CI and HA are not well established for the growing population of bimodal recipients. Purpose The study aim was to compare the effects of three different HA frequency responses, when fitting a CI and an HA for bimodal use, on speech recognition and localization in children/young adults. Specifically, the three frequency responses were wideband, restricted high frequency, and nonlinear frequency compression (NLFC), which were compared with measures of word recognition in quiet, sentence recognition in noise, talker discrimination, and sound localization. Research Design The HA frequency responses were evaluated using an A B1 A B2 test design: wideband frequency response (baseline-A), restricted high-frequency response (experimental-B1), and NLFC-activated (experimental-B2). All participants were allowed 3–4 weeks between each test session for acclimatization to each new HA setting. Bimodal benefit was determined by comparing the bimodal score to the CI-alone score. Study Sample Participants were 14 children and young adults (ages 7–21 yr) who were experienced users of bimodal devices. All had been unilaterally implanted with a Nucleus CI24 internal system and used either a Freedom or CP810 speech processor. All received a Phonak Naida IX UP behind-the-ear HA at the beginning of the study. Data Collection and Analysis Group results for the three bimodal conditions (HA frequency response with wideband, restricted high frequency, and NLFC) on each outcome measure were analyzed using a repeated measures analysis of variance. Group results using the individual “best bimodal” score were analyzed and confirmed using a resampling procedure. Correlation analyses examined the effects of audibility (aided and unaided hearing

  17. 33 CFR 155.1052 - Response plan development and evaluation criteria for vessels carrying group V petroleum oil as a...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... evaluation criteria for vessels carrying group V petroleum oil as a primary cargo. 155.1052 Section 155.1052....1052 Response plan development and evaluation criteria for vessels carrying group V petroleum oil as a primary cargo. (a) Owners and operators of vessels that carry group V petroleum oil as a primary...

  18. 33 CFR 155.1052 - Response plan development and evaluation criteria for vessels carrying group V petroleum oil as a...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... evaluation criteria for vessels carrying group V petroleum oil as a primary cargo. 155.1052 Section 155.1052....1052 Response plan development and evaluation criteria for vessels carrying group V petroleum oil as a primary cargo. (a) Owners and operators of vessels that carry group V petroleum oil as a primary...

  19. 33 CFR 155.5052 - Response plan development and evaluation criteria for nontank vessels carrying group V petroleum...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... evaluation criteria for nontank vessels carrying group V petroleum oil. 155.5052 Section 155.5052 Navigation... Response plan development and evaluation criteria for nontank vessels carrying group V petroleum oil. Owners or operators of nontank vessels that carry group V petroleum oil as fuel or cargo must meet...

  20. 33 CFR 155.1052 - Response plan development and evaluation criteria for vessels carrying group V petroleum oil as a...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... evaluation criteria for vessels carrying group V petroleum oil as a primary cargo. 155.1052 Section 155.1052....1052 Response plan development and evaluation criteria for vessels carrying group V petroleum oil as a primary cargo. (a) Owners and operators of vessels that carry group V petroleum oil as a primary...

  1. 33 CFR 155.1052 - Response plan development and evaluation criteria for vessels carrying group V petroleum oil as a...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... evaluation criteria for vessels carrying group V petroleum oil as a primary cargo. 155.1052 Section 155.1052....1052 Response plan development and evaluation criteria for vessels carrying group V petroleum oil as a primary cargo. (a) Owners and operators of vessels that carry group V petroleum oil as a primary...

  2. 33 CFR 155.1052 - Response plan development and evaluation criteria for vessels carrying group V petroleum oil as a...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... evaluation criteria for vessels carrying group V petroleum oil as a primary cargo. 155.1052 Section 155.1052....1052 Response plan development and evaluation criteria for vessels carrying group V petroleum oil as a primary cargo. (a) Owners and operators of vessels that carry group V petroleum oil as a primary...

  3. Analysis of skin conductance response during evaluation of preferences for cosmetic products

    PubMed Central

    Ohira, Hideki; Hirao, Naoyasu

    2015-01-01

    We analyzed skin conductance response (SCR) as a psychophysiological index to evaluate affective aspects of consumer preferences for cosmetic products. To examine the test-retest reliability of association between preferences and SCR, we asked 33 female volunteers to complete two experimental sessions approximately 1 year apart. The participants indicated their preferences in a typical paired comparison task by choosing the better option from a combination of two products among four products. We measured anticipatory SCR prior to expressions of the preferences. We found that the mean amplitude of the SCR elicited by the preferred products was significantly larger than that elicited by the non-preferred products. The participants' preferences and corresponding SCR patterns were well preserved at the second session 1 year later. Our results supported cumulating findings that SCR is a useful index of consumer preferences that has future potential, both in laboratory and marketing settings. PMID:25709593

  4. Evaluating the effectiveness of personal response system technology on millennial student learning.

    PubMed

    McCurry, Mary K; Hunter Revell, Susan M

    2011-08-01

    As nurse educators, we must explore new technologies that capitalize on the characteristics of millennial learners. One such technology, the personal response system (PRS), is an effective way to promote active learning and increase comprehension. Few nursing studies have examined the benefits of PRS technology on student outcomes. The purpose of this study was to evaluate the effectiveness of PRS technology on learning outcomes in two sections of an undergraduate nursing research course. A crossover design compared class quiz averages between and within groups. Findings related to between and within class quiz scores were mixed, whereas the effectiveness of in-class PRS questions on paper-and-pencil quiz scores and PRS-targeted quiz items was significant. Knowledge gained from this study can be used to enhance our ability to actively engage our technologically savvy undergraduate students. By threading technology into the undergraduate curriculum, learning outcomes may be improved.

  5. A participatory action research pilot study of urban health disparities using rapid assessment response and evaluation.

    PubMed

    Brown, David Richard; Hernández, Agueda; Saint-Jean, Gilbert; Evans, Siân; Tafari, Ida; Brewster, Luther G; Celestin, Michel J; Gómez-Estefan, Carlos; Regalado, Fernando; Akal, Siri; Nierenberg, Barry; Kauschinger, Elaine D; Schwartz, Robert; Page, J Bryan

    2008-01-01

    Healthy People 2010 made it a priority to eliminate health disparities. We used a rapid assessment response and evaluation (RARE) to launch a program of participatory action research focused on health disparities in an urban, disadvantaged Black community serviced by a major south Florida health center. We formed partnerships with community members, identified local health disparities, and guided interventions targeting health disparities. We describe the RARE structure used to triangulate data sources and guide intervention plans as well as findings and conclusions drawn from scientific literature and epidemiological, historic, planning, clinical, and ethnographic data. Disenfranchisement and socioeconomic deprivation emerged as the principal determinants of local health disparities and the most appropriate targets for intervention.

  6. Analysis of skin conductance response during evaluation of preferences for cosmetic products.

    PubMed

    Ohira, Hideki; Hirao, Naoyasu

    2015-01-01

    We analyzed skin conductance response (SCR) as a psychophysiological index to evaluate affective aspects of consumer preferences for cosmetic products. To examine the test-retest reliability of association between preferences and SCR, we asked 33 female volunteers to complete two experimental sessions approximately 1 year apart. The participants indicated their preferences in a typical paired comparison task by choosing the better option from a combination of two products among four products. We measured anticipatory SCR prior to expressions of the preferences. We found that the mean amplitude of the SCR elicited by the preferred products was significantly larger than that elicited by the non-preferred products. The participants' preferences and corresponding SCR patterns were well preserved at the second session 1 year later. Our results supported cumulating findings that SCR is a useful index of consumer preferences that has future potential, both in laboratory and marketing settings.

  7. Laboratory test methods for evaluating the fire response of aerospace materials

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.

    1979-01-01

    The test methods which were developed or evaluated were intended to serve as means of comparing materials on the basis of specific responses under specific sets of test conditions, using apparatus, facilities, and personnel that would be within the capabilities of perhaps the majority of laboratories. Priority was given to test methods which showed promise of addressing the pre-ignition state of a potential fire. These test methods were intended to indicate which materials may present more hazard than others under specific test conditions. These test methods are discussed and arranged according to the stage of a fire to which they are most relevant. Some observations of material performance which resulted from this work are also discussed.

  8. Further evaluation of response interruption and redirection as treatment for stereotypy.

    PubMed

    Ahrens, Erin N; Lerman, Dorothea C; Kodak, Tiffany; Worsdell, April S; Keegan, Courtney

    2011-01-01

    The effects of 2 forms of response interruption and redirection (RIRD)-motor RIRD and vocal RIRD-were examined with 4 boys with autism to evaluate further the effects of this intervention and its potential underlying mechanisms. In Experiment 1, the effects of motor RIRD and vocal RIRD on vocal stereotypy and appropriate vocalizations were compared for 2 participants. In Experiment 2, the effects of both RIRD procedures on both vocal and motor stereotypy and appropriate vocalizations were compared with 2 additional participants. Results suggested that RIRD was effective regardless of the procedural variation or topography of stereotypy and that vocal RIRD functioned as a punisher. This mechanism was further explored with 1 participant by manipulating the schedule of RIRD in Experiment 3. Results were consistent with the punishment interpretation.

  9. Loneliness accentuates age differences in cardiovascular responses to social evaluative threat.

    PubMed

    Ong, Anthony D; Rothstein, Jeremy D; Uchino, Bert N

    2012-03-01

    The effects of aging and loneliness on cardiovascular stress responses were examined in 91 young (18-30 years) and 91 older (65-80 years) normotensive adults. Participants completed the revised UCLA Loneliness Scale and a modified version of the Trier Social Stress Test. Piece-wise linear growth-curve analysis was used to model group differences in resting, reactivity, and recovery levels of systolic blood pressure (SBP) and diastolic blood pressure (DBP). Replicating and extending prior research, analyses revealed age-related increases in resting SBP and DBP. Adjusting for demographics and health covariates, interactions were found for SBP in which age differences in stress reactivity and recovery were greater among lonely than nonlonely participants. Findings provide further evidence that loneliness interacts with age to augment cardiovascular risk to social evaluative threat.

  10. Evaluation of Three Constitutive Models for the Prediction of Hastelloy X Elevated Temperature Cyclic Response

    NASA Technical Reports Server (NTRS)

    Moreno, V.

    1983-01-01

    The approach for the method development assumes that, for a thermally loaded structure, the overall strain history is defined by linear elastic analysis. The local stress history at a fatigue critical location is then determined from a one dimensional material behavior model and the local strain and temperature conditions. Three material models are currently being evaluated to assess their ability to predict relevant high temperature cyclic material response characteristics. They are: a time independent classical plasticity and creep representation, a time dependent viscoplastic model capable of predicting combined creep and plasticity effects, and an approximate elastic analysis approach that uses a series of stress-strain curves and a cyclic hardening model to determine reverse plasticity.

  11. A Participatory Action Research Pilot Study of Urban Health Disparities Using Rapid Assessment Response and Evaluation

    PubMed Central

    Brown, David Richard; Hernández, Agueda; Saint-Jean, Gilbert; Evans, Siân; Tafari, Ida; Brewster, Luther G.; Celestin, Michel J.; Gómez-Estefan, Carlos; Regalado, Fernando; Akal, Siri; Nierenberg, Barry; Kauschinger, Elaine D.; Schwartz, Robert; Page, J. Bryan

    2008-01-01

    Healthy People 2010 made it a priority to eliminate health disparities. We used a rapid assessment response and evaluation (RARE) to launch a program of participatory action research focused on health disparities in an urban, disadvantaged Black community serviced by a major south Florida health center. We formed partnerships with community members, identified local health disparities, and guided interventions targeting health disparities. We describe the RARE structure used to triangulate data sources and guide intervention plans as well as findings and conclusions drawn from scientific literature and epidemiological, historic, planning, clinical, and ethnographic data. Disenfranchisement and socioeconomic deprivation emerged as the principal determinants of local health disparities and the most appropriate targets for intervention. PMID:18048802

  12. Evaluation of a wind-tunnel gust response technique including correlations with analytical and flight test results

    NASA Technical Reports Server (NTRS)

    Redd, L. T.; Hanson, P. W.; Wynne, E. C.

    1979-01-01

    A wind tunnel technique for obtaining gust frequency response functions for use in predicting the response of flexible aircraft to atmospheric turbulence is evaluated. The tunnel test results for a dynamically scaled cable supported aeroelastic model are compared with analytical and flight data. The wind tunnel technique, which employs oscillating vanes in the tunnel throat section to generate a sinusoidally varying flow field around the model, was evaluated by use of a 1/30 scale model of the B-52E airplane. Correlation between the wind tunnel results, flight test results, and analytical predictions for response in the short period and wing first elastic modes of motion are presented.

  13. Evaluation of Neutron Response of Criticality Accident Alarm System Detector to Quasi-Monoenergetic 24 keV Neutrons

    NASA Astrophysics Data System (ADS)

    Tsujimura, Norio; Yoshida, Tadayoshi; Yashima, Hiroshi

    The criticality accident alarm system (CAAS), which was recently developed and installed at the Japan Atomic Energy Agency's Tokai Reprocessing Plant, consists of a plastic scintillator combined with a cadmium-lined polyethylene moderator and thereby responds to both neutrons and gamma rays. To evaluate the neutron absorbed dose rate response of the CAAS detector, a 24 keV quasi-monoenergetic neutron irradiation experiment was performed at the B-1 facility of the Kyoto University Research Reactor. The detector's evaluated neutron response was confirmed to agree reasonably well with prior computer-predicted responses.

  14. Evaluating mountain meadow groundwater response to Pinyon-Juniper and temperature in a great basin watershed

    USGS Publications Warehouse

    Carroll, Rosemary W.H.; Huntington, Justin L.; Snyder, Keirith A.; Niswonger, Richard; Morton, Charles; Stringham, Tamzen K.

    2017-01-01

    This research highlights development and application of an integrated hydrologic model (GSFLOW) to a semiarid, snow-dominated watershed in the Great Basin to evaluate Pinyon-Juniper (PJ) and temperature controls on mountain meadow shallow groundwater. The work used Google Earth Engine Landsat satellite and gridded climate archives for model evaluation. Model simulations across three decades indicated that the watershed operates on a threshold response to precipitation (P) >400 mm/y to produce a positive yield (P-ET; 9%) resulting in stream discharge and a rebound in meadow groundwater levels during these wetter years. Observed and simulated meadow groundwater response to large P correlates with above average predicted soil moisture and with a normalized difference vegetation index threshold value >0.3. A return to assumed pre-expansion PJ conditions or an increase in temperature to mid-21st century shifts yielded by only ±1% during the multi-decade simulation period; but changes of approximately ±4% occurred during wet years. Changes in annual yield were largely dampened by the spatial and temporal redistribution of evapotranspiration across the watershed: Yet the influence of this redistribution and vegetation structural controls on snowmelt altered recharge to control water table depth in the meadow. Even a small-scale removal of PJ (0.5 km2) proximal to the meadow will promote a stable, shallow groundwater system resilient to droughts, while modest increases in temperature will produce a meadow susceptible to declining water levels and a community structure likely to move toward dry and degraded conditions.

  15. EVALUATION OF SMOKE AND GAS SENSOR RESPONSES FOR FIRES OF COMMON MINE COMBUSTIBLES

    PubMed Central

    Perera, Inoka Eranda; Litton, Charles D.

    2015-01-01

    Experiments were conducted to evaluate the response characteristics of commercially available gas, smoke, and flame sensors to fires of common combustible mine materials. The experiments were conducted in the large-scale Fire gallery located at the National Institute for Occupational Safety and Health (NIOSH) Lake Lynn Laboratory (LLL) in Fairchance, PA, using Ponderosa Pine, Red Oak, Douglas-fir, high and low volatile coals, PVC and SBR conveyor belt, No. 2 diesel fuel, and diesel exhaust. All the experiments (except those using No. 2 diesel fuel and the diesel exhaust tests) were conducted in a similar manner, with combustible materials heated rapidly by electrical strip heaters producing smoldering fires that quickly transitioned into flaming fires. The sensors included a diffusion-type carbon monoxide (CO) sensor, photoelectric- and ionization-type smoke sensors, a video smoke/flame detector, and an optical flame detector. Simultaneous measurements were obtained for average gas concentrations, smoke mass concentrations, and smoke optical densities in order to quantify the levels of combustion products at the alert and alarm times of the sensors. Because the required sensor alarm levels are 10 ppm and 0.044 m−1 optical density for CO and smoke sensors, respectively, the different sensor alarms are compared to the time at which the CO and smoke reached these alarm levels (1). In addition, the potential impact of using smoke sensors that have met the performance standards from accredited testing laboratories is also evaluated using the response of an Underwriters’ Laboratory (UL)-approved combination photoelectric/ionization smoke detector. The results are discussed relative to fire sensor needs that can have a positive impact on mine fire safety. PMID:26229418

  16. Evaluation of outbreak response immunization in the control of pertussis using agent-based modeling

    PubMed Central

    Qian, Weicheng; Osgood, Nathaniel D.

    2016-01-01

    10 years of a campaign, respectively. During the same time periods, 53, 96, and 163 cases were averted in the 10–14 age group, and 6, 11, 20 in infants under 1 (p < 0.001, all groups). Numbers needed to vaccinate ranged from 49 to 221, from 130 to 519 and from 1,031 to 4,903 for all ages, the 10–14 age group and for infants, respectively. Most sensitivity analyses resulted in minimal impact on a number of cases averted. Discussion Our model generated 30 years of longitudinal data to evaluate effects of outbreak response immunization in a controlled study. Immunization campaign implemented as an outbreak response measure among adolescents may confer benefits across all ages accruing over a 10-year period. Our inference is dependent on having an outbreak of significant magnitude affecting predominantly the selected age and achieving a comprehensive vaccine coverage during the campaign. Economic evaluations and comparisons with other control measures can add to conclusions generated by our work. PMID:27602299

  17. UAV Deployment Exercise for Mapping Purposes: Evaluation of Emergency Response Applications.

    PubMed

    Boccardo, Piero; Chiabrando, Filiberto; Dutto, Furio; Tonolo, Fabio Giulio; Lingua, Andrea

    2015-07-02

    Exploiting the decrease of costs related to UAV technology, the humanitarian community started piloting the use of similar systems in humanitarian crises several years ago in different application fields, i.e., disaster mapping and information gathering, community capacity building, logistics and even transportation of goods. Part of the author's group, composed of researchers in the field of applied geomatics, has been piloting the use of UAVs since 2006, with a specific focus on disaster management application. In the framework of such activities, a UAV deployment exercise was jointly organized with the Regional Civil Protection authority, mainly aimed at assessing the operational procedures to deploy UAVs for mapping purposes and the usability of the acquired data in an emergency response context. In the paper the technical features of the UAV platforms will be described, comparing the main advantages/disadvantages of fixed-wing versus rotor platforms. The main phases of the adopted operational procedure will be discussed and assessed especially in terms of time required to carry out each step, highlighting potential bottlenecks and in view of the national regulation framework, which is rapidly evolving. Different methodologies for the processing of the acquired data will be described and discussed, evaluating the fitness for emergency response applications.

  18. Evaluation drought response of tropical dry forests using advanced wireless sensor networks

    NASA Astrophysics Data System (ADS)

    Sanchez-Azofeifa, G. A.

    2015-12-01

    Understanding of the effects of persistent drought in tropical dry forests has not been fully studied until today. In this presentation we will discuss one of the first results on the response of tropical dry forests to drought using advanced wireless sensor networks and canopy phenology towers, that provide hyper-temporal information on micro-meteorological variables such Temperature, relative humidity, and Vapor Pressure Deficit (VPD). In addition, we will evaluate drought response to as function of the Fraction of the Photosynthetic Active Radiation (FPAR), and the Normalized Difference Vegetation Index (NDVI). Our work is conducted at the Santa Rosa Environmental Monitoring Super Site (NR-EMSS) located at the Guancaste Province, Costa Rica, Central America. Our results indicate significant changes in terms of FPAR, VPD manifested via strong changes on NDVI. Our results pose questions about the resilience of these understudied tropical ecosystems and their long-term survival under severe and persistent drought conditions. This results provide a reference framework for the need of more integrated research on the Central American Dry Forest corridor where just between Costa Rica and Nicaragua over 100,000 families are facing strong drought conditions.

  19. Evaluation of sprayable fixatives on a sandy soil for potential use in a dirty bomb response.

    PubMed

    Fritz, Brad G; Whitaker, John D

    2008-06-01

    After the events of 11 September 2001, the possibility of a dirty bomb being detonated within the United States seems more realistic. Development of tools for use in response to a dirty bomb detonation has become a topic of both discussion and research. While it has been reported that the health risk to the public from such an event would likely be small, it is thought that the psychological impact could be considerable. One response option that has been considered is adapting sprayable solutions for the purpose of fixing contamination in place, thereby limiting the spread of contamination by wind and rain and facilitating subsequent cleanup. This work evaluated two commercially available particle fixatives (IsoFIX-HT and IsoFIX-RC) for their effectiveness in preventing dispersal of simulated contamination. Nonradioactive cesium chloride and cobalt oxide particles were selected as the simulated contamination and applied to the surface of three outdoor test plots. Two test plots were treated with fixatives; the third plot provided a control. Samples were collected over 95 days to observe changes in tracer concentration on the surface of the test plots. One fixative (IsoFIX-RC) effectively held the tracer in place with no net loss of tracer, while the other fixative (IsoFIX-HT) had no impact on the loss of tracer relative to the control. Under the conditions tested, IsoFIX-RC appears capable of fixing surface contamination in place for at least several months.

  20. Evaluating the impact of aquifer layer properties on geomechanical response during CO2 geological sequestration

    SciTech Connect

    Bao, Jie; Xu, Zhijie; Lin, Guang; Fang, Yilin

    2013-04-01

    Numerical models play an essential role in understanding the facts of carbon dioxide (CO2) geological sequestration in the life cycle of a storage reservoir. We present a series of test cases that reflect a broad and realistic range of aquifer reservoir properties to systematically evaluate and compare the impacts on the geomechanical response to CO2 injection. In this study, a coupled hydro-mechanical model was introduced to simulate the sequestration process, and a quasi-Monte Carlo sampling method was introduced to efficiently sample the value of aquifer properties and geometry parameters. Aquifer permeability was found to be of significant importance to the geomechanical response to the injection. To study the influence of uncertainty of the permeability distribution in the aquifer, an additional series of tests is presented, based on a default permeability distribution site sample with various distribution deviations generated by the Monte Carlo sampling method. The results of the test series show that different permeability distributions significantly affect the displacement and possible failure zone.

  1. An evaluation of higher-order model methods for calculating transient structural response

    NASA Technical Reports Server (NTRS)

    Camarda, Charles J.; Haftka, Raphael T.; Riley, Michael F.

    1987-01-01

    A higher-order modal method proposed by Leung for transient structural analysis entitled the force-derivative method is evaluated. This method repeatedly integrates by parts with respect to time the convolution-integral form of the structural response to produce successively better approximations to the contribution of the higher modes which are neglected in the modal summation. Comparisons are made of the force-derivative, the mode-displacement, and the mode-acceleration methods for several numerical example problems for various times, levels of damping, and forcing functions. The example problems include a tip-loaded cantilevered beam and a simply-supported multispan beam. The force-derivative method is shown to converge to an accurate solution in fewer modes than either the mode-displacement or the mode-acceleration methods. In addition, for problems in which there are a large number of closely-spaced frequencies whose mode shapes have a negligible contribution to the response, the force-derivative method is very effective in representing the effect of the important, but otherwise neglected, higher modes.

  2. UAV Deployment Exercise for Mapping Purposes: Evaluation of Emergency Response Applications

    PubMed Central

    Boccardo, Piero; Chiabrando, Filiberto; Dutto, Furio; Giulio Tonolo, Fabio; Lingua, Andrea

    2015-01-01

    Exploiting the decrease of costs related to UAV technology, the humanitarian community started piloting the use of similar systems in humanitarian crises several years ago in different application fields, i.e., disaster mapping and information gathering, community capacity building, logistics and even transportation of goods. Part of the author’s group, composed of researchers in the field of applied geomatics, has been piloting the use of UAVs since 2006, with a specific focus on disaster management application. In the framework of such activities, a UAV deployment exercise was jointly organized with the Regional Civil Protection authority, mainly aimed at assessing the operational procedures to deploy UAVs for mapping purposes and the usability of the acquired data in an emergency response context. In the paper the technical features of the UAV platforms will be described, comparing the main advantages/disadvantages of fixed-wing versus rotor platforms. The main phases of the adopted operational procedure will be discussed and assessed especially in terms of time required to carry out each step, highlighting potential bottlenecks and in view of the national regulation framework, which is rapidly evolving. Different methodologies for the processing of the acquired data will be described and discussed, evaluating the fitness for emergency response applications. PMID:26147728

  3. Evaluation of antibody response to vaccination against West Nile virus in thick billed parrots (Rhynchopsitta pachyrhyncha).

    PubMed

    Glavis, Jennifer; Larsen, R Scott; Lamberski, Nadine; Gaffney, Patricia; Gardner, Ian

    2011-09-01

    West Nile virus (WNV) was first documented in North America in New York City in 1999. Several deaths attributable to WNV have been reported in captive thick-billed parrots (Rhynchopsitta pachyrhyncha), an endangered psittacine native to North America. The serologic responses in 12 captive adult thick-billed parrots after a series of three initial WNV vaccine injections with annual boosters over 6 yr was evaluated. In addition, the serologic responses of 11 thick-billed parrot chicks following an initial vaccination series to determine if there were seroconversions were also reported. Most adults (67%) had seroconverted after 5 yr of annual vaccination, with a median titer of 1:80 (range 1:40-1:160) for those that seroconverted. After the first year, birds were likely naturally exposed to WNV, which limited interpretation of titers. None of the chicks seroconverted during the initial three-vaccine series; only two of four chicks (50%) had seroconverted when tested at the 1-yr yearly booster, and at 2 yr, three of four chicks had seroconverted. Although some birds had detectable antibody titers, it is unclear whether this vaccine can reliably provide protection against WNV in thick-billed parrots.

  4. Evaluation of an automated procedure for detecting frequency-following responses in American and Chinese neonates.

    PubMed

    Jeng, Fuh-Cherng; Peris, Kevin S; Hu, Jiong; Lin, Chia-Der

    2013-04-01

    To date, observations of the scalp-recorded frequency-following response (FFR) to voice pitch have depended on subjective interpretation of the experimenter. The purpose of this study was to develop and evaluate an automated procedure for detecting the presence of a response. Twenty American (9 boys, 1-3 days) and 20 Chinese (10 boys, 1-3 days) neonates were recruited. A Chinese monosyllable that mimicked the English vowel /i/ with a rising pitch (117-166 Hz) was used as the stimulus. Three objective indices (Frequency Error, Tracking Accuracy, and Pitch Strength) were computed from the recorded brain waves and the test results were compared with human judgments to calculate the sensitivity and specificity values. Results demonstrated that the automated procedure produced sensitivity values between 53-90% and specificity values between 80-100%, and could be used to assess the presence of an FFR for neonates who were born in a tonal or non-tonal language environment.

  5. Dynamic response evaluation of tall noise barrier on high speed railway structures

    NASA Astrophysics Data System (ADS)

    Tokunaga, Munemasa; Sogabe, Masamichi; Santo, Tetsuo; Ono, Kiyoshi

    2016-03-01

    The aim of this paper is to obtain a fundamental understanding of the dynamic response of tall noise barriers during the passage of high speed train and to develop a practical method for evaluating this in anticipation of planned increases in running speed in the future. Tall noise barriers recently installed on Japanese high speed railway structures have a low natural frequency; therefore, they may resonate with the train draft pressure that up until now has not been a crucial condition for practical design. As a result of field measurements and numerical simulations, it was found that the dynamic response of noise barriers excited by passing trains can be explained by the resonance effect between pulse excitation of the train draft and the natural frequency of the noise barriers and by the tail-pulses overlap effect. Methods to generalize the resonance effect with the multi-body system and the tail-pulses overlap effect with the free vibration theory of the single-degree-of-freedom system were shown. Finally, two design methods were proposed: a precise method based on simulation and a simple method based on static design load. The simple method uses a design train draft pressure which is a function of noise barrier natural frequency when train speed is 260 m/h or 360 m/h.

  6. Evaluating Skill of Process-Based Models of Tree-Ring Response to Climate

    NASA Astrophysics Data System (ADS)

    Meko, D. M.; Stahle, D. W.

    2008-12-01

    Process-based models of tree-growth driven by climate input can deal with nonlinear processes and ideally are capable of modeling responses to climate fluctuations outside the range of climate variability in the observed instrumental record. Information from such models can be useful in assessing likely vegetation responses to projected climate change, and in posing climate scenarios associated with outstanding tree-ring anomalies of the past. An essential step in the evaluation of process-based models is assessment of skill, typically defined as accuracy of predictions relative to those generated by some reasonable alternative. A statistical framework for such an assessment is presented, with the alternative a dynamic black-box time series model. The black-box model is illustrated with prediction of the standard chronology tree-ring index for a Quercus douglasii (blue oak) tree-ring site in California from a PRISM-based precipitation record. A time series model with weights on current and past years' winter (Nov-Mar) precipitation is calibrated on data for 1896-1950 and used to predict the tree-ring index for 1951-2007. The variance of tree-ring index explained in the prediction period exceeds 75 percent, but prediction errors are slightly positively autocorrelated, and are negative for 12 consecutive years during a period that includes the drought of the late 1980s to early 1990s. Statistically-based predictions such as these are proposed as test data for skill assessment of process- based models. In such assessment it is essential that the calibration and prediction datasets are kept absolutely separate. No part of the calibration process, including identification of the "season" of climate response, should be allowed to access the data from the prediction interval. Likewise any tuning of the process-based model should be restricted to data outside the prediction period.

  7. Posaconazole exposure-response relationship: evaluating the utility of therapeutic drug monitoring.

    PubMed

    Dolton, Michael J; Ray, John E; Marriott, Deborah; McLachlan, Andrew J

    2012-06-01

    Posaconazole has become an important part of the antifungal armamentarium in the prophylaxis and salvage treatment of invasive fungal infections (IFIs). Structurally related to itraconazole, posaconazole displays low oral bioavailability due to poor solubility, with significant drug interactions and gastrointestinal disease also contributing to the generally low posaconazole plasma concentrations observed in patients. While therapeutic drug monitoring (TDM) of plasma concentrations is widely accepted for other triazole antifungal agents such as voriconazole, the utility of TDM for posaconazole is controversial due to debate over the relationship between posaconazole exposure in plasma and clinical response to therapy. This review examines the available evidence for a relationship between plasma concentration and clinical efficacy for posaconazole, as well as evaluating the utility of TDM and providing provisional target concentrations for posaconazole therapy. Increasing evidence supports an exposure-response relationship for plasma posaconazole concentrations for prophylaxis and treatment of IFIs; a clear relationship has not been identified between posaconazole concentration and toxicity. Intracellular and intrapulmonary concentrations have been studied for posaconazole but have not been correlated to clinical outcomes. In view of the high mortality and cost associated with the treatment of IFIs, increasing evidence of an exposure-response relationship for posaconazole efficacy in the prevention and treatment of IFIs, and the common finding of low posaconazole concentrations in patients, TDM for posaconazole is likely to be of significant clinical utility. In patients with subtherapeutic posaconazole concentrations, increased dose frequency, administration with high-fat meals, and withdrawal of interacting medications from therapy are useful strategies to improve systemic absorption.

  8. Evaluation of chemotherapy response in ovarian cancer treatment using quantitative CT image biomarkers: a preliminary study

    NASA Astrophysics Data System (ADS)

    Qiu, Yuchen; Tan, Maxine; McMeekin, Scott; Thai, Theresa; Moore, Kathleen; Ding, Kai; Liu, Hong; Zheng, Bin

    2015-03-01

    The purpose of this study is to identify and apply quantitative image biomarkers for early prediction of the tumor response to the chemotherapy among the ovarian cancer patients participated in the clinical trials of testing new drugs. In the experiment, we retrospectively selected 30 cases from the patients who participated in Phase I clinical trials of new drug or drug agents for ovarian cancer treatment. Each case is composed of two sets of CT images acquired pre- and post-treatment (4-6 weeks after starting treatment). A computer-aided detection (CAD) scheme was developed to extract and analyze the quantitative image features of the metastatic tumors previously tracked by the radiologists using the standard Response Evaluation Criteria in Solid Tumors (RECIST) guideline. The CAD scheme first segmented 3-D tumor volumes from the background using a hybrid tumor segmentation scheme. Then, for each segmented tumor, CAD computed three quantitative image features including the change of tumor volume, tumor CT number (density) and density variance. The feature changes were calculated between the matched tumors tracked on the CT images acquired pre- and post-treatments. Finally, CAD predicted patient's 6-month progression-free survival (PFS) using a decision-tree based classifier. The performance of the CAD scheme was compared with the RECIST category. The result shows that the CAD scheme achieved a prediction accuracy of 76.7% (23/30 cases) with a Kappa coefficient of 0.493, which is significantly higher than the performance of RECIST prediction with a prediction accuracy and Kappa coefficient of 60% (17/30) and 0.062, respectively. This study demonstrated the feasibility of analyzing quantitative image features to improve the early predicting accuracy of the tumor response to the new testing drugs or therapeutic methods for the ovarian cancer patients.

  9. Design and evaluation of novel fast forming pilocarpine-loaded ocular hydrogels for sustained pharmacological response

    PubMed Central

    Anumolu, SivaNaga S.; Singh, Yashveer; Gao, Dayuan; Stein, Stanley; Sinko, Patrick J.

    2009-01-01

    Fast forming hydrogels prepared by crosslinking a poly(ethylene glycol) (PEG)-based copolymer containing multiple thiol (SH) groups were evaluated for the controlled ocular delivery of pilocarpine and subsequent pupillary constriction. Physical properties of the hydrogels were characterized using UV-Vis spectrophotometry, transmission electron microscopy (TEM), rheometry, and swelling kinetics. Pilocarpine loading efficiency and release properties were measured in simulated tear fluid. The hydrogel formulations exhibited high drug loading efficiency (~74%). Pilocarpine release was found to be biphasic with release half times of ~2 and 94 h, respectively, and 85–100% of the drug was released over 8-days. Pilocarpine-loaded (2% w/v) hydrogels were evaluated in a rabbit model and compared to a similar dose of drug in aqueous solution. The hydrogels were retained in the eye for the entire period of the study with no observed irritation. Pilocarpine-loaded hydrogels sustained pupillary constriction for 24 h after administration as compared to 3 h for the solution, an 8-fold increase in duration of action. A strong correlation between pilocarpine release and pupillary response was observed. In conclusion, the current studies demonstrate that in situ forming PEG hydrogels possess the viscoelastic, retention, and sustained delivery properties required for an efficient ocular drug delivery system. PMID:19341773

  10. Evaluation of Sleeping Comfort of Bed Mattresses using Physiological and Psychological Response Measurements

    NASA Astrophysics Data System (ADS)

    Aoi, Masataka; Kamijo, Masayoshi; Yoshida, Hiroaki

    The purpose of this study is to create a method of evaluating the quality of sleep based on the elastic properties of bed mattresses through measurement of physiological and psychological responses while sleeping. We gathered Profile of Mood States (POMS) results before and after sleep, and investigated changes in subjects' moods according to sleep. A total of 4 bed mattresses with different degrees of elasticity were prepared. They were all pocket coil mattresses. We conducted polysomnography (PSG) testing on subjects with a bioamplifier while they slept in each bed mattress, so that sleeping depth indicating the quality of sleep could be estimated. PSG is a comprehensive recording of the biophysiological changes that occur during sleep. As a result, the sleep depth of bed mattress with a high degree of elasticity increased in the PSG evaluation. Because the hip sinks in deeply from the waist, it is not easy to turn over on mattresses with a low degree of elasticity. We have therefore considered that the sleep depth of the subjects became shallow as a result. We have concluded that it is possible to estimate the quality of sleep through analysis of PSG and POMS results.

  11. Evaluating stomatal models and their atmospheric drought response in a land surface scheme: A multibiome analysis

    NASA Astrophysics Data System (ADS)

    Knauer, Jürgen; Werner, Christiane; Zaehle, Sönke

    2015-10-01

    Stomatal conductance (gs) is a key variable in Earth system models as it regulates the transfer of carbon and water between the terrestrial biosphere and the lower atmosphere. Various approaches have been developed that aim for a simple representation of stomatal regulation applicable at the global scale. These models differ, among others, in their response to atmospheric humidity, which induces stomatal closure in a dry atmosphere. In this study, we compared the widely used empirical Ball-Berry and Leuning stomatal conductance models to an alternative empirical approach, an optimization-based approach, and a semimechanistic hydraulic model. We evaluated these models using evapotranspiration (ET) and gross primary productivity (GPP) observations derived from eddy covariance measurements at 56 sites across multiple biomes and climatic conditions. The different models were embedded in the land surface model JSBACH. Differences in performance across plant functional types or climatic conditions were small, partly owing to the large variations in the observational data. The models yielded comparable results at low to moderate atmospheric drought but diverged under dry atmospheric conditions, where models with a low sensitivity to air humidity tended to overestimate gs. The Ball-Berry model gave the best fit to the data for most biomes and climatic conditions, but all evaluated approaches have proven adequate for use in land surface models. Our findings further encourage future efforts toward a vegetation-type-specific parameterization of gs to improve the modeling of coupled terrestrial carbon and water dynamics.

  12. Comparative evaluation of test methods to simulate acoustic response of shroud-enclosed spacecraft structures

    NASA Technical Reports Server (NTRS)

    On, F. J.

    1975-01-01

    Test methods were evaluated to ascertain whether a spacecraft, properly tested within its shroud, could be vibroacoustic tested without the shroud, with adjustments made in the acoustic input spectra to simulate the acoustic response of the missing shroud. The evaluation was based on vibroacoustic test results obtained from a baseline model composed (1) of a spacecraft with adapter, lower support structure, and shroud; (2) of the spacecraft, adapter, and lower structure, but without the shroud; and (3) of the spacecraft and adapter only. Emphasis was placed on the magnitude of the acoustic input changes required to substitute for the shroud and the difficulty of making such input changes, and the degree of missimulation which can result from the performance of a particular, less-than optimum test. Conclusions are drawn on the advantages and disadvantages derived from the use of input spectra adjustment methods and lower support structure simulations. Test guidelines were also developed for planning and performing a launch acoustic-environmental test.

  13. Evaluation of dynamic coastal response to sea-level rise modifies inundation likelihood

    USGS Publications Warehouse

    Lentz, Erika E.; Thieler, E. Robert; Plant, Nathaniel G.; Stippa, Sawyer R.; Horton, Radley M.; Gesch, Dean B.

    2016-01-01

    Sea-level rise (SLR) poses a range of threats to natural and built environments1, 2, making assessments of SLR-induced hazards essential for informed decision making3. We develop a probabilistic model that evaluates the likelihood that an area will inundate (flood) or dynamically respond (adapt) to SLR. The broad-area applicability of the approach is demonstrated by producing 30 × 30 m resolution predictions for more than 38,000 km2 of diverse coastal landscape in the northeastern United States. Probabilistic SLR projections, coastal elevation and vertical land movement are used to estimate likely future inundation levels. Then, conditioned on future inundation levels and the current land-cover type, we evaluate the likelihood of dynamic response versus inundation. We find that nearly 70% of this coastal landscape has some capacity to respond dynamically to SLR, and we show that inundation models over-predict land likely to submerge. This approach is well suited to guiding coastal resource management decisions that weigh future SLR impacts and uncertainty against ecological targets and economic constraints.

  14. Preparation and evaluation of reduction-responsive nano-micelles for miriplatin delivery

    PubMed Central

    Zhang, Ying; Hu, Dejian; Han, Shangcong; Yan, Guowen; Ma, Chao; Wei, Chen; Yu, Miao; Sun, Yong

    2016-01-01

    A reduction-responsive amphiphilic core-shell micelle for miriplatin delivery was prepared and evaluated. A pyrene-terminated poly(2-(dimethylamino) ethyl acrylate) was synthesized through reversible addition–fragmentation chain transfer polymerization with 4-cyano-4-(ethylthiocarbonothioylthio) pentanoic acid as reversible addition–fragmentation chain transfer reagent and further modified by 2,2′-dithiodiethanol and 1-pyrenebutyric acid. Self-assembled blank micelles and drug-loaded micelles were obtained by dialysis method, and the particle size was proved to be about 40 nm with narrow dispersity by dynamic laser light scattering. Morphology results showed that blank micelles and drug-loaded micelles were spherical nanoparticles confirmed by transmission electron microscope, and the critical micelle concentration was as low as 6.09 µg/mL via pyrene fluorescence probe method. The reductive sensitivity of disulfide bond in BMs was further verified by changes in particle size, pyrene fluorescence intensity ratio (I338/I333), and morphology after treatment by dithiothreitol. Moreover, drug release rate in vitro of drug-loaded micelles was evaluated and the results suggested that this amphiphilic pyrene-modified poly(2-(dimethylamino) ethyl acrylate) can be used as reduction-triggered controlled release drug delivery carrier for hydrophobic drug. PMID:26743756

  15. Energy harvesting from the discrete gust response of a piezoaeroelastic wing: Modeling and performance evaluation

    NASA Astrophysics Data System (ADS)

    Xiang, Jinwu; Wu, Yining; Li, Daochun

    2015-05-01

    The objective of this paper is to investigate energy harvesting from the unfavorable gust response of a piezoelectric wing. An aeroelectroelastic model is built for the evaluation and improvement of the harvesting performance. The structural model is built based on the Euler-Bernoulli beam theory. The unsteady aerodynamics, combined with 1-cosine gust load, are obtained from Jones' approximation of the Wagner function. The state-space equation of the aeroelectroelastic model is derived and solved numerically. The energy conversion efficiency and output density are defined to evaluate the harvesting performance. The effects of the sizes and location of the piezoelectric transducers, the load resistance in the external circuit, and the locations of the elastic axis and gravity center axis of the wing are studied, respectively. The results show that, under a given width of the transducers in chordwise direction, there are one thickness of the transducers corresponding to highest conversion efficiency and one smaller optimal value for the output density. The conversion efficiency has an approximate linear relationship with the width. As the transducers are placed at the wing root, a maximum conversion efficiency is reached under a certain length in the spanwise direction, whereas a smaller length helps reaching a larger output density. One optimal resistance is found to maximize the conversion efficiency. The rearward shift of either the elastic axis or gravity center axis improves the energy output while reducing the conversion efficiency.

  16. Evaluation of Dynamic Coastal Response to Sea-level Rise Modifies Inundation Likelihood

    NASA Technical Reports Server (NTRS)

    Lentz, Erika E.; Thieler, E. Robert; Plant, Nathaniel G.; Stippa, Sawyer R.; Horton, Radley M.; Gesch, Dean B.

    2016-01-01

    Sea-level rise (SLR) poses a range of threats to natural and built environments, making assessments of SLR-induced hazards essential for informed decision making. We develop a probabilistic model that evaluates the likelihood that an area will inundate (flood) or dynamically respond (adapt) to SLR. The broad-area applicability of the approach is demonstrated by producing 30x30m resolution predictions for more than 38,000 sq km of diverse coastal landscape in the northeastern United States. Probabilistic SLR projections, coastal elevation and vertical land movement are used to estimate likely future inundation levels. Then, conditioned on future inundation levels and the current land-cover type, we evaluate the likelihood of dynamic response versus inundation. We find that nearly 70% of this coastal landscape has some capacity to respond dynamically to SLR, and we show that inundation models over-predict land likely to submerge. This approach is well suited to guiding coastal resource management decisions that weigh future SLR impacts and uncertainty against ecological targets and economic constraints.

  17. Self-compassion training modulates alpha-amylase, heart rate variability, and subjective responses to social evaluative threat in women

    PubMed Central

    Arch, Joanna J.; Brown, Kirk Warren; Dean, Derek J.; Landy, Lauren N.; Brown, Kimberley; Laudenslager, Mark L.

    2014-01-01

    A growing body of research has revealed that social evaluative stressors trigger biological and psychological responses that in chronic forms have been linked to aging and disease. Recent research suggests that self-compassion may protect the self from typical defensive responses to evaluation. We investigated whether brief training in self-compassion moderated biopsychological responses to the Trier Social Stress Test (TSST) in women. Compared to attention (placebo) and no-training control conditions, brief self-compassion training diminished sympathetic (salivary alpha-amylase), cardiac parasympathetic, and subjective anxiety responses, though not HPA-axis (salivary cortisol) responses to the TSST. Self-compassion training also led to greater self-compassion under threat relative to the control groups. In that social stress pervades modern life, self-compassion represents a promising approach to diminishing its potentially negative psychological and biological effects. PMID:24636501

  18. Providing Reliability Services through Demand Response: A Prelimnary Evaluation of the Demand Response Capabilities of Alcoa Inc.

    SciTech Connect

    Starke, Michael R; Kirby, Brendan J; Kueck, John D; Todd, Duane; Caulfield, Michael; Helms, Brian

    2009-02-01

    Demand response is the largest underutilized reliability resource in North America. Historic demand response programs have focused on reducing overall electricity consumption (increasing efficiency) and shaving peaks but have not typically been used for immediate reliability response. Many of these programs have been successful but demand response remains a limited resource. The Federal Energy Regulatory Commission (FERC) report, 'Assessment of Demand Response and Advanced Metering' (FERC 2006) found that only five percent of customers are on some form of demand response program. Collectively they represent an estimated 37,000 MW of response potential. These programs reduce overall energy consumption, lower green house gas emissions by allowing fossil fuel generators to operate at increased efficiency and reduce stress on the power system during periods of peak loading. As the country continues to restructure energy markets with sophisticated marginal cost models that attempt to minimize total energy costs, the ability of demand response to create meaningful shifts in the supply and demand equations is critical to creating a sustainable and balanced economic response to energy issues. Restructured energy market prices are set by the cost of the next incremental unit of energy, so that as additional generation is brought into the market, the cost for the entire market increases. The benefit of demand response is that it reduces overall demand and shifts the entire market to a lower pricing level. This can be very effective in mitigating price volatility or scarcity pricing as the power system responds to changing demand schedules, loss of large generators, or loss of transmission. As a global producer of alumina, primary aluminum, and fabricated aluminum products, Alcoa Inc., has the capability to provide demand response services through its manufacturing facilities and uniquely through its aluminum smelting facilities. For a typical aluminum smelter, electric power

  19. Evaluation of Patients’ Response Toward Osteoporosis Letter Intervention Versus Phone Call Plus Letter Intervention

    PubMed Central

    O’Brien, Lisa K.; Armstrong, April D.; Hassenbein, Susan E.

    2015-01-01

    Introduction: The aim of this study was to compare the effectiveness of 2 interventions in prompting patients to obtain osteoporosis follow-up after a fracture. Our hypothesis was that a phone call plus letter would yield greater response toward osteoporosis evaluation versus a letter alone to patients after sustaining a fragility fracture. Materials and Methods: Prospective study randomized 141 patients age 50 years and older with a fragility fracture into 3 groups for comparison. Group 1 (letter only) patients received a letter 3 months after their diagnosis of fracture indicating their risk for osteoporosis and urging them to follow-up for evaluation. Group 2 (phone call plus letter) patients were contacted via phone 3 months after their diagnosis of fracture. A letter followed the phone call. Group 3 (control) patients were neither contacted via phone nor sent a letter. All groups were contacted via phone 6 months after their initial visit to determine if they followed up for evaluation. Results: In group 1, 23 (52.27%) of 44 had follow-up, and 21 (47.73%) of 44 did not follow-up. In group 2, 30 (62.5%) of 48 had follow-up, and 18 (37.50%) of 48 did not follow-up. In group 3, 6 (12.24%) of 49 had some sort of follow-up, and 43 (87.76%) of 49 did not have any follow-up. A statistical significance was achieved between group 3 (control) and both groups 1 and 2 with regard to follow-up (P < .0001). The results did not show a statistically significant difference between Groups 1 and 2, however, there was a trend toward improved response with a phone call plus letter (P = .321). Conclusion: A more personalized approach with a phone call plus follow-up letter to patients increased osteoporosis follow-up care by an additional 10%, however, this was not a statistically significant difference from just sending out a letter alone. PMID:26623157

  20. Investigating Assessment Bias for Constructed Response Explanation Tasks: Implications for Evaluating Performance Expectations for Scientific Practice

    NASA Astrophysics Data System (ADS)

    Federer, Meghan Rector

    Assessment is a key element in the process of science education teaching and research. Understanding sources of performance bias in science assessment is a major challenge for science education reforms. Prior research has documented several limitations of instrument types on the measurement of students' scientific knowledge (Liu et al., 2011; Messick, 1995; Popham, 2010). Furthermore, a large body of work has been devoted to reducing assessment biases that distort inferences about students' science understanding, particularly in multiple-choice [MC] instruments. Despite the above documented biases, much has yet to be determined for constructed response [CR] assessments in biology and their use for evaluating students' conceptual understanding of scientific practices (such as explanation). Understanding differences in science achievement provides important insights into whether science curricula and/or assessments are valid representations of student abilities. Using the integrative framework put forth by the National Research Council (2012), this dissertation aimed to explore whether assessment biases occur for assessment practices intended to measure students' conceptual understanding and proficiency in scientific practices. Using a large corpus of undergraduate biology students' explanations, three studies were conducted to examine whether known biases of MC instruments were also apparent in a CR instrument designed to assess students' explanatory practice and understanding of evolutionary change (ACORNS: Assessment of COntextual Reasoning about Natural Selection). The first study investigated the challenge of interpreting and scoring lexically ambiguous language in CR answers. The incorporation of 'multivalent' terms into scientific discourse practices often results in statements or explanations that are difficult to interpret and can produce faulty inferences about student knowledge. The results of this study indicate that many undergraduate biology majors

  1. Coordination of cortisol response to social evaluative threat with autonomic and inflammatory responses is moderated by stress appraisals and affect.

    PubMed

    Laurent, Heidemarie K; Lucas, Todd; Pierce, Jennifer; Goetz, Stefan; Granger, Douglas A

    2016-07-01

    Recent approaches to stress regulation have emphasized coordination among multiple biological systems. This study builds on evidence that hypothalamic-pituitary-adrenal (HPA) axis activity should be considered in coordination with other stress-sensitive biological systems to characterize healthy responses. Healthy African-Americans (n=115) completed the Trier Social Stress Test, and biological responses were assessed through salivary cortisol, dehydroepiandrosterone-sulfate (DHEA-S), alpha amylase (sAA), and C-reactive protein (sCRP). Multilevel modeling demonstrated that cortisol responses typically aligned with changes in DHEA-S, sAA, and sCRP across the session. At the same time, the degree of cortisol coordination with sAA and sCRP varied by participants' subjective stress following the task; participants with higher secondary stress appraisals showed greater cortisol-sAA alignment, whereas those experiencing more negative affect showed greater cortisol-sCRP alignment. Results highlight the importance of a multisystem approach to stress and suggest that positive HPA axis coordination with the autonomic response, but not with the immune/inflammatory response, may be adaptive.

  2. Carbon monoxide-releasing molecule-2 enhances coagulation in rabbit plasma and decreases bleeding time in clopidogrel/aspirin-treated rabbits.

    PubMed

    Nielsen, Vance G; Chawla, Nikhil; Mangla, Dipty; Gomes, Sheldon B; Arkebauer, Matthew R; Wasko, Kimberly A; Sadacharam, Kesavan; Vosseller, Keith

    2011-12-01

    Administration of carbon monoxide derived from carbon monoxide-releasing molecules has been demonstrated to enhance coagulation in vitro at small concentrations (100-200 μmol/l) in human and rabbit plasma. We sought to determine if carbon monoxide-releasing molecule-2 [tricarbonyldichlororuthenium (II) dimer, CORM-2] would improve coagulation in rabbit plasma in vitro via thrombelastography and in an in vivo preclinical rabbit model of ear bleeding time following administration of clopidogrel (20 mg/kg) with aspirin (10 mg/kg) via gavage. Addition of 100 μmol/l CORM-2 to rabbit plasma significantly improved coagulation. This procoagulant effect was blocked by pre-exposure of plasma to an agent that converts hemefibrinogen to methemefibrinogen in human plasma, preventing carbon monoxide binding and enhancement of coagulation. Rabbit ear bleeding time was 5.8 ± 1.1 min 2-3 h after clopidogrel/aspirin administration. Bleeding time significantly decreased to 2.6 ± 0.6 min, 5 min after administration of CORM-2 (10 mg/kg; 279 μmol/l 'best-case' instantaneous concentration) intravenously. CORM-2 enhances plasmatic coagulation in a manner similar to that of human plasma in vitro, and plasmatic coagulation is enhanced in vivo by CORM-2 as well. Additional preclinical investigation of the effects of CORM-2 on coagulopathy (e.g. heparin or hemodilution mediated) utilizing this rabbit model is planned.

  3. The risk of bleeding of triple therapy with vitamin K-antagonists, aspirin and clopidogrel after coronary stent implantation: Facts and questions

    PubMed Central

    Rubboli, Andrea

    2011-01-01

    Background Triple therapy (TT) with vitamin K-antagonists (VKA), aspirin and clopidogrel is the recommended antithrombotic treatment following percutaneous coronary intervention with stent implantation (PCI-S) in patients with an indication for oral anticoagulation. TT is associated with an increased risk of bleeding, but available evidence is flawed by important limitations, including the limited size and the retrospective design of most of the studies, as well as the rare reporting of the incidence of in-hospital bleeding and the treatment which was actually ongoing at the time of bleeding. Since the perceived high bleeding risk of TT may deny patients effective strategies, the determination of the true safety profile of TT is of paramount importance. Methods All the 27 published studies where the incidence of bleeding at various time points during follow-up has been reported separately for patients on TT were reviewed, and the weakness of the data was analyzed. Results The absolute incidence of major bleeding upon discharge at in-hospital, ≤ 1 month, 6 months, 12 months and ≥ 12 months was: 3.3% ± 1.9%, 5.1% ± 6.7%, 8.0% ± 5.2%, 9.0% ± 8.0, and 6.2% ± 7.8%, respectively, and not substantially different from that observed in previous studies with prolonged dual antiplatelet treatment with aspirin and clopidogrel. Conclusions While waiting for the ongoing, large-scale, registries and clinical trials to clarify the few facts and to answer the many questions regarding the risk of bleeding of TT, this treatment should not be denied to patients with an indication for VKA undergoing PCI-S provided that the proper measures and cautions are implemented. PMID:22783307

  4. Evaluating Cumulative Ecosystem Response to Restoration Projects in the Columbia River Estuary, Annual Report 2004

    SciTech Connect

    Diefenderfer, Heida L.; Roegner, Curtis; Thom, Ronald M.; Dawley, Earl M.; Whiting, Allan H.; Johnson, Gary E.; Sobocinski, Kathryn L.; Anderson, Michael G.; Ebberts, Blaine

    2005-12-15

    The restoration of wetland salmon habitat in the tidal portion of the Columbia River is occurring at an accelerating pace and is anticipated to improve habitat quality and effect hydrological reconnection between existing and restored habitats. Currently multiple groups are applying a variety of restoration strategies in an attempt to emulate historic estuarine processes. However, the region lacks both a standardized means of evaluating the effectiveness of individual projects as well as methods for determining the cumulative effects of all restoration projects on a regional scale. This project is working to establish a framework to evaluate individual and cumulative ecosystem responses to restoration activities in order to validate the effectiveness of habitat restoration activities designed to benefit salmon through improvements to habitat quality and habitat opportunity (i.e. access) in the Columbia River from Bonneville Dam to the ocean. The review and synthesis of approaches to measure the cumulative effects of multiple restoration projects focused on defining methods and metrics of relevance to the CRE, and, in particular, juvenile salmon use of this system. An extensive literature review found no previous study assessing the cumulative effects of multiple restoration projects on the fundamental processes and functions of a large estuarine system, although studies are underway in other large land-margin ecosystems including the Florida Everglades and the Louisiana coastal wetlands. Literature from a variety of scientific disciplines was consulted to identify the ways that effects can accumulate (e.g., delayed effects, cross-boundary effects, compounding effects, indirect effects, triggers and thresholds) as well as standard and innovative tools and methods utilized in cumulative effects analyses: conceptual models, matrices, checklists, modeling, trends analysis, geographic information systems, carrying capacity analysis, and ecosystem analysis. Potential

  5. Building Effectiveness in Teaching through Targeted Evaluation and Response: Connecting Evaluation to Teaching Improvement in Higher Education

    ERIC Educational Resources Information Center

    Smith, Calvin

    2008-01-01

    This paper describes the development of a model for integrating student evaluation of teaching results with academic development opportunities, in new ways that take into account theoretical and practical developments in both fields. The model is described in terms of five phases or components: (1) the basic student evaluation system; (2) an…

  6. SU-E-QI-20: A Review of Advanced PET and CT Image Features for the Evaluation of Tumor Response

    SciTech Connect

    Lu, W

    2014-06-15

    Purpose: To review the literature in using quantitative PET and CT image features for the evaluation of tumor response. Methods: We reviewed and summarized more than fifty papers that use advanced, quantitative PET/CT image features for the evaluation of tumor response. We also discussed future works on extracting disease-specific features, combining multiple and complementary features in response modeling, delineating tumor in multimodality images, and exploring biological explanations of these advanced features. Results: Advanced PET image features considering spatial information, such as tumor volume, tumor shape, total glycolytic volume, histogram distance, and texture features (characterizing spatial distribution of FDG uptake) have been found more informative than the traditional SUVmax for the prediction of tumor response. Advanced CT features, including volumetric, attenuation, morphologic, structure, and texture descriptors, have also been found advantage over the traditional RECIST and WHO criteria in certain tumor types. Conclusions: Advanced, quantitative FDG PET/CT image features have been shown promising for the evaluation of tumor response. With the emerging multi-modality imaging performed at multiple time points for each patient, it becomes more important to analyze the serial images quantitatively, select and combine both complementary and contradictory information from various sources, for accurate and personalized evaluation of tumor response to therapy.

  7. An evaluation of the Barnes objective analysis response - Two-dimensional theoretical response, sensitivity to observing networks, and 'actual' response. [in meteorology

    NASA Technical Reports Server (NTRS)

    Wu, Xiaohua; Pauley, Patricia M.

    1989-01-01

    A principal advantage of the Barnes (1964, 1973) scheme is its theoretical response function through which the response of the analysis at a particular wavelength can be predicted. The objective of this paper is to examine the accuracy and efficiency of the Barnes scheme for different data distributions. Then, the 'actual' response is used to estimate the true attenuation of a wave in the filtered field.

  8. Response

    ERIC Educational Resources Information Center

    Higgins, Chris

    2012-01-01

    This article presents the author's response to the reviews of his book, "The Good Life of Teaching: An Ethics of Professional Practice." He begins by highlighting some of the main concerns of his book. He then offers a brief response, doing his best to address the main criticisms of his argument and noting where the four reviewers (Charlene…

  9. 33 CFR Appendix C to Part 154 - Guidelines for Determining and Evaluating Required Response Resources for Facility Response Plans

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ....1047 of subpart F, or § 154.1135 of subpart G, as appropriate. An on water speed of 5 knots and a land... used in close-to-shore response activities in shallow water. The following percentages of the on-water...-water recovery must take into account a loss of some oil to the environment due to evaporative...

  10. 33 CFR Appendix C to Part 154 - Guidelines for Determining and Evaluating Required Response Resources for Facility Response Plans

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... refer to the applicable local contingency plan or ACP, as appropriate, to determine if ice, debris, and... the applicable response capability caps in Table 5 of this appendix shall identify sources of... contracting caps in Table 5 shall identify sources of additional equipment equal to twice the cap listed...

  11. 33 CFR Appendix C to Part 154 - Guidelines for Determining and Evaluating Required Response Resources for Facility Response Plans

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... refer to the applicable local contingency plan or ACP, as appropriate, to determine if ice, debris, and... the applicable response capability caps in Table 5 of this appendix shall identify sources of... contracting caps in Table 5 shall identify sources of additional equipment equal to twice the cap listed...

  12. 33 CFR Appendix C to Part 154 - Guidelines for Determining and Evaluating Required Response Resources for Facility Response Plans

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... refer to the applicable local contingency plan or ACP, as appropriate, to determine if ice, debris, and... the applicable response capability caps in Table 5 of this appendix shall identify sources of... contracting caps in Table 5 shall identify sources of additional equipment equal to twice the cap listed...

  13. 33 CFR Appendix C to Part 154 - Guidelines for Determining and Evaluating Required Response Resources for Facility Response Plans

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... refer to the applicable local contingency plan or ACP, as appropriate, to determine if ice, debris, and... the applicable response capability caps in Table 5 of this appendix shall identify sources of... contracting caps in Table 5 shall identify sources of additional equipment equal to twice the cap listed...

  14. Linear Modeling and Evaluation of Controls on Flow Response in Western Post-Fire Watersheds

    NASA Astrophysics Data System (ADS)

    Saxe, S.; Hogue, T. S.; Hay, L.

    2015-12-01

    This research investigates the impact of wildfires on watershed flow regimes throughout the western United States, specifically focusing on evaluation of fire events within specified subregions and determination of the impact of climate and geophysical variables in post-fire flow response. Fire events were collected through federal and state-level databases and streamflow data were collected from U.S. Geological Survey stream gages. 263 watersheds were identified with at least 10 years of continuous pre-fire daily streamflow records and 5 years of continuous post-fire daily flow records. For each watershed, percent changes in runoff ratio (RO), annual seven day low-flows (7Q2) and annual seven day high-flows (7Q10) were calculated from pre- to post-fire. Numerous independent variables were identified for each watershed and fire event, including topographic, land cover, climate, burn severity, and soils data. The national watersheds were divided into five regions through K-clustering and a lasso linear regression model, applying the Leave-One-Out calibration method, was calculated for each region. Nash-Sutcliffe Efficiency (NSE) was used to determine the accuracy of the resulting models. The regions encompassing the United States along and west of the Rocky Mountains, excluding the coastal watersheds, produced the most accurate linear models. The Pacific coast region models produced poor and inconsistent results, indicating that the regions need to be further subdivided. Presently, RO and HF response variables appear to be more easily modeled than LF. Results of linear regression modeling showed varying importance of watershed and fire event variables, with conflicting correlation between land cover types and soil types by region. The addition of further independent variables and constriction of current variables based on correlation indicators is ongoing and should allow for more accurate linear regression modeling.

  15. Evaluation of Rock Mass Responses Using High Resolution Water-level Tiltmeter Arrays

    NASA Astrophysics Data System (ADS)

    Roberts, J. S.; Wang, H. F.; Fratta, D.; Stetler, L. D.; Volk, J. T.; Geox^Tm

    2010-12-01

    External forces act on the surface of the earth and produce deformation across all spatial and temporal scales. This research study focuses on the deformation evaluation of the rock-mass subjected to tidal, earthquake and surface forces. The events are monitored over horizontal distances of over 100 meters with tilt measurement arrays with a resolution of 10-8 radians. These measurements are obtained from hydrostatic leveling system (HLS) arrays that have been installed in the LaFarge mine in North Aurora, IL by Fermilab. Each sensor in the array is equipped with a water-filled reservoir beneath a capacitor. The amount of water in the reservoir is calculated as a function of the measured capacitance. Individual sensors are connected in a closed system via a water and air line. As the host rock expands and contracts sensors are raised relative to another and water is displaced. The water level in each reservoir is sent to a computer in the mine and recorded. In order to measure the tilt of the rock between two points, the difference in water levels between adjacent sensors is computed. The difference between the end sensors is also calculated to determine the larger-scale tilt of the array. The tiltmeters in LaFarge mine are supported by concrete pedestals installed on the floor of the drift. In the Homestake mine the tiltmeters are placed on similar pedestals, as well as platforms made of artificial wood decking. These platforms are fixed to the wall of the drift with a rock bolt. Time and frequency domain analyses were performed on time series ranging from hours to six months to capture relevant time scales including the response to the 2010 Chile Earthquake (hour-long scale), the stages of the moon (month scale), Fox River floods (flooding week long scales and pressure dissipation month-long scales). By monitoring tiltmeter array responses to different forces, we aim at making predictions about the material properties of rock masses.

  16. Functional Analysis: Evaluation of Response Intensities - Tailoring ANOVA for Lists of Expression Subsets

    PubMed Central

    2010-01-01

    Background Microarray data is frequently used to characterize the expression profile of a whole genome and to compare the characteristics of that genome under several conditions. Geneset analysis methods have been described previously to analyze the expression values of several genes related by known biological criteria (metabolic pathway, pathology signature, co-regulation by a common factor, etc.) at the same time and the cost of these methods allows for the use of more values to help discover the underlying biological mechanisms. Results As several methods assume different null hypotheses, we propose to reformulate the main question that biologists seek to answer. To determine which genesets are associated with expression values that differ between two experiments, we focused on three ad hoc criteria: expression levels, the direction of individual gene expression changes (up or down regulation), and correlations between genes. We introduce the FAERI methodology, tailored from a two-way ANOVA to examine these criteria. The significance of the results was evaluated according to the self-contained null hypothesis, using label sampling or by inferring the null distribution from normally distributed random data. Evaluations performed on simulated data revealed that FAERI outperforms currently available methods for each type of set tested. We then applied the FAERI method to analyze three real-world datasets on hypoxia response. FAERI was able to detect more genesets than other methodologies, and the genesets selected were coherent with current knowledge of cellular response to hypoxia. Moreover, the genesets selected by FAERI were confirmed when the analysis was repeated on two additional related datasets. Conclusions The expression values of genesets are associated with several biological effects. The underlying mathematical structure of the genesets allows for analysis of data from several genes at the same time. Focusing on expression levels, the direction of the

  17. Evaluating the Efficacy of a Sternocleidomastoid Flap via Galvanic Skin Responses in Superficial Parotidectomy.

    PubMed

    Basut, Oguz; Noyan, Behzat; Demirci, Ugur

    2014-01-01

    In the present study, we evaluated the efficacy of flaps via measurement of galvanic skin responses (GSR) in patients who had undergone superficial parotidectomy either with or without sternocleidomastoid (SCM) muscle flaps. Retrospective study design was used. The setting included University of Uludag School of Medicine Department of Otorhinolaryngology. Eleven patients who had undergone superficial parotidectomy for benign diseases in our clinic between June 2003 and August 2006 were included in the study. SCM muscle flaps were used in four patients. The GSR of the patients were measured using a MP 30 System. The Mann-Whitney U test was used for the analysis of data. There were complaints that resembled Frey's syndrome in three patients in whom flaps had not been performed. Patients with flaps had no complaints. In patients with flaps, no significant GSR changes were observed between the control and operated sides (P > 0.05). In patients without flaps, the GSR levels were significantly higher on the operated side compared to the control side (P < 0.05). GSR values on the control side did not show any differences between patients with and without a flap. However, there were significantly higher GSR values for the operated side in patients without flaps compared to patients with flaps (P < 0.05). Application of a SCM flap is an efficient method by which to prevent Frey's syndrome, and the GSR test is beneficial both in diagnosiing and determining the severity of the disease as well as evaluating the efficacy of surgical techniques used to prevent Frey's syndrome.

  18. Evaluating multi-level models to test occupancy state responses of Plethodontid salamanders

    USGS Publications Warehouse

    Kroll, Andrew J.; Garcia, Tiffany S.; Jones, Jay E.; Dugger, Catherine; Murden, Blake; Johnson, Josh; Peerman, Summer; Brintz, Ben; Rochelle, Michael

    2015-01-01

    Plethodontid salamanders are diverse and widely distributed taxa and play critical roles in ecosystem processes. Due to salamander use of structurally complex habitats, and because only a portion of a population is available for sampling, evaluation of sampling designs and estimators is critical to provide strong inference about Plethodontid ecology and responses to conservation and management activities. We conducted a simulation study to evaluate the effectiveness of multi-scale and hierarchical single-scale occupancy models in the context of a Before-After Control-Impact (BACI) experimental design with multiple levels of sampling. Also, we fit the hierarchical single-scale model to empirical data collected for Oregon slender and Ensatina salamanders across two years on 66 forest stands in the Cascade Range, Oregon, USA. All models were fit within a Bayesian framework. Estimator precision in both models improved with increasing numbers of primary and secondary sampling units, underscoring the potential gains accrued when adding secondary sampling units. Both models showed evidence of estimator bias at low detection probabilities and low sample sizes; this problem was particularly acute for the multi-scale model. Our results suggested that sufficient sample sizes at both the primary and secondary sampling levels could ameliorate this issue. Empirical data indicated Oregon slender salamander occupancy was associated strongly with the amount of coarse woody debris (posterior mean = 0.74; SD = 0.24); Ensatina occupancy was not associated with amount of coarse woody debris (posterior mean = -0.01; SD = 0.29). Our simulation resu